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Sample records for greater genistein bioavailability

  1. Eudragit nanoparticles containing genistein: formulation, development, and bioavailability assessment

    Directory of Open Access Journals (Sweden)

    Tang J

    2011-10-01

    Full Text Available Jingling Tang2, Na Xu1,2, Hongyu Ji1, Hongmei Liu1, Zhiyong Wang1, Linhua Wu1,2 1Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University, Key Laboratory of College in Heilongjiang Province; 2Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, China Background: Genistein, one of the major isoflavones, has received great attention as a phytoestrogen and potential cancer chemoprevention agent. However, the dissolution and bioavailability of genistein from solid oral preparations is low due to its poor water solubility. Methods: In order to improve the oral bioavailability of genistein, genistein nanoparticles were prepared by the nanoprecipitation technique using Eudragit® E100 as carriers and an optimized formulation of mass ratio (genistein:Eudragit E100, 1:10. The mean particle size of genistein nanoparticles was approximately 120 nm when diluted 100 times with distilled water. The drug-loaded nanoparticles were spherical on observation by transmission electric microscopy. Results: Encapsulation efficiency and drug loading of the genistein nanoparticles were approximately 50.61% and 5.02%, respectively. Release of drug from the genistein nanoparticles was two times greater than that from the conventional capsules. After administration of genistein suspension or genistein nanoparticles at a single dose of 100 mg/kg to fasted rats, the relative bioavailability of genistein from the nanoparticles compared with the reference suspension was 241.8%. Conclusion: These results suggested that a nanoparticle system is a potentially promising formulation for the efficient delivery of poorly water-soluble drugs by oral administration. Keywords: bioavailability, dissolution, genistein, nanoparticles, nanoprecipitation technique

  2. Bioavailability

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    Jensen, J. [National Environmental Research Inst., Silkeborg (Denmark). Dept. of Terrestrial Ecology

    2003-07-01

    Although commonly discussed and debated the scientific basis for adequately using bioavailability in ecological risk assessment is still relatively weak. One of the first obstacles to solve is to define the term properly. It must be recognised that bioavailability is dynamic processes comprising several distinct phases. One is the adsorption/desorption process (chemical availability) controlled by parameters like pH, clay, CEC and organic matter. Another one is a physiological driven uptake process (biological availability) controlled by species-specific parameters like anatomy, feeding strategy, preferences in micro-habitat etc. The last one is an internal allocation process (toxicological availability) controlled by species specific parameters like metabolism, detoxification, storage, excretion, energy resources etc. The complexity of bioavailability means that there seems no straight way forward how to handle bioavailability in the risk assessment procedure. Nevertheless, what almost all people - from scientists to problem holders and responsible authorities - agree upon is that there is a need for alternatives to the common use of the 'total concentration approach'. From an ecological perspective, biological tools would be preferred when assessing risk to ecosystems. However, due to the lower cost and higher reproducibility chemical tools may often be the best suitable solutions. The outcome of mild extraction procedures like CaCl{sub 2} have for example been shown to correlated relatively well to ecotoxicological effects of heavy metals. Bioavailability of organic pollutants has less frequently been correlated to ecological effects of organisms within the soil compartment and adjacent water systems. It has nevertheless been documented that mild extractors like n-butanol, propanol, ethyl acetate and acetonitrile are useful in predicting the uptake of PAHs in earthworms and plants as well as microbial toxicity. (orig.)

  3. Genistein genotoxicity: Critical considerations of in vitro exposure dose

    International Nuclear Information System (INIS)

    Klein, Catherine B.; King, Audrey A.

    2007-01-01

    The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein > 5 μM as non-physiological, and thus 'high' doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of 'the dose defines the poison' applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein

  4. Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor.

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    Honma, Daisuke; Kanno, Osamu; Watanabe, Jun; Kinoshita, Junzo; Hirasawa, Makoto; Nosaka, Emi; Shiroishi, Machiko; Takizawa, Takeshi; Yasumatsu, Isao; Horiuchi, Takao; Nakao, Akira; Suzuki, Keisuke; Yamasaki, Tomonori; Nakajima, Katsuyoshi; Hayakawa, Miho; Yamazaki, Takanori; Yadav, Ajay Singh; Adachi, Nobuaki

    2017-10-01

    Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing either EZH2 or EZH1. Tumorigenic functions of EZH2 and its synthetic lethality with some subunits of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes have been observed. However, little is known about the function of EZH1 in tumorigenesis. Herein, we developed novel, orally bioavailable EZH1/2 dual inhibitors that strongly and selectively inhibited methyltransferase activity of both EZH2 and EZH1. EZH1/2 dual inhibitors suppressed trimethylation of histone H3 lysine 27 in cells more than EZH2 selective inhibitors. They also showed greater antitumor efficacy than EZH2 selective inhibitor in vitro and in vivo against diffuse large B-cell lymphoma cells harboring gain-of-function mutation in EZH2. A hematological cancer panel assay indicated that EZH1/2 dual inhibitor has efficacy against some lymphomas, multiple myeloma, and leukemia with fusion genes such as MLL-AF9, MLL-AF4, and AML1-ETO. A solid cancer panel assay demonstrated that some cancer cell lines are sensitive to EZH1/2 dual inhibitor in vitro and in vivo. No clear correlation was detected between sensitivity to EZH1/2 dual inhibitor and SWI/SNF mutations, with a few exceptions. Severe toxicity was not seen in rats treated with EZH1/2 dual inhibitor for 14 days at drug levels higher than those used in the antitumor study. Our results indicate the possibility of EZH1/2 dual inhibitors for clinical applications. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  5. Endocrine disruptors and hypospadias: role of genistein and the fungicide vinclozolin.

    Science.gov (United States)

    Vilela, Marcelo L B; Willingham, Emily; Buckley, Jill; Liu, Ben Chun; Agras, Koray; Shiroyanagi, Yoshiyuki; Baskin, Laurence S

    2007-09-01

    The phytoestrogen (plant estrogen) genistein, present in soy products, is of interest because in utero exposure to genistein can cause hypospadias in our mouse model and maternal consumption of soy is prevalent in human populations. Another compound of interest is the fungicide vinclozolin, which also causes hypospadias in the mouse and rat and can occur concurrently with genistein in the diet as a residue on exposed foods. A study in the United Kingdom found no relationship between a maternal organic vegetarian diet and hypospadias frequency, but women who consumed nonorganic vegetarian diets had a greater percentage of sons with hypospadias. Because nonorganic diets can include residues of pesticides such as vinclozolin, we sought to assess the interaction of realistic daily exposures to genistein and vinclozolin and their effects on the incidence of hypospadias. Pregnant mice were fed a soy-free diet and orally gavaged from gestational days 13 to 17 with 0.17 mg/kg/day of genistein, 10 mg/kg/day of vinclozolin, or genistein and vinclozolin together at the same doses, all in 100 microL of corn oil. The controls received the corn oil vehicle. The male fetuses were examined at gestational day 19 for hypospadias, both macroscopically and histologically. We identified no hypospadias in the corn oil group. The incidence of hypospadias was 25% with genistein alone, 42% with vinclozolin alone, and 41% with genistein and vinclozolin together. These findings support the idea that exposure to these compounds during gestation could contribute to the development of hypospadias.

  6. Genistein cooperates with the histone deacetylase inhibitor vorinostat to induce cell death in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Phillip Cornel J

    2012-04-01

    there are a number of pathways that are affected with genistein and vorinostat treatment such as Wnt, TNF, G2/M DNA damage checkpoint, and androgen signaling pathways. In addition, genistein cooperates with vorinostat to induce cell death in prostate cancer cell lines with a greater effect on early stage prostate cancer.

  7. Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A.

    Science.gov (United States)

    Ullah, Mohd Fahad; Shamim, Uzma; Hanif, Sarmad; Azmi, Asfar S; Hadi, Sheikh M

    2009-11-01

    Epidemiological studies have indicated that populations with high isoflavone intake through soy consumption have lower rates of breast, prostate, and colon cancer. The isoflavone polyphenol genistein in soybean is considered to be a potent chemopreventive agent against cancer. In order to explore the chemical basis of chemopreventive activity of genistein, in this paper we have examined the structure-activity relationship between genistein and its structural analogue biochanin A. We show that both genistein and its methylated derivative biochanin A are able to mobilize nuclear copper in human lymphocyte, leading to degradation of cellular DNA. However, the relative rate of DNA breakage was greater in the case of genistein. Further, the cellular DNA degradation was inhibited by copper chelator (neocuproine/bathocuproine) but not by compounds that specifically bind iron and zinc (desferrioxamine mesylate and histidine, respectively). We also compared the antioxidant activity of the two isoflavones against tert-butylhydroperoxide-induced oxidative breakage in lymphocytes. Again genistein was found to be more effective than biochanin A in providing protection against oxidative stress induced by tert-butylhydroperoxide. It would therefore appear that the structural features of isoflavones that are important for antioxidant properties are also the ones that contribute to their pro-oxidant action through a mechanism that involves redox cycling of chromatin-bound nuclear copper.

  8. Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells.

    Science.gov (United States)

    Zhang, Zhiyu; Wang, Chong-Zhi; Du, Guang-Jian; Qi, Lian-Wen; Calway, Tyler; He, Tong-Chuan; Du, Wei; Yuan, Chun-Su

    2013-07-01

    Soybean isoflavones have been used as a potential preventive agent in anticancer research for many years. Genistein is one of the most active flavonoids in soybeans. Accumulating evidence suggests that genistein alters a variety of biological processes in estrogen-related malignancies, such as breast and prostate cancers. However, the molecular mechanism of genistein in the prevention of human colon cancer remains unclear. Here we attempted to elucidate the anticarcinogenic mechanism of genistein in human colon cancer cells. First we evaluated the growth inhibitory effect of genistein and two other isoflavones, daidzein and biochanin A, on HCT-116 and SW-480 human colon cancer cells. In addition, flow cyto-metry was performed to observe the morphological changes in HCT-116/SW-480 cells undergoing apoptosis or cell cycle arrest, which had been visualized using Annexin V-FITC and/or propidium iodide staining. Real-time PCR and western blot analyses were also employed to study the changes in expression of several important genes associated with cell cycle regulation. Our data showed that genistein, daidzein and biochanin A exhibited growth inhibitory effects on HCT-116/SW-480 colon cancer cells and promoted apoptosis. Genistein showed a significantly greater effect than the other two compounds, in a time- and dose-dependent manner. In addition, genistein caused cell cycle arrest in the G2/M phase, which was accompanied by activation of ATM/p53, p21waf1/cip1 and GADD45α as well as downregulation of cdc2 and cdc25A demonstrated by q-PCR and immunoblotting assay. Interestingly, genistein induced G2/M cell cycle arrest in a p53-dependent manner. These findings exemplify that isoflavones, especially genistein, could promote colon cancer cell growth inhibition and facilitate apoptosis and cell cycle arrest in the G2/M phase. The ATM/p53-p21 cross-regulatory network may play a crucial role in mediating the anticarcinogenic activities of genistein in colon cancer.

  9. Iron Bioavailability from Ferric Pyrophosphate in Extruded Rice Cofortified with Zinc Sulfate Is Greater than When Cofortified with Zinc Oxide in a Human Stable Isotope Study.

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    Hackl, Laura; Zimmermann, Michael B; Zeder, Christophe; Parker, Megan; Johns, Paul W; Hurrell, Richard F; Moretti, Diego

    2017-03-01

    Background: Extruded rice grains are often cofortified with iron and zinc. However, it is uncertain if the addition of zinc to iron-fortified rice affects iron absorption and whether this is zinc-compound specific. Objective: We investigated whether zinc, added as zinc oxide (ZnO) or zinc sulfate (ZnSO 4 ), affects human iron absorption from extruded rice fortified with ferric pyrophosphate (FePP). Methods: In 19 iron-depleted Swiss women (plasma ferritin ≤16.5 μ/L) aged between 20 and 39 y with a normal body mass index (in kg/m 2 ; 18.7-24.8), we compared iron absorption from 4 meals containing fortified extruded rice with 4 mg Fe and 3 mg Zn. Three of the meals contained extruded rice labeled with FePP ( 57 FePP): 1 ) 1 meal without added zinc ( 57 FePP-Zn), 2 ) 1 cofortified with ZnO ( 57 FePP+ZnO), and 3 ) 1 cofortified with ZnSO 4 ( 57 FePP+ZnSO 4 ). The fourth meal contained extruded rice without iron or zinc, extrinsically labeled with ferrous sulfate ( 58 FeSO 4 ) added as a solution after cooking. All 4 meals contained citric acid. Iron bioavailability was measured by isotopic iron ratios in red blood cells. We also measured relative in vitro iron solubility from 57 FePP-Zn, 57 FePP+ZnO, and 57 FePP+ZnSO 4 expressed as a fraction of FeSO 4 solubility. Results: Geometric mean fractional iron absorption (95% CI) from 57 FePP+ZnSO 4 was 4.5% (3.4%, 5.8%) and differed from 57 FePP+ZnO (2.7%; 1.8%, 4.1%) ( P iron bioavailabilities compared with 58 FeSO 4 were 62%, 57%, and 38% from 57 FePP+ZnSO 4 , 57 FePP-Zn, and 57 FePP+ZnO, respectively. In vitro solubility from 57 FePP+ZnSO 4 differed from that of 57 FePP-Zn (14.3%; P iron-depleted women, iron absorption from FePP-fortified extruded rice cofortified with ZnSO 4 was 1.6-fold (95% CI: 1.4-, 1.9-fold) that of rice cofortified with ZnO. These findings suggest that ZnSO 4 may be the preferable zinc cofortificant for optimal iron bioavailability of iron-fortified extruded rice. This trial was registered at

  10. Bioavailability of intranasal metoclopramide.

    OpenAIRE

    Ward, M J; Buss, D C; Ellershaw, J; Nash, A; Routledge, P A

    1989-01-01

    After intranasal administration of metoclopramide, (5 mg in 0.5 ml sterile water) the maximum plasma concentration of 13.5 +/- 7.3 (mean +/- s.d.) ng ml-1 was achieved. Absolute bioavailability was 50.5 +/- 29.5%, 110 +/- 41 min later. We conclude that the intranasal route does not allow rapid absorption of the drug and is not associated with greater bioavailability than the oral route.

  11. Effects of genistein on early-stage cutaneous wound healing

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    Park, Eunkyo [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lee, Seung Min [Research Institute of Health Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Jung, In-Kyung [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lim, Yunsook [Department of Foods and Nutrition, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Jung-Hyun, E-mail: jjhkim@cau.ac.kr [Department of Home Economics Education, Chung-Ang University, Seoul 156-756 (Korea, Republic of)

    2011-07-08

    Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected by antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These results

  12. Genistein-induced alterations of radiation-responsive gene expression

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    Grace, M.B. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)], E-mail: grace@afrri.usuhs.mil; Blakely, W.F.; Landauer, M.R. [Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603 (United States)

    2007-07-15

    In order to clarify the molecular mechanism of radioprotection and understand biological dosimetry in the presence of medical countermeasure-radioprotectants, their effects on ionizing radiation (IR)-responsive molecular biomarkers must be examined. We used genistein in a radiation model system and measured gene expression by multiplex QRT-PCR assay in drug-treated healthy human blood cultures. Genistein has been demonstrated to be a radiosensitizer of malignant cells and a radioprotector against IR-induced lethality in a mouse model. Whole-blood cultures were supplemented with 50, 100, and 200{mu}M concentrations of genistein, 16 h prior to receiving a 2-Gy ({sup 60}Co-{gamma} rays, 10 cGy/min) dose of IR. Total RNA was isolated from whole blood 24 h postirradiation for assessments. Combination treatments of genistein and IR resulted in no significant genistein effects on ddb2 and bax downstream transcripts to p53, or proliferating cell-nuclear antigen, pcna, necessary for DNA synthesis and cell-cycle progression. Use of these radiation-responsive targets would be recommended for dose-assessment applications. We also observed decreased expression of pro-survival transcript, bcl-2. Genistein and IR-increased expression of cdkn1a and gadd45a, showing that genistein also stimulates p53 transcriptional activity. These results confirm published molecular signatures for genistein in numerous in vitro models. Evaluation of gene biomarkers may be further exploited for devising novel radiation countermeasure and/or therapeutic strategies.

  13. Effects of genistein following fractionated lung irradiation in mice

    International Nuclear Information System (INIS)

    Para, Andrea E.; Bezjak, Andrea; Yeung, Ivan W.T.; Van Dyk, Jake; Hill, Richard P.

    2009-01-01

    Background and purpose: This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response. Material and methods: C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet (∼10 mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of small lung nodules (KHT fibrosarcoma). Results: Genistein caused about a 50% reduction in the MN damage observed during the fractionated radiation treatment and this damage continued to decrease at later times to background levels by 16 weeks. In mice not receiving Genistein MN levels remained well above background out to 28 weeks after irradiation. Genistein reduced macrophage accumulation by 22% and reduced collagen deposition by 28%. There was minimal protection against increases in breathing rate or severe morbidity during pneumonitis. No tumor protection by genistein treatment was observed. Conclusions: Genistein at the dose levels used in this study partially reduced the extent of fibrosis developing in mouse lung caused by irradiation but gave minimal protection against pneumonitis. There was no evidence that genistein caused protection of small tumors growing in the lung.

  14. The Cooperative Effect of Genistein and Protein Hydrolysates on the Proliferation and Survival of Osteoblastic Cells (hFOB 1.19

    Directory of Open Access Journals (Sweden)

    Shuo Wang

    2016-11-01

    Full Text Available Chum salmon skin gelatin, de-isoflavoned soy protein, and casein were hydrolyzed at two degrees of hydrolysis. Genistein, the prepared hydrolysates, and genistein-hydrolysate combinations were assessed for their proliferative and anti-apoptotic effects on human osteoblasts (hFOB 1.19 to clarify potential cooperative effects between genistein and these hydrolysates in these two activities. Genistein at 2.5 μg/L demonstrated the highest proliferative activity, while the higher dose of genistein inhibited cell growth. All hydrolysates promoted osteoblast proliferation by increasing cell viability to 102.9%–131.1%. Regarding etoposide- or NaF-induced osteoblast apoptosis, these hydrolysates at 0.05 g/L showed both preventive and therapeutic effects against apoptosis. In the mode of apoptotic prevention, the hydrolysates decreased apoptotic cells from 32.9% to 15.2%–23.7% (etoposide treatment or from 23.6% to 14.3%–19.6% (NaF treatment. In the mode of apoptotic rescue, the hydrolysates lessened the extent of apoptotic cells from 15.9% to 13.0%–15.3% (etoposide treatment or from 13.3% to 10.9%–12.7% (NaF treatment. Gelatin hydrolysates showed the highest activities among all hydrolysates in all cases. All investigated combinations (especially the genistein-gelatin hydrolysate combination had stronger proliferation, apoptotic prevention, and rescue than genistein itself or their counterpart hydrolysates alone, suggesting that genistein cooperated with these hydrolysates, rendering greater activities in osteoblast proliferation and anti-apoptosis.

  15. Folate bioavailability

    OpenAIRE

    Öhrvik, Veronica

    2009-01-01

    An inadequate folate status is associated with increased risk of anaemia and neural tube defects. In many countries a folate intake below recommendations has been reported for women in childbearing age. However, data on folate intake and status are not always associated, since factors other than intake, e.g. bioavailability, affect folate status. This thesis studied the bioavailability of folate using in vivo and in vitro models. The effect of two pieces of Swedish nutritional advice on folat...

  16. Bioavailability enhancers of herbal origin: An overview

    Science.gov (United States)

    Kesarwani, Kritika; Gupta, Rajiv

    2013-01-01

    Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds. PMID:23620848

  17. Estrogenic activity of flavonoids in mice. The importance of estrogen receptor distribution, metabolism and bioavailability

    DEFF Research Database (Denmark)

    Breinholt, Vibeke; Hossaini, A.; Svendsen, Gitte W.

    2000-01-01

    The in vivo estrogenic potential of the flavonoids apigenin, kaempferol, genistein and equol was investigated in immature female mice. Genistein and equol, administered by gavage for 4 consecutive days [post-natal day (PND) 17-20, 100 mg/kg body weight], was found to significantly increase uterine...... or lower potency. Bioavailability, metabolism, the ability to alter ER alpha distribution in the uterus and the estrogenic potential of parent compound and metabolites may thus contribute to the differences in in vivo estrogenicity of dietary flavonoids....

  18. Methotrexate bioavailability

    NARCIS (Netherlands)

    van Roon, E. N.; van de Laar, M. A. F. J.

    2010-01-01

    The clinical relevance of the concept of bioavailability rests on two main principles. First, that measurement of the active component at the site of action is generally not possible and, secondly, that a relationship exists between on the one hand efficacy and/or safely and on the other hand

  19. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Shreya, E-mail: Shreya.patel214@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Peretz, Jackye, E-mail: Jackye.peretz@gmail.com [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Pan, Yuan-Xiang, E-mail: yxpan@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Helferich, William G., E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

    2016-02-15

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes.

  20. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles

    International Nuclear Information System (INIS)

    Patel, Shreya; Peretz, Jackye; Pan, Yuan-Xiang; Helferich, William G.; Flaws, Jodi A.

    2016-01-01

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36 μM) for 18–96 h. Every 24 h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36 μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36 μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96 h, and the expression of cell cycle regulators at 18 h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. - Highlights: • Genistein exposure inhibits antral follicle growth. • Genistein exposure alters expression of cell cycle regulators. • Genistein exposure alters sex steroid hormones. • Genistein exposure alters expression of steroidogenic enzymes.

  1. Improved bioavailability

    Directory of Open Access Journals (Sweden)

    Nadia M. Morsi

    2016-09-01

    Full Text Available Timolol maleate (TiM, a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from extensive first pass effect, resulting in a reduction of oral bioavailability (F% to 50% and a short elimination half-life of 4 h; parameters necessitating its frequent administration. The current study was therefore, designed to formulate and optimize the transfersomal TiM gel for transdermal delivery. TiM loaded transfersomal gel was optimized using two 23 full factorial designs; where the effects of egg phosphatidyl choline (PC: surfactant (SAA molar ratio, solvent volumetric ratio, and the drug amount were evaluated. The formulation variables; including particle size, drug entrapment efficiency (%EE, and release rate were characterized. The optimized transfersomal gel was prepared with 4.65:1 PC:SAA molar ratio, 3:1 solvent volumetric ratio, and 13 mg drug amount with particle size of 2.722 μm, %EE of 39.96%, and a release rate of 134.49 μg/cm2/h. The permeation rate of the optimized formulation through the rat skin was excellent (151.53 μg/cm2/h and showed four times increase in relative bioavailability with prolonged plasma profile up to 72 h compared with oral aqueous solution. In conclusion, a potential transfersomal transdermal system was successfully developed and the factorial design was found to be a smart tool, when optimized.

  2. Genistein and daidzein: different molecular effects on prostate cancer.

    Science.gov (United States)

    Adjakly, Mawussi; Ngollo, Marjolaine; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2013-01-01

    Diet is believed to play an important role in cancer. It has been revealed by epidemiological studies that Asian populations, who consume phytoestrogens in large amounts, have a lower incidence of prostate cancer in comparison with the Western world, where consumption of soy is lower. Genistein and daidzein, the soy phytoestrogens most widely studied, are believed to be potent anticancer agents and have been shown to possess anticancer properties. It has been shown that these compounds inhibit the growth of cancer cells through the modulation of genes controlling cell-cycle progression. Genistein inhibits the activation of the kappa light polypeptide gene enhancer in B-cells (NF-κB), signaling pathway, which is implicated in the balance between cell survival and programmed cell death (apoptosis). Antioxidant and antiangiogenesis properties of genistein have been also described. Soy isoflavones are also implicated in reversion of epigenetic events observed in prostate cancer. Significant advances have been made for understanding how soy isoflavones are implicated in protection against prostate cancer. However, more studies are needed to better-understand and elucidate all pathways mobilized by genistein and daidzein, in order to fully exploit their anticancer properties.

  3. Increased induction of aberrant crypt foci by 1,2-dimethylhydrazine in rats fed diets containing purified genistein of genistein-rich soya protein

    NARCIS (Netherlands)

    Gee, J.M.; Noteborn, H.P.J.M.; Polley, A.C.J.; Johnson, I.T.

    2000-01-01

    The isoflavonoid genistein inhibits mitosis and increases apoptosis in a variety of tumour cell lines in vitro, and may exert anticarcinogenic effects in vivo. To assess its effects on the colon, rats were fed a semi-synthetic control diet, or similar diets enriched with genistein (0.25 g/kg),

  4. Extraction of Genistein from Sophora flavescens with Supercritical Carbon Dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chang-Nam; Kang, Choon-Hyoung [Chonnam National University, Gwangju (Korea, Republic of)

    2015-08-15

    This study was directed to finding an optimum extraction condition of genistein from the S. flavescens with supercritical carbon dioxide as a solvent. In this effort, effects of the extraction conditions including pressure, temperature and a co-solvent on the extraction efficiency were investigated. The aqueous ethanol and methanol solutions were used as co-solvents while the tested operating pressure and temperature ranges were from 200 bar to 300 bar and from 308.15 K to 323.15 K, respectively. The concentration of genistein was determined by means of HPLC equipped with a UV detector. From the results, it was observed that an increase in pressure led to the higher extraction efficiency. Further, methanol showed better performance as a co-solvent than ethanol. The DPPH radical scavenging activities were measured to compare antioxidant activities of S. flavescens extracts.

  5. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

    NARCIS (Netherlands)

    Seppen, Jurgen

    2012-01-01

    Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by

  6. Aluminum bioavailability from tea infusion.

    Science.gov (United States)

    Yokel, Robert A; Florence, Rebecca L

    2008-12-01

    The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer (26)Al. (26)Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous (27)Al infusion. Oral Al bioavailability (F) was calculated from the area under the (26)Al, compared to (27)Al, serum concentration x time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F=0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F=0.1-0.3%), but greater than acidic SALP in a biscuit (F=0.1%). Time to maximum serum (26)Al concentration was 1.25, 1.5, 8 and 4.8h, respectively. These results of oral Al bioavailability x daily consumption by the human suggest tea can provide a significant amount of the Al that reaches systemic circulation. This can allow distribution to its target organs of toxicity, the central nervous, skeletal and hematopoietic systems. Further testing of the hypothesis that Al contributes to Alzheimer's disease may be more warranted with studies focusing on total average daily food intake, including tea and other foods containing appreciable Al, than drinking water.

  7. Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury

    International Nuclear Information System (INIS)

    Hernandez-Montes, Eva; Pollard, Susan E.; Vauzour, David; Jofre-Montseny, Laia; Rota, Cristina; Rimbach, Gerald; Weinberg, Peter D.; Spencer, Jeremy P.E.

    2006-01-01

    Cellular actions of isoflavones may mediate the beneficial health effects associated with high soy consumption. We have investigated protection by genistein and daidzein against oxidative stress-induced endothelial injury. Genistein but not daidzein protected endothelial cells from damage induced by oxidative stress. This protection was accompanied by decreases in intracellular glutathione levels that could be explained by the generation of glutathionyl conjugates of the oxidised genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone. Both isoflavones evoked increased protein expression of γ-glutamylcysteine synthetase-heavy subunit (γ-GCS-HS) and increased cytosolic accumulation and nuclear translocation of Nrf2. However, only genistein led to increases in the cytosolic accumulation and nuclear translocation of Nrf1 and the increased expression of and activity of glutathione peroxidase. These results suggest that genistein-induced protective effects depend primarily on the activation of glutathione peroxidase mediated by Nrf1 activation, and not on Nrf2 activation or increases in glutathione synthesis

  8. Combined treatment of ionizing radiation with genistein on cervical cancer HeLa cells

    International Nuclear Information System (INIS)

    Zhang Bei; Liu Jiayin; Han Suping; Pan Jinshun; Yin Xiaoxing; Wang Bing; Hu Gang

    2006-01-01

    The anticancer agent genistein inhibits cell growth of tumor cell lines from various malignancies. In our study, we investigated the effectiveness of combined treatment of ionizing radiation (IR) with genistein on cervical HeLa cells and its possible mechanism. It was found that the inhibitory rate in cells with combined treatment was significantly higher than that of the cells treated with IR or genistein alone. After treatments of IR (4 Gy) combined with genistein (40 μmol/L), the apoptotic index of the cells was significantly increased and the cells were arrested in the G2/M phase. Survivin mRNA expression increased after IR (4 Gy), while it significantly decreased after combined treatment. These findings indicated that genistein enhanced the radiosensitivity of cervical cancer HeLa cells, and the mechanisms for this action might include increase of apoptosis, decrease of survivin expression, and prolongation of cell cycle arrest. (author)

  9. Effect of Genistein on vasculogenic mimicry formation by human uveal melanoma cells

    Directory of Open Access Journals (Sweden)

    Gu Haijuan

    2009-09-01

    Full Text Available Abstract Background Vasculogenic mimicry (VM was increasingly recognized as a form of aggressive melanoma acquiring blood supply. Genistein had attracted much attention as a potential anticancer agent. Therefore, we examined the effect of Genistein on VM in human uveal melanoma cells. Methods VM structure was detected by periodic acid-Schiff (PAS staining for uveal melanoma C918 cells cultured on the three-dimensional type I collagen gels after exposed to Genistein. We used reverse transcription polymerase chain reaction (RT-PCR and Western Blot analysis to examine the effect of Genistein on vascular endothelial cadherin (VE-cadherin mRNA and protein expression. The nude mice models of human uveal melanoma C918 cells were established to assess the number of VM using immunohistochemical and PAS double-staining. Results Genistein inhibited the survival of C918 cells in vitro. The ectopic model study showed that VM in tumor tissue sections were significantly reduced by Genistein in vivo. In vitro, the VM structure was found in control, 25 and 50 μM Genistein-treatment groups but not in 100 and 200 μM. RT-PCR and Western Blot showed that 100 and 200 μM concentration of Genistein could significantly decrease VE-cadherin mRNA and protein expression of C918 cells compared with control (P 0.05. Conclusion Genistein inhibits VM formation of uveal melanoma cells in vivo and in vitro. One possible underlying molecular mechanism by which Genistein could inhibit VM formation of uveal melanoma is related to down-regulation of VE-cadherin.

  10. Neonatal exposure to daidzein, genistein, or the combination modulates bone development in female CD-1 mice.

    Science.gov (United States)

    Kaludjerovic, Jovana; Ward, Wendy E

    2009-03-01

    Neonatal exposure to genistein (GEN), an isoflavone abundant in soy, favorably modulates bone mineral density (BMD) and bone strength in mice at adulthood. The study objective was to determine whether early exposure to a combination of the soy isoflavones daidzein (DAI) and GEN that naturally exists in soy protein-based infant formula results in greater benefits to bone at adulthood than either treatment alone. Male and female CD-1 mice (n = 8-16 pups per group per gender) were randomized to subcutaneous injections of DAI (2 mg x kg body weight(-1) x d(-1)), GEN (5 mg x kg body weight(-1) x d(-1)), DAI+GEN (7 mg x kg body weight(-1) x d(-1)), diethylstilbesterol (DES; positive control) (2 mg x kg body weight(-1) x d(-1)), or control (CON) from postnatal d 1-5 and were studied to 4 mo of age. BMD, biomechanical bone strength, and bone microarchitecture were assessed at the femur and lumbar vertebrae (LV). Females treated with DAI, GEN, DAI+GEN, or DES had greater (P GEN resulted in greater (P GEN had a positive effect on the skeleton of female mice at adulthood, but, compared with individual treatments, DAI+GEN did not have a greater benefit to bone in females or males.

  11. Hyaluronic acid concentration in postmenopausal facial skin after topical estradiol and genistein treatment: a double-blind, randomized clinical trial of efficacy.

    Science.gov (United States)

    Patriarca, Marisa Teresinha; Barbosa de Moraes, Andréa Regina; Nader, Helena B; Petri, Valeria; Martins, João Roberto Maciel; Gomes, Regina Célia Teixeira; Soares, José Maria

    2013-03-01

    The aim of this work was to compare the effects of estradiol and genistein treatment on hyaluronic acid (HA) concentration in postmenopausal facial skin. In this study, 30 postmenopausal women were evaluated in a prospective, randomized, double-blind trial. The volunteers were postmenopausal women treated in the Gynecology Department of the Federal University of São Paulo. The participants were divided into two groups: group E, treated with 0.01% 17β-estradiol gel (n = 15), and group G, treated with 4% genistein gel (isoflavones, n = 15). The treatment lasted for 24 consecutive weeks. Preauricular skin biopsies were performed for each participant at baseline (E1 and G1) and after treatment (E2 and G2) to evaluate HA concentration in tissue. The materials were processed using immunohistochemical and biochemical methods. After 24 weeks of treatment, HA concentration increased in both groups, but the effect was greater for estradiol treatment than for genistein treatment. Our data suggest that both treatments may enhance HA concentration in postmenopausal skin but that estrogen produces results that are greater than those produced by isoflavones.

  12. Improved Chromatographic Bioavailability Estimations

    National Research Council Canada - National Science Library

    Dorsey, John

    1996-01-01

    .... Since the inception of reversed phase liquid chromatography there have been many attempts to correlate chromatographic retention with bioavailability and the most often used bulk measure, the octanol...

  13. [Response surface method optimize of nano-silica solid dispersion technology assistant enzymatic hydrolysis preparation genistein].

    Science.gov (United States)

    Jin, Xin; Zhang, Zhen-Hai; Zhu, Jing; Sun, E; Yu, Dan-Hong; Chen, Xiao-Yun; Liu, Qi-Yuan; Ning, Qing; Jia, Xiao-Bin

    2012-04-01

    This article reports that nano-silica solid dispersion technology was used to raise genistein efficiency through increasing the enzymatic hydrolysis rate. Firstly, genistin-nano-silica solid dispersion was prepared by solvent method. And differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) were used to verify the formation of solid dispersion, then enzymatic hydrolysis of solid dispersion was done by snailase to get genistein. With the conversion of genistein as criteria, single factor experiments were used to study the different factors affecting enzymatic hydrolysis of genistin and its solid dispersion. And then, response surface method was used to optimize of nano-silica solid dispersion technology assistant enzymatic hydrolysis. The optimum condition to get genistein through enzymatic hydrolysis of genistin-nano-silica solid dispersion was pH 7.1, temperature 52.2 degrees C, enzyme concentration 5.0 mg x mL(-1) and reaction time 7 h. Under this condition, the conversion of genistein was (93.47 +/- 2.40)%. Comparing with that without forming the genistin-nano-silica solid dispersion, the conversion increased 2.62 fold. At the same time, the product of hydrolysis was purified to get pure genistein. The method of enzymatic hydrolysis of genistin-nano-silica solid dispersion by snailase to obtain genistein is simple, efficiency and suitable for the modern scale production.

  14. Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats.

    Science.gov (United States)

    Ball, Evan R; Caniglia, Mary Kay; Wilcox, Jenna L; Overton, Karla A; Burr, Marra J; Wolfe, Brady D; Sanders, Brian J; Wisniewski, Amy B; Wrenn, Craige C

    2010-03-01

    Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods. Copyright 2009 Elsevier Inc. All rights reserved.

  15. Effects of dietary genistein on GH/IGF-I axis of Nile tilapia Oreochromis niloticus

    Science.gov (United States)

    Chen, Dong; Wang, Wei; Ru, Shaoguo

    2016-09-01

    There is considerable concern that isoflavones, such as genistein in fish feed composed of soybean protein, aff ects somatic growth in fish. Our previous works demonstrated that 30 and 300 μg/g dietary genistein had no significant eff ect on growth performance in Nile tilapia ( Oreochromis niloticus), but the higher level of genistein (3 000 μg/g) significantly depressed growth. This study was conducted to further examine the eff ects of dietary genistein on the endocrine disruption on growth hormone/insulin-like growth factor-I (GH/IGF-I) axis in Nile tilapia ( O. niloticus). Juvenile fish were fed by hand twice daily to satiation with one of four isonitrogenous and isoenergetic diets, each containing either 0, 30, 300 or 3 000 μg/g genistein. Following an 8-week feeding period, plasma GH and IGF-I levels were investigated by radioimmunoassay and gene expression levels of gh, ghrelin, gnrhs, ghr, npy, npyrs, pacap, ghrs, i gf-I, igf-Ir, and igfbp3 were examined by real-time PCR. The results show that no significant change in plasma GH and IGF-I levels in fish fed with diets containing 30 μg/g and 300 μg/g genistein. mRNA expression of genes along the GH/IGF-I axis remained unaff ected, except for igf-Ir, which was stimulated by the 300 μg/g genistein diet. While in fish fed the 3 000 μg/g genistein diet, the plasma GH and IGF-I levels decreased, and mRNA expression of gh, ghr2, npyr1, igf-I, and igf-Ir were also significantly depressed. In contrast, npy and igfbp3 mRNA expression were enhanced. This study provides convincing evidence for growth impediment by genistein by disturbing the GH/IGF-I axis in Nile tilapia O. niloticus.

  16. Flavonoid Bioavailability and Attempts for Bioavailability Enhancement

    Science.gov (United States)

    Thilakarathna, Surangi H.; Rupasinghe, H. P. Vasantha

    2013-01-01

    Flavonoids are a group of phytochemicals that have shown numerous health effects and have therefore been studied extensively. Of the six common food flavonoid classes, flavonols are distributed ubiquitously among different plant foods whereas appreciable amounts of isoflavones are found in leguminous plant-based foods. Flavonoids have shown promising health promoting effects in human cell culture, experimental animal and human clinical studies. They have shown antioxidant, hypocholesterolemic, anti-inflammatory effects as well as ability to modulate cell signaling and gene expression related disease development. Low bioavailability of flavonoids has been a concern as it can limit or even hinder their health effects. Therefore, attempts to improve their bioavailability in order to improve the efficacy of flavonoids are being studied. Further investigations on bioavailability are warranted as it is a determining factor for flavonoid biological activity. PMID:23989753

  17. Synthesis and Cytotoxicity of 2,3-Enopyranosyl C-Linked Conjugates of Genistein

    Directory of Open Access Journals (Sweden)

    Wieslaw Szeja

    2014-05-01

    Full Text Available A series of glycoconjugates, derivatives of genistein containing a C-glycosylated carbohydrate moiety, were synthesized and their anticancer activity was tested in vitro in the human cell lines HCT 116 and DU 145. The target compounds 15–17 were synthesized by treating ω-bromoalkyl C-glycosides derived from L-rhamnal (1 with a tetrabutylammonium salt of genistein. The new, metabolically stable analogs of previously studied O-glycosidic genistein derivatives inhibited proliferation of cancer cell lines through inhibition of the cell cycle.

  18. Bioconversion of isoflavone glycosides to aglycones, mineral bioavailability and vitamin B complex in fermented soymilk by probiotic bacteria and yeast.

    Science.gov (United States)

    Rekha, C R; Vijayalakshmi, G

    2010-10-01

    To study the role of β-glucosidase producing probiotic bacteria and yeast in the biotransformation of isoflavone glycosides to aglycones, mineral bioavailability and vitamin B complex in fermented soymilk. Five isolates of probiotic lactic acid bacteria (LAB), Lactobacillus acidophilus B4496, Lactobacillus bulgaricus CFR2028, Lactobacillus casei B1922, Lactobacillus plantarum B4495 and Lactobacillus fermentum B4655 with yeast Saccharomyces boulardii were used to ferment soymilk to obtain the bioactive isoflavones, genistein and daidzein. High-performance liquid chromatography was used to analyse the concentration of isoflavones. Bioactive aglycones genistein and daidzein after 24 and 48 h of fermentation ranged from 97.49 to 98.49% and 62.71 to 92.31% respectively with different combinations of LAB with yeast. Increase in bioavailability of minerals and vitamin B complex were also observed in fermented soymilk. LAB in combination with yeast S. boulardii has great potential for the enrichment of bioactive isoflavones, enhancing the viability of LAB strains, decreasing the antinutrient phytic acid and increasing the mineral bioavailability in soymilk fermentation. Fermentation of soymilk with probiotic organisms improves the bioavailability of isoflavones, assists in digestion of protein, provides more soluble calcium, enhances intestinal health and supports immune system. Increased isoflavone aglycone content in fermented soymilk improves the biological functionality of soymilk. © 2010 The Authors. Journal compilation © 2010 The Society for Applied Microbiology.

  19. Higher bioavailability of isoflavones after a single ingestion of a soya-based supplement than a soya-based food in young healthy males.

    Science.gov (United States)

    Vergne, Sébastien; Bennetau-Pelissero, Catherine; Lamothe, Valérie; Chantre, Philippe; Potier, Mylène; Asselineau, Julien; Perez, Paul; Durand, Marlène; Moore, Nicholas; Sauvant, Patrick

    2008-02-01

    Soya isoflavones, genistein and daidzein, are the focus of numerous studies investigating their potential effects on health and results remain controversial. Bioavailability is clearly a crucial factor influencing their bioefficacy and could explain these discrepancies. This study aimed at assessing: (1) the isoflavone content of sixty-nine European soya-derivative products sold on the French market; (2) the bioavailability of isoflavones comparing supplement with food. Twelve healthy volunteers were recruited in a randomized two-way crossover trial and received 35 mg isoflavones equivalent aglycone either through supplements or through cheese, both containing different patterns of isoflavone conjugates and different daidzein:genistein ratios. A specific ELISA method was used to assess the plasma and urinary concentrations of isoflavones and thus the pharmacokinetic parameters, which were then normalized to mg of each isoflavone ingested. Results showed that the normalized Cmax of daidzein (P = 0.002) and similarly the normalized AUC0 --> infinity and Cmax of genistein (P = 0.002) from soya-based capsules were higher than that from soya-based cheese. In conclusion, this work completes studies on isoflavone bioavailability and presents new data regarding isoflavone concentrations in soya-derivative products. Assuming that isoflavone conjugation patterns do not influence isoflavone bioavailability, this study shows that isoflavones contained in capsules are more bioavailable than those contained in soya-based cheese. Although the supplement is more bioavailable, the relative importance of this is difficult to interpret as there is little evidence that supplements are biologically active in human subjects to date and further studies will be necessary for this specific supplement to prove its efficacy.

  20. A study on the protein-tyrosine kinase inhibitor, Genistein against radiation mortality on Swiss albino mice

    International Nuclear Information System (INIS)

    Lata, Manju; Patni, Shikha; Gaur, Ajay; Bhatia, A.L.

    2007-01-01

    Full text: The radioprotective effects of an acute administration of the isoflavone, Genistein (4', 5, 7-trihydroxyflavone) obtained from Soya foods has been investigated in adult mice. Genistein is also classified as a phytoestrogen. Genistein (4', 5, 7-trihydroxyflavone) is a naturally occurring isoflavone mainly found in legumes, such as soyabeans. Genistein has gained increasing attention because of its association with beneficial effects for treatment of cardiovascular disease, high blood pressure, osteoporosis, breast cancer, and prostate cancer. Genistein block protein-tyrosine kinase and other enzymes that trigger tumor formation. Genistein apparently reverse the process in which cancerous cells loose their individual identity. Mice were administered with different doses (100, 200, 300 and 400 mg/kg body weight) of Genistein before 8 Gy gamma radiations and optimum dose (200 mg/kg) was worked out for the experiment. The dose of Genistein (200 mg/kg) was administered intra peritoneally (I.P.; in 0.5 ml) to mice 15 minutes and 24 hrs before gamma irradiation. Mice treated with Genistein (200 mg/kg), 24 hr before irradiation demonstrated a significant increase in 30-day survival in contrast to mice treated with Genistein 15 minutes before irradiation

  1. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

    International Nuclear Information System (INIS)

    Seppen, Jurgen

    2012-01-01

    Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed diets with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements. -- Highlights: ► Gunn rats are partially deficient in detoxification by UDP glucuronyltransferases. ► Female Gunn rats are infertile on a soy containing diet. ► Soy contains genistein, a potent phytoestrogen. ► Inefficient glucuronidation of genistein causes female infertility.

  2. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Seppen, Jurgen, E-mail: j.seppen@amc.uva.nl

    2012-11-01

    Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed diets with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements. -- Highlights: ► Gunn rats are partially deficient in detoxification by UDP glucuronyltransferases. ► Female Gunn rats are infertile on a soy containing diet. ► Soy contains genistein, a potent phytoestrogen. ► Inefficient glucuronidation of genistein causes female infertility.

  3. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

    International Nuclear Information System (INIS)

    Hillman, Gilda G; Wang, Yu; Che, Mingxin; Raffoul, Julian J; Yudelev, Mark; Kucuk, Omer; Sarkar, Fazlul H

    2007-01-01

    We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory. The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Our studies in both RCC and prostate tumor models demonstrate that the combination of genistein with primary tumor irradiation is a more

  4. Effect of Genistein on reproductive parameter and serum nitric oxide levels in morphine-treated mice

    Directory of Open Access Journals (Sweden)

    Cyrus Jalili

    2016-02-01

    Full Text Available Background: The predominant phytoestrogen in soy and derived products is the isoflavone Genistein. Genistein has antioxidant properties. Morphine is a main psychoactive chemical in opium that can increase the generation of free radicals and therefore it could adversely affects the spermatogenesis. Objective: The main goal was to investigate whether the Genistein could protect morphine adverse effects on sperm cells viability, count, motility, and testis histology and testosterone hormone and nitric oxide in blood serum. Materials and Methods: In this study, various doses of Genistein (0, 1, 2, and 3 mg/kg and Genistein plus morphine (0, 1, 2, and 3 mg/kg were administered interaperitoneally to 48 male mice for 30 consequent days. These mice were randomly assigned to 8 groups (n=6 and sperm parameters (sperm cells viability, count, motility and morphology, testis weight and histology, testosterone hormone (ELISA method, FSH and LH hormones (immunoradiometry and serum nitric oxide (griess assay were analyzed and compared. Results: The results indicated that morphine administration significantly decreased testosterone (0.03 ng/mg LH and FSH level, histological parameters, count, viability (55.3%, morphology and motility of sperm cells (1%, testis weight (0.08 gr and increase nitric oxide compared to saline group (p=0.00. However, administration of Genistein and Genistein plus morphine significantly boosted motility, morphology, count, viability of sperm cells, seminiferous tubules diameter, germinal thickness, testosterone, LH and FSH while decrease nitric oxide level in all groups compared to morphine group (p<0.025. Conclusion: It seems that Genistein administration could increase the quality of spermatozoa and prevent morphine- induced adverse effects on sperm parameters.

  5. Peningkatan Laju Disolusi Dispersi Padat Amorf Genistein dengan PVP K-30

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    Erizal Zaini

    2017-12-01

    Full Text Available Amorphous solid dispersions of a poorly water-soluble drug genistein in PVP K-30 were prepared by solvent co-evaporation technique using organic solvent methanol. Solid dispersions system was prepared with several variations of drug to polymer 2:1, 1:1 dan 1:2 w/w. Solid state properties of solid dispersion system were evaluated by powder X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry, and microscopic SEM. Dissolution rate profile were conducted in distilled water medium by using dissolution tester apparatus type II USP. Base on X-ray diffractometry analysis, differential scanning calorimetry and microscopic SEM, crystalline phase of genistein decreased in crystallinity index and formation of amophous state. Dissolution rate profile showed that genistein in amorphous solid dispersion had a faster dissolution rate in comparison to intact genistein. This study proved that preparation of solid dispersion of genistein in PVP K-30 is an effective approach to improve dissolution rate of genistein.

  6. Effect of single neonatal treatment with the soy bean phytosteroid, genistein on the sexual behavior of adult rats.

    Science.gov (United States)

    Csaba, G; Karabélyos, Cs

    2002-01-01

    Hormonal imprinting develops during the perinatal critical period, when the target hormone meets the yet unmatured receptor. As a consequence of imprinting the receptor accomplishes its maturation reaching the binding capacity characteristic to adults. In this period in the presence of foreign molecules similar to the target hormone faulty imprinting may occur with life-long consequences. Soy bean contains phytosteroids which can mimic estrogen effects. In the present experiments single genistein (20 microg) or combined genistein + benzpyrene (20 microg) treatments were done neonatally and the sexual behavior of male and female adult animals was studied. Genistein significantly increased the lordosis quotient of females, which was compensated by neonatal benzpyrene treatment. Genistein also enhanced the sexual activity of males, and this was significantly not reduced by parallel benzpyrene treatment. The results show that neonatal genistein exposure can imprint sexual activity for life and the presence of a second imprinter can modify genistein's behavioral effect.

  7. The effect of the phytoestrogen genistein on myocardial protection, preconditioning and oxidative stress.

    Science.gov (United States)

    Sbarouni, Eftihia; Iliodromitis, Efstathios K; Zoga, Anastasia; Vlachou, Georgia; Andreadou, Ioanna; Kremastinos, Dimitrios Th

    2006-08-01

    We have previously shown that estrogen administered in ovariectomized female rabbits significantly reduce myocardial infarct size. We now investigated whether the phytoestrogen genistein similarly protects ischemic myocardium and whether this is associated with its antioxidant properties. In addition, we examined whether genistein abolishes preconditioning, since at high doses, it inhibits tyrosine kinase. We studied five groups of New Zealand white female rabbits. Group A (n = 12) were normal controls, group B (n = 14) were ovariectomized 4 weeks prior to the experiment, group C (n = 10) were ovariectomized and treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment, group D (n = 12) had intact gonads and were treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment and group E (n = 8) were ovariectomized 4 weeks prior to the experiment and treated with a single dose of genistein (0.2 mg kg(-1) day(-1) subcutaneously) just prior to the experiment. All animals underwent 30 min of heart ischemia and 120 min of reperfusion, with (subgroup I) or without (subgroup II) preconditioning. Malondialdehyde (MDA) concentration just before the experiment was determined. We found significant differences between the groups-p protect ischemic myocardium in either ovariectomized or non-ovariectomized animals-BII vs CII and AII vs DII, p = NS. There was no significant difference between the preconditioned animals, with intact gonads or ovariectomized (AI vs BI, p = NS), ovariectomized with or without genistein (BI vs CI, p = NS) and non-ovariectomized whether treated with genistein or not (AI vs DI, p = NS). A single dose of genistein did not offer any protection (EII vs BII, p = NS), nor did it modify the preconditioning effect (EI vs BI, p = NS). We found no significant difference in MDA plasma levels between the groups. Genistein, at this dose, does not reduce infarct size per se nor abolishes the

  8. Effects of the phytoestrogen genistein on the development of the reproductive system of Sprague Dawley rats

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    Siti Rosmani Md Zin

    2013-01-01

    Full Text Available OBJECTIVES: Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats. METHODS: Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i a control group that received vehicle (distilled water and Tween 80; (ii a group treated with 10 mg/kg body weight (BW of Genistein (Gen 10; and (iii a group treated with a higher dose of Genistein (Gen 100. The rats were treated daily for three weeks from postnatal day 22 (P22 to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study. RESULTS: A reduction of the mean weekly BW gain and organ weights (uteri and ovaries were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05. These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-a in the uterine tissues of the Genistein-treated animals compared to the control animals. CONCLUSION: Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors.

  9. Factors influencing zinc bioavailability in rats

    International Nuclear Information System (INIS)

    Mahalko, J.R.; Johnson, P.E.; Swan, P.B.

    1986-01-01

    The amount of Zn fed, its source, and the Zn status of experimental animals may affect Zn bioavailability. To test this, rats were fed doses of Zn from ZnCl 2 or from various foods labeled extrinsically. Three weeks before and after the test meal, rats were fed an AIN diet modified in Zn content. Absorption was calculated by monitoring whole body retention and extrapolating to zero time. In rats fed 12 ppm Zn and test doses of 6 to 275 μg, absorption decreased from 80 to 50%, and the amount absorbed increased quadratically (r 2 = 0.998), but turnover was unaffected. Rats fed 38 or 77 ppm Zn absorbed less of test doses of 290, 613, or 1700 μg Zn than did those fed 12 ppm, and their Zn turnover rate was higher. In two 2 x 7 factorial experiments, rats fed 12 or 38 ppm Zn were given 16 or 98 μg Zn from 7 Zn sources. Bioavailability from some foods was higher than from ZnCl 2 except in rats eating only 12 ppm Zn and receiving the small dose. There were greater differences in bioavailability among foods when tested at the higher Zn status or dose. This may explain inconsistencies seen in comparing Zn bioavailability by traditional growth assay with that seen in 65 Zn tracer studies. The authors conclude that Zn status of the experimental animal, as well as the amount of Zn and its source, will affect Zn bioavailability

  10. Micronutrient bioavailability: Dietary Reference Intakes and a future perspective1234

    Science.gov (United States)

    2010-01-01

    This article provides a review of how the challenge of bioavailability was approached in establishing the Dietary Reference Intakes, with a special focus on folic acid, vitamin B-12, β-carotene, iron, selenium, and zinc, the targeted micronutrients for this workshop. In a future perspective, the necessity of having a clear working definition of bioavailability is emphasized. The bioavailability of micronutrients should be considered, with advantage, under subheadings determined by the broad factors that affect bioavailability. Special emphasis is given to giving greater and specific attention to factors involved in the maintenance of homeostasis. These factors, it is argued, are best considered separately from even a broad definition of bioavailability and have the potential to provide new insights into some micronutrient requirements. PMID:20200261

  11. Genistein induces estrogen-like effects in ovariectomized rats but fails to increase cardiac GLUT4 and oxidative stress.

    Science.gov (United States)

    Al-Nakkash, Layla; Markus, Brandon; Batia, Lyn; Prozialeck, Walter C; Broderick, Tom L

    2010-12-01

    This study aimed to determine whether a 2-week genistein treatment induced estrogen-like effects in ovariectomized (OVX) Sprague-Dawley rats, after 2 weeks of subcutaneous genistein injections (250 mg/kg of body weight/day). Uterine weight, uterine-to-body weight ratio, femur weight, and femur-to-body weight ratio were all significantly increased with genistein in OVX rats. Body weight was significantly decreased with genistein in OVX rats. Genistein had no effect on the weights of heart, heart-to-body ratio, and fat pad but significantly decreased heart rate and pulse pressure. Genistein had no effect on cardiac GLUT4 protein, oxidative stress, plasma glucose, nonesterified fatty acids, or low-density lipoprotein levels; however, plasma insulin levels were significantly increased. Our results show that a 2-week genistein treatment produced favorable estrogen-like effects on some physical and physiological characteristics in OVX rats. However, based on our experimental conditions, the effects of genistein were not associated with changes in cardiac GLUT4 or oxidative stress.

  12. Genistein inhibited ammonia induced astrocyte swelling by inhibiting NF-κB activation-mediated nitric oxide formation.

    Science.gov (United States)

    Dai, Hongliang; Jia, Guizhi; Wang, Wei; Liang, Chunguang; Han, Siyu; Chu, Minghui; Mei, Xifan

    2017-06-01

    Our previous study has indicated the involvement of epidermal growth factor receptor (EGFR) transactivation in ammonia-induced astrocyte swelling, which represents a major pathogenesis of brain edema in hepatic encephalopathy. In this study, we examined the effect of genistein, a naturally occurred broad-spectrum protein tyrosine kinase (PTK) inhibitor, on ammonia-induced cell swelling. We found that genistein pretreatment significantly prevented ammonia-induced astrocyte swelling. Mechanistically, ammonia triggered EGFR/extracellular signal-regulated kinase (ERK) association and subsequent ERK phosphorylation were alleviated by genistein pretreatment. Moreover, ammonia-induced NF-κB nuclear location, iNOS expression, and consequent NO production were all prevented by AG1478 and genistein pretreatment. This study suggested that genistein could alleviate ammonia-induced astrocyte swelling, which may be, at least partly, related to its PTK-inhibiting activity and repression of NF-κB mediated iNOS-derived NO accumulation.

  13. Adsorption and recognition characteristics of surface molecularly imprinted polymethacrylic acid/silica toward genistein.

    Science.gov (United States)

    Zhang, Yanyan; Gao, Baojiao; An, Fuqiang; Xu, Zeqing; Zhang, Tingting

    2014-09-12

    In this paper, on the basis of surface-initiated graft polymerization, a new surface molecular imprinting technique is established by molecular design. And molecularly imprinted polymer MIP-PMAA/SiO2 is successfully prepared with genistein as template. The adsorption and recognition characteristics of MIP-PMAA/SiO2 for genistein are studied in depth by using static method, dynamic method and competitive adsorption experiment. The experimental results show that MIP-PMAA/SiO2 possesses very strong adsorption affinity and specific recognition for genistein. The saturated adsorption capacity could reach to 0.36mmolg(-1). The selectivity coefficients relative to quercetin and rutin are 5.4 and 11.8, respectively. Besides, MIP-PMAA/SiO2 is regenerated easily and exhibits excellent reusability. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial.

    Science.gov (United States)

    Marini, Herbert; Minutoli, Letteria; Polito, Francesca; Bitto, Alessandra; Altavilla, Domenica; Atteritano, Marco; Gaudio, Agostino; Mazzaferro, Susanna; Frisina, Alessia; Frisina, Nicola; Lubrano, Carla; Bonaiuto, Michele; D'Anna, Rosario; Cannata, Maria Letizia; Corrado, Francesco; Adamo, Elena Bianca; Wilson, Steven; Squadrito, Francesco

    2007-06-19

    Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive. To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women. Randomized, double-blind, placebo-controlled trial. 3 university medical centers in Italy. 389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions. After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n = 191) or 54 mg of genistein (n = 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D. The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected. At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm2 [95% CI, 0.035 to 0.059] vs. -0.053 g/cm2 [CI, -0.058 to -0.035]; difference, 0.10 g/cm2 [CI, 0.08 to 0.12]; P power to evaluate adverse effects. Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.

  15. Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein

    Directory of Open Access Journals (Sweden)

    Argenta DF

    2014-10-01

    Full Text Available Débora Fretes Argenta,1 Cristiane Bastos de Mattos,1 Fabíola Dallarosa Misturini,1 Leticia Scherer Koester,1 Valquiria Linck Bassani,1 Cláudia Maria Oliveira Simões,2 Helder Ferreira Teixeira1 1Programa de Pós-graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 2Programa de Pós-graduação em Farmácia da Universidade Federal de Santa Catarina, Florianópolis, Brazil Abstract: The aim of this study was to optimize topical nanoemulsions containing genistein, by means of a 23 full factorial design based on physicochemical properties and skin retention. The experimental arrangement was constructed using oil type (isopropyl myristate or castor oil, phospholipid type (distearoylphosphatidylcholine [DSPC] or dioleylphosphaditylcholine [DOPC], and ionic cosurfactant type (oleic acid or oleylamine as independent variables. The analysis of variance showed effect of third order for particle size, polydispersity index, and skin retention of genistein. Nanoemulsions composed of isopropyl myristate/DOPC/oleylamine showed the smallest diameter and highest genistein amount in porcine ear skin whereas the formulation composed of isopropyl myristate/DSPC/oleylamine exhibited the lowest polydispersity index. Thus, these two formulations were selected for further studies. The formulations presented positive ζ potential values (>25 mV and genistein content close to 100% (at 1 mg/mL. The incorporation of genistein in nanoemulsions significantly increased the retention of this isoflavone in epidermis and dermis, especially when the formulation composed by isopropyl myristate/DOPC/oleylamine was used. These results were supported by confocal images. Such formulations exhibited antiherpetic activity in vitro against herpes simplex virus 1 (strain KOS and herpes simplex virus 22 (strain 333. Taken together, the results show that the genistein-loaded nanoemulsions developed in this study are promising

  16. Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation

    International Nuclear Information System (INIS)

    Day, R.M.; Barshishat-Kupper, M.; Mog, S.R.; Mccart, E.A.; Prasanna, P.G.S.; Landauer, M.R.; Davis, T.A.

    2008-01-01

    The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60 Co, 0.6 Gy/min). Experimental groups were: No treatment+Sham (NC), Vehicle+Sham (VC), Genistein+Sham (GC), Radiation only (NR), Vehicle+Radiation (VR), Genistein+Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13-28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. (author)

  17. Genistein Protects Against Biomarkers of Delayed Lung Sequelae in Mice Surviving High-Dose Total Body Irradiation

    Science.gov (United States)

    DAY, Regina M.; BARSHISHAT-KUPPER, Michal; MOG, Steven R.; MCCART, Elizabeth A.; PRASANNA, P. G. S.; DAVIS, Thomas A.; LANDAUER, Michael R.

    2008-01-01

    The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60Co, 0.6 Gy/min). Experimental groups were: No treatment + Sham (NC), Vehicle + Sham (VC), Genistein + Sham (GC), Radiation only (NR), Vehicle + Radiation (VR), Genistein + Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13–28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. PMID:18434686

  18. Preparation of a 1:1 cocrystal of genistein with 4,4‧-bipyridine

    Science.gov (United States)

    Zhang, Yu-Nan; Yin, He-Mei; Zhang, Yu; Zhang, Da-Jun; Su, Xin; Kuang, Hai-Xue

    2017-01-01

    Based on analysing the relationship between the possible number of intermolecular O-H···N hydrogen bonds and the stoichiometric ratio, a 1:1 C15H10O5·C10H8N2 (genistein-4,4‧-bipyridine) cocrystal has been prepared by solution evaporation and characterized. This work successfully demonstrates that the stoichiometric ratio could be inferred by analysing the possible number of intermolecular hydrogen bonds between flavonoids and amines. The strategy provides a facile route for rational designing cocrystal of flavonoids with amines. Additionally, the title cocrystal shows advantages in terms of solubility and antibacterial properties in comparison to pure genistein.

  19. Combined Effects of Phytoestrogen Genistein and Silicon on Ovariectomy-Induced Bone Loss in Rat.

    Science.gov (United States)

    Qi, Shanshan; Zheng, Hongxing

    2017-06-01

    This study was performed to evaluate the effect of concomitant supplementation of genistein and silicon on bone mineral density and bone metabolism-related markers in ovariectomized rat. Three-month-old Sprague Dawley female rats were subjected to bilateral ovariectomy (OVX) or sham surgery, and then the OVX rats were randomly divided into four groups: OVX-GEN, OVX-Si, OVX-GEN-Si, and OVX. Genistein and silicon supplementation was started immediately after OVX and continued for 10 weeks. In the OVX-GEN group, 5 mg genistein per gram body weight was injected subcutaneously. The OVX-Si group was given soluble silicon daily in demineralized water (Si 20 mg/kg body weight/day). The OVX-GEN-Si group was given subcutaneous injections of 5 mg genistein per gram body weight, at the same time, given soluble silicon daily (Si 20 mg/kg body weight/day). The results showed that the genistein supplementation in the OVX rats significantly prevented the loss of uterus weight; however, the silicon supplementation showed no effect on the uterus weight loss. The lumbar spine and femur bone mineral density was significantly decreased after OVX surgery; however, this decrease was inhibited by the genistein and/or silicon, and the BMD of the lumbar spine and femur was the highest in the OVX-GEN-Si-treated group. Histomorphometric analyses showed that the supplementation of genistein and/or silicon restored bone volume and trabecular thickness of femoral trabecular bone in the OVX group. Besides, the treatment with genistein and silicon for 10 weeks increased the serum levels of calcium and phosphorus in the OVX rats; serum calcium and serum phosphorus in the OVX-GEN-Si group were higher than those in the OVX-GEN and OVX-Si group (P silicon decreased serum alkaline phosphatase (ALP) and osteocalcin, which were increased by ovariectomy; serum ALP and osteocalcin in the OVX-GEN-Si group were lower than those in the OVX-GEN and OVX-Si groups (P silicon have synergistic effects on

  20. Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein

    International Nuclear Information System (INIS)

    Wang, Jun; Jenkins, Sarah; Lamartiniere, Coral A

    2014-01-01

    Humans are exposed to an array of both harmful and beneficial hormonally active compounds in the environment and through diet. Two such chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while genistein suppressed cancer in a chemically-induced model of rodent mammary cancer. The purpose of this research was to determine the effects of combinational exposure to genistein and BPA on cell proliferation, apoptosis, and associated proteins as markers of cancer in mammary glands of rats exposed prepubertally to these environmental chemicals. Prepubertal rats (postpartum days (PND) 2–20) were exposed through lactation via nursing dams treated orally with sesame oil (SO), BPA, genistein, or a combination of BPA and genistein (BPA + Gen). Cell proliferation, apoptosis and protein expressions were investigated for mechanistic studies in mammary glands of rats exposed to these environmental chemicals. Prepubertal exposure to genistein increased cell proliferation in mammary glands of PND21 rats, while BPA increased cell proliferation in adult (PND50) rats. Prepubertal combinational exposure to BPA + Gen increased cell proliferation and reduced apoptosis in PND21 rats, but reduced cell proliferation and increased apoptosis in PND50 rats. The altered mechanisms behind these cellular responses appear to be centered on differential protein expression of caspases, PARP, Bad, p21, Akts, PTEN, ER-β and SRCs 1–3, in the rat mammary gland. Prepubertal BPA exposure resulted in increased cell proliferation in mammary glands of PND50 rats, a process associated with increased risk of cancer development in a chemically-induced mammary cancer. On the other hand, genistein stimulated cell proliferation at PND21, a process that correlates with mammary gland maturation and chemoprevention. In contrast to single chemical exposure, combinational exposure to BPA + Gen performed most similarly to

  1. A phase I dose escalation trial of AXP107-11, a novel multi-component crystalline form of genistein, in combination with gemcitabine in chemotherapy-naive patients with unresectable pancreatic cancer.

    Science.gov (United States)

    Löhr, Johannes-Matthias; Karimi, Masoud; Omazic, Brigitta; Kartalis, Nikolaos; Verbeke, Caroline Sabine; Berkenstam, Anders; Frödin, Jan-Erik

    2016-01-01

    AXP107-11 is a novel, multi-component crystalline form of the naturally occurring compound genistein. AXP107-11 has improved physiochemical properties and oral bioavailability compared to the natural form of genistein, and it is possible that combining AXP107-11 with chemotherapy may increase the effect and reduce chemoresistance. The purpose of this dose escalation phase Ib study was to assess the safety, maximum tolerated dose (MTD) and pharmacokinetics (PK) of AXP107-11 in combination with gemcitabine in treatment-naïve patients with inoperable pancreatic carcinoma. AXP107-11 was given orally in escalating doses (400 mg-1600 mg daily) in combination with standard gemcitabine treatment (1000 mg/m(2)/week) for the first seven of eight weeks and thereafter for a maximum of four × four-week treatment cycles. PK, safety, MTD and efficacy of AXP107-11 in combination with gemcitabine were evaluated. Sixteen patients were enrolled and received AXP107-11. The maximum concentration in serum of unconjugated (free) genistein was 1 μM. Neither dose-limiting toxicities (DLTs) nor signs of hematological or non-hematological toxicities related to AXP107-11 were observed over a period ranging from 0.7 to 13.2 months. The median overall survival time was 4.9 months (range 1.5-19.5 months). Seven patients (44%) survived longer than six months and 19% were alive at the one-year follow-up. Treatment of pancreatic cancer patients with AXP107-11 in combination with gemcitabine resulted in a favorable PK-profile with high serum levels without signs of either hematological or non-hematological toxicity. Accordingly, we suggest further studies with AXP107-11 in pancreatic cancer patients. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  2. Estrogen agonist genistein differentially influences the cognitive and motor disorders in an ovariectomized animal model of Parkinsonism

    Directory of Open Access Journals (Sweden)

    Elaheh Arbabi

    2016-12-01

    Full Text Available Objective(s: Parkinson's disease (PD is a progressive neurological disorder associated with motor disabilities and cognitive dysfunction as well. Evidence indicates that PD occurs less frequently in women than men, confirming a role for steroid hormones in protection of dopaminergic nigrostriatal neurons. It is reported that soy genistein, an estrogen agonist phytoestrogen, display neuroprotective effects against neuronal death. In this study we evaluated the effect of genistein in animal models of Parkinsonism (P and Parkinsonism + ovariectomized (OP. Materials and Methods: The experiments were carried out on the control, P and OP animals. Learning and memory abilities were evaluated using Morris water maze. The latency and speed of locating the platform were measured as cognitive indices. Motor behaviors were assessed by testing the animals in rota rod and the latency to fall from the rod was scored. Results: We found that Parkinsonism leads to the cognitive and motor disabilities; ovariectomy intensified these disorders. Whereas genistein treatment improved the maze performances in both P and OP animals it failed to influence the kinetic problems. Genistein displayed a neuroprotective effect on dopaminergic neurons. Conclusion: Positive impact of genistein on the spatial learning and memory may reflect its effects on the nigrostriatal pathway and striatum. Nevertheless, ineffectiveness of genistein on the motor disorders, despite its neuroprotective impacts, led us to conclude that the cognitive improvement by genistein may also contribute to its effects in other areas of brain.

  3. Genistein alleviates anxiety-like behaviors in post-traumatic stress disorder model through enhancing serotonergic transmission in the amygdala.

    Science.gov (United States)

    Wu, Zhong-Min; Ni, Gui-Lian; Shao, Ai-Min; Cui, Rong

    2017-09-01

    Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder, characterized by intense fear, and increased arousal and avoidance of traumatic events. The current available treatments for PTSD have limited therapeutic value. Genistein, a natural isoflavone, modulates a variety of cell functions. In this study, we tested anti-anxiety activity and underlying mechanisms of genistein in a PTSD rat model. The rats were trained to associate a tone with foot shock delivery on day 0, then fear conditioning was performed on day 7, 14 and 21. Genistein (2-8mg/kg) was injected intraperitoneally daily for 7 days. The anti-anxiety effects of genistein were measured by contextual freezing behavior and elevated plus maze. By the end of the experiments, the amygdala was extracted and subject to neurochemistry analysis. Genistein alleviated contextual freezing behavior and improved performance in elevated plus maze dose-dependently in PTSD rats. Furthermore, in these rats, genistein enhanced serotonergic transmission in the amygdala, including upregulation of tryptophan hydroxylase, serotonin, and phosphorylated (p)-CaMKII and p-CREB, as well. Genistein exerts anti-anxiety effects on a PTSD model probably through enhancing serotonergic system and CaMKII/CREB signaling pathway in the amygdala. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  4. Therapeutic potential of genistein in ovariectomy-induced pancreatic injury in diabetic rats: The regulation of MAPK pathway and apoptosis

    Directory of Open Access Journals (Sweden)

    Hadi Yousefi

    2017-09-01

    Full Text Available Objective(s: Genistein, as a phytoestrogen found in legumes, has several biological activities in general and anti-diabetic activity particularly. In this study, we investigated the effect of genistein on proteins involved in β-cell proliferation, survival and apoptosis to further reveal its anti-diabetic potential in the ovariectomized diabetic rat. Materials and Methods: We used three-month-old female Wistar rats that either underwent ovariectomy (OVX or received a sham surgery (Sham. In a subsequent series of experiments, OVX rats received high-fat diet and low dose STZ to induce diabetes (OVX.D and genistein treatment (OVX.D.G. Western blot analysis was used for the assessment of phosphorylation of ERK1/2 and AKT and expression of Bcl-2 and caspase-3 in pancreas tissue. Hematoxylin-Eosin (H&E staining was used for histopathological assessment. Results: Genistein induced AKT and ERK1/2 phosphorylation protein expression of Bcl-2 in the pancreas. In addition, genistein suppressed protein level of caspase-3. Administration of genistein significantly improved hyperglycemia in ovariectomized diabetic rat, concomitant with improved islet β-cell morphology and mass. Conclusion: These findings suggest that the beneficial antidiabetic effect of genistein partially mediated by directly modulating pancreatic β-cell function via activation of the AKT, ERK1/2, and Bcl-2, as cell survival and anti-apoptotic factors, and decreasing of proapoptotic caspase-3.

  5. Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of ERK activity in ovariectomized mice.

    Science.gov (United States)

    Wang, Shiquan; Wei, Haidong; Cai, Min; Lu, Yan; Hou, Wugang; Yang, Qianzi; Dong, Hailong; Xiong, Lize

    2014-01-01

    Stroke has severe consequences in postmenopausal women. As replacement therapy of estrogen have various adverse effects and the undermined outcomes. Genistein, a natural phytoestrogen, has been suggested to be a potential neuroprotective agent for such stroke patients. However, the role of genistein and its underlying mechanism in ovariectomized mice has not yet been evaluated. In the present study, ovariectomized mice were treated with genistein (10 mg/kg) or vehicle daily for two weeks before developing transient cerebral ischemia (middle cerebral artery occlusion). The neurological manifestation was evaluated, and infarct volumes were demonstrated by 2,3,5-triphenyltetrazolium chloride staining at 24 h after reperfusion. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) was detected by Western blotting and immunofluorescence staining, and cellular apoptosis was evaluated in the ischemic penumbra. We found that treatment with genistein reduced infarct volumes, improved neurological outcomes and attenuated cellular apoptosis at 24 h after reperfusion. ERK1/2 showed increased phosphorylation by genistein treatment after reperfusion, and an ERK1/2 inhibitor U0126 abolished this protective effect of genistein in terms of infarct volumes, neurological scores and cellular apoptosis. Our findings indicate that treatment with genistein can reduce the severity of subsequent stroke episodes, and that this beneficial function is associated with ERK activation.

  6. Biotransformation and recovery of the isoflavones genistein and daidzein from industrial antibiotic fermentations

    Science.gov (United States)

    Weber, J. Mark; Reeves, Andrew R.; Seshadri, Ramya; Cernota, William H.; Gonzalez, Melissa C.; Gray, Danielle L.; Wesley, Roy K.

    2013-01-01

    The objective of this study was to follow the metabolic fate of isoflavone glucosides from the soybean meal in a model industrial fermentation to determine if commercially useful isoflavones could be harvested as coproducts from the spent broth at the end of the fermentation. The isoflavone aglycones, genistein and daidzein, together make up 0.1 - 0.2% of the soybean meal by weight but serve no known function in the manufacturing process. After feeding genistein to washed cells of the erythromycin-producing organism, Saccharopolyspora erythraea, the first biotransformation product (Gbp1) was determined by x-ray crystallography to be genistein-7-O-α-rhamnoside (rhamnosylgenistein). Subsequent feeding of rhamnosylgenistein to growing cells of S. erythraea led to the production of a second biotransformation product, Gbp2. Chromatographic evidence suggested that Gbp2 accumulated in the spent broth of the erythromycin fermentation. When the spent broth was hydrolyzed with acid or industrial enzyme preparations the isoflavone biotransformation products were returned back to their parental forms, genistein and daidzein, which were then recovered as coproducts. Desirable features of this method are that it does not require modification of the erythromycin manufacturing process or genetic engineering of the producing organism to be put into practice. A preliminary investigation of five additional antibiotic fermentations of industrial importance were also found to have isoflavone coproduct potential. PMID:23604533

  7. Production of soybean isoflavone genistein in non-legume plants via genetically modified secondary metabolism pathway.

    Science.gov (United States)

    Liu, Rongrong; Hu, Yuanlei; Li, Jialin; Lin, Zhongping

    2007-01-01

    Genetic modification of secondary metabolic pathways to produce desirable natural products is an attractive approach in plant biotechnology. In our study, we attempted to produce a typical soybean isoflavone genistein, a well-known health-promoting metabolite, in non-legume plants via genetic engineering. Both overexpression and antisense suppression strategies were used to manipulate the expression of several genes encoding key enzymes in the flavonoids/isoflavonoids pathway in transgenic tobacco, lettuce, and petunia. Introducing soybean isoflavone synthase (IFS) into these plants, which naturally do not produce isoflavonoids due to a lack of this leguminous enzyme, resulted in genistein biosynthesis in tobacco petals, petunia leaves and petals, and lettuce leaves. In tobacco, when flavanone 3-hydroxylase (F3H) expression was suppressed by its antisense gene while soybean IFS was overexpressed at the same time, genistein yield increased prominently. In addition, overexpression of phenylalanine ammonia-lyase (PAL) also led to an enhanced genistein production in tobacco petals and lettuce leaves in the presence of IFS than in the plants that overexpressed only IFS.

  8. Differential effects of genistein on prostate cancer cells depend on mutational status of the androgen receptor.

    Directory of Open Access Journals (Sweden)

    Abeer M Mahmoud

    Full Text Available Blocking the androgen receptor (AR activity is the main goal of therapies for advanced prostate cancer (PCa. However, relapse with a more aggressive, hormone refractory PCa arises, which harbors restored AR activity. One mechanism of such reactivation occurs through acquisition of AR mutations that enable its activation by various steroidal and non-steroidal structures. Thus, natural and chemical compounds that contribute to inappropriate (androgen-independent activation of the AR become an area of intensive research. Here, we demonstrate that genistein, a soy phytoestrogen binds to both the wild and the Thr877Ala (T877A mutant types of AR competitively with androgen, nevertheless, it exerts a pleiotropic effect on PCa cell proliferation and AR activity depending on the mutational status of the AR. Genistein inhibited, in a dose-dependent way, cell proliferation and AR nuclear localization and expression in LAPC-4 cells that have wild AR. However, in LNCaP cells that express the T877A mutant AR, genistein induced a biphasic effect where physiological doses (0.5-5 µmol/L stimulated cell growth and increased AR expression and transcriptional activity, and higher doses induced inhibitory effects. Similar biphasic results were achieved in PC-3 cells transfected with AR mutants; T877A, W741C and H874Y. These findings suggest that genistein, at physiological concentrations, potentially act as an agonist and activate the mutant AR that can be present in advanced PCa after androgen ablation therapy.

  9. Growth performance, carcass characteristics and bioavailability of isoflavones in pigs fed soy bean based diets.

    Science.gov (United States)

    Kuhn, Gerda; Hennig, U; Kalbe, Claudia; Rehfeldt, Charlotte; Ren, M Q; Moors, S; Degen, Gisela H

    2004-08-01

    A growth trial with 38 weaners (castrated male pigs) was designed to compare the growth performance and carcass quality of pigs fed diets containing either soy bean meal or soy protein concentrate in a pair-feeding design. Soy bean meal (SBM) and soy protein concentrate (SPC) differed in isoflavone (daidzein plus genistein) content (782 microg/g in SBM and 125 microg/g in SPC, respectively). During the experiment, all pigs were fed four-phases-diets characterized by decreasing protein concentrations with increasing age (weaner I, weaner II, grower, finisher diets). Rations of control and experimental groups were isoenergetic, isonitrogenous, and isoaminogen. The weanling pigs with an initial live weight of 8.4 +/- 1.1 kg were allotted to flat deck boxes. During the growing/finishing period (days 70-170 of age), the pigs were housed in single boxes. Both, the weaning and the grower/finishing performances (daily body weight gain, feed intake, feed conversion ratio) were similar in both groups. No differences were found between the groups in carcass composition (percentages of cuts, tissues, and protein/fat), and meat quality of pigs. Moreover, the IGF-1R mRNA expression in longissimus muscle was not influenced by the kind of soy product. However, circulating levels of isoflavones were clearly different between pigs fed SBM (genistein 239 +/- 44; daidzein 162 +/- 42; equol 12 +/- 4 ng/ml plasma) and animals fed SPC (genistein 22 +/- 9 and daidzein 8 +/- 3, and equol 10 +/- 3 ng/ml plasma). The results confirm the expected differences in the bioavailability of soy isoflavones, yet, there were no significant differences in performance of pigs fed either soy bean meal or soy protein concentrate.

  10. Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin.

    Science.gov (United States)

    El Sheikh Saad, H; Meduri, G; Phrakonkham, P; Bergès, R; Vacher, S; Djallali, M; Auger, J; Canivenc-Lavier, M C; Perrot-Applanat, M

    2011-07-01

    The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and GV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of GV- and to a lesser extent, V-exposed animals displayed abnormal hyperplasic alveolar structures at PND50. Thus, gestational and lactational exposure to low doses of genistein plus vinclozolin may seriously affect peripubertal development of the rat mammary gland. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tzu-Chin [Chest Clinic, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Yi-Chin [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Chen, Hsiao-Ling [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Huang, Pei-Ru; Liu, Shang-Yu [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Yeh, Shu-Lan, E-mail: suzyyeh@csmu.edu.tw [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

    2016-02-01

    Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

  12. The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

    International Nuclear Information System (INIS)

    Wu, Tzu-Chin; Lin, Yi-Chin; Chen, Hsiao-Ling; Huang, Pei-Ru; Liu, Shang-Yu; Yeh, Shu-Lan

    2016-01-01

    Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

  13. Genistein inhibits cell invasion and motility by inducing cell differentiation in murine osteosarcoma cell line LM8.

    Science.gov (United States)

    Nakamura, Atsushi; Aizawa, Junichi; Sakayama, Kenshi; Kidani, Teruki; Takata, Tomoyo; Norimatsu, Yoshiaki; Miura, Hiromasa; Masuno, Hiroshi

    2012-09-26

    One of the problems associated with osteosarcoma is the frequent formation of micrometastases in the lung prior to diagnosis because the development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of pulmonary metastases during the early stage of tumor development is critical for the improvement of the prognosis of osteosarcoma patients. In Japan, soy is consumed in a wide variety of forms, such as miso soup and soy sauce. The purpose of this study is to investigate the effect of genistein, an isoflavone found in soy, on the invasive and motile potential of osteosarcoma cells. LM8 cells were treated for 3 days with various concentrations of genistein. The effect of genistein on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine (BrdU) incorporation study. The assays of cell invasion and motility were performed using the cell culture inserts with either matrigel-coated membranes or uncoated membranes in the invasion chambers. The expression and secretion of MMP-2 were determined by immunohistochemistry and gelatin zymography. The subcellular localization and cellular level of β-catenin were determined by immunofluorescence and Western blot. For examining cell morphology, the ethanol-fixed cells were stained with hematoxylin-eosin (H&E). The expression of osteocalcin mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). Genistein dose-dependently inhibits cell proliferation. Genistein-treated cells were less invasive and less motile than untreated cells. The expression and secretion of MMP-2 were lower in the genistein-treated cultures than in the untreated cultures. β-Catenin in untreated cells was located in the cytoplasm and/or nucleus, while in genistein-treated cells it was translocated near to the plasma membrane. The level of β-catenin was higher in genistein-treated cells than in untreated cells. Treatment of LM8 cells with genistein induced morphological

  14. Genistein inhibits cell invasion and motility by inducing cell differentiation in murine osteosarcoma cell line LM8

    Directory of Open Access Journals (Sweden)

    Nakamura Atsushi

    2012-09-01

    Full Text Available Abstract Background One of the problems associated with osteosarcoma is the frequent formation of micrometastases in the lung prior to diagnosis because the development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of pulmonary metastases during the early stage of tumor development is critical for the improvement of the prognosis of osteosarcoma patients. In Japan, soy is consumed in a wide variety of forms, such as miso soup and soy sauce. The purpose of this study is to investigate the effect of genistein, an isoflavone found in soy, on the invasive and motile potential of osteosarcoma cells. Methods LM8 cells were treated for 3 days with various concentrations of genistein. The effect of genistein on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2’-deoxyuridine (BrdU incorporation study. The assays of cell invasion and motility were performed using the cell culture inserts with either matrigel-coated membranes or uncoated membranes in the invasion chambers. The expression and secretion of MMP-2 were determined by immunohistochemistry and gelatin zymography. The subcellular localization and cellular level of β-catenin were determined by immunofluorescence and Western blot. For examining cell morphology, the ethanol-fixed cells were stained with hematoxylin-eosin (H&E. The expression of osteocalcin mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR. Results Genistein dose-dependently inhibits cell proliferation. Genistein-treated cells were less invasive and less motile than untreated cells. The expression and secretion of MMP-2 were lower in the genistein-treated cultures than in the untreated cultures. β-Catenin in untreated cells was located in the cytoplasm and/or nucleus, while in genistein-treated cells it was translocated near to the plasma membrane. The level of β-catenin was higher in genistein-treated cells than in untreated cells

  15. Mixture Effects of 3 Mechanistically Different Steroidogenic Disruptors (Prochloraz, Genistein, and Ketoconazole) in the H295R Cell Assay

    DEFF Research Database (Denmark)

    Nielsen, Frederik Knud; Hansen, Cecilie Hurup; Fey, Jennifer Anna

    2015-01-01

    Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β-estradiol......Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β...

  16. Genistein, a phytoestrogen, improves total cholesterol, and Synergy, a prebiotic, improves calcium utilization, but there were no synergistic effects.

    Science.gov (United States)

    Legette, LeeCole L; Lee, Wang-Hee; Martin, Berdine R; Story, Jon A; Arabshahi, Ali; Barnes, Stephen; Weaver, Connie M

    2011-08-01

    Prebiotics and phytoestrogens have sparked great interest because evidence indicates that the consumption of these dietary constituents leads to lower cholesterol levels and inhibition of postmenopausal bone loss. The aim of this study was to determine the effect of both a prebiotic (Synergy) and a phytoestrogen (genistein) on bone and blood lipid levels in an animal model of postmenopausal women. A 4-week feeding study was conducted in 5-month-old ovariectomized (OVX) Sprague-Dawley rats to examine the effect of genistein, Synergy (a prebiotic), and genistein and Synergy combined on bone density and strength, calcium metabolism, and lipid biomarkers. There were six treatment groups: sham control, OVX control, OVX rats receiving daily estradiol injections, and OVX rats receiving an AIN-93M diet supplement with 200 ppm genistein, with 5% Synergy or with 200 ppm genistein and 5% Synergy combined. The rats receiving genistein had significantly lower total serum cholesterol concentrations than OVX rats in the control group (17%), OVX rats receiving daily estradiol injections (14%), and OVX rats fed the 5% Synergy diet (19%). Consumption of Synergy improved calcium absorption efficiency (41%) compared with nonconsumption (OVX control). Sham control rats had a significantly higher femoral bone density, as determined by underwater weighing, than did the rats in all of the OVX groups. Genistein consumption restored total and trabecular bone mineral density at the distal femur similar to the levels of sham rats. Genistein supplementation imparts modest heart health benefits and improves bone geometry at the distal femur, and prebiotic consumption (Synergy) results in improved calcium utilization strength in ovariectomized rats, but the combination produced no synergistic effects.

  17. Effects of genistein, a soybean-derived isoflavone, on proliferation and differentiation of B16-BL6 mouse melanoma cells.

    Science.gov (United States)

    Yan, C H; Chen, X G; Li, Y; Han, R

    1999-01-01

    Genistein, a soybean-derived isoflavone, may contribute to the lower cancer incidence in South Asian countries. In this study, the effects and molecular mechanisms of genistein on growth and differentiation of B16-BL6 mouse melanoma cells were investigated. Genistein suppressed the growth of these melanoma cells. The IC50 value is 15.5 microM. On the other hand, genistein induced the changes of cell shape and cytoskeletal network. The cytoskeletal filaments were induced to form a bundle along the direction of elongation of the cells. Moreover, tyrosine phosphorylation levels of cytoskeleton-associated proteins decreased after the cells were exposed to 20 or 30 microM of genistein for 3 days. All these morphological and molecular changes were accompanied by appearance of the differentiated phenotypes. Genistein induced the increase of cellular melanin content, enhancement of tyrosinase activity, and decrease of colonization potentials in soft agar in a time-dependent and dose-dependent manner. The effective concentration was no more than 10 microM after 3 days' exposure. The tumorigenic potentials of B16-BL6 cells in C57BL/6 mouse also decreased after exposure to 20 or 30 microM of genistein for 3 days. When expressions of tumor-related genes were investigated in the differentiation-induced cells, the content of P53 dramatically increased while that of c-Myc protein decreased. Therefore, due to its ability to induce cellular and molecular changes, genistein suppressed the growth and induced differentiated phenotypes in B16-BL6 melanoma cells.

  18. Effects of phytoestrogens genistein and daidzein on progesterone and estrogen (estradiol) production of human term trophoblast cells in vitro.

    Science.gov (United States)

    Richter, Dagmar Ulrike; Mylonas, Ioannis; Toth, Bettina; Scholz, Christoph; Briese, Volker; Friese, Klaus; Jeschke, Udo

    2009-01-01

    Phytoestrogens are a diverse group of nonsteroidal plant compounds that occur naturally in many plants. Because they possess a ring system similar to estrogens they are able to bind on estrogen receptors alpha and beta in humans. The effects of the phytoestrogens genistein and daidzein on the production of progesterone and estrogen in isolated human term trophoblast cells in vitro were tested in this study. Cytotrophoblast cells were isolated from human term placentas. Phytoestrogens genistein and daidzein were incubated in different concentrations with trophoblast cells. Untreated cells were used as controls. After 24 h aliquots were removed and tested for progesterone and estrogen production. The production of the steroid hormones progesterone and estrogen are influenced by phytoestrogens genistein and daidzein in human term trophoblast cells. A strong inhibition effect of both phytoestrogens tested in the production of progesterone was demonstrated. In addition, a significant stimulating effect on estrogen production by genistein and daidzein was observed. Results obtained with this study show that phytoestrogens (genistein and daidzein) sufficiently reduce progesterone production in human term trophoblast cells. Because blockade of progesterone is a possible mechanism involved in initiation of labor, we may speculate that high doses of phytoestrogens at the feto-maternal interphase could play a negative role in maintenance of pregnancy. Stimulation of estrogen production by genistein and daidzein in trophoblast cells is probably due to estrogen receptor blocking effects of both phytoestrogens. Trophoblast cells seem to compensate blocking of its estrogen receptors by higher estrogen production.

  19. Bioaccessibility and bioavailability of phenolic compounds in bread: a review.

    Science.gov (United States)

    Angelino, Donato; Cossu, Marta; Marti, Alessandra; Zanoletti, Miriam; Chiavaroli, Laura; Brighenti, Furio; Del Rio, Daniele; Martini, Daniela

    2017-07-19

    Cereal-based products, like breads, are a vehicle for bioactive compounds, including polyphenols. The health effects of polyphenols like phenolic acids (PAs) are dependent on their bioaccessibility and bioavailability. The present review summarizes the current understanding of potential strategies to improve phenolic bioaccessibility and bioavailability and the main findings of in vitro and in vivo studies investigating these strategies applied to breads, including the use of raw ingredients with greater phenolic content and different pre-processing technologies, such as fermentation and enzymatic treatment of ingredients. There is considerable variability between in vitro studies, mainly resulting from the use of different methodologies, highlighting the need for standardization. Of the few in vivo bioavailability studies identified, acute, single-dose studies demonstrate that modifications to selected raw materials and bioprocessing of bran could increase the bioavailability, but not necessarily the net content, of bread phenolics. The two medium-term identified dietary interventions also demonstrated greater phenolic content, resulting from the modification of the raw materials used. Overall, the findings suggest that several strategies can be used to develop new bread products with greater phenolic bioaccessibility and bioavailability. However, due to the large variability and the few studies available, further investigations are required to determine better the usefulness of these innovative processes.

  20. NODULATION OF YELLOW LUPIN (Lupinus luteus L. DEPENDING ON THE FORECROP, SEED INOCULATION WITH Bradyrhizobium lupini AND GENISTEIN

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    Janusz PRUSIŃSKI

    2012-12-01

    Full Text Available A strict two-factor field ‘Mister’ yellow lupin experiment was made in a split-plot design in poor rye complex soil (soil valuation class IVb at the Experiment Station of the Faculty of Agriculture and Biotechnology, the University of Technology and Life Sciences at Mochełek over 2008-2011. The experiment design covered 2 factors: growing yellow lupin after intercrops of ‘Bardena’ white mustard and ‘Pastar’ winter rye as well as seed inoculation with Bradyrhizobium lupini with or without genistein added. Growing intercrops in the poor rye complex soil considerably decreased neither the Nmin content in early spring nor the size of nodulation in yellow lupin. After lupin harvest, slightly more Nmin was noted for the treatments where intercrops were applied, especially rye in the 0-30 cm layer. The weather pattern, especially moisture conditions, pointed to a special sensitivity of nodulation to water deficit or excess in the rhizosphere. The method of preparing seeds for sowing did not play a greater role in developing the Nmin content in both soil profile layers analysed. White mustard showed a negative effect on the dry weight of nodules and the total N content in the plants and the seeds of yellow lupin as well as created the least favourable conditions for the survival and the capacity for symbiosis by symbiotic bacteria remaining in soil after lupin harvest. The state of yellow lupin plant nitrogen nutrition did not depend on the experimental factors.

  1. Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation

    OpenAIRE

    Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-01-01

    Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured s...

  2. The morpho-functional parameters of rat pituitary hormone producing cells after genistein treatment

    Directory of Open Access Journals (Sweden)

    Svetlana Trifunović

    2018-03-01

    Full Text Available Phytoestrogens are a diverse group of steroid–like compounds that occur naturally in many plants. There are various types of phytoestrogens, including the best-researched isoflavones which are commonly found in soy. The consumption of soy products has many health benefits, including protection against breast cancer, prostate cancer, menopausal symptoms, heart disease and osteoporosis. In contrast, use of hormonally active compounds-isoflavones may unfortunately interfere with the endocrine system and can have far-reaching consequences. Genistein, the most abundant soy-bean derived isoflavone, possesses a ring system similar to estrogens and acts through an estrogen receptor (ER-mediated mechanism, by increasing or decreasing the transcription of ER-dependent target genes. Also, genistein can act on cells through ER non-dependent mechanisms, such as tyrosine kinase inhibitor. The neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, and stress responsiveness. It is well known, that estrogen is important for development of the neuroendocrine system in both sexes. At the pituitary level, estrogen is known to affect the regulation of all hormone producing (HP cells, by direct and/or indirect mechanisms. Due to structural and functional resemblance to estrogen, the question may arise of whether and how genistein affects the morphofunctional features of pituitary HP cells. This review deals with the consequences of genistein’s effects on morphological, stereological and hormonal features of HP cells within the anterior pituitary gland. Transparency on this issue is needed because isoflavones are presently highly consumed. Inter alia, genistein as well as other isoflavones, are present in various dietary supplements and generally promoted as an accepted alternative to estrogen replacement therapy. Potential isoflavone biomedical exploitation is not

  3. Genistein in 1:1 Inclusion Complexes with Ramified Cyclodextrins: Theoretical, Physicochemical and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Corina Danciu

    2014-01-01

    Full Text Available Genistein is one of the most studied phytocompound in the class of isoflavones, presenting a notable estrogenic activity and in vitro and/or in vivo benefits in different types of cancer such as those of the bladder, kidney, lung, pancreatic, skin and endometrial cancer. A big inconvenience for drug development is low water solubility, which can be solved by using hydrophilic cyclodextrins. The aim of this study is to theoretically analyze, based on the interaction energy, the possibility of a complex formation between genistein (Gen and three different ramified cyclodextrins (CD, using a 1:1 molar ratio Gen:CD. Theoretical data were correlated with a screening of both in vitro and in vivo activity. Proliferation of different human cancer cell lines, antimicrobial activity and angiogenesis behavior was analyzed in order to see if complexation has a beneficial effect for any of the above mentioned activities and if so, which of the three CDs is the most suitable for the incorporation of genistein, and which may lead to future improved pharmaceutical formulations. Results showed antiproliferative activity with different IC50 values for all tested cell lines, remarkable antimicrobial activity on Bacillus subtilis and antiangiogenic activity as revealed by CAM assay. Differences regarding the intensity of the activity for pure and the three Gen complexes were noticed as explained in the text. The data represent a proof that the three CDs can be used for furtherer research towards practical use in the pharmaceutical and medical field.

  4. Effect of dietary genistein on growth performance, digestive enzyme activity, and body composition of Nile tilapia Oreochromis niloticus

    Science.gov (United States)

    Chen, Dong; Wang, Wei; Ru, Shaoguo

    2015-01-01

    An 8-week feeding experiment was performed to evaluate the effect of dietary genistein on growth performance, body composition, and digestive enzymes activity of juvenile Nile tilapia ( Oreochromis niloticus). Four isonitrogenous and isoenergetic diets were formulated containing four graded supplements of genistein: 0, 30, 300, and 3 000 μg/g. Each diet was randomly assigned in triplicate to tanks stocked with 15 juvenile tilapia (10.47±1.24 g). The results show that 30 and 300 μg/g dietary genistein had no significant effect on growth performance of Nile tilapia, but the higher level of genistein (3 000 μg/g) significantly depressed the final body weight and specific growth rate. There was no significant difference in survival rate, feed intake, feed efficiency ratio or whole body composition among all dietary treatments. An assay of digestive enzymes showed that the diet containing 3 000 μg/ggenistein decreased stomach and hepatopancreas protease activity, and amylase activity in the liver and intestine, while a dietary level of 300 μg/g genistein depressed stomach protease and intestine amylase activities. However, no significant difference in stomach amylase activity was found among dietary treatments. Overall, the results of the present study indicate that a high level of dietary genistein (3 000 μg/g, or above) would significantly reduce the growth of Nile tilapia, partly because of its inhibitory effect on the activity of major digestive enzymes. Accordingly, the detrimental effects of genistein, as found in soybean products, should not be ignored when applied as an alternative ingredient source in aquaculture.

  5. Genistein up-regulates tumor suppressor microRNA-574-3p in prostate cancer.

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    Takeshi Chiyomaru

    Full Text Available Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs. In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control. The expression of miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues compared with normal prostate cells (RWPE-1 and adjacent normal tissues. Low expression level of miR-574-3p was correlated with advanced tumor stage and higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells significantly inhibited cell proliferation, migration and invasion in vitro and in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and activating caspase-9 and caspase-3. Using GeneCodis software analysis, several pathways affected by miR-574-3p were identified, such as 'Pathways in cancer', 'Jak-STAT signaling pathway', and 'Wnt signaling pathway'. Luciferase reporter assays demonstrated that miR-574-3p directly binds to the 3' UTR of several target genes (such as RAC1, EGFR and EP300 that are components of 'Pathways in cancer'. Quantitative real-time PCR and Western analysis showed that the mRNA and protein expression levels of the three target genes in PCa cells were markedly down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the three target genes significantly affect cell proliferation, migration and invasion in PCa cell lines. Our results show that genistein up-regulates tumor suppressor miR-574-3p expression targeting several cell signaling pathways. These findings enhance understanding of how genistein regulates with miRNA in PCa.

  6. Zinc bioavailability in the chick

    International Nuclear Information System (INIS)

    Hempe, J.M.

    1987-01-01

    Methods for assessing zinc bioavailability were evaluated in the chick. A low-zinc chick diet was developed using rehydrated, spray-dried egg white autoclaved at 121 C for 30 min as the primary protein source. The relative bioavailability of zinc from soy flour and beef was determined by whole-body retention of extrinsic 65 Zn, and in slope ratio assays for growth rate and tissue zinc. Compared to zinc carbonate added to an egg white-based diet, all methods gave similar estimates of approximately 100% zinc bioavailability for beef but estimates for soy flour varied widely. The slope ratio assay for growth rate gave the best estimate of zinc bioavailability for soy flour. True absorption, as measured by percent isotope retention from extrinsically labeled soy flour, was 47%

  7. Genistein modulates the estrogen receptor and suppresses angiogenesis and inflammation in the murine model of peritoneal endometriosis

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    Sutrisno Sutrisno

    2018-04-01

    Full Text Available The purpose of this study was to investigate the effect of genistein administration on the modulation of the estrogen receptor, inhibition of inflammation and angiogenesis in the murine model of peritoneal endometriosis. A total of thirty-six mice (Mus musculus were divided into six groups (n = 6, including the control group, endometriosis group, endometriosis group treated with various doses of genistein (0.78; 1.04; 1.3 mg/day, and endometriosis group treated with leuprolide acetate (0.00975 mg/day every 5 days for 15 days. Analysis of estrogen receptor-α, estrogen receptor-β, TNF-α, IL-6, VEGF, and HIF-1α were performed immunohistochemically. Expression of estrogen receptor-α, estrogen receptor-β, TNF-α, IL-6, VEGF and HIF-1α increased significantly compared with the control group (p  0.05. Genistein also decreased the expression of TNF-α and IL-6 (1.04 and 1.3 mg/day compared with the endometriosis group, reaching level comparable to that of the control group (p > 0.05. It was concluded that genistein is able to modulate estrogen receptor-α and estrogen receptor-β and inhibit the development of inflammation and angiogenesis in the murine model of peritoneal endometriosis. Thus, genistein can be a candidate in the treatment of endometriosis. Keywords: Estrogen receptor, Growth factor, Inflammation, Angiogenesis, Peritoneum

  8. Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study

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    Gaurav Gupta

    2015-01-01

    Full Text Available The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n=6 for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST; and forced swim test (FST and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p>0.05. Chronic treatment of combination of genistein (10 mg/kg and amitriptyline (5 mg/kg and 10 mg/kg significantly reduced the immobility time as compared to control group (p<0.001 and was comparable to amitriptyline alone (10 mg/kg. However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg and amitriptyline (5 mg/kg were observed. Genistein at its standard dose (10 mg/kg rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg.

  9. Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer's disease.

    Science.gov (United States)

    Bagheri, Maryam; Joghataei, Mohammad-Taghi; Mohseni, Simin; Roghani, Mehrdad

    2011-03-01

    Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by increased β-amyloid (Aβ) deposition and neuronal dysfunction leading to impaired learning and recall. Ageing, heredity, and induced oxidative stress are among proposed risk factors. The increased frequency of the disease in women also suggests a role for estrogen in development of AD. In the present study, effects of the phytoestrogen genistein (10mg/kg) on learning and memory impairments was assessed in intrahippocampal Aβ(1-40)-injected rats. The estrogen receptor antagonist fulvestrant was injected intracerebroventricularly in a group of Aβ-lesioned rats. The Aβ-injected animals exhibited the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in the RAM task. Genistein, but not genistein and fulvestrant, significantly improved most of these parameters. Measurements of oxidative stress markers in hippocampal tissue of Aβ-injected rats showed an elevation of malondialdehyde (MDA) and nitrite content, and a reduction of superoxide dismutase (SOD) activity. Genistein significantly attenuated the increased MDA content but did not affect the nitrite content or SOD activity. These results indicate that genistein pretreatment ameliorates Aβ-induced impairment of short-term spatial memory in rats through an estrogenic pathway and by inducing attenuation of oxidative stress. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Genistein preserves the lungs of ovariectomized diabetic rats: addition to apoptotic and inflammatory markers in the lung

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    Faeze Daghigh

    2017-12-01

    Full Text Available Objective(s: The role of isoflavones in pulmonary structure and function during menopause is not well studied. Moreover, the important role of estrogen in the physiological function of respiratory system has been revealed. Genistein, as an isoflavone, mimics estrogenic in diabetic and ovariectomized rats. Here, we hypothesized that genistein would reverse changes in the protein expression levels related to estrogen deficiency in the lung of ovariectomized diabetic rats. Materials and Methods: Wistar female rats were assigned to four experimental groups (n=10 in each group: sham, rats underwent laparotomy without removing the ovaries; OVX, rats that underwent ovariectomy; OVX.D, rats underwent bilateral ovariectomy and were fed a high-fat diet (HFD; OVX.D.G, ovariectomized diabetic rats with genistein administration (1 mg/kg /day. After ovariectomy, rats continued to feed HFD for a 4-week period. After 4 weeks of HFD feeding, a single dose of 30 mg/kg of streptozotocin was administered in the diabetic group. Genistein was administered for eight weeks. At the end of the experiment, lung tissue was removed and Western blotting technique and hematoxylin-eosin staining were used for evaluation of the lung. Results: Treatment with genistein significantly decreased inflammatory and apoptotic biomarkers in the ovariectomized diabetic rats compared to non-treated animals (P

  11. Genistein suppresses adhesion-induced protein tyrosine phosphorylation and invasion of B16-BL6 melanoma cells.

    Science.gov (United States)

    Yan, C; Han, R

    1998-07-03

    Protein tyrosine phosphorylation occurs as one of the earlier events in cancer cell-extracellular matrix (ECM) interaction. With immunoblot analysis and immunofluorescence microscopy, genistein was found to suppress the tyrosine phosphorylation of proteins located at the cell periphery, including a 125 kDa protein, when B16-BL6 melanoma cells attached to and interacted with ECM. When accompanied by the suppression of adhesion-induced protein tyrosine phosphorylation, the invasive potential of B16-BL6 cells through reconstituted basement membrane was decreased significantly. However, neither adhesive capability nor cell growth was significantly affected by genistein. Therefore, the interruption of cancer cell-ECM interaction by suppression of protein tyrosine phosphorylation may contribute to invasion prevention of genistein.

  12. Genistein Stimulates Jejunum Chloride Secretion via an Akt-Mediated Pathway in Intact Female Mice

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    Lana Leung

    2015-02-01

    Full Text Available Background/Aims: We have previously shown that daily subcutaneous injections with the naturally occurring phytoestrogen genistein (600 mg genistein/kg body weight/day, 600G results in a significantly increased basal intestinal chloride, Cl-, secretion (Isc, a measure of transepithelial secretion in intact C57BL/6J female mice after 1-week of treatment, compared to controls (DMSO vehicle injected. Removal of endogenous estrogen via ovariectomy (OVX had no effect on the 600G-mediated increase in basal Isc. Methods: Given the estrogen-like characteristics of genistein, we compared the effects of daily estradiol (E2 injections (10 mg E2/kg body weight/day, 10E2 on basal Isc in intact and OVX mice. In intact mice, 10E2 was without effect on basal Isc, however, in OVX mice, 10E2 significantly increased basal Isc (mimicked 600G. The goal of the current study was to characterize the intracellular signaling pathways responsible for mediating 600G- or 10E2-stimulated increases in basal Isc in intact female or OVX mice. Results: We measured total protein expression in isolated segments of jejunum using western blot from the following six groups of mice; intact or OVX with; 600G, 10E2 or control. The proteins of interest were: Akt, p-Akt, p-PDK1, p-PTEN, p-c-Raf, p-GSK-3β, rap-1 and ERK1/2. All blots were normalized to GAPDH levels (n = 6-18/group. Conclusion: These data suggest that the presence of the endogenous sex steroid, estrogen, modifies the intracellular signaling pathway required to mediate Cl- secretion when the intestine is exposed to exogenous 600G or E2. These studies may have relevance for designing pharmacological tools for women with intestinal chloride secretory dysfunctions.

  13. In planta assays involving epigenetically silenced genes reveal inhibition of cytosine methylation by genistein

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    Arase Sachiko

    2012-03-01

    Full Text Available Abstract Background Cytosine methylation is involved in epigenetic control of gene expression in a wide range of organisms. An increasing number of examples indicate that changing the frequency of cytosine methylation in the genome is a feasible tool to engineer novel traits in plants. Although demethylating effects of compounds have been analyzed in human cultured cells in terms of suppressing cancer, their effect in plant cells has not been analyzed extensively. Here, we developed in planta assay systems to detect inhibition of cytosine methylation using plants that contain a transgene transcriptionally silenced by an epigenetic mechanism. Results Seeds of two transgenic plants were used: a petunia line that has been identified as a revertant of the co-suppression of the chalcone synthase-A (CHS-A gene and contains CHS-A transgenes whose transcription is repressed; Nicotiana benthamiana plants that contain the green fluorescent protein (GFP reporter gene whose transcription is repressed through virus-induced transcriptional gene silencing. Seeds of these plants were sown on a medium that contained a demethylating agent, either 5-azacytidine or trichostatin A, and the restoration of the transcriptionally active state of the transgene was detected in seedlings. Using these systems, we found that genistein, a major isoflavonoid compound, inhibits cytosine methylation, thus restoring transgene transcription. Genistein also restored the transcription of an epigenetically silenced endogenous gene in Arabidopsis plants. Conclusions Our assay systems allowed us to assess the inhibition of cytosine methylation, in particular of maintenance of methylation, by compounds in plant cells. These results suggest a novel role of flavonoids in plant cells and that genistein is useful for modifying the epigenetic state of plant genomes.

  14. Molecular Basis of the Anti-Cancer Effects of Genistein Isoflavone in LNCaP Prostate Cancer Cells.

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    Hartmann J

    2011-03-01

    Full Text Available Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic side effects to the patient. In this study, we investigated the effect of genistein isoflavone, a soy derivative, on expression levels of genes involved in these pathways. The mechanism of genistein-induced cell death was also investigated. The chemosensitivity of the LNCaP prostate cancer cells to genistein was investigated using ATP and MTS assays, and a caspase binding assay was used to determine apoptosis induction. Several molecular targets were determined using cDNA microarray and RT-PCR analysis.Results: The overall data revealed that genistein induces cell death in a time- and dose-dependent manner, and regulates expression levels of several genes involved in carcinogenesis and immunity. Several cell-cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin-dependent kinases. Various members of the Bcl-2 family of apoptotic proteins were also affected. The DefB1 and the HLA membrane receptor genes involved in immunogenicity were also up-regulated.Conclusion: The results indicate that genistein inhibits growth of the hormone-dependent prostate cancer cells, LNCaP, via apoptosis induction through regulation of some of the genes involved in carcinogenesis of many tumors, and immunogenicity. This study augments the potential phytotherapeutic and immunotherapeutic significance of genistein isoflavone.

  15. Enhanced Expression of Sodium Hydrogen Exchanger (NHE)-1, 2 and 4 in the Cervix of Ovariectomised Rats by Phytoestrogen Genistein.

    Science.gov (United States)

    Ismail, Nurain; Giribabu, Nelli; Muniandy, Sekaran; Salleh, Naguib

    2015-01-01

    Restoring the pH of cervicovaginal fluid is important for the cervicovaginal health after menopause. Genistein, which is a widely consumed dietary health supplement to overcome the post-menopausal complications could help to restore the cervicovaginal fluid pH. We hypothesized that genistien effect involves changes in expression of NHE-1, 2 and 4 proteins and mRNAs in the cervix. This study investigated effect of genistein on NHE-1, 2 and 4 protein and mRNA expression in the cervix in order to elucidate the mechanisms underlying possible effect of this compound on cervicovaginal fluid pH after menopause. Ovariectomised adult female rats received 25, 50 and 100 mg/kg/day genistein for seven consecutive days. At the end of the treatment, animals were sacrificed and cervix was harvested. Expression of Nhe-1, 2 and 4 mRNA were analyzed by Real-time PCR while distribution of NHE-1, 2 and 4 protein were observed by immunohistochemistry. Treatment with 50 and 100 mg/kg/day genistein caused marked increase in the levels of expression and distribution of NHE-1, 2 and 4 proteins in the endocervical epithelia. Levels of Nhe-1, 2 and 4 mRNA in the cervix were also increased. Coadministration of ICI 182 780 and genistein reduced the expression levels of NHE-1, 2 and 4 proteins and mRNAs in the cervix. Enhanced expression of NHE-1, 2 and 4 proteins and mRNAs expression in cervix under genistein influence could help to restore the cervicovaginal fluid pH that might help to prevent cervicovaginal complications related to menopause.

  16. High-performance liquid chromatographic assay for genistein in biological fluids.

    Science.gov (United States)

    Supko, J G; Phillips, L R

    1995-04-07

    A specific, sensitive and technically convenient HPLC method for assaying genistein in biological fluids has been developed. The compound and 4-hydroxybenzophenone, added as an internal standard, were efficiently isolated from both plasma and urine by extraction with tert-butyl methyl ether. Following evaporation of the organic solvent, the extract was reconstituted with methanol-0.05 M ammonium acetate buffer, pH 4.7 (30:70, v/v), and loaded onto a 4 microns Nova-Pak C8 column (15 cm x 3.9 mm I.D.). Chromatography was performed at ambient temperature using a mobile phase of acetonitrile-0.05 M ammonium formate buffer, pH 4.0 (27:73, v/v), at a flow-rate of 1.0 ml/min, with UV detection at 260 nm. Mean values of the tR for the drug and internal standard, determined from chromatograms of the 1 microgram/ml plasma standard during a 6 month period, were 8.27 +/- 0.55 and 11.92 +/- 0.71 min, respectively (S.D., n = 29). With a sample volume of 50 microliters, the lowest concentration of genistein included in the plasma standard curve, 0.020 microgram/ml, was quantified with a 10.7% R.S.D. over a 5 month period. Plasma standards having concentrations of 0.050 to 1.02 micrograms/ml exhibited R.S.D. values ranging from 2.3 to 6.1%. The drug was quantified in urine with similar reproducibility. The sensitivity of the assay was adequate for characterizing the plasma pharmacokinetics of genistein in the mouse and dog. However, a 10-fold improvement in sensitivity was afforded by increasing the sample size to 250 microliters, without otherwise modifying the method. Thus, this procedure may prove suitable for determining plasma and urine levels of genistein in humans consuming dietary isoflavonoids in a much more convenient manner than permitted by existing methodology.

  17. Bioavailability: implications for science/cleanup policy

    Energy Technology Data Exchange (ETDEWEB)

    Denit, Jeffery; Planicka, J. Gregory

    1998-12-01

    This paper examines the role of bioavailability in risk assessment and cleanup decisions. Bioavailability refers to how chemicals ''behave'' and their ''availability'' to interact with living organisms. Bioavailability has significant implications for exposure risks, cleanup goals, and site costs. Risk to human health and the environment is directly tied to the bioavailability of the chemicals of concern.

  18. Bioavailability of Promethazine during Spaceflight

    Science.gov (United States)

    Boyd, Jason L.; Wang, Zuwei; Putcha, Lakshmi

    2009-01-01

    Promethazine (PMZ) is the choice anti-motion sickness medication for treating space motion sickness (SMS) during flight. The side effects associated with PMZ include dizziness, drowsiness, sedation, and impaired psychomotor performance which could impact crew performance and mission operations. Early anecdotal reports from crewmembers indicate that these central nervous system side effects of PMZ are absent or greatly attenuated in microgravity, potentially due to changes in pharmacokinetics (PK) and pharmacodynamics in microgravity. These changes could also affect the therapeutic effectiveness of drugs in general and PMZ, in particular. In this investigation, we examined bioavailability and associated pharmacokinetics of PMZ in astronauts during and after space flight. Methods. Nine astronauts received, per their preference, PMZ (25 or 50 mg as intramuscular injection, oral tablet, or rectal suppository) on flight day one for the treatment of SMS and subsequently collected saliva samples and completed sleepiness scores for 72 h post dose. Thirty days after the astronauts returned to Earth, they repeated the protocol. Bioavailability and PK parameters were calculated and compared between flight and ground. Results. Maximum concentration (Cmax) was lower and time to reach Cmax (tmax) was longer in flight than on the ground. Area under the curve (AUC), a measure of bioavailability, was lower and biological half-life (t1/2) was longer in flight than on the ground. Conclusion. Results indicate that bioavailability of PMZ is reduced during spaceflight. Number of samples, sampling method, and sampling schedule significantly affected PK parameter estimates.

  19. protective effect of combined administration of isoflavones genistein and daidzein against irradiation -induced damage in female rats

    International Nuclear Information System (INIS)

    Ashry, O.M.

    2009-01-01

    The renewed interests in the search for plant-derived drugs in the field of alternative medicine necessitate further studies. the present work aimed to evaluate the efficacy of diet phyto estrogens such as diadzein and genistein on repairing oxidative damage and protecting calcium homeostatic system against radiation induced disorders in female rats. soybean isoflavones were orally administered in a dose of 9 mg/kg body wt/day for 21 and 26 days. irradiated animals received diadzein and genistein for 11 consecutive days before exposing female rats to 6 Gy gamma irradiation and continued to receive soybean isoflavones until sacrificed 10 and 15 days post irradiation . Irradiation induced significant decrease in white blood cells(WBCs), red blood cells (RBCs), haemoglobin (HB), haematocrit (Ht %), glutathione (GSH), calcium (CA) and estradiol, while it induced significant elevation in serum malondialdehyde(MDA), inorganic phosphorus, thyroxine 3 (T 3 ) and thyroxine 4 (T 4 ), 10 and 15 days post -irradiation . diadzein and genistein treatment before and through irradiation accelerated the recovery of circulating WBCs and RBCs, elevated HB, Hct % GSH meanwhile hindered the depression in CA. Soy isoflavones depressed MDA and ameliorated the increase in T 3 , T 4 and elevated estradiol and phosphorus levels 10 and 15 days post irradiation. the results recommend combined treatment with genistein and daidzein to mitigate irradiation-induced damage and bon loss and suggest clinical application of these isoflavones in radiotherapy

  20. Antagonistic effects of gestational dietary exposure to low-dose vinclozolin and genistein on rat fetal germ cell development.

    Science.gov (United States)

    Lehraiki, Abdelali; Messiaen, Sébastien; Berges, Raymond; Canivenc-Lavier, Marie-Chantal; Auger, Jacques; Habert, René; Levacher, Christine

    2011-05-01

    Continuous, low-dose exposure to a phytoestrogen (1 mg/kg/day genistein) and/or to an antiandrogenic food contaminant (1 mg/kg/day vinclozolin) has been recently reported to affect male reproductive tract and fertility [1] in adults. We investigated whether alterations of the testis are already present at the end of in utero exposure using the same rat model and doses following exposure from conception to delivery. After vinclozolin exposure, we observed in the neonate a slight but significant alteration of steroidogenesis and gametogenesis with a reduction of testosterone secretion and of the number of gonocytes. In contrast, genistein exposure had no effect. While the vinclozolin-genistein mixture acts in a synergistic manner to induce the most significant alterations in the adult, interestingly, genistein antagonized the deleterious effect of vinclozolin on germ cells in the neonate. This difference emphasizes the importance of studying the effects of endocrine disruptors during various developmental stages to understand their effects. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Platelet-activating factor stimulation of tyrosine kinase and its relationship to phospholipase C in rabbit platelets: Studies with genistein and monoclonal antibody to phosphotyrosine

    International Nuclear Information System (INIS)

    Dhar, A.; Paul, A.K.; Shukla, S.D.

    1990-01-01

    Platelet-activating factor (PAF) is a proinflammatory lipid that has platelet-stimulating property. PAF receptor-coupled activation of phosphoinositide-specific phospholipase C (PLC) and phosphorylation of several proteins has already been established in our laboratory. To investigate further the molecular mechanism and relationship between activation of PLC and protein phosphorylation, we have used Genistein (a putative inhibitor of tyrosine-specific protein kinases), phosphotyrosine antibody, and phosphoamino acid analysis to probe the involvement of tyrosine kinase in this process. Washed rabbit platelets were loaded with myo-[2-3H]inositol and challenged with PAF (100 nM) after pretreatment with Genistein. PLC-mediated production of radioactive inositol monophosphate, inositol diphosphate, and inositol triphosphate was monitored. PAF alone caused stimulation of PLC activity [( 3H]inositol triphosphate production), whereas pretreatment with Genistein (0.5 mM) diminished PAF-stimulated PLC activity to basal level. Genistein also blocked PAF-stimulated platelet aggregation at this dose. In contrast to Genistein, staurosporine which inhibits protein kinase C, potentiated PAF-stimulated [3H]inositol triphosphate production. Genistein substantially inhibited the combined effects of staurosporine and PAF on inositol triphosphate production. Genistein also reduced PAF-induced phosphorylation of Mr 20,000 and 50,000 proteins. Phorbol 12-myristate 13-acetate-induced Mr 40,000 protein phosphorylation was also affected by Genistein. The above results suggested that Genistein inhibited tyrosine kinase at an early stage of signal transduction by inhibiting PLC. This, in turn, decreased the activation of protein kinase C and, therefore, caused a reduction in Mr 40,000 protein phosphorylation

  2. Nanoparticulation improves bioavailability of Erlotinib.

    Science.gov (United States)

    Yang, Kyung Mi; Shin, In Chul; Park, Joo Won; Kim, Kab-Sig; Kim, Dae Kyong; Park, Kyungmoon; Kim, Kunhong

    2017-09-01

    Nanoparticulation using fat and supercritical fluid (NUFS TM ) is a drug delivery platform technology enabling efficient and effective formulation of poorly soluble drugs. We performed experiments to examine whether NUFS™ could improve poor bioavailability and reduce fed-fasted bioavailability variances of erlotinib (Ert). NUFS-Ert was prepared using NUFS™ technology; its physical properties were characterized, and drug release was measured. Furthermore, in vitro and in vivo efficacy tests and pharmacokinetic analysis were performed. NUFS-Ert nanoparticles had an average size of 250 nm and were stable for 2 months at 40 °C, 4 °C, and room temperature. The dissolution rate of NUFS-Ert increased in bio-relevant dissolution media. NUFS-Ert was more potent in inhibiting EGF signaling and in suppressing the proliferation of A549, a human non-small cell lung cancer cell line. Furthermore, A549 xenografts in BALB/c nude mice treated with NUFS-Ert regressed more efficiently than those in the mice treated with vehicle or Tarceva ® . In addition, experimental lung metastasis was more efficiently inhibited by NUFS-Ert than by Tarceva ® . The relative bioavailability of NUFS-Ert compared with that of Tarceva ® was 550% and the ratio of the area under the concentration-time curve (AUC) of fed state to the AUC of fasted state was 1.8 for NUFS-Ert and 5.8 for Tarceva ® . NUFS-Ert could improve poor bioavailability and reduce fed-fasted bioavailability variances of Ert. NUFS-Ert was more efficacious than Tarceva ® .

  3. The Impacts of Genistein and Daidzein on Estrogen Conjugations in Human Breast Cancer Cells: A Targeted Metabolomics Approach

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    Stefan Poschner

    2017-10-01

    Full Text Available The beneficial effect of dietary soy food intake, especially for women diagnosed with breast cancer, is controversial, as in vitro data has shown that the soy isoflavones genistein and daidzein may even stimulate the proliferation of estrogen-receptor alpha positive (ERα+ breast cancer cells at low concentrations. As genistein and daidzein are known to inhibit key enzymes in the steroid metabolism pathway, and thus may influence levels of active estrogens, we investigated the impacts of genistein and daidzein on the formation of estrogen metabolites, namely 17β-estradiol (E2, 17β-estradiol-3-(β-D-glucuronide (E2-G, 17β-estradiol-3-sulfate (E2-S and estrone-3-sulfate (E1-S in estrogen-dependent ERα+ MCF-7 cells. We found that both isoflavones were potent inhibitors of E1 and E2 sulfation (85–95% inhibition at 10 μM, but impeded E2 glucuronidation to a lesser extent (55–60% inhibition at 10 μM. The stronger inhibition of E1 and E2 sulfation compared with E2 glucuronidation was more evident for genistein, as indicated by significantly lower inhibition constants for genistein [Kis: E2-S (0.32 μM < E1-S (0.76 μM < E2-G (6.01 μM] when compared with those for daidzein [Kis: E2-S (0.48 μM < E1-S (1.64 μM < E2-G (7.31 μM]. Concomitant with the suppression of E1 and E2 conjugation, we observed a minor but statistically significant increase in E2 concentration of approximately 20%. As the content of genistein and daidzein in soy food is relatively low, an increased risk of breast cancer development and progression in women may only be observed following consumption of high-dose isoflavone supplements. Further long-term human studies monitoring free estrogens and their conjugates are therefore highly warranted to evaluate the potential side effects of high-dose genistein and daidzein, especially in patients diagnosed with ERα+ breast cancer.

  4. Genistein enhances the effect of trichostatin A on inhibition of A549 cell growth by increasing expression of TNF receptor-1

    International Nuclear Information System (INIS)

    Wu, Tzu-Chin; Yang, Ying-Chihi; Huang, Pei-Ru; Wen, Yu-Der; Yeh, Shu-Lan

    2012-01-01

    Our previous study has shown that genistein enhances apoptosis in A549 lung cancer cells induced by trichostatin A (TSA). The precise molecular mechanism underlying the effect of genistein, however, remains unclear. In the present study, we investigated whether genistein enhances the anti-cancer effect of TSA through up-regulation of TNF receptor-1 (TNFR-1) death receptor signaling. We incubated A549 cells with TSA (50 ng/mL) alone or in combination with genistein and then determined the mRNA and protein expression of TNFR-1 as well as the activation of downstream caspases. Genistein at 5 and 10 μM significantly enhanced the TSA-induced decrease in cell number and apoptosis in a dose-dependent manner. The combined treatment significantly increased mRNA and protein expression of TNFR-1 at 6 and 12 h, respectively, compared with that of the control group; while TSA alone had no effect. TSA in combination with 10 μM of genistein increased TNFR-1 mRNA and protein expression by about 70% and 40%, respectively. The underlying mechanism for this effect of genistein may be partly associated with the estrogen receptor pathway. The combined treatment also increased the activation of caspase-3 and ‐10 as well as p53 protein expression in A549 cells. The enhancing effects of genistein on the TSA-induced decrease in cell number and on the expression of caspase-3 in A549 cells were suppressed by silencing TNFR-1 expression. These data demonstrated that the upregulation of TNFR-1 death receptor signaling plays an important role, at least in part, in the enhancing effect of genistein on TSA-induced apoptosis in A549 cells. -- Highlights: ► TSA combined with genistein rather than TSA alone increases the expression of TNFR-1. ► Genistein may exert such an effect partly through estrogen receptor pathway. ► The combined treatment increases the activation of caspase-10 and caspase-3. ► The combined treatment also increases the expression of p53 protein. ► TNFR-1 si

  5. Radiosensitization dependent on p53 function in bronchial carcinoma cells by the isoflavone genistein and estradiol in vitro

    International Nuclear Information System (INIS)

    Hermann, R.M.; Fest, J.; Christiansen, H.; Hille, A.; Rave-Fraenk, M.; Nitsche, M.; Gruendker, C.; Viereck, V.; Jarry, H.; Schmidberger, H.

    2007-01-01

    Background and Purpose: Simultaneous radiotherapy with chemotherapy is a standard treatment for inoperable non-small cell lung cancer (NSCLC), but the clinical outcome still remains poor. To further intensify treatment, substances need to be identified, which increase the effect of radiation on tumor cells without further enhancing toxicity to normal tissue. Hormones have a different toxicity profile than radiation or cytostatic drugs. As NSCLC often express estrogen receptors (ERs), the combination of genistein or estradiol and radiation in vitro was investigated. Material and Methods: A549 NSCLC cells with an inducible expression of a mutated TP53 and fibroblasts of a male donor (DF-18) were examined. ER expression was immunocytologically confirmed in all studied cell lines. Clonogenic survival was measured after incubation of the cells with genistein or estradiol (0.01 μM and 10 μM as maximum clinically applicable dose) and irradiation with different doses (0-4 Gy). The differentiation state of fibroblasts after combined therapy was analyzed. Results: A549 cells expressing mutated TP53 were more radioresistant than TP53 wild-type cells. Incubation of nonfunctional TP53 cells with genistein or estradiol increased radiosensitivity in both tested concentrations. By contrast, radiosensitivity of A549 with wild-type TP53 and DF-18 was not altered by hormonal incubation. In DF-18 radiation induced growth arrest that was not increased by additional hormonal incubation. Conclusion: NSCLC cells with nonfunctional TP53 might be sensitized against radiation by genistein or estradiol. As genistein is better tolerable than estradiol in patients, additional studies are warranted to assess potential gains of this combination therapy

  6. Modulation of Oxidative Stress by 17 β-Estradiol and Genistein in Human Hepatic Cell Lines In Vitro

    Directory of Open Access Journals (Sweden)

    Daniela Surico

    2017-06-01

    Full Text Available Background/Aims: estrogens and phytoestrogens exert hepatoprotection through mechanisms not clearly examined yet. Here, we investigated the protective effects exerted by 17β-estradiol and genistein against oxidative stress in hepatocytes and hepatic stellate cells (HSCs and the involvement of specific receptors and the intracellular signalling. Methods: Huh7.5 and LX-2, alone or in co-culture with Huh7.5, were treated with 17β-estradiol and genistein alone or in the presence of menadione and of estrogen receptors (ERs and G protein-coupled-estrogenic-receptors (GPER blockers. Cell viability, mitochondrial membrane potential and oxidant/antioxidant system were measured by specific kits. Western Blot was used for the analysis of Akt and p38-mitogen-activated-protein kinases (MAPK activation and α-smooth-muscle actin expression. Results: In Huh7.5, 17β-estradiol and genistein prevented the effects of peroxidation by modulating Akt and p38MAPK activation. Similar antioxidant and protective findings were obtained in LX-2 of co-culture experiments, only. ERs and GPER blockers were able to prevent the effects of 17β-estradiol and genistein. Conclusion: In Huh7.5 and LX-2, 17β-estradiol and genistein counteract the effects of peroxidation through the involvement of ERs and GPER and by an intracellular signalling related to Akt and p38MAPK. As concerning LX-2, paracrine factors released by Huh7.5 play a key role in protection against oxidative stress.

  7. Agrobacterium rhizogenes transformed soybean roots differ in their nodulation and nitrogen fixation response to genistein and salt stress.

    Science.gov (United States)

    Dolatabadian, Aria; Modarres Sanavy, Seyed Ali Mohammad; Ghanati, Faezeh; Gresshoff, Peter M

    2013-07-01

    We evaluated response differences of normal and transformed (so-called 'hairy') roots of soybean (Glycine max L. (Merr.), cv L17) to the Nod-factor inducing isoflavone genistein and salinity by quantifying growth, nodulation, nitrogen fixation and biochemical changes. Composite soybean plants were generated using Agrobacterium rhizogenes-mediated transformation of non-nodulating mutant nod139 (GmNFR5α minus) with complementing A. rhizogenes K599 carrying the wild-type GmNFR5α gene under control of the constitutive CaMV 35S promoter. We used genetic complementation for nodulation ability as only nodulated roots were scored. After hairy root emergence, primary roots were removed and composite plants were inoculated with Bradyrhizobium japonicum (strain CB1809) pre-induced with 10 μM genistein and watered with NaCl (0, 25, 50 and 100 mM). There were significant differences between hairy roots and natural roots in their responses to salt stress and genistein application. In addition, there were noticeable nodulation and nitrogen fixation differences. Composite plants had better growth, more root volume and chlorophyll as well as more nodules and higher nitrogenase activity (acetylene reduction) compared with natural roots. Decreased lipid peroxidation, proline accumulation and catalase/peroxidase activities were found in 'hairy' roots under salinity stress. Genistein significantly increased nodulation and nitrogen fixation and improved roots and shoot growth. Although genistein alleviated lipid peroxidation under salinity stress, it had no significant effect on the activity of antioxidant enzymes. In general, composite plants were more competitive in growth, nodulation and nitrogen fixation than normal non-transgenic even under salinity stress conditions.

  8. Activation of the intrinsic-apoptotic pathway in LNCaP prostate cancer cells by genistein- topotecan combination treatments

    Directory of Open Access Journals (Sweden)

    Vanessa Hörmann

    2013-03-01

    Full Text Available ABSTRACTBackground: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments.Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i growth inhibition through trypan blue exclusion assay and microphotography , ii classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients.

  9. Deteksi senyawa isoflavon daidzein dan genistein pada kultur invitro kalus kedelai Glycine max Merr

    Directory of Open Access Journals (Sweden)

    Tintrim Rahayu

    2013-10-01

    Full Text Available The aim of this research is to identify the isofl avon compounds in the in-vitro cultured callus of soybean (Glycine max Merr.. This is an explorative research, in which callus were cultured in the B5 medium supplemented with 2 ppm 2,4 D. The friable callus were found when it was cultured in the solid medium containing 8 g/l agar and 20 g/l sucrose. When the callus and soybean were extracted with ethanol, a yellow colored substance appeared. If further analysis was done with thin layer chromatography (TLC method employing 0,2 mm thin layer silica gel 60 F254 (DC-Plastikfolien Schicht-dicke, and eluent consisting n-Butanol - HCL 0.1 N (1:1, six light blue color nodes appeared under 366 nm UV light. The nodes have the following Rf: 0,14; 0,30; 0,52; 0,63; 0,79 and 0,92 respectively. This TLC result is comparable with the TLC result from soybeans since they have two nodes with the same Rf and color, namely blue color at Rf 0,81 and 0,92 respectively. Further confi rmation using HPLC (High Performance Liquid Chromatography equipped with UVvis detector and Lichrospher 100RP–18, (10 μm colom, as well as Hitachi D–2500 Chromato-integrator indicated that those similar two nodes identifi ed in the TLC were either daidzein or genistein. They can be detected by HPLC at 250 nm and 260 nm, when they were eluated at the 80% metanol. The HPLC quantitative calculation indicated that concentration of daidzein is four time higher as it was compared with the daidzein concentration in the bean. The concentration of daidzein in the callus remained high up to 4–5 weeks after plantation. It’s concentration will decrease when the callus reached 6 weeks after plantation. Genistein as another component of isofl avon is not appear upon callus, while on soybean seeds extracts, both daidzen and genistein are detected.

  10. Physicochemical Properties, Permeability and Bioavailability of Geraniin and Geraniin-Phospholipid Complex

    OpenAIRE

    SUMITA ELENDRAN

    2017-01-01

    Geraniin has been credited with a range of bioactive properties and therefore merits greater research into its potential pharmaceutical, nutraceutical and cosmetic applications. To clarify its functionalities and to explore future applications, a more comprehensive understanding of geraniin; its physiochemical, permeability, bioavailability and pharmacokinetic properties has become necessity. In light of geraniin’s anticipated poor bioavailability and to be considered as an oral drug candidat...

  11. Greater autonomy at work

    NARCIS (Netherlands)

    Houtman, I.L.D.

    2004-01-01

    In the past 10 years, workers in the Netherlands increasingly report more decision-making power in their work. This is important for an economy in recession and where workers face greater work demands. It makes work more interesting, creates a healthier work environment, and provides opportunities

  12. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    International Nuclear Information System (INIS)

    Matsukura, Hiroshi; Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun; Muramatsu, Masaaki; Sudo, Katsuko; Sato, Noriko

    2011-01-01

    Highlights: → Genistein (GEN) is a phytoestrogen found in soy products. → GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. → GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. → A high-resolution melting assay was used to screen for epigenetic change. → We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.

  13. Genistein promotes DNA demethylation of the steroidogenic factor 1 (SF-1) promoter in endometrial stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsukura, Hiroshi, E-mail: hmatsukura.epi@mri.tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Aisaki, Ken-ichi; Igarashi, Katsuhide; Matsushima, Yuko; Kanno, Jun [Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Muramatsu, Masaaki [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Sudo, Katsuko [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Animal Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402 (Japan); Sato, Noriko, E-mail: nsato.epi@tmd.ac.jp [Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)

    2011-08-26

    Highlights: {yields} Genistein (GEN) is a phytoestrogen found in soy products. {yields} GEN demethylated/unsilenced the steroidogenic factor 1 gene in endometrial tissue. {yields} GEN thus altered mRNA expression in uteri of ovariectomized (OVX) mice. {yields} A high-resolution melting assay was used to screen for epigenetic change. {yields} We isolated an endometrial cell clone that was epigenetically modulated by GEN. -- Abstract: It has recently been demonstrated that genistein (GEN), a phytoestrogen in soy products, is an epigenetic modulator in various types of cells; but its effect on endometrium has not yet been determined. We investigated the effects of GEN on mouse uterine cells, in vivo and in vitro. Oral administration of GEN for 1 week induced mild proliferation of the endometrium in ovariectomized (OVX) mice, which was accompanied by the induction of steroidogenic factor 1 (SF-1) gene expression. GEN administration induced demethylation of multiple CpG sites in the SF-1 promoter; these sites are extensively methylated and thus silenced in normal endometrium. The GEN-mediated promoter demethylation occurred predominantly on the luminal side, as opposed to myometrium side, indicating that the epigenetic change was mainly shown in regenerated cells. Primary cultures of endometrial stromal cell colonies were screened for GEN-mediated alterations of DNA methylation by a high-resolution melting (HRM) method. One out of 20 colony-forming cell clones showed GEN-induced demethylation of SF-1. This clone exhibited a high proliferation capacity with continuous colony formation activity through multiple serial clonings. We propose that only a portion of endometrial cells are capable of receiving epigenetic modulation by GEN.

  14. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity

    International Nuclear Information System (INIS)

    Qi, Wentao; Weber, Christopher R; Wasland, Kaarin; Savkovic, Suzana D

    2011-01-01

    Soy consumption is associated with a lower incidence of colon cancer which is believed to be mediated by one of its of components, genistein. Genistein may inhibit cancer progression by inducing apoptosis or inhibiting proliferation, but mechanisms are not well understood. Epidermal growth factor (EGF)-induced proliferation of colon cancer cells plays an important role in colon cancer progression and is mediated by loss of tumor suppressor FOXO3 activity. The aim of this study was to assess if genistein exerts anti-proliferative properties by attenuating the negative effect of EGF on FOXO3 activity. The effect of genistein on proliferation stimulated by EGF-mediated loss of FOXO3 was examined in human colonic cancer HT-29 cells. EGF-induced FOXO3 phosphorylation and translocation were assessed in the presence of genistein. EGF-mediated loss of FOXO3 interactions with p53 (co-immunoprecipitation) and promoter of p27kip1 (ChIP assay) were examined in presence of genistein in cells with mutated p53 (HT-29) and wild type p53 (HCT116). Silencing of p53 determined activity of FOXO3 when it is bound to p53. Genistein inhibited EGF-induced proliferation, while favoring dephosphorylation and nuclear retention of FOXO3 (active state) in colon cancer cells. Upstream of FOXO3, genistein acts via the PI3K/Akt pathway to inhibit EGF-stimulated FOXO3 phosphorylation (i.e. favors active state). Downstream, EGF-induced disassociation of FOXO3 from mutated tumor suppressor p53, but not wild type p53, is inhibited by genistein favoring FOXO3-p53(mut) interactions with the promoter of the cell cycle inhibitor p27kip1 in colon cancer cells. Thus, the FOXO3-p53(mut) complex leads to elevated p27kip1 expression and promotes cell cycle arrest. These novel anti-proliferative mechanisms of genistein suggest a possible role of combining genistein with other chemoreceptive agents for the treatment of colon cancer

  15. Membrane depolarization-induced RhoA/Rho-associated kinase activation and sustained contraction of rat caudal arterial smooth muscle involves genistein-sensitive tyrosine phosphorylation

    Science.gov (United States)

    Mita, Mitsuo; Tanaka, Hitoshi; Yanagihara, Hayato; Nakagawa, Jun-ichi; Hishinuma, Shigeru; Sutherland, Cindy; Walsh, Michael P.; Shoji, Masaru

    2013-01-01

    Rho-associated kinase (ROK) activation plays an important role in K+-induced contraction of rat caudal arterial smooth muscle (Mita et al., Biochem J. 2002; 364: 431–40). The present study investigated a potential role for tyrosine kinase activity in K+-induced RhoA activation and contraction. The non-selective tyrosine kinase inhibitor genistein, but not the src family tyrosine kinase inhibitor PP2, inhibited K+-induced sustained contraction (IC50 = 11.3 ± 2.4 µM). Genistein (10 µM) inhibited the K+-induced increase in myosin light chain (LC20) phosphorylation without affecting the Ca2+ transient. The tyrosine phosphatase inhibitor vanadate induced contraction that was reversed by genistein (IC50 = 6.5 ± 2.3 µM) and the ROK inhibitor Y-27632 (IC50 = 0.27 ± 0.04 µM). Vanadate also increased LC20 phosphorylation in a genistein- and Y-27632-dependent manner. K+ stimulation induced translocation of RhoA to the membrane, which was inhibited by genistein. Phosphorylation of MYPT1 (myosin-targeting subunit of myosin light chain phosphatase) was significantly increased at Thr855 and Thr697 by K+ stimulation in a genistein- and Y-27632-sensitive manner. Finally, K+ stimulation induced genistein-sensitive tyrosine phosphorylation of proteins of ∼55, 70 and 113 kDa. We conclude that a genistein-sensitive tyrosine kinase, activated by the membrane depolarization-induced increase in [Ca2+]i, is involved in the RhoA/ROK activation and sustained contraction induced by K+. Ca2+ sensitization, myosin light chain phosphatase, RhoA, Rho-associated kinase, tyrosine kinase PMID:24133693

  16. Bioavailability of cadmium from soy isolate

    International Nuclear Information System (INIS)

    Lee, Y.H.; Fox, M.R.S.; Tao, S.H.

    1986-01-01

    Studies with 109 Cd showed that more Cd was taken up by duodenum (D) and jejunum-ileum (J-I) of Japanese Quail (JQ) with soy isolate (SI) than with casein gelatin (CG) diet. The purpose of this study was to compare the bioavailability of endogenous Cd from SI with CdCl 2 added to a CG diet. Day-old JQ were fed either SI or CG diet containing 121 ppb of Cd. Beginning at 7 d of age, 109 CdCl 2 was incorporated into both diets at 100 uci/kg and a group of birds from each diet was killed on 8, 9, 11, 14 and 21 d. Growth was normal with both diets and food intake was similar. Cd concentration (determined by ICAP and AAS furnace) was significantly higher with CG than with SI on all days in D and up to 11 d of age in J-I. Although much less Cd accumulated in liver and kidneys than in D and J-I, the levels were also higher with CG. Total Cd uptake by liver and kidneys increased gradually with CG whereas there was little increase with SI. Specific activity of Cd in D and J-I with CG remained the same throughout the experiment, but increased significantly with SI up to 11 d of age. The specific activity of Cd in liver and kidneys from both CG and SI increased with time but the rate was greater with SI. The patterns of specific activity indicate differences among tissues and between CG and SI for time required to reach equilibrium between 109 Cd and non-radioactive Cd. These data also show that endogenous Cd in SI is less bioavailable than CdCl 2 added to CG diet

  17. Suppression of adhesion-induced protein tyrosine phosphorylation decreases invasive and metastatic potentials of B16-BL6 melanoma cells by protein tyrosine kinase inhibitor genistein.

    Science.gov (United States)

    Yan, C; Han, R

    1997-01-01

    Protein tyrosine kinase (PTK) appears to be involved in the activation of signaling during cell attachment to and spreading on extracellular matrix (ECM) in the metastatic cascade. To verify the assumption that PTK inhibitors might impair ECM signaling and prevent cancer metastasis, the highly metastatic B16-BL6 mouse melanoma cells were exposed to the PTK inhibitor genistein for 3 days. The ability of the cells to invade through reconstituted basement membrane (Matrigel) and to establish experimental pulmonary metastatic foci in C57BL/6 mice decreased after genistein exposure. The genistein-treated cells were also prevented from attaching to Matrigel and spread extremely poorly on the ECM substratum. Immunoblot analysis showed that tyrosine phosphorylation of a 125-kD protein in response to cell spreading on Matrigel was suppressed in the genistein-treated cells. Adhesion-induced protein tyrosine phosphorylation represents the earlier and specific event in the activation of ECM signaling, so this result implied ECM signaling was impaired in the treated cells. With immunofluorescence microscopy, the adhesion-induced tyrosine phosphorylated proteins were located at the pericytoplasms of well-spread cells, but not at the periphery of poorly spread genistein-treated cells. Therefore, this paper suggests that genistein might impair ECM signaling and subsequently prevent cancer cells from spreading well and invading or establishing metastasis through the suppression of adhesion-induced protein tyrosine phosphorylation. PTKs and adhesion-induced protein tyrosine phosphorylation might play a role in the control of invasion and metastasis.

  18. Ameliorative effect of dietary genistein on diabetes induced hyper-inflammation and oxidative stress during early stage of wound healing in alloxan induced diabetic mice.

    Science.gov (United States)

    Eo, Hyeyoon; Lee, Hea-Ji; Lim, Yunsook

    2016-09-23

    Among the diabetic complications, diabetic foot ulcer due to delayed wound healing is one of the most significant clinical problems. Early inflammatory stage is important for better prognosis during wound healing. Thus, regulation of inflammatory response during early stage of wound healing is main target for complete cutaneous recovery. This study investigated the role of genistein supplementation in inflammation and oxidative stress, which are related to NLRP3 inflammasome, NFκB and Nrf2 activation, during cutaneous wound healing in alloxan-induced diabetic mice. Mice with diabetes with fasting blood glucose (FBG) levels > 250 mg/dl were fed diets with AIN-93G rodent diet containing 0%, 0.025% (LG) or 0.1% (HG) genistein. After 2 weeks of genistein supplementation, excisional wounds were made by biopsy punches (4 mm). Genistein supplementation improved fasting glucose levels and wound closure rate. Moreover, genistein supplementation restored NLRP3 inflammasome (NLRP3, ASC and caspase-1) at the basal level and ameliorated both inflammation (TNFα, iNOS, COX2 and NFκB) and antioxidant defense system (Nrf2, HO-1, GPx, and catalase) during early stage of wound healing in diabetic mice. Taken together, genistein supplementation would be a potential therapeutic nutrient in prevention and treatment of delayed wound healing by modulation of inflammation and oxidative stress during inflammatory stage. Copyright © 2016. Published by Elsevier Inc.

  19. Aluminum bioavailability from basic sodium aluminum phosphate, an approved food additive emulsifying agent, incorporated in cheese.

    Science.gov (United States)

    Yokel, Robert A; Hicks, Clair L; Florence, Rebecca L

    2008-06-01

    Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability results were intermediate to previously reported results from drinking water (F approximately 0.3%) and acidic-SALP incorporated into a biscuit (F approximately 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human's daily Al intake ( approximately 95% and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract.

  20. Greater-confinement disposal

    International Nuclear Information System (INIS)

    Trevorrow, L.E.; Schubert, J.P.

    1989-01-01

    Greater-confinement disposal (GCD) is a general term for low-level waste (LLW) disposal technologies that employ natural and/or engineered barriers and provide a degree of confinement greater than that of shallow-land burial (SLB) but possibly less than that of a geologic repository. Thus GCD is associated with lower risk/hazard ratios than SLB. Although any number of disposal technologies might satisfy the definition of GCD, eight have been selected for consideration in this discussion. These technologies include: (1) earth-covered tumuli, (2) concrete structures, both above and below grade, (3) deep trenches, (4) augered shafts, (5) rock cavities, (6) abandoned mines, (7) high-integrity containers, and (8) hydrofracture. Each of these technologies employ several operations that are mature,however, some are at more advanced stages of development and demonstration than others. Each is defined and further described by information on design, advantages and disadvantages, special equipment requirements, and characteristic operations such as construction, waste emplacement, and closure

  1. More features, greater connectivity.

    Science.gov (United States)

    Hunt, Sarah

    2015-09-01

    Changes in our political infrastructure, the continuing frailties of our economy, and a stark growth in population, have greatly impacted upon the perceived stability of the NHS. Healthcare teams have had to adapt to these changes, and so too have the technologies upon which they rely to deliver first-class patient care. Here Sarah Hunt, marketing co-ordinator at Aid Call, assesses how the changing healthcare environment has affected one of its fundamental technologies - the nurse call system, argues the case for wireless such systems in terms of what the company claims is greater adaptability to changing needs, and considers the ever-wider range of features and functions available from today's nurse call equipment, particularly via connectivity with both mobile devices, and ancillaries ranging from enuresis sensors to staff attack alert 'badges'.

  2. Greater oil investment opportunities

    International Nuclear Information System (INIS)

    Arenas, Ismael Enrique

    1997-01-01

    Geologically speaking, Colombia is a very attractive country for the world oil community. According to this philosophy new and important steps are being taken to reinforce the oil sector: Expansion of the exploratory frontier by including a larger number of sedimentary areas, and the adoption of innovative contracting instruments. Colombia has to offer, Greater economic incentives for the exploration of new areas to expand the exploratory frontier, stimulation of exploration in areas with prospectivity for small fields. Companies may offer Ecopetrol a participation in production over and above royalties, without it's participating in the investments and costs of these fields, more favorable conditions for natural gas seeking projects, in comparison with those governing the terms for oil

  3. Relative Bioavailability and Bioaccessability and Speciation of ...

    Science.gov (United States)

    Background: Assessment of soil arsenic (As) bioavailability may profoundly affect the extent of remediation required at contaminated sites by improving human exposure estimates. Because small adjustments in soil As bioavailability estimates can significantly alter risk assessments and remediation goals, convenient, rapid, reliable, and inexpensive tools are needed to determine soil As bioavailability. Objectives: We evaluated inexpensive methods for assessing As bioavailability in soil as a means to improve human exposure estimates and potentially reduce remediation costs. Methods: Nine soils from residential sites affected by mining or smelting activity and two National Institute of Standards and Technology standard reference materials were evaluated for As bioavailability, bioaccessibility, and speciation. Arsenic bioavailability was determined using an in vivo mouse model, and As bioaccessibility was determined using the Solubility/Bioavailability Research Consortium in vitro assay. Arsenic speciation in soil and selected soil physicochemical properties were also evaluated to determine whether these parameters could be used as predictors of As bio¬availability and bioaccessibility. Results: In the mouse assay, we compared bioavailabilities of As in soils with that for sodium arsenate. Relative bioavailabilities (RBAs) of soil As ranged from 11% to 53% (mean, 33%). In vitro soil As bioaccessibility values were strongly correlated with soil As RBAs (R

  4. The Effect of Electroporation of a Lyotroic Liquid Crystal Genistein-Based Formulation in the Recovery of Murine Melanoma Lesions.

    Science.gov (United States)

    Danciu, Corina; Berkó, Szilvia; Varju, Gábor; Balázs, Boglárka; Kemény, Lajos; Németh, István Balázs; Cioca, Andreea; Petruș, Alexandra; Dehelean, Cristina; Cosmin, Citu Ioan; Amaricai, Elena; Toma, Claudia Crina

    2015-07-08

    A lamellar lyotropic liquid crystal genistein-based formulation (LLC-Gen) was prepared in order to increase the aqueous solubility of the lipophilic phytocompound genistein. The formulation was applied locally, in a murine model of melanoma, with or without electroporation. The results demonstrated that, when the formulation was applied by electroporation, the tumors appeared later. During the 21 days of the experiment, the LLC-Gen formulation decreased the tumor volume, the amount of melanin and the degree of erythema, but when electroporation was applied, all these parameters indicated a better prognosis even (lower tumor volume, amount of melanin and degree of erythema). Although hematoxylin-eosin (HE) staining confirmed the above events, application of the LLC-Gen formulation by electroporation did not lead to a significant effect in terms of the serum concentrations of the protein S100B and serum neuron specific enolase (NSE), or the tissue expression of the platelet-derived growth factor receptor β (PDGFRβ) antibody.

  5. Production of isoflavones, daidzein and genistein in callus cultures of Pueraria candollei Wall. ex Benth. var. mirifica

    Directory of Open Access Journals (Sweden)

    Sanha Panichajakul

    2006-03-01

    Full Text Available Callus cultures of Pueraria candollei var. mirifica were first established from various parts of explants with the objective of isoflavones, daidzein and genistein production. The cultures were studied on their growth and isoflavone production by various combinations of growth regulators, auxins and cytokinins at 25±2ºC. Daidzein and genistein accumulated in the cells were determined. The results revealed that callus of P. candollei var. mirifica was capable of producing high level of both isoflavones consistently. The culture temperature played an important role in the growth and isoflavone production. Over twofold of growth and threefold of isoflavone production were demonstrated at 32±2ºC. The callus established from the stems in MS medium supplemented with 4.5 µM 2,4-D and 0.46 µM kinetin produced the highest yield of daidzein (5.12 mg/g, DW and genistein (2.77 mg/g, DW, which was remarkably higher than the intact plants.

  6. Antimony bioavailability in mine soils

    International Nuclear Information System (INIS)

    Flynn, Helen C.; Meharg, Andy A.; Bowyer, Phillipa K.; Paton, Graeme I.

    2003-01-01

    Antimony has low bioavailability in mining and smelting contaminated soils and bacterial biosensors are not suitable for its detection. - Five British former mining and smelting sites were investigated and found to have levels of total Sb of up to 700 mg kg -1 , indicating high levels of contamination which could be potentially harmful. However, this level of Sb was found to be biologically unavailable over a wide range of pH values, indicating that Sb is relatively unreactive and immobile in the surface layers of the soil, remaining where it is deposited rather than leaching into lower horizons and contaminating ground water. Sb, sparingly soluble in water, was unavailable to the bacterial biosensors tested. The bioluminescence responses were correlated to levels of co-contaminants such as arsenic and copper, rather than to Sb concentrations. This suggests that soil contamination by Sb due to mining and smelting operations is not a severe risk to the environment or human health provided that it is present as immobile species and contaminated sites are not used for purposes which increase the threat of exposure to identified receptors. Co-contaminants such as arsenic and copper are more bioavailable and may therefore be seen as a more significant risk

  7. Effects of the soya isoflavone genistein in early life stages of the Senegalese sole, Solea senegalensis: Thyroid, estrogenic and metabolic biomarkers.

    Science.gov (United States)

    Sarasquete, Carmen; Úbeda-Manzanaro, Maria; Ortiz-Delgado, Juan Bosco

    2017-09-01

    This study examines the effects induced by environmentally relevant concentrations of the isoflavone genistein (3mg/L and 10mg/L) during early life stages of the Senegalese sole. Throughout the hypothalamus-pituitary-thyroid (HPT) axis, several neurohormonal regulatory thyroid signalling patterns (thyroglobulin/Tg, thyroid peroxidase/TPO, transthyretin/TTR, thyroid receptors/TRβ, and iodothrynonine deiodinases, Dio2 and Dio3) were analysed. Furthermore, the expression patterns of estrogen receptor ERβ and haemoprotein Cyp1a were also evaluated. In the control larvae, progressive increases of constitutive hormonal signalling pathways have been evidenced from the pre-metamorphosis phase onwards, reaching the highest expression basal levels at the metamorphosis (Tg, TPO, Dio2) and/or during post-metamorphosis (TTR, TRβ, ERβ). When the early larvae were exposed to both genistein concentrations (3mg/L and 10mg/L), a statistically significant down-regulation of TPO, TTR and Tg mRNA levels was clearly detected at the metamorphic stages. In addition, the Dio2 and Dio3 transcript expression levels were also down and up-regulated when exposed to both genistein concentrations. In the larvae exposed to genistein, no statistically significant responses were recorded for the TRβ expression patterns. Nevertheless, the ERβ and Cyp1a transcript levels were up-regulated at the middle metamorphic stage (S2, at 16 dph) in the larvae exposed to high genistein concentrations and, only the ERβ was down-regulated (S1, at 12dph) at the lower doses. Finally, all these pointed out imbalances were only temporarily disrupted by exposure to genistein, since most of the modulated transcriptional signals (i.e. up or down-regulation) were quickly restored to the baseline levels. Additionally, the control and genistein-exposed Senegalese sole specimens showed characteristic ontogenetic patterns and completely suitable for an optimal development, metamorphosis, and growth. Copyright © 2017

  8. Liver X receptor alpha mediated genistein induction of human dehydroepiandrosterone sulfotransferase (hSULT2A1) in Hep G2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yue; Zhang, Shunfen [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Zhou, Tianyan [Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083 (China); Huang, Chaoqun; McLaughlin, Alicia [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States); Chen, Guangping, E-mail: guangping.chen@okstate.edu [Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078 (United States)

    2013-04-15

    Cytosolic sulfotransferases are one of the major families of phase II drug metabolizing enzymes. Sulfotransferase-catalyzed sulfonation regulates hormone activities, metabolizes drugs, detoxifies xenobiotics, and bioactivates carcinogens. Human dehydroepiandrosterone sulfotransferase (hSULT2A1) plays important biological roles by sulfating endogenous hydroxysteroids and exogenous xenobiotics. Genistein, mainly existing in soy food products, is a naturally occurring phytoestrogen with both chemopreventive and chemotherapeutic potential. Our previous studies have shown that genistein significantly induces hSULT2A1 in Hep G2 and Caco-2 cells. In this study, we investigated the roles of liver X receptor (LXRα) in the genistein induction of hSULT2A1. LXRs have been shown to induce expression of mouse Sult2a9 and hSULT2A1 gene. Our results demonstrate that LXRα mediates the genistein induction of hSULT2A1, supported by Western blot analysis results, hSULT2A1 promoter driven luciferase reporter gene assay results, and mRNA interference results. Chromatin immunoprecipitation (ChIP) assay results demonstrate that genistein increase the recruitment of hLXRα binding to the hSULT2A1 promoter. These results suggest that hLXRα plays an important role in the hSULT2A1 gene regulation. The biological functions of phytoestrogens may partially relate to their induction activity toward hydroxysteroid SULT. - Highlights: ► Liver X receptor α mediated genistein induction of hSULT2A1 in Hep G2 cells. ► LXRα and RXRα dimerization further activated this induction. ► Western blot results agreed well with luciferase reporter gene assay results. ► LXRs gene silencing significantly decreased hSULT2A1 expression. ► ChIP analysis suggested that genistein enhances hLXRα binding to the hSULT2A1 promoter.

  9. The effect of genistein on TGF-β signal, dysregulation of apoptosis, cyclooxygenase-2 pathway, and NF-kB pathway in mice peritoneum of endometriosis model

    Directory of Open Access Journals (Sweden)

    Sutrisno Sutrisno

    2017-12-01

    Full Text Available This research aimed to investigate the effect of genistein on TGF-β, dysregulation of apoptosis, NF-κB pathway, COX-2 pathway in mice of endometriosis model. Twenty-eight female mice (Mus musculus were divided into seven groups (n = 4, involving control (normal non-treated group; endometriosis group; the endometriosis group treated with various genistein dosages (0.78; 1.04; 1.3 mg/day for 15 days, and endometriosis group treated with standard drug, namely leuprolide acetate (0.00975 mg each day for 15 days or dienogest (0.0052 mg/day for 15 days. Mice of endometriosis model were made by implanting myometrial and endometrial tissues under the condition of immunodeficiency. The TGF-β, Bcl-2, Bax, NF-κB, COX-2, and PGE-2 were analyzed immunohistochemically. The increase of Bcl-2 expression in endometriosis was decreased significantly by genistein dosage of 0.78 and 1.3 mg/day (p < 0.05. The decrease of Bax expression in endometriosis was increased significantly by genistein dosage of 1.04 and 1.3 mg/day (p < 0.05. The implantation increased the expression of NF-κB, COX-2, and PGE significantly compared with the control group (p < 0.05. This increase was reduced significantly by the administration of genistein at dosage of 0.78 and 1.3 mg/day (p < 0.05. It can be concluded that genistein potentially inhibits endometriosis development through the normalization of apoptosis dysregulation, the inhibition of NF-κB and COX-2 pathways in the peritoneal tissues. Therefore, genistein can be used as a holistic treatment strategy for endometriosis.

  10. Genistein suppresses Prevotella intermedia lipopolysaccharide-induced inflammatory response in macrophages and attenuates alveolar bone loss in ligature-induced periodontitis.

    Science.gov (United States)

    Choi, Eun-Young; Bae, Seung Han; Ha, Min Hee; Choe, So-Hui; Hyeon, Jin-Yi; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2016-02-01

    Genistein is a major isoflavone subclass of flavonoids found in soybean and a potent tyrosine kinase inhibitor. The present study aimed to assess the effect of genistein on the production of proinflammatory mediators in murine macrophages stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen associated with different forms of periodontal disease, and to evaluate its possible influence on alveolar bone loss in ligature-induced periodontitis using micro-computed tomography (micro-CT) analysis as well. LPS was isolated from P. intermedia ATCC 25611 by using the standard hot phenol-water method. Culture supernatants were analyzed for nitric oxide (NO) and interleukin-6 (IL-6). Inducible NO synthase (iNOS) protein expression was evaluated by immunoblot analysis. Real-time PCR was carried out to measure iNOS and IL-6 mRNA expression. In addition, effect of genistein on alveolar bone loss was evaluated in a rat model of experimental periodontitis using micro-CT analysis. Genistein significantly attenuated P. intermedia LPS-induced production of iNOS-derived NO and IL-6 with attendant decrease in their mRNA expression in RAW264.7 cells. In addition, when genistein was administered to rats, decreases in alveolar bone height and bone volume fraction induced by ligature placement were significantly inhibited. Genistein administration also prevented ligature-induced alterations in the microstructural parameters of trabecular bone, including trabecular thickness, trabecular separation, bone mineral density and structure model index. While additional studies are required, we suggest that genistein could be utilized for the therapy of human periodontitis in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Bioavailability and biodistribution of nanodelivered lutein

    Science.gov (United States)

    The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein ...

  12. Pharmaceutical and pharmacological approaches for bioavailability

    Indian Academy of Sciences (India)

    Much research has been done to determine drug–drug and herb–drug interactions for improving the bioavailability of etoposide. The present article gives insight on pharmaceutical and pharmacological attempts made from time to time to overcome the erratic inter- and intra-patient variability for improving the bioavailability ...

  13. Bioavailability of voriconazole in hospitalised patients

    NARCIS (Netherlands)

    Veringa, Anette; Geling, Sanne; Span, Lambert F R; Vermeulen, Karin M; Zijlstra, Jan G; van der Werf, Tjip S; Kosterink, Jos G W; Alffenaar, Jan-Willem C

    An important element in antimicrobial stewardship programmes is early switch from intravenous (i.v.) to oral antimicrobial treatment, especially for highly bioavailable drugs. The antifungal agent voriconazole is available both in i.v. and oral formulations and bioavailability is estimated to be

  14. Bioavailability as a tool in site management

    NARCIS (Netherlands)

    Harmsen, J.; Naidu, R.

    2013-01-01

    Bioavailability can form the basis for describing potential risks that contaminants pose to the environment and human health, and for determining remedial options to reduce risks of contaminant dispersal and toxicity. In assessments of polluted sites, methods to measure bioavailability can lead to a

  15. The Nutraceutical Bioavailability Classification Scheme: Classifying Nutraceuticals According to Factors Limiting their Oral Bioavailability.

    Science.gov (United States)

    McClements, David Julian; Li, Fang; Xiao, Hang

    2015-01-01

    The oral bioavailability of a health-promoting dietary component (nutraceutical) may be limited by various physicochemical and physiological phenomena: liberation from food matrices, solubility in gastrointestinal fluids, interaction with gastrointestinal components, chemical degradation or metabolism, and epithelium cell permeability. Nutraceutical bioavailability can therefore be improved by designing food matrices that control their bioaccessibility (B*), absorption (A*), and transformation (T*) within the gastrointestinal tract (GIT). This article reviews the major factors influencing the gastrointestinal fate of nutraceuticals, and then uses this information to develop a new scheme to classify the major factors limiting nutraceutical bioavailability: the nutraceutical bioavailability classification scheme (NuBACS). This new scheme is analogous to the biopharmaceutical classification scheme (BCS) used by the pharmaceutical industry to classify drug bioavailability, but it contains additional factors important for understanding nutraceutical bioavailability in foods. The article also highlights potential strategies for increasing the oral bioavailability of nutraceuticals based on their NuBACS designation (B*A*T*).

  16. [Bioavailability and factors influencing its rate].

    Science.gov (United States)

    Vraníková, Barbora; Gajdziok, Jan

    Bioavailability can be defined as the rate and range of active ingredient absorption, when it becomes available in the systemic circulation or at the desired site of drug action, respectively. Drug bioavailability after oral administration is affected by anumber of different factors, including physicochemical properties of the drug, physiological aspects, the type of dosage form, food intake, biorhythms, and intra- and interindividual variability of the human population. This article is the first from the series dealing with the bioavailability and methods leading to its improvement. The aim of the present paper is to provide an overview of aspects influencing the rate of bioavailability after oral administration of the active ingredient. Subsequentarticles will provide detailed descriptions of methods used for dug bioavailability improvement, which are here only summarized.

  17. [Effects of genistein on contractility of isolated right ventricular muscles in guinea pig].

    Science.gov (United States)

    Wu, Jin-xia; Li, Hong-fang; Liu, Chong-bin; Tian, Zhi-feng

    2008-11-01

    To study the effect of genistein (GEN) on contractility of isolated right ventricular muscles in guinea pig and its mechanisms. Isolated guinea pig ventricular muscles were suspended in organ baths containing K-H solution.After an equilibration period, the effect of GEN on contraction of myocardium was observed. GEN and isoprenaline hydrochloride had the positive inotropic effects on contractity of myocardium. Meanwhile, the effect of GEN (1-100 micromol x L(-1)) was in dose-dependent manner. Propranolol (1 micromol x L(-1)) and verapamil hydrochloride (0.5 micromol x L(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride (1 micromol x L(-1)), but did not change the effect of GEN (50 micromol x L(-1)). Further more, the enhancement of the contraction induced by elevation of extracellular Ca2+ concentration in ventricular muscles had no change after pretreatment with GEN (1.10 micromol x L(-1)). In addition,the positive inotropic effect of GEN was inhibited partially by tamoxifen (1 micromol x L(-1)) and SQ22536 (1 micromol x L(-1)), also, could be attenuated by bpV (1 micromol x L(-1)). GEN has the positive inotropic effect on guinea pig ventricular muscles, which is not related to the activation of beta adrenoceptor, Ca2+ channel on cell membrane,but may involve in cAMP of intracellular signal transduction and tyrosine kinase pathway.

  18. Prepubertal Exposure to Genistein Alleviates Di-(2-ethylhexyl Phthalate Induced Testicular Oxidative Stress in Adult Rats

    Directory of Open Access Journals (Sweden)

    Lian-Dong Zhang

    2014-01-01

    Full Text Available Di-(2-ethylhexyl phthalate (DEHP is the most widely used plastizer in the world and can suppress testosterone production via activation of oxidative stress. Genistein (GEN is one of the isoflavones ingredients exhibiting weak estrogenic and potentially antioxidative effects. However, study on reproductive effects following prepubertal multiple endocrine disrupters exposure has been lacking. In this study, DEHP and GEN were administrated to prepubertal male Sprague-Dawley rats by gavage from postnatal day 22 (PND22 to PND35 with vehicle control, GEN at 50 mg/kg body weight (bw/day (G, DEHP at 50, 150, 450 mg/kg bw/day (D50, D150, D450 and their mixture (G + D50, G + D150, G + D450. On PND90, general morphometry (body weight, AGD, organ weight, and organ coefficient, testicular redox state, and testicular histology were studied. Our results indicated that DEHP could significantly decrease sex organs weight, organ coefficient, and testicular antioxidative ability, which largely depended on the dose of DEHP. However, coadministration of GEN could partially alleviate DEHP-induced reproductive injuries via enhancement of testicular antioxidative enzymes activities, which indicates that GEN has protective effects on DEHP-induced male reproductive system damage after prepubertal exposure and GEN may have promising future in its curative antioxidative role for reproductive disorders caused by other environmental endocrine disruptors.

  19. Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation.

    Science.gov (United States)

    Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-03-01

    Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured spatial learning and memory, the time of normal rats was shortened by GEN treatment compared to the vehicle group, but only in the early stages of testing. In the glucose-loaded group, GEN treatment improved performance as mazes were advanced. In the open-field test, GEN treatment delayed habituation to the new environment in normal rats, and increased the exploratory behaviors of glucose-loaded rats. There were no significant differences observed for emotionality or fear-motivated learning and memory. Together, these results indicate that GEN treatment improved spatial learning and memory only in the early stages of testing in the normal state, but improved spatial learning and memory when glucose levels increased during memory consolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. The effect of genistein on intracerebroventricular streptozotocin-induced cognitive deficits in male rat

    Directory of Open Access Journals (Sweden)

    Tourandokht Balouchnejadmojarad

    2009-01-01

    Full Text Available Abstract  Introduction: Intracerebroventricular (ICV injection of streptozotocin (STZ causes cognitive impairment in rats. The beneficial effect of genistein (GEN was investigated on ICV STZ-induced learning, memory, and cognitive impairment in male rats. Methods: For this purpose, rats were injected with ICV STZ bilaterally, on days 1 and 3 (3 mg/kg. The STZ-injected rats received GEN (1 mg/kg/day, p.o. starting one day pre-surgery for two weeks. The learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, radial eight-arm maze (RAM task was used.  Results: It was found out that GEN-treated STZ-injected rats show higher correct choices and lower errors in RAM than vehicle-treated STZ-injected rats. In addition, GEN administration significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test.Discussion: These results demonstrate the effectiveness of GEN in preventing the cognitive deficits caused by ICV STZ in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD.

  1. The effect of genistein on intracerebroventricular streptozotocin-induced cognitive deficits in male rat

    Directory of Open Access Journals (Sweden)

    Tourandokht Balouchnejadmojarad

    2009-01-01

    Full Text Available   Abstract  Introduction: Intracerebroventricular (ICV injection of streptozotocin (STZ causes cognitive impairment in rats. The beneficial effect of genistein (GEN was investigated on ICV STZ-induced learning, memory, and cognitive impairment in male rats. Methods: For this purpose, rats were injected with ICV STZ bilaterally, on days 1 and 3 (3 mg/kg. The STZ-injected rats received GEN (1 mg/kg/day, p.o. starting one day pre-surgery for two weeks. The learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, radial eight-arm maze (RAM task was used.  Results: It was found out that GEN-treated STZ-injected rats show higher correct choices and lower errors in RAM than vehicle-treated STZ-injected rats. In addition, GEN administration significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test.Discussion: These results demonstrate the effectiveness of GEN in preventing the cognitive deficits caused by ICV STZ in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD.  

  2. Impact of three endocrine disruptors, Bisphenol A, Genistein and Vinclozolin on female rat enamel.

    Science.gov (United States)

    Jedeon, K; Berdal, A; Babajko, A

    2016-06-28

    Concerns about the potential adverse effectsof endocrine disruptors (EDs) have been increasingover the last three decades. BisphenolA (BPA), genistein (G) and vinclozolin (V) arethree widely used EDs sharing similar effects.Since populations are exposed to many diverseEDs simultaneously, we demonstratedrecently their impact alone or combined onmale rat tooth enamel. The purpose of thisstudy was therefore to assess their effects onfemale rat tooth enamel in order to understandwhy they are differentially sensitive. Ratswere exposed daily in utero and after birth tolow doses of EDs during the critical fetal andsuckling periods when amelogenesis takesplace. Enamel of rats exposed to EDs presentedopaque areas of hypomineralization. Theproportion of affected rats was the highestin the groups of rats treated with BPA aloneand higher in males than in females (in all thegroups). Comparison of enamel key gene expressionlevels showed modulations of Klk4and Enamelin in males but no significant variationsin females. These findings show thatfemale rats are less affected than males bythe three EDs chosen in this study and suggestthat enamel hypomineralization may differbetween males and females.

  3. Inhibitory effect of genistein on PLC/PRF5 hepatocellular carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Mehdi Nikbakht Dastjerdi

    2015-01-01

    Full Text Available Background: Natural compounds including flavonoids like genistein (GE are able to inhibit cell proliferation and induce apoptosis. GE is the main representative of these groups. GE inhibits carcinogenic tumors such as colon, stomach, lung, and pancreas tumors. The aim of the present study was to analyze the apoptotic effect of GE in the hepatocellular carcinoma (HCC PLC/PRF5 cell line. Methods: Cells were treated with various doses of GE (1, 5, 10, 25, 50, 75, and 100 μM/L at different times (24, 48, and 72 h and the MTT assay was commonly used. Furthermore, cells were treated with single dose of GE (25 μM at different times and flow cytometry was performed. Results: GE inhibited the growth of liver cancer cells significantly with a time- and dose-dependent manner. The percentage of living cells in GE treatment groups with a concentration of 25 μM at different times were 53, 48 and 47%, respectively (P < 0.001. Result of flow cytometry demonstrated that GE at a 25 μM concentration induces apoptosis significantly in a time-dependent manner. The percentage of apoptotic cells at different times were 44, 56, and 60%, respectively (P < 0.001. Conclusions: GE can significantly inhibit the growth of HCC cells and plays a significant role in apoptosis of this cell line.

  4. Collagen concentration on the facial skin of postmenopausal women after topical treatment with estradiol and genistein: a randomized double-blind controlled trial.

    Science.gov (United States)

    Silva, Lidia Aragão; Ferraz Carbonel, Adriana Aparecida; de Moraes, Andréa Regina Barbosa; Simões, Ricardo S; Sasso, Gisela Rodrigues da Silva; Goes, Lívia; Nunes, Winnie; Simões, Manuel Jesus; Patriarca, Marisa Teresinha

    2017-11-01

    The objective of this study is to compare the effects of topical estrogen and genistein (a soy isoflavone) on the facial skin collagen of postmenopausal women not undergoing systemic hormonal therapy. This is a prospective, double blind, randomized, controlled clinical trial. Volunteer women (N = 30) 45-55 year old from the Endocrine Gynecology sector of the Gynecology Department of the Federal University of São Paulo (UNIFESP). The Ethical Committee of the Federal University of São Paulo approved the study (report no. 386/2004; registration on ClinicalTrials.gov NCT01553773), were assigned to topical treatment with either estrogen or genistein for 24 weeks. We quantified and compared facial collagen concentration before and after each treatment by performing pre-auricular skin biopsies. Our data showed an increase in the amount of both type I and type III facial collagen by the end of both treatments. However, the outcomes of the estrogen GI (ER) group were superior to the genistein GII (GEN) group, with statistical significance p < 000.1 Conclusion: Treatment with topical estrogen is superior to genistein, but both have positive impacts on facial skin collagen. Nevertheless, it is still unclear whether prolonged use of genistein and other topical phytoestrogens could produce systemic effects and further research is needed to clarify this question.

  5. Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro: Possible involvement of inhibition of survival signal transduction pathways

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Nonaka, Tetsuo; Ishikawa, Hitoshi; Sakurai, Hideyuki; Saitoh, Jun-ichi; Takahashi, Takeo; Mitsuhashi, Norio

    2001-01-01

    Purpose: The effect of genistein, a tyrosine kinase inhibitor, on radiosensitivity was examined, especially focusing on 'survival signal transduction pathways'. Methods and Materials: Two human esophageal squamous cell cancer cell lines, TE-1 (p53, mutant) and TE-2 (p53, wild), were used. Radiosensitivity was determined by clonogenic assay, and activation of survival signals was examined by Western blot. Results: Genistein (30 μM) greatly enhanced radiosensitivity in these cell lines by suppressing radiation-induced activation of survival signals, p42/p44 extracellular signal-regulated kinase and AKT/PKB. Significant increase in the percentage of apoptotic cells and increased poly[ADP-ribose] polymerase cleavage were observed in TE-2, but not in TE-1 even after combination of genistein with irradiation. In terms of changes in expression of p53-related proteins, increase in expression of Bax and decrease in that of Bcl-2 were observed in TE-2 but not in TE-1, suggesting that the main mode of cell death induced by genistein in a cell line with wild type p53 differed from that with mutant p53. Conclusions: This study suggested that survival signals, including p42/p44 ERK and AKT/PKB, may be involved in determining radiosensitivity, and genistein would be a potent therapeutic agent that has an enhancing effect on radiation

  6. Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

    Science.gov (United States)

    Cho, Kwan Hyung; Jee, Jun-Pil; Yang, Da A; Kim, Sung Tae; Kang, Dongjin; Kim, Dae-Young; Sim, Taeyong; Park, Sang Yeob; Kim, Kyeongsoon; Jang, Dong-Jin

    2018-02-01

    The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

  7. Bioavailability and Pharmacokinetics of Oral Cocaine in Humans.

    Science.gov (United States)

    Coe, Marion A; Jufer Phipps, Rebecca A; Cone, Edward J; Walsh, Sharon L

    2018-06-01

    The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions. Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis, and a two-factor model was used to assess for dose and sex differences. The mean ± SEM oral cocaine bioavailability was 0.32 ± 0.04 after 100 and 0.45 ± 0.06 after 200 mg oral cocaine. Volume of distribution (Vd) and clearance (CL) were both greatest after 100 mg oral (Vd = 4.2 L/kg; CL = 116.2 mL/[min kg]) compared to 200 mg oral (Vd = 2.9 L/kg; CL = 87.5 mL/[min kg]) and 40 mg IV (Vd = 1.3 L/kg; CL = 32.7 mL/[min kg]). Oral cocaine area-under-thecurve (AUC) and peak concentration increased in a dose-related manner. AUC metabolite-to-parent ratios of benzoylecgonine and ecgonine methyl ester were significantly higher after oral compared to IV administration and highest after the lower oral dose. In addition, minor metabolites were detected in higher concentrations after oral compared to IV cocaine. Oral cocaine produced a pharmacokinetic profile different from IV cocaine, which appears as a rightward and downward shift in the concentration-time profile. Cocaine bioavailability values were similar to previous estimates. Oral cocaine also produced a unique metabolic profile, with greater concentrations of major and minor metabolites.

  8. Organoclays reduce arsenic bioavailability and bioaccessibility in contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Binoy; Naidu, Ravi; Rahman, Mohammad Mahmudur; Megharaj, Mallavarapu; Xi, Yunfei [South Australia Univ., Mawson Lakes, SA (AU). Centre for Environmental Risk Assessment and Remediation (CERAR); South Australia Univ., Mawson Lakes, SA (AU). Cooperative Research Centre for Contamination Assessment and Remediation of the Environment (CRC CARE)

    2012-05-15

    assessing bioaccessibility. The greater the loading rate of organoclays, the better was the stabilisation of As in soils. Conclusions: Organobentonites prepared from HDTMA and Arquad at surfactant loadings greater than the CEC of the bentonite effectively remove As from aqueous solutions. Also, when applied to As-contaminated soils, both the organoclays reduce the bioavailability of soil As. The Arquad-modified bentonite performs better than HDTMA-modified bentonite. Data from this initial study can be used to further improve the stabilisation of soil As by using organoclays. (orig.)

  9. 21 CFR 320.38 - Retention of bioavailability samples.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Retention of bioavailability samples. 320.38... (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.38 Retention of bioavailability samples...

  10. Bioavailability of higher dose methotrexate comparing oral and subcutaneous administration in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Hoekstra, Monique; Haagsma, C.; Neef, C; Proost, Johannes H; Knuif, A.; van der Laar, M.

    Objective. To determine the bioavailability of higher oral doses of methotrexate (MTX) in adult patients with rheumatoid arthritis (RA). Methods. A pharmacokinetic analysis was performed in 15 patients with RA taking a stable dose of MTX (greater than or equal to25 mg weekly). Separated by 2 weeks,

  11. Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway

    Directory of Open Access Journals (Sweden)

    Barańska Sylwia

    2009-03-01

    Full Text Available Abstract Background Mucopolysaccharidoses (MPS are inherited metabolic disorders caused by mutations leading to dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs. Due to their impaired degradation, GAGs accumulate in cells of patients, which results in dysfunction of tissues and organs. Substrate reduction therapy is one of potential treatment of these diseases. It was demonstrated previously that genistein (4', 5, 7-trihydroxyisoflavone inhibits synthesis and reduces levels of GAGs in cultures of fibroblasts of MPS patients. Recent pilot clinical study indicated that such a therapy may be effective in MPS III (Sanfilippo syndrome. Methods To learn on details of the molecular mechanism of genistein-mediated inhibition of GAG synthesis, efficiency of this process was studied by measuring of incorporation of labeled sulfate, storage of GAGs in lysosomes was estimated by using electron microscopic techniques, and efficiency of phosphorylation of epidermal growth factor (EGF receptor was determined by using an ELISA-based assay with fluorogenic substrates. Results Effects of genistein on inhibition of GAG synthesis and accumulation in fibroblasts from patients suffering from various MPS types were abolished in the presence of an excess of EGF, and were partially reversed by an increased concentration of genistein. No such effects were observed when an excess of 17β-estradiol was used instead of EGF. Moreover, EGF-mediated stimulation of phsophorylation of the EGF receptor was impaired in the presence of genistein in both wild-type and MPS fibroblasts. Conclusion The results presented in this report indicate that the mechanism of genistein-mediated inhibition of GAG synthesis operates through epidermal growth factor (EGF-dependent pathway.

  12. Genistein, a Phytoestrogen in Soybean, Induces the Expression of Acetylcholinesterase via G Protein-Coupled Receptor 30 in PC12 Cells

    Directory of Open Access Journals (Sweden)

    Etta Y. L. Liu

    2018-02-01

    Full Text Available Genistein, 4′,5,7-trihydroxyisoflavone, is a major isoflavone in soybean, which is known as phytestrogen having known benefit to brain functions. Being a common phytestrogen, the possible role of genistein in the brain protection needs to be further explored. In cultured PC12 cells, application of genistein significantly induced the expression of neurofilaments (NFs, markers for neuronal differentiation. In parallel, the expression of tetrameric form of proline-rich membrane anchor (PRiMA-linked acetyl-cholinesterase (G4 AChE, a key enzyme to hydrolyze acetylcholine in cholinergic synapses, was induced in a dose-dependent manner: this induction included the associated protein PRiMA. The genistein-induced AChE expression was fully blocked by the pre-treatment of H89 (an inhibitor of protein kinase A, PKA and G15 (a selective G protein-coupled receptor 30 (GPR30 antagonist, which suggested a direct involvement of a membrane-bound estrogen receptor (ER, named as GPR30 in the cultures. In parallel, the estrogen-induced activation of GPR30 induced AChE expression in a dose-dependent manner. The genistein/estrogen-induced AChE expression was triggered by a cyclic AMP responding element (CRE located on the ACHE gene promoter. The binding of this CRE site by cAMP response element-binding protein (CREB induced ACHE gene transcription. In parallel, increased expression levels of miR132 and miR212 were found when cultured PC12 cells were treated with genistein or G1. Thus, a balance between production and destruction of AChE by the activation of GPR30 was reported here. We have shown for the first time that the activation of GPR30 could be one way for estrogen or flavonoids, possessing estrogenic properties, to enhance cholinergic functions in the brain, which could be a good candidate for possible treatment of neurodegenerative diseases.

  13. Dietary factors that affect carotenoid bioavailability

    NARCIS (Netherlands)

    Hof, van het K.H.

    1999-01-01

    Carotenoids are thought to contribute to the beneficial effects of increased vegetable consumption. To better understand the potential benefits of carotenoids, we investigated the bioavailability of carotenoids from vegetables and dietary factors which might influence carotenoid

  14. Enhancement of Solubility and Bioavailability of Candesartan ...

    African Journals Online (AJOL)

    Purpose: To enhance the otherwise poor solubility and bioavailability of candesartan cilexetil (CDS). Methods: This ... PEG 6000-based solid dispersions showed 1st order drug release kinetics. ..... the liver due to quercetin's inhibitory effect on.

  15. Postharvest dehydration of wine white grapes to increase genistein, daidzein and the main carotenoids.

    Science.gov (United States)

    De Sanctis, Federica; Silvestrini, Maria Grazia; Luneia, Roberto; Botondi, Rinaldo; Bellincontro, Andrea; Mencarelli, Fabio

    2012-12-01

    Wine white grape bunches of the Grechetto variety were dehydrated at 10, 20 and 30°C, RH 45% and forced air ventilation of 1.5m/s. Chemical and metabolic changes due to the effect of dehydration were studied at various stages of weight loss: 10%, 20%, 30% and 40%. Berry colour at 10 and 20°C tended to become greener with dehydration but at 30°C, at the final sampling, the colour darkened. Acidity decreased in all samples, while sugars increased. Total phenol content increased at 10°C until 30% weight loss was reached and then declined, while at 20 and 30°C the concentration decreased immediately. The contents of lutein and β-carotene (respectively 68 and 58mg/kg d.w.), representing the 80% of total carotenoids, did not change significantly until the 30% of weight loss, when at 30°C the value increased above all for lutein while at 10 and 20°C, the contents decreased significantly. Daidzein, at 10°C, rose significantly from about 150μg/kg d.w. to 1434μg/kg d.w. at 20% weight loss and then declined; at the same weight loss percentage, the genistein concentration began to increase. At 20°C both isoflavones rose until the end of the experiment, reaching values similar to the sample at 10°C. A temperature of 30°C was deleterious to grape isoflavones. A discussion on the changes in isoflavones related to temperature and time is reported. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Bioavailability of glucosinolates and their breakdown products

    DEFF Research Database (Denmark)

    Barba Orellana, Francisco Jose; Nikmaram, Nooshin; Roohinejad, Shahin

    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 ...... 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....

  17. Bioavailability in the boris assessment model

    International Nuclear Information System (INIS)

    Norden, M.; Avila, R.; Gonze, M.A.; Tamponnet, C.

    2004-01-01

    The fifth framework EU project BORIS (Bioavailability Of Radionuclides In Soils: role of biological components and resulting improvement of prediction models) has three scientific objectives. The first is to improve understanding of the mechanisms governing the transfer of radionuclides to plants. The second is to improve existing predictive models of radionuclide interaction with soils by incorporating the knowledge acquired from the experimental results. The last and third objective is to extract from the experimental results some scientific basis for the development of bioremediation methods of radionuclides contaminated soils and to apprehend the role of additional non-radioactive pollutants on radionuclide bio-availability. This paper is focused on the second objective. The purpose of the BORIS assessment model is to describe the behaviour of radionuclides in the soil-plant system with the aim of making predictions of the time dynamics of the bioavailability of radionuclides in soil and the radionuclides concentrations in plants. To be useful the assessment model should be rather simple and use only a few parameters, which are commonly available or possible to measure for different sites. The model shall take into account, as much as possible, the results of the experimental studies and the mechanistic models developed in the BORIS project. One possible approach is to introduce in the assessment model a quantitative relationship between bioavailability of the radionuclides in soil and the soil properties. To do this an operational definition of bioavailability is needed. Here operational means experimentally measurable, directly or indirectly, and that the bioavailability can be translated into a mathematical expression. This paper describes the reasoning behind the chosen definition of bioavailability for the assessment model, how to derive operational expressions for the bioavailability and how to use them in the assessment model. (author)

  18. Assessing the relative bioavailability of DOC in regional groundwater systems

    Science.gov (United States)

    Chapelle, Francis H.; Bradley, Paul M.; Journey, Celeste A.; McMahon, Peter B.

    2013-01-01

    It has been hypothesized that the degree to which a hyperbolic relationship exists between concentrations of dissolved organic carbon (DOC) and dissolved oxygen (DO) in groundwater may indicate the relative bioavailability of DOC. This hypothesis was examined for 73 different regional aquifers of the United States using 7745 analyses of groundwater compiled by the National Water Assessment (NAWQA) program of the U.S. Geological Survey. The relative reaction quotient (RRQ), a measure of the curvature of DOC concentrations plotted versus DO concentrations and regressed to a decaying hyperbolic equation, was used to assess the relative bioavailability of DOC. For the basalt aquifer of Oahu, Hawaii, RRQ values were low (0.0013 mM−2), reflecting a nearly random relationship between DOC and DO concentrations. In contrast, on the island of Maui, treated sewage effluent injected into a portion of the basalt aquifer resulted in pronounced hyperbolic DOC-DO behavior and a higher RRQ (142 mM−2). RRQ values for the 73 aquifers correlated positively with mean concentrations of ammonia, dissolved iron, and manganese, and correlated negatively with mean pH. This indicates that greater RRQ values are associated with greater concentrations of the final products of microbial reduction reactions. RRQ values and DOC concentrations were negatively correlated with the thickness of the unsaturated zone (UNST) and depth to the top of the screened interval. Finally, RRQ values were positively correlated with mean annual precipitation (MAP), and the highest observed RRQ values were associated with aquifers receiving MAP rates ranging between 900 and 1300 mm/year. These results are uniformly consistent with the hypothesis that the hyperbolic behavior of DOC-DO plots, as quantified by the RRQ metric, can be an indicator of relative DOC bioavailability in groundwater systems.

  19. Assessing the relative bioavailability of DOC in regional groundwater systems.

    Science.gov (United States)

    Chapelle, Francis H; Bradley, Paul M; Journey, Celeste A; McMahon, Peter B

    2013-01-01

    It has been hypothesized that the degree to which a hyperbolic relationship exists between concentrations of dissolved organic carbon (DOC) and dissolved oxygen (DO) in groundwater may indicate the relative bioavailability of DOC. This hypothesis was examined for 73 different regional aquifers of the United States using 7745 analyses of groundwater compiled by the National Water Assessment (NAWQA) program of the U.S. Geological Survey. The relative reaction quotient (RRQ), a measure of the curvature of DOC concentrations plotted versus DO concentrations and regressed to a decaying hyperbolic equation, was used to assess the relative bioavailability of DOC. For the basalt aquifer of Oahu, Hawaii, RRQ values were low (0.0013 mM(-2)), reflecting a nearly random relationship between DOC and DO concentrations. In contrast, on the island of Maui, treated sewage effluent injected into a portion of the basalt aquifer resulted in pronounced hyperbolic DOC-DO behavior and a higher RRQ (142 mM(-2)). RRQ values for the 73 aquifers correlated positively with mean concentrations of ammonia, dissolved iron, and manganese, and correlated negatively with mean pH. This indicates that greater RRQ values are associated with greater concentrations of the final products of microbial reduction reactions. RRQ values and DOC concentrations were negatively correlated with the thickness of the unsaturated zone (UNST) and depth to the top of the screened interval. Finally, RRQ values were positively correlated with mean annual precipitation (MAP), and the highest observed RRQ values were associated with aquifers receiving MAP rates ranging between 900 and 1300 mm/year. These results are uniformly consistent with the hypothesis that the hyperbolic behavior of DOC-DO plots, as quantified by the RRQ metric, can be an indicator of relative DOC bioavailability in groundwater systems. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  20. A combination of genistein and magnesium enhances the vasodilatory effect via an eNOS pathway and BK(Ca) current amplification.

    Science.gov (United States)

    Sun, Lina; Hou, Yunlong; Zhao, Tingting; Zhou, Shanshan; Wang, Xiaoran; Zhang, Liming; Yu, Guichun

    2015-04-01

    The phytoestrogen genistein (GST) and magnesium have been independently shown to regulate vascular tone; however, their individual vasodilatory effects are limited. The aim of this study was to examine the combined effects of GST plus magnesium on vascular tone in mesenteric arteries. The effects of pretreatment with GST (0-200 μmol/L), MgCl2 (0-4.8 mmol/L) and GST plus MgCl2 on 10 μmol/L phenylephrine (PE) precontracted mesenteric arteries in rats were assessed by measuring isometric force. BK(Ca) currents were detected by the patch clamp method. GST caused concentration- and partial endothelium-dependent relaxation. Magnesium resulted in dual adjustment of vascular tone. Magnesium-free solution eliminated the vasodilatation of GST in both endothelium-intact and denuded rings. GST (50 μmol/L) plus magnesium (4.8 mmol/L) caused stronger relaxation in both endothelium-intact and denuded rings. Pretreatment with the nitric oxide synthase (NOS) inhibitor L-N-nitroarginine methyl ester (L-NAME, 100 μmol/L) significantly inhibited the effects of GST, high magnesium, and the combination of GST and magnesium. BK(Ca) currents were amplified to a greater extent when GST (50 μmol/L) was combined with 4.8 versus 1.2 mmol/L Mg(2+). Our data suggest that GST plus magnesium provides enhanced vasodilatory effects in rat mesenteric arteries compared with that observed when either is used separately, which was related to an eNOS pathway and BK(Ca) current amplification.

  1. Bioavailability in ecological risk. Assessment for radionuclides

    International Nuclear Information System (INIS)

    Garnier-Laplace, J.; Gilbin, R.; Della-Vedova, C.; Adam, C.; Simon, O.; Denison, F.; Beaugelin, K.

    2005-01-01

    The guidance for performing Ecological Risk Assessments (ERA) in Europe has been published in 2003 in the EC's Technical Guidance Document. This document constitutes the official reference in which current water quality standards and risk assessment approach for metals/metalloids are still mainly based on total or dissolved concentrations. However, it has been recognized that accurate assessment of the bio-available metal fraction is crucial, even if the way to incorporate bioavailability into these procedures is still under discussion. The speciation of a pollutant in the exposure medium is the first factor that regulates its bioavailability and consequently its bioaccumulation and the induced biological effects. Therefore, within any ecological risk assessment, bioavailability has obvious implications: firstly in exposure analysis which aim is to determine Predicted Exposure Concentration (PEC); secondly in effect analysis while deriving the so-called Predicted No-Effect Concentrations (PNEC) as toxicity is often linked to the amount of the contaminant incorporated into the tissues of biota. Similarities between metals/metalloids and radionuclides are limited to the biogeochemical behaviour of the element considered and to the need to use bioavailability models. In addition, for radionuclides, emitted ionising radiations (type and energy) need to be taken into account for both exposure and effect analyses whilst performing dosimetric calculations appropriate to the exposure scenarios. A methodology for properly implementing bioavailability models is explained and illustrated for aqueous U(VI), starting from a comprehensive review of the thermodynamic data relevant to environmentally-realistic physico-chemical conditions. Then, the use of thermodynamic equilibrium modelling as a tool for interpreting the bioavailability of U(VI) is presented. Using a systematic approach, different bioavailability models of increasing complexity were tested to model U bio

  2. The Effect of Electroporation of a Lyotroic Liquid Crystal Genistein-Based Formulation in the Recovery of Murine Melanoma Lesions

    Directory of Open Access Journals (Sweden)

    Corina Danciu

    2015-07-01

    Full Text Available A lamellar lyotropic liquid crystal genistein-based formulation (LLC-Gen was prepared in order to increase the aqueous solubility of the lipophilic phytocompound genistein. The formulation was applied locally, in a murine model of melanoma, with or without electroporation. The results demonstrated that, when the formulation was applied by electroporation, the tumors appeared later. During the 21 days of the experiment, the LLC-Gen formulation decreased the tumor volume, the amount of melanin and the degree of erythema, but when electroporation was applied, all these parameters indicated a better prognosis even (lower tumor volume, amount of melanin and degree of erythema. Although hematoxylin–eosin (HE staining confirmed the above events, application of the LLC-Gen formulation by electroporation did not lead to a significant effect in terms of the serum concentrations of the protein S100B and serum neuron specific enolase (NSE, or the tissue expression of the platelet-derived growth factor receptor β (PDGFRβ antibody.

  3. Genistein and Glyceollin Effects on ABCC2 (MRP2 and ABCG2 (BCRP in Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Chandler Schexnayder

    2015-12-01

    Full Text Available The goal of the present study was to determine the effects of glyceollins on intestinal ABCC2 (ATP Binding Cassette C2, multidrug resistance protein 2, MRP2 and ABCG2 (ATP Binding Cassette G2, breast cancer resistance protein, BCRP function using the Caco-2 cell intestinal epithelial cell model. Glyceollins are soy-derived phytoestrogens that demonstrate anti-proliferative activity in several sources of cancer cells. 5 (and 6-carboxy-2′,7′-dichloroflourescein (CDF was used as a prototypical MRP2 substrate; whereas BODIPY-prazosin provided an indication of BCRP function. Comparison studies were conducted with genistein. Glyceollins were shown to inhibit MRP2-mediated CDF transport, with activity similar to the MRP2 inhibitor, MK-571. They also demonstrated concentration-dependent inhibition BCRP-mediated efflux of BODIPY-prazosin, with a potency similar to that of the recognized BCRP inhibitor, Ko143. In contrast, genistein did not appear to alter MRP2 activity and even provided a modest increase in BCRP efflux of BODIPY-prazosin. In particular, glyceollin inhibition of these two important intestinal efflux transporters suggests the potential for glyceollin to alter the absorption of other phytochemicals with which it might be co-administered as a dietary supplement, as well as alteration of the absorption of pharmaceuticals that may be administered concomitantly.

  4. A novel UHPLC method for the rapid and simultaneous determination of daidzein, genistein and equol in human urine.

    Science.gov (United States)

    Redruello, Begoña; Guadamuro, Lucía; Cuesta, Isabel; Álvarez-Buylla, Jorge R; Mayo, Baltasar; Delgado, Susana

    2015-11-15

    This work reports on a novel method involving reverse-phased ultra-high performance liquid chromatography (UHPLC) plus a spectrophotometric photodiode array/fluorescence (FLR) detection system for determining the concentration of equol and major soy isoflavones (daidzein and genistein) in human urine. The proposed method was validated in terms of its linearity, sensitivity, accuracy (recovery) and precision (intra- and inter-day repeatability). The isoflavone profiles of urine samples from a group of menopausal women following oral soy isoflavone supplementation were determined and compared. Screening for equol-producer status was accomplished with high sensitivity (detection limit of the FLR detector 2.93nM). The method involves a short chromatographic run time compared to conventional HPLC methods while allowing for the simultaneous and reliable quantification of daidzein, genistein and equol in human urine. It also allows for the rapid screening of multiple urine samples when testing for equol production status and checking patient adherence to isoflavone treatment regimens. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Bioavailability in rats of bound residues from radishes treated with either radiolabeled dieldrin or carbofuran

    International Nuclear Information System (INIS)

    Khan, S.U.; Kacew, S.; Dupont, S.; Stratton, G.D. Jr.; Wheeler, W.B.

    1987-01-01

    The bioavailability of bound residues from radishes treated with [ 14 C]dieldrin and [ 14 C]carbofuran was investigated by feeding the rats 14 C material obtained after exhaustive solvent extraction. For comparison, nonextracted radishes were also fed to rats. The 14 C residues were predominantly excreted in feces. Urinary excretion of 14 C from rats fed nonextracted material was relatively greater than from those fed extracted radishes. The excreted material from rats fed dieldrin-treated radishes contained mainly parent compounds as residue. However, carbofuran and two of its metabolites, 3-hydroxycarbofuran and 3-ketocarbofuran, were present in feces and urine samples of rats fed carbofuran-treated radishes. These data demonstrated that bound residues in radishes treated with dieldrin and carbofuran have a low degree of bioavailability in rats. The results also show that bound residues in dieldrin-treated radishes would be more bioavailable than in the carbofuran-treated samples

  6. Genistein inhibits phorbol ester-induced NF-κB transcriptional activity and COX-2 expression by blocking the phosphorylation of p65/RelA in human mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Myung-Hoon; Kim, Do-Hee [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Na, Hye-Kyung [Department of Food and Nutrition, Sungshin Women' s University, Seoul (Korea, Republic of); Kim, Jung-Hwan; Kim, Ha-Na [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Haegeman, Guy [LEGEST, University of Gent (Belgium); Surh, Young-Joon, E-mail: surh@snu.ac.kr [Research Institute for Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul (Korea, Republic of)

    2014-10-15

    Genistein, an isoflavone present in soy products, has chemopreventive effects on mammary carcinogenesis. In the present study, we have investigated the effects of genistein on phorbol ester-induced expression of cyclooxygenase-2 (COX-2) that plays an important role in the pathophysiology of inflammation-associated carcinogenesis. Pretreatment of cultured human breast epithelial (MCF10A) cells with genistein reduced COX-2 expression induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). There are multiple lines of evidence supporting that the induction of COX-2 is regulated by the eukaryotic transcription factor NF-κB. Genistein failed to inhibit TPA-induced nuclear translocation and DNA binding of NF-κB as well as degradation of IκB. However, genistein abrogated the TPA-induced transcriptional activity of NF-κB as determined by the luciferase reporter gene assay. Genistein inhibited phosphorylation of the p65 subunit of NF-κB and its interaction with cAMP regulatory element-binding protein-binding protein (CBP)/p300 and TATA-binding protein (TBP). TPA-induced NF-κB phosphorylation was abolished by pharmacological inhibition of extracellular signal-regulated kinase (ERK). Likewise, pharmacologic inhibition or dominant negative mutation of ERK suppressed phosphorylation of p65. The above findings, taken together, suggest that genistein inhibits TPA-induced COX-2 expression in MCF10A cells by blocking ERK-mediated phosphorylation of p65 and its subsequent interaction with CBP and TBP.

  7. Extractability and bioavailability of Pb and As in historically contaminated orchard soil: Effects of compost amendments

    International Nuclear Information System (INIS)

    Fleming, Margaret; Tai, Yiping; Zhuang, Ping; McBride, Murray B.

    2013-01-01

    The availability of Pb and As in an historically contaminated orchard soil, after amendment with compost and aging in the field, was determined by single-step chemical extraction with 1.0 M ammonium acetate at pH 4.8, sequential extraction using the modified BCR test, and a redworm bioassay in the laboratory. The efficiency of soil Pb extraction by ammonium acetate was greater at higher total soil Pb but was reduced by compost amendment. Conversely, the extraction efficiency of total soil As increased with compost amendment, but was not sensitive to total soil As. The redworm bioassay indicated Pb (but not As) bioavailability to be reduced by soil amendment with compost, a result consistent with the ammonium acetate extraction test but not reflected in modified BCR test. Electron microprobe studies of the orchard soil revealed Pb and As to be spatially associated in discrete particles along with phosphorus and iron. -- Highlights: ► Soil Pb and As in an old orchard were concentrated in discrete particles. ► Compost amendment of contaminated soil reduced Pb bioavailability. ► Compost amendment of contaminated soil did not reduce As bioavailability. ► Ammonium acetate extraction test reflected bioavailability of soil Pb and As. -- Remediating metal-contaminated orchard soils with compost reduced lead bioavailability but had little effect on arsenic

  8. Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin.

    Science.gov (United States)

    Ullah, Shafi; Shah, Muhammad Raza; Shoaib, Mohammad; Imran, Muhammad; Shah, Syed Wadood Ali; Ali, Imdad; Ahmed, Farid

    2017-06-01

    Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs. This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability. Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug-excipient interaction using zetasizer, atomic force microscope (AFM), LC-MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits. The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits. The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.

  9. Bioavailability of nanoparticulate hematite to Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Marusenko, Yevgeniy; Shipp, Jessie; Hamilton, George A.; Morgan, Jennifer L.L.; Keebaugh, Michael; Hill, Hansina; Dutta, Arnab; Zhuo, Xiaoding; Upadhyay, Nabin; Hutchings, James; Herckes, Pierre; Anbar, Ariel D.; Shock, Everett; Hartnett, Hilairy E.

    2013-01-01

    The environmental effects and bioavailability of nanoparticulate iron (Fe) to plants are currently unknown. Here, plant bioavailability of synthesized hematite Fe nanoparticles was evaluated using Arabidopsis thaliana (A. thaliana) as a model. Over 56-days of growing wild-type A. thaliana, the nanoparticle-Fe and no-Fe treatments had lower plant biomass, lower chlorophyll concentrations, and lower internal Fe concentrations than the Fe-treatment. Results for the no-Fe and nanoparticle-Fe treatments were consistently similar throughout the experiment. These results suggest that nanoparticles (mean diameter 40.9 nm, range 22.3–67.0 nm) were not taken up and therefore not bioavailable to A. thaliana. Over 14-days growing wild-type and transgenic (Type I/II proton pump overexpression) A. thaliana, the Type I plant grew more than the wild-type in the nanoparticle-Fe treatment, suggesting Type I plants cope better with Fe limitation; however, the nanoparticle-Fe and no-Fe treatments had similar growth for all plant types. -- Highlights: ► Iron nanoparticles were synthesized and assessed for bioavailability to Arabidopsis. ► Arabidopsis grew better in the presence of EDTA-bound iron than nanoparticulate iron. ► Arabidopsis grew the same in the presence of nanoparticulate iron compared to no iron. -- Synthesized iron nanoparticles were not bioavailable to Arabidopsis thaliana in agar nutrient media

  10. Design, characterization, and in vitro cellular inhibition and uptake of optimized genistein-loaded NLC for the prevention of posterior capsular opacification using response surface methodology.

    Science.gov (United States)

    Zhang, Wenji; Li, Xuedong; Ye, Tiantian; Chen, Fen; Sun, Xiao; Kong, Jun; Yang, Xinggang; Pan, Weisan; Li, Sanming

    2013-09-15

    This study was to design an innovative nanostructured lipid carrier (NLC) for drug delivery of genistein applied after cataract surgery for the prevention of posterior capsular opacification. NLC loaded with genistein (GEN-NLC) was produced with Compritol 888 ATO, Gelucire 44/14 and Miglyol 812N, stabilized by Solutol(®) HS15 by melt emulsification method. A 2(4) central composite design of 4 independent variables was performed for optimization. Effects of drug concentration, Gelucire 44/14 concentration in total solid lipid, liquid lipid concentration, and surfactant concentration on the mean particle size, polydispersity index, zeta potential and encapsulation efficiency were investigated. Analysis of variance (ANOVA) statistical test was used to assess the optimization. The optimized GEN-NLC showed a homogeneous particle size of 90.16 nm (with PI=0.33) of negatively charged surface (-25.08 mv) and high encapsulation efficiency (91.14%). Particle morphology assessed by TEM revealed a spherical shape. DSC analyses confirmed that GEN was mostly entrapped in amorphous state. In vitro release experiments indicated a prolonged and controlled genistein release for 72 h. In vitro growth inhibition assay showed an effective growth inhibition of GEN-NLCs on human lens epithelial cells (HLECs). Preliminary cellular uptake test proved a enhanced penetration of genistein into HLECs when delivered in NLC. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein

    NARCIS (Netherlands)

    Sotoca Covaleda, A.M.; Sollewijn Gelpke, M.D.; Boeren, S.; Ström, A.; Gustafsson, J.A.; Murk, A.J.; Rietjens, I.M.C.M.; Vervoort, J.J.M.

    2011-01-01

    The present study addresses, by transcriptomics and quantitative SILAC-based proteomics, the estrogen receptor alpha (ER) and beta (ERß)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line

  12. The expression of vascular endothelial growth factor is affected by hypoxia inducible factor-1α in peritoneum of endometriosis mice treated with genistein

    Directory of Open Access Journals (Sweden)

    Sylvi Wafda Nur Amellia

    2016-09-01

    Full Text Available This study aimed to investigate whether the genistein is able to decrease the expressions of vascular endothelial growth factor-A (VEGF-A and hypoxia inducible factor-1α (HIF-1α in mouse model of endometriosis. Forty female mice (Mus musculus were divided into eight groups (n = 5 each, including the control (untreated group, endometriosis group, and endometriosis groups treated with various doses of genistein (50; 100; 200; 300; 400; and 500 mg/day. VEGF-A and HIF-1α analyses were performed by immunohistochemistry. We found significant increases in the VEGF-A and HIF-α expressions in endometriosis group compared to the control group. The increased expressions of VEGF-A and HIF-1α were significantly (p < 0.05 attenuated by the administration of all doses of genistein. In conclusion, in mouse model of endometriosis, genistein potentially inhibits the increase in angiogenesis in peritoneal tissue. Therefore, this result may provide a novel anti-angiogenic treatment strategy for the therapy of endometriosis.

  13. An overview of BORIS: Bioavailability of Radionuclides in Soils

    International Nuclear Information System (INIS)

    Tamponnet, C.; Martin-Garin, A.; Gonze, M.-A.; Parekh, N.; Vallejo, R.; Sauras-Yera, T.; Casadesus, J.; Plassard, C.; Staunton, S.; Norden, M.; Avila, R.; Shaw, G.

    2008-01-01

    The ability to predict the consequences of an accidental release of radionuclides relies mainly on the level of understanding of the mechanisms involved in radionuclide interactions with different components of agricultural and natural ecosystems and their formalisation into predictive models. Numerous studies and databases on contaminated agricultural and natural areas have been obtained, but their use to enhance our prediction ability has been largely limited by their unresolved variability. Such variability seems to stem from incomplete knowledge about radionuclide interactions with the soil matrix, soil moisture, and biological elements in the soil and additional pollutants, which may be found in such soils. In the 5th European Framework Programme entitled Bioavailability of Radionuclides in Soils (BORIS), we investigated the role of the abiotic (soil components and soil structure) and biological elements (organic compounds, plants, mycorrhiza, and microbes) in radionuclide sorption/desorption in soils and radionuclide uptake/release by plants. Because of the importance of their radioisotopes, the bioavailability of three elements, caesium, strontium, and technetium has been followed. The role of one additional non-radioactive pollutant (copper) has been scrutinised in some cases. Role of microorganisms (e.g., K d for caesium and strontium in organic soils is much greater in the presence of microorganisms than in their absence), plant physiology (e.g., changes in plant physiology affect radionuclide uptake by plants), and the presence of mycorrhizal fungi (e.g., interferes with the uptake of radionuclides by plants) have been demonstrated. Knowledge acquired from these experiments has been incorporated into two mechanistic models CHEMFAST and BIORUR, specifically modelling radionuclide sorption/desorption from soil matrices and radionuclide uptake by/release from plants. These mechanistic models have been incorporated into an assessment model to enhance its

  14. An overview of BORIS: Bioavailability of Radionuclides in Soils

    Energy Technology Data Exchange (ETDEWEB)

    Tamponnet, C. [Institute of Radioprotection and Nuclear Safety, DEI/SECRE, CADARACHE, B.P. 1, 13108 Saint-Paul-lez-Durance, Cedex (France)], E-mail: christian.tamponnet@irsn.fr; Martin-Garin, A.; Gonze, M.-A. [Institute of Radioprotection and Nuclear Safety, DEI/SECRE, CADARACHE, B.P. 1, 13108 Saint-Paul-lez-Durance, Cedex (France); Parekh, N. [Center for Ecology and Hydrology, Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ (United Kingdom); Vallejo, R.; Sauras-Yera, T.; Casadesus, J. [Department of Plant Biology, University of Barcelona, 08028 Barcelona (Spain); Plassard, C.; Staunton, S. [INRA, UMR Rhizosphere and Symbiosis, Place Viala, 34060 Montpellier (France); Norden, M. [Swedish Radiation Protection Institute, 171 16 Stockholm (Sweden); Avila, R. [Facilia AB, Valsgaerdevaegen 12, 168 53 Bromma, Stockholm (Sweden); Shaw, G. [Division of Agricultural and Environmental Sciences University Park, Nottingham NG7 2RD (United Kingdom)

    2008-05-15

    The ability to predict the consequences of an accidental release of radionuclides relies mainly on the level of understanding of the mechanisms involved in radionuclide interactions with different components of agricultural and natural ecosystems and their formalisation into predictive models. Numerous studies and databases on contaminated agricultural and natural areas have been obtained, but their use to enhance our prediction ability has been largely limited by their unresolved variability. Such variability seems to stem from incomplete knowledge about radionuclide interactions with the soil matrix, soil moisture, and biological elements in the soil and additional pollutants, which may be found in such soils. In the 5th European Framework Programme entitled Bioavailability of Radionuclides in Soils (BORIS), we investigated the role of the abiotic (soil components and soil structure) and biological elements (organic compounds, plants, mycorrhiza, and microbes) in radionuclide sorption/desorption in soils and radionuclide uptake/release by plants. Because of the importance of their radioisotopes, the bioavailability of three elements, caesium, strontium, and technetium has been followed. The role of one additional non-radioactive pollutant (copper) has been scrutinised in some cases. Role of microorganisms (e.g., K{sub d} for caesium and strontium in organic soils is much greater in the presence of microorganisms than in their absence), plant physiology (e.g., changes in plant physiology affect radionuclide uptake by plants), and the presence of mycorrhizal fungi (e.g., interferes with the uptake of radionuclides by plants) have been demonstrated. Knowledge acquired from these experiments has been incorporated into two mechanistic models CHEMFAST and BIORUR, specifically modelling radionuclide sorption/desorption from soil matrices and radionuclide uptake by/release from plants. These mechanistic models have been incorporated into an assessment model to enhance

  15. Genistein and tyrphostin AG556 decrease ultra-rapidly activating delayed rectifier K+ current of human atria by inhibiting EGF receptor tyrosine kinase.

    Science.gov (United States)

    Xiao, Guo-Sheng; Zhang, Yan-Hui; Wu, Wei; Sun, Hai-Ying; Wang, Yan; Li, Gui-Rong

    2017-03-01

    The ultra-rapidly activating delayed rectifier K + current I Kur (encoded by K v 1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). Whole-cell patch voltage clamp technique and immunoprecipitation and Western blotting analysis were used to investigate whether the PTK inhibitors genistein, tyrphostin AG556 (AG556) and PP2 regulate human atrial I Kur and hKv1.5 channels stably expressed in HEK 293 cells. Human atrial I Kur was decreased by genistein (a broad-spectrum PTK inhibitor) and AG556 (a highly selective EGFR TK inhibitor) in a concentration-dependent manner. Inhibition of I Kur induced by 30 μM genistein or 10 μM AG556 was significantly reversed by 1 mM orthovanadate (a protein tyrosine phosphatase inhibitor). Similar results were observed in HEK 293 cells stably expressing hK v 1.5 channels. On the other hand, the Src family kinase inhibitor PP2 (1 μM) slightly enhanced I Kur and hK v 1.5 current, and the current increase was also reversed by orthovanadate. Immunoprecipitation and Western blotting analysis showed that genistein, AG556, and PP2 decreased tyrosine phosphorylation of hK v 1.5 channels and that the decrease was countered by orthovanadate. The PTK inhibitors genistein and AG556 decrease human atrial I Kur and cloned hK v 1.5 channels by inhibiting EGFR TK, whereas the Src kinase inhibitor PP2 increases I Kur and hK v 1.5 current. These results imply that EGFR TK and the soluble Src kinases may have opposite effects on human atrial I Kur . © 2017 The British Pharmacological Society.

  16. Bioavailability of Metal Ions and Evolutionary Adaptation

    Directory of Open Access Journals (Sweden)

    Rolando P. Hong Enriquez

    2012-10-01

    Full Text Available The evolution of life on earth has been a long process that began nearly 3,5 x 109 years ago. In their initial moments, evolution was mainly influenced by anaerobic environments; with the rise of O2 and the corresponding change in bioavailability of metal ions, new mechanisms of survival were created. Here we review the relationships between ancient atmospheric conditions, metal ion bioavailability and adaptation of metals homeostasis during early evolution. A general picture linking geochemistry, biochemistry and homeostasis is supported by the reviewed literature and is further illustrated in this report using simple database searches.

  17. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    International Nuclear Information System (INIS)

    Guo, Tai L.; Wang, Yunbiao; Xiong, Tao; Ling, Xiao; Zheng, Jianfeng

    2014-01-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  18. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Wang, Yunbiao [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102 (China); Xiong, Tao [College of Animal Science, Yangtze University, Jingzhou City, Hubei Province 434025 (China); Ling, Xiao [Institute for Food and Drug Control of Shandong Province, Jinan City, Shandong 250012 (China); Zheng, Jianfeng [Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613 (United States)

    2014-11-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  19. Mouse Assay for Determination of Arsenic Bioavailability in Contaminated Soils

    Science.gov (United States)

    Background: Accurate assessment of human exposure estimates from arsenic-contaminated soils depends upon estimating arsenic (As) soil bioavailability. Development of bioavailability assays provides data needed for human health risk assessments and supports development and valida...

  20. Bioavailability of cadmium from linseed and cocoa

    DEFF Research Database (Denmark)

    Hansen, Max; Sloth, Jens Jørgen; Rasmussen, Rie Romme

    In Denmark and EU the exposure of cadmium from food is at a level that is relatively close to the Tolerable Daily Intake (TDI). This report describes an investigation of the bioavailability of cadmium in selected food items known to contain high levels of cadmium. The purpose was to provide data...

  1. Phosphorous bioavailability along a soil chronosequence

    Science.gov (United States)

    Roberts, K.; Vokhshoori, N. L.; Rosenthanl, A.; Turner, B. L.; Condron, L.; Paytan, A.

    2011-12-01

    In humid environments, as soils age nutrient loss through leaching and chemical trasformations affect the succession and composition of the biological communities. In particular phosphorus (P), often a limiting nutrient in terrestrial systems, tends to evolve into less bio-available forms over time, compounding loss through leaching. Thus P availability has the potential to strongly affect community productivity and structure. Low standing stock of P may not necessarily imply P limitation as the bio-available P pool is continuously recycled and re-utilized. Thus extensive recycling can reduce to varying extents the effect of P limitation. The bio-availability and recycling rates of P are difficult to measure; multiple sequential extraction processes have been developed to try to define and quantify the bio-availability of both inorganic and organic forms of P. In this preliminary study, we will present results of P concentrations in different soil fractions and oxygen isotopes in phosphate. These data together increase our understanding of P dynamics as soils age. The work is being done with a well characterized and dated chronosequence from the west coast of the South Island of New Zealand near the Haast River.

  2. Nitric oxide bioavailability dysfunction involves in atherosclerosis.

    Science.gov (United States)

    Chen, Jing-Yi; Ye, Zi-Xin; Wang, Xiu-Fen; Chang, Jian; Yang, Mei-Wen; Zhong, Hua-Hua; Hong, Fen-Fang; Yang, Shu-Long

    2018-01-01

    The pathological characteristics of atherosclerosis (AS) include lipid accumulation, fibrosis formation and atherosclerotic plaque produced in artery intima, which leads to vascular sclerosis, lumen stenosis and irritates the ischemic changes of corresponding organs. Endothelial dysfunction was closely associated with AS. Nitric oxide (NO) is a multifunctional signaling molecule involved in the maintenance of metabolic and cardiovascular homeostasis. NO is also a potent endogenous vasodilator and enters for the key processes that suppresses the formation vascular lesion even AS. NO bioavailability indicates the production and utilization of endothelial NO in organisms, its decrease is related to oxidative stress, lipid infiltration, the expressions of some inflammatory factors and the alteration of vascular tone, which plays an important role in endothelial dysfunction. The enhancement of arginase activity and the increase in asymmetric dimethylarginine and hyperhomocysteinemia levels all contribute to AS by intervening NO bioavailability in human beings. Diabetes mellitus, obesity, chronic kidney disease and smoking, etc., also participate in AS by influencing NO bioavailability and NO level. Here, we reviewed the relationship between NO bioavailability and AS according the newest literatures. Copyright © 2017. Published by Elsevier Masson SAS.

  3. Enhanced bioavailability of opiates after intratracheal administration

    International Nuclear Information System (INIS)

    Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

    1986-01-01

    Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities [codeine (84%), ethylmorphine (100%), and morphine (87%)] of drugs with poor oral availabilities were all markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability

  4. Bioavailability of curcumin: problems and promises.

    Science.gov (United States)

    Anand, Preetha; Kunnumakkara, Ajaikumar B; Newman, Robert A; Aggarwal, Bharat B

    2007-01-01

    Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.

  5. Enhanced bioavailable contaminant stripping (EBCS): metal bioavailability for evaluation of phytoextraction success

    OpenAIRE

    Petruzzelli, Gianniantonio; Pedron, Francesca; Gorini, Francesca; Pezzarossa, Beatrice; Tassi, Eliana; Barbafieri, Meri

    2013-01-01

    Phytoextraction may be applied at field scale when the removal of bioavailable metals is the specific target of the technology. Residual metals in soil can be considered substantially inert or to be evaluated by site specific risk analysis.

  6. Bioavailability and mobility of organic contaminants in soil: new three-step ecotoxicological evaluation.

    Science.gov (United States)

    Prokop, Zbyněk; Nečasová, Anežka; Klánová, Jana; Čupr, Pavel

    2016-03-01

    A novel approach was developed for rapid assessment of bioavailability and potential mobility of contaminants in soil. The response of the same test organism to the organic extract, water extract and solid phase of soil was recorded and compared. This approach was designed to give an initial estimate of the total organic toxicity (response to organic extractable fraction), as well as the mobile (response to water extract) and bioavailable fraction (response to solid phase) of soil samples. Eighteen soil samples with different levels of pollution and content of organic carbon were selected to validate the novel three-step ecotoxicological evaluation approach. All samples were chemically analysed for priority contaminants, including aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), hexachlorocyclohexane (HCH) and dichlordiphenyltrichloroethane (DDT). The ecotoxicological evaluation involved determination of toxicity of the organic, mobile and bioavailable fractions of soil to the test organism, bacterium Bacillus cereus. We found a good correlation between the chemical analysis and the toxicity of organic extract. The low toxicity of water extracts indicated low water solubility, and thus, low potential mobility of toxic contaminants present in the soil samples. The toxicity of the bioavailable fraction was significantly greater than the toxicity of water-soluble (mobile) fraction of the contaminants as deduced from comparing untreated samples and water extracts. The bioavailability of the contaminants decreased with increasing concentrations of organic carbon in evaluated soil samples. In conclusion, the three-step ecotoxicological evaluation utilised in this study can give a quick insight into soil contamination in context with bioavailability and mobility of the contaminants present. This information can be useful for hazard identification and risk assessment of soil-associated contaminants. Graphical Abstract New three-step ecotoxicological

  7. Epigenetic regulation of multiple tumor-related genes leads to suppression of breast tumorigenesis by dietary genistein.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Li

    Full Text Available Breast cancer is one of the most lethal diseases in women; however, the precise etiological factors are still not clear. Genistein (GE, a natural isoflavone found in soybean products, is believed to be a potent chemopreventive agent for breast cancer. One of the most important mechanisms for GE inhibition of breast cancer may involve its potential in impacting epigenetic processes allowing reversal of aberrant epigenetic events during breast tumorigenesis. To investigate epigenetic regulation for GE impedance of breast tumorigenesis, we monitored epigenetic alterations of several key tumor-related genes in an established breast cancer transformation system. Our results show that GE significantly inhibited cell growth in a dose-dependent manner in precancerous breast cells and breast cancer cells, whereas it exhibited little effect on normal human mammary epithelial cells. Furthermore, GE treatment increased expression of two crucial tumor suppressor genes, p21(WAF1 (p21 and p16(INK4a (p16, although it decreased expression of two tumor promoting genes, BMI1 and c-MYC. GE treatment led to alterations of histone modifications in the promoters of p21 and p16 as well as the binding ability of the c-MYC-BMI1 complex to the p16 promoter contributing to GE-induced epigenetic activation of these tumor suppressor genes. In addition, an orally-fed GE diet prevented breast tumorigenesis and inhibited breast cancer development in breast cancer mice xenografts. Our results suggest that genistein may repress early breast tumorigenesis by epigenetic regulation of p21 and p16 by impacting histone modifications as well as the BMI1-c-MYC complex recruitment to the regulatory region in the promoters of these genes. These studies will facilitate more effective use of soybean product in breast cancer prevention and also help elucidate the mechanisms during the process of early breast tumorigenesis.

  8. Epigenetic regulation of multiple tumor-related genes leads to suppression of breast tumorigenesis by dietary genistein.

    Science.gov (United States)

    Li, Yuanyuan; Chen, Huaping; Hardy, Tabitha M; Tollefsbol, Trygve O

    2013-01-01

    Breast cancer is one of the most lethal diseases in women; however, the precise etiological factors are still not clear. Genistein (GE), a natural isoflavone found in soybean products, is believed to be a potent chemopreventive agent for breast cancer. One of the most important mechanisms for GE inhibition of breast cancer may involve its potential in impacting epigenetic processes allowing reversal of aberrant epigenetic events during breast tumorigenesis. To investigate epigenetic regulation for GE impedance of breast tumorigenesis, we monitored epigenetic alterations of several key tumor-related genes in an established breast cancer transformation system. Our results show that GE significantly inhibited cell growth in a dose-dependent manner in precancerous breast cells and breast cancer cells, whereas it exhibited little effect on normal human mammary epithelial cells. Furthermore, GE treatment increased expression of two crucial tumor suppressor genes, p21(WAF1) (p21) and p16(INK4a) (p16), although it decreased expression of two tumor promoting genes, BMI1 and c-MYC. GE treatment led to alterations of histone modifications in the promoters of p21 and p16 as well as the binding ability of the c-MYC-BMI1 complex to the p16 promoter contributing to GE-induced epigenetic activation of these tumor suppressor genes. In addition, an orally-fed GE diet prevented breast tumorigenesis and inhibited breast cancer development in breast cancer mice xenografts. Our results suggest that genistein may repress early breast tumorigenesis by epigenetic regulation of p21 and p16 by impacting histone modifications as well as the BMI1-c-MYC complex recruitment to the regulatory region in the promoters of these genes. These studies will facilitate more effective use of soybean product in breast cancer prevention and also help elucidate the mechanisms during the process of early breast tumorigenesis.

  9. Prebiotics increase heme iron bioavailability and do not affect non-heme iron bioavailability in humans.

    Science.gov (United States)

    Weinborn, Valerie; Valenzuela, Carolina; Olivares, Manuel; Arredondo, Miguel; Weill, Ricardo; Pizarro, Fernando

    2017-05-24

    The aim of this study was to establish the effect of a prebiotic mix on heme and non-heme iron (Fe) bioavailability in humans. To this purpose, twenty-four healthy women were randomized into one of two study groups. One group ate one yogurt per day for 12 days with a prebiotic mix (prebiotic group) and the other group received the same yogurt but without the prebiotic mix (control group). Before and after the intake period, the subjects participated in Fe absorption studies. These studies used 55 Fe and 59 Fe radioactive isotopes as markers of heme Fe and non-heme Fe, respectively, and Fe absorption was measured by the incorporation of radioactive Fe into erythrocytes. The results showed that there were no significant differences in heme and non-heme Fe bioavailability in the control group. Heme Fe bioavailability of the prebiotic group increased significantly by 56% post-prebiotic intake. There were no significant differences in non-heme Fe bioavailability in this group. We concluded that daily consumption of a prebiotic mix increases heme Fe bioavailability and does not affect non-heme iron bioavailability.

  10. Effects of the isoflavone genistein in early life stages of the Senegalese sole, Solea senegalensis: role of the Survivin and proliferation versus apoptosis pathways.

    Science.gov (United States)

    Sarasquete, Carmen; Úbeda-Manzanaro, María; Ortiz-Delgado, Juan B

    2018-01-17

    Phytochemical flavonoids are widely distributed in the environment and are derived from many anthropogenic activities. The isoflavone genistein is a naturally occurring compound found in soya products that are habitual constituents of the aquafeeds. This isoflavone possesses oestrogenic biological activity and also apoptotic properties. The present study has been performed to determine the effects of the genistein in the early life stages of the flatfish Senegalese sole during the first month of larval life, and it is focused especially at the metamorphosis, analysing the expression transcript levels and the immunohistochemical protein patterns implicated in the cell proliferation and apoptosis pathways (proliferation cellular/PCNA, anti-apoptosis Survivin/BIRC-5, death receptors/Fas, and Caspases). The isoflavone genistein induced some temporal disrupting effects in several pro-apoptotic signalling pathways (Fas, CASP-6) at both genistein doses (3 mg/L and 10 mg/L), with increased Fas transcripts and also decreasing CASP-6 mRNA expression levels during metamorphic and post-metamorphic stages of the Senegalese sole. On the other hand, the anti-apoptotic BIRC-5 expression levels were weakly down-regulated with both the highest and lowest doses, but all of these imbalances were stabilised to the baseline levels. In early life stages of the controls, the constitutive basal transcript levels were temporarily and differentially expressed, reaching the highest levels at the pre-metamorphosis phase, as especially in endotrophic larvae (i.e. BIRC-5 mRNA), as well as in the metamorphic (i.e. CASP-6 mRNA) and post-metamorphic stages (i.e. Fas mRNA). In general, through development, continuous and progressive increases in the protein patterns of cell proliferation-PCNA (e.g. mitotic nuclei), anti-apoptotic Survivin (e.g. haematopoietic system, brain, digestive system, gills) and CASP-2 and -6 (e.g. brain, gills, kidney, digestive system, vascular systems, among others

  11. Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study

    Science.gov (United States)

    Dian, Linghui; Yang, Zhiwen; Li, Feng; Wang, Zhouhua; Pan, Xin; Peng, Xinsheng; Huang, Xintian; Guo, Zhefei; Quan, Guilan; Shi, Xuan; Chen, Bao; Li, Ge; Wu, Chuanbin

    2013-01-01

    In order to improve the oral bioavailability of ibuprofen, ibuprofen-loaded cubic nanoparticles were prepared as a delivery system for aqueous formulations. The cubic inner structure was verified by cryogenic transmission electron microscopy. With an encapsulation efficiency greater than 85%, the ibuprofen-loaded cubic nanoparticles had a narrow size distribution around a mean size of 238 nm. Differential scanning calorimetry and X-ray diffraction determined that ibuprofen was in an amorphous and molecular form within the lipid matrix. The in vitro release of ibuprofen from cubic nanoparticles was greater than 80% at 24 hours, showing sustained characteristics. The pharmacokinetic study in beagle dogs showed improved absorption of ibuprofen from cubic nanoparticles compared to that of pure ibuprofen, with evidence of a longer half-life and a relative oral bioavailability of 222% (P ibuprofen-loaded cubic nanoparticles provide a promising carrier candidate with an efficient drug delivery for therapeutic treatment. PMID:23468008

  12. Mineralogy affects geoavailability, bioaccessibility and bioavailability of zinc

    International Nuclear Information System (INIS)

    Molina, Ramon M.; Schaider, Laurel A.; Donaghey, Thomas C.; Shine, James P.; Brain, Joseph D.

    2013-01-01

    We correlated mineralogical and particle characteristics of Zn-containing particles with Zn geoavailability, bioaccessibility, and bioavailability following gavage and intranasal (IN) administration in rats. We compared samples of Zn/Pb mine waste and five pulverized pure-phase Zn minerals ( 65 Zn. We assessed geoavailability using sequential extractions and bioaccessibility using in vitro extraction tests simulating various pH and biological conditions. Zn in vivo bioavailability and in vitro bioaccessibility decreased as follows: mine waste > hydrozincite > hemimorphite > zincite ≈ smithsonite >> sphalerite. We found significant correlations among geoavailability, bioaccessibility and bioavailability. In particular, Zn bioavailability post-gavage and post-IN was significantly correlated with bioaccessibility in simulated phagolysosomal fluid and gastric fluid. These data indicate that solid phase speciation influences biological uptake of Zn and that in vitro tests can be used to predict Zn bioavailability in exposure assessment and effective remediation design. Highlights: •Zinc particle mineralogy influences bioaccessibility and bioavailability. •Zn bioavailability via gavage was 1.2–1.6 times higher than via intranasal route. •Zn particle geoavailability correlates with bioaccessibility. •In vitro bioaccessibility tests can predict in vivo Zn bioavailability. •Metal speciation and geochemical alterations can impact Zn bioavailability. -- Zinc mineralogy influences in vitro bioaccessibility and in vivo bioavailability and in vitro extraction tests can be used to predict Zn bioavailability from particles

  13. Bioavailability of indomethacin-saccharin cocrystals.

    Science.gov (United States)

    Jung, Min-Sook; Kim, Jeong-Soo; Kim, Min-Soo; Alhalaweh, Amjad; Cho, Wonkyung; Hwang, Sung-Joo; Velaga, Sitaram P

    2010-11-01

    Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee. Scale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies.   The bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P0.05). The study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs. © 2010 The Authors. JPP © 2010 Royal

  14. Influence of PEG coating on the oral bioavailability of gold nanoparticles in rats.

    Science.gov (United States)

    Alalaiwe, Ahmed; Roberts, Georgia; Carpinone, Paul; Munson, John; Roberts, Stephen

    2017-11-01

    Metallic nanoparticles can be produced in a variety of shapes, sizes, and surface chemistries, making them promising potential tools for drug delivery. Most studies to date have evaluated uptake of metallic nanoparticles from the GI tract with methods that are at best semi-quantitative. This study used the classical method of comparing blood concentration area under the curve (AUC) following intravenous and oral doses to determine the oral bioavailability of 1, 2 and 5 kDa PEG-coated 5 nm gold nanoparticles (AuNPs). Male rats were given a single intravenous dose (0.8 mg/kg) or oral (gavage) dose (8 mg/kg) of a PEG-coated AuNP, and the concentration of gold was measured in blood over time and in tissues (liver, spleen and kidney) at sacrifice. Blood concentrations following oral administration were inversely related to PEG size, and the AUC in blood was significantly greater for the 1 kDa PEG-coated AuNPs than particles coated with 2 or 5 kDa PEG. However, bioavailabilities of all of the particles were very low (bioavailability of AuNPs coated with PEG in the 1-5 kDa range, this study demonstrates the utility of applying the blood AUC approach to assess the quantitative oral bioavailability of metallic nanoparticles.

  15. Comparison of the gastrointestinal absorption and bioavailability of fenofibrate and fenofibric acid in humans.

    Science.gov (United States)

    Zhu, Tong; Ansquer, Jean-Claude; Kelly, Maureen T; Sleep, Darryl J; Pradhan, Rajendra S

    2010-08-01

    This study compared the gastrointestinal (GI) absorption characteristics and absolute bioavailability of fenofibric acid and fenofibrate (which is converted to fenofibric acid in vivo) in healthy volunteers. Treatments were delivered to the proximal small bowel, distal small bowel, and colon using a site-specific delivery system (Enterion capsule) and to the stomach by oral administration of equimolar doses. Serial blood samples were collected for 120 hours postdose and assayed for plasma fenofibric acid concentrations. The absolute bioavailability of each treatment was determined relative to 50 mg of fenofibric acid administered intravenously. Plasma exposure to fenofibric acid following fenofibric acid administration was approximately 1.5 times higher than that following fenofibrate administration for delivery to the proximal and distal small bowel and following oral administration, and it was approximately 5 times higher following colon delivery. The absolute bioavailability in the stomach, proximal small bowel, distal small bowel, and colon was approximately 81%, 88%, 84%, and 78%, respectively, for fenofibric acid and 69%, 73%, 66%, and 22%, respectively, for fenofibrate (P < .0001 and P = .033 for fenofibric acid vs fenofibrate in the colon and distal small bowel, respectively). In conclusion, fenofibric acid is well absorbed throughout the GI tract and has greater bioavailability than fenofibrate in all GI regions.

  16. Effect of type of TAG fatty acids on lutein and zeaxanthin bioavailability.

    Science.gov (United States)

    Gleize, Béatrice; Tourniaire, Franck; Depezay, Laurence; Bott, Romain; Nowicki, Marion; Albino, Lionel; Lairon, Denis; Kesse-Guyot, Emmanuelle; Galan, Pilar; Hercberg, Serge; Borel, Patrick

    2013-07-14

    The xanthophylls lutein and zeaxanthin probably play a role in visual function and may participate in the prevention of age-related eye diseases. Although a minimum amount of TAG is required for an optimal bioavailability of these carotenoids, the effect of the type of TAG fatty acids (FA) is less clear. The aim was to assess the effect of the type of TAG FA on bioavailability of these xanthophylls. A total of three complementary models were used: an in vitro digestion model to study bioaccessibility, Caco-2 cells to study uptake efficiency and orally administered rats to study in vivo bioavailability. Results showed that lutein and zeaxanthin bioaccessibility was greater (about 20-30 %, Pxanthophyll uptake by Caco-2 cells, but some compounds present in natural oils significantly affected xanthophyll uptake. Oral administration of rats with spinach and butter over 3 d led to a higher fasting plasma lutein concentration than oral administration with olive or fish oils. In conclusion, dietary fats rich in SFA lead to a higher bioavailability of lutein and zeaxanthin, as compared with fats rich in MUFA and PUFA. This is due partly to the higher bioaccessibility of these xanthophylls in the smaller mixed micelles produced when SFA are incorporated into mixed micelles.

  17. Mobility and Bioavailability of Radionuclides in Soils

    International Nuclear Information System (INIS)

    Iurian, A.; Olufemi Phaneuf, M.; Mabit, L.

    2016-01-01

    It is crucial to understand the behavior of radionuclides in the environment, their potential mobility and bioavailability related to long-term persistence, radiological hazards, and impact on human health. Such key information is used to develop strategies that support policy decisions. The environmental behavior of radionuclides depends on ecosystem characteristics. A given soil’s capacity to immobilize radionuclides has been proved to be the main factor responsible for their resulting activity concentrations in plants. The mobility and bioavailability of radionuclides in soils is complex, depending on clay-sized soil fraction, clay mineralogy, organic matter, cation exchange capacity, pH and quantities of competing cations. Moreover, plant species have different behaviors regarding radionuclide absorption depending on soil and plan characteristics

  18. Bioavailability and variability of biphasic insulin mixtures

    DEFF Research Database (Denmark)

    Søeborg, Tue; Rasmussen, Christian Hove; Mosekilde, Erik

    2012-01-01

    Absorption of subcutaneously administered insulin is associated with considerable variability. Some of this variability was quantitatively explained for both soluble insulin and insulin suspensions in a recent contribution to this journal (Søeborg et al., 2009). In the present article......, the absorption kinetics for mixtures of insulins is described. This requires that the bioavailability of the different insulins is considered. A short review of insulin bioavailability and a description of the subcutaneous depot thus precede the presentation of possible mechanisms associated with subcutaneous...... insulin degradation. Soluble insulins are assumed to be degraded enzymatically in the subcutaneous tissue. Suspended insulin crystals form condensed heaps that are assumed to be degraded from their surface by invading macrophages. It is demonstrated how the shape of the heaps affects the absorption...

  19. Extraction, bioavailability, and bioefficacy of capsaicinoids

    Directory of Open Access Journals (Sweden)

    Muwen Lu

    2017-01-01

    Full Text Available Capsaicinoids are active constituents responsible for the pungent and spicy flavor in chili peppers. During the past few decades, various extraction methods of capsaicinoids from peppers have been developed with high yields. Through biological studies, pharmacological benefits have been reported such as pain relief, antiinflammation, anticancer, cardio-protection, as well as weight loss. In this paper, the extraction methods and bioavailability of capsaicinoids are reviewed and discussed. In addition, the pharmacological effects and their underlying mechanisms are also studied.

  20. Extraction, bioavailability, and bioefficacy of capsaicinoids

    OpenAIRE

    Muwen Lu; Chi-Tang Ho; Qingrong Huang

    2017-01-01

    Capsaicinoids are active constituents responsible for the pungent and spicy flavor in chili peppers. During the past few decades, various extraction methods of capsaicinoids from peppers have been developed with high yields. Through biological studies, pharmacological benefits have been reported such as pain relief, antiinflammation, anticancer, cardio-protection, as well as weight loss. In this paper, the extraction methods and bioavailability of capsaicinoids are reviewed and discussed. In ...

  1. KIRLIANOGRAPHY ESTIMATION OF BIOAVAILABILITY OF SUBSTANCE

    Directory of Open Access Journals (Sweden)

    M. V. Kuryk

    2013-11-01

    The method of classical kirlianography with X ray film allows assessing the bioavailability condition, which is important for the prediction of absorption and physiological effects of a man consumed food and phytomedicines. Therefore, these studies are relevant and require further development. Used such standard methods of mathematical processing as histograms and pixel brightness profile for the analysis of Kirlian images are informative enough for the individual samples, and can be the basis for the batch processing of data.

  2. Bioavailability of cadmium from linseed and cocoa

    DEFF Research Database (Denmark)

    Hansen, Max; Rasmussen, Rie Romme; Sloth, Jens Jørgen

    2014-01-01

    The exposure of the European population to cadmium from food is high compared with the tolerable weekly intake of 2.5 μg/kg bodyweight set by EFSA in 2009. Only few studies on the bioavailability of cadmium from different food sources has been performed but this information in very important...... for the food authorities in order to give correct advises to the population. The aim of this study was to investigate the bioavailability of cadmium from whole linseed, crushed linseed, cocoa and cadmium chloride in rats. An experiment where 40 rats were divided into 4 groups and a control group and dosed...... be measured in the kidney compared to the calculated total intake was as follows: Control 2.0 %, Crushed linseed 0.9 %, whole linseed, 1.5 %, cocoa 0.7 % and CdCl2 4.6 %. Based on this study it could not be concluded that the bioavailability in rats form whole linseed is lower that for crushed linseed...

  3. Potassium Intake, Bioavailability, Hypertension, and Glucose Control

    Directory of Open Access Journals (Sweden)

    Michael S. Stone

    2016-07-01

    Full Text Available Potassium is an essential nutrient. It is the most abundant cation in intracellular fluid where it plays a key role in maintaining cell function. The gradient of potassium across the cell membrane determines cellular membrane potential, which is maintained in large part by the ubiquitous ion channel the sodium-potassium (Na+-K+ ATPase pump. Approximately 90% of potassium consumed (60–100 mEq is lost in the urine, with the other 10% excreted in the stool, and a very small amount lost in sweat. Little is known about the bioavailability of potassium, especially from dietary sources. Less is understood on how bioavailability may affect health outcomes. Hypertension (HTN is the leading cause of cardiovascular disease (CVD and a major financial burden ($50.6 billion to the US public health system, and has a significant impact on all-cause morbidity and mortality worldwide. The relationship between increased potassium supplementation and a decrease in HTN is relatively well understood, but the effect of increased potassium intake from dietary sources on blood pressure overall is less clear. In addition, treatment options for hypertensive individuals (e.g., thiazide diuretics may further compound chronic disease risk via impairments in potassium utilization and glucose control. Understanding potassium bioavailability from various sources may help to reveal how specific compounds and tissues influence potassium movement, and further the understanding of its role in health.

  4. Rapid screening assay for calcium bioavailability studies

    International Nuclear Information System (INIS)

    Luhrsen, K.R.; Hudepohl, G.R.; Smith, K.T.

    1986-01-01

    Calcium bioavailability has been studied by numerous techniques. The authors report here the use of the gamma emitting isotope of calcium ( 47 Ca) in a whole body retention assay system. In this system, calcium sources are administered by oral gavage and subsequent counts are determined and corrected for isotopic decay. Unlike iron and zinc retention curves, which exhibit a 2-3 day equilibration period, calcium reaches equilibration after 24 hours. Autoradiographic analysis of the femurs indicate that the newly absorbed calcium is rapidly distributed to the skeletal system. Moreover, the isotope is distributed along the entire bone. Comparisons of calcium bioavailability were made using intrinsic/extrinsic labeled milk from two species i.e. rat and goat as well as CaCO 3 . In addition, extrinsic labeled cow milk was examined. In the rat, the extrinsic labeled calcium from milk was better absorbed than the intrinsic calcium. This was not the case in goat milk or the calcium carbonate which exhibited no significant differences. Chromatographic analysis of the labeled milk indicates a difference in distribution of the 47 Ca. From these data, the authors recommend the use of this assay system in calcium bioavailability studies. The labeling studies and comparisons indicate caution should be used, however, in labeling techniques and species milk comparison

  5. The immune system of geriatric mice is modulated by estrogenic endocrine disruptors (diethylstilbestrol, α-zearalanol, and genistein): Effects on interferon-γ

    International Nuclear Information System (INIS)

    Calemine, Jillian; Zalenka, Julie; Karpuzoglu-Sahin, Ebru; Ward, Daniel L.; Lengi, Andrea; Ahmed, S. Ansar

    2003-01-01

    The immune system is a potential target for estrogenic endocrine disrupters. To date, there is limited information on whether estrogenic endocrine disruptors modulate the immune system of aged individuals. To address this issue, groups of 74-week-old mice were given nine oral doses of selected estrogenic endocrine disrupters: diethylstilbestrol (DES, 3 μg/100 g bw), α-zearalanol (0.5 mg/100 g bw), or genistein (0.15 mg/100 g bw) in corn oil, or corn oil alone, over 2.5 weeks. Both developmental (thymus) and mature (spleen) lymphoid organs were affected, although specific effects varied with the chemical. DES significantly decreased thymocyte numbers. However, relative percentages of thymocyte subsets were not altered. While splenic cellularity and percentages of T and B cells were unchanged, splenocytes from DES-exposed mice had significantly decreased ability to proliferate in response to Concanavalin-A (Con-A). Con-A-activated splenocytes from mice treated with genistein or α-zearalanol had decreased levels of interferon-γ (IFNγ) protein in their culture supernatants compared to similar cultures from oil-treated mice. RT-PCR analysis of Con-A-activated splenocytes revealed that the expression of IFNγ gene is altered by DES or genistein treatment. Together, these results suggest that estrogenic endocrine disruptors modulate the immune system of aged mice

  6. [Autoerotic fatalities in Greater Dusseldorf].

    Science.gov (United States)

    Hartung, Benno; Hellen, Florence; Borchard, Nora; Huckenbeck, Wolfgang

    2011-01-01

    Autoerotic fatalities in the Greater Dusseldorf area correspond to the relevant medicolegal literature. Our results included exclusively young to middle-aged, usually single men who were found dead in their city apartments. Clothing and devices used showed a great variety. Women's or fetish clothing and complex shackling or hanging devices were disproportionately frequent. In most cases, death occurred due to hanging or ligature strangulation. There was no increased incidence of underlying psychiatric disorders. In most of the deceased no or at least no remarkable alcohol intoxication was found. Occasionally, it may be difficult to reliably differentiate autoerotic accidents, accidents occurring in connection with practices of bondage & discipline, dominance & submission (BDSM) from natural death, suicide or homicide.

  7. Planning for greater confinement disposal

    International Nuclear Information System (INIS)

    Gilbert, T.L.; Luner, C.; Meshkov, N.K.; Trevorrow, L.E.; Yu, C.

    1985-01-01

    A report that provides guidance for planning for greater-confinement disposal (GCD) of low-level radioactive waste is being prepared. The report addresses procedures for selecting a GCD technology and provides information for implementing these procedures. The focus is on GCD; planning aspects common to GCD and shallow-land burial are covered by reference. Planning procedure topics covered include regulatory requirements, waste characterization, benefit-cost-risk assessment and pathway analysis methodologies, determination of need, waste-acceptance criteria, performance objectives, and comparative assessment of attributes that support these objectives. The major technologies covered include augered shafts, deep trenches, engineered structures, hydrofracture, improved waste forms, and high-integrity containers. Descriptive information is provided, and attributes that are relevant for risk assessment and operational requirements are given. 10 refs., 3 figs., 2 tabs

  8. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy

    Science.gov (United States)

    Rein, Maarit J.; Renouf, Mathieu; Cruz‐Hernandez, Cristina; Actis‐Goretta, Lucas; Thakkar, Sagar K.; da Silva Pinto, Marcia

    2013-01-01

    Bioavailability is a key step in ensuring bioefficacy of bioactive food compounds or oral drugs. Bioavailability is a complex process involving several different stages: liberation, absorption, distribution, metabolism and elimination phases (LADME). Bioactive food compounds, whether derived from various plant or animal sources, need to be bioavailable in order to exert any beneficial effects. Through a better understanding of the digestive fate of bioactive food compounds we can impact the promotion of health and improvement of performance. Many varying factors affect bioavailability, such as bioaccessibility, food matrix effect, transporters, molecular structures and metabolizing enzymes. Bioefficacy may be improved through enhanced bioavailability. Therefore, several technologies have been developed to improve the bioavailability of xenobiotics, including structural modifications, nanotechnology and colloidal systems. Due to the complex nature of food bioactive compounds and also to the different mechanisms of absorption of hydrophilic and lipophilic bioactive compounds, unravelling the bioavailability of food constituents is challenging. Among the food sources discussed during this review, coffee, tea, citrus fruit and fish oil were included as sources of food bioactive compounds (e.g. (poly)phenols and polyunsaturated fatty acids (PUFAs)) since they are examples of important ingredients for the food industry. Although there are many studies reporting on bioavailability and bioefficacy of these bioactive food components, understanding their interactions, metabolism and mechanism of action still requires extensive work. This review focuses on some of the major factors affecting the bioavailability of the aforementioned bioactive food compounds. PMID:22897361

  9. Incorporation of Heavy metals bioavailability into risk characterization

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Hyerim; Chung, Jae Shik; Nam, Taekwoo; Nam, Kyoungphile [Department of Civil and Environmental Engineering, Seoul National University, Seoul (Korea, Republic of); Moon, Hee Sun [School of Earth and Environmental Sciences, Seoul National University, Seoul (Korea, Republic of)

    2010-09-15

    The bioavailability of field-aged Cd and Cu was calculated, and compared to the total concentrations determined by acid digestion. Only 0.60-4.15% for Cd and 0.59-9.43% for Cu were found to be bioavailable when determined by stomach-phase extraction. The incorporation of bioavailability reduced more than 90% of the calculated risk of the metals at the site of study. It should be noted that such a reduction may not be generalized and the site-specific bioavailability needs to be determined case by case. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  10. The bioavailability of chemicals in soil for earthworms

    Science.gov (United States)

    Lanno, R.; Wells, J.; Conder, Jason M.; Bradham, K.; Basta, N.

    2004-01-01

    The bioavailability of chemicals to earthworms can be modified dramatically by soil physical/chemical characteristics, yet expressing exposure as total chemical concentrations does not address this problem. In order to understand the effects of modifying factors on bioavailability, one must measure and express chemical bioavailability to earthworms in a consistent, logical manner. This can be accomplished by direct biological measures of bioavailability (e.g., bioaccumulation, critical body residues), indirect biological measures of bioavailability (e.g., biomarkers, reproduction), or indirect chemical measures of bioavailability (e.g., chemical or solid-phase extracts of soil). If indirect chemical measures of bioavailability are to be used, they must be correlated with some biological response. Bioavailability can be incorporated into ecological risk assessment during risk analysis, primarily in the estimation of exposure. However, in order to be used in the site-specific ecological risk assessment of chemicals, effects concentrations must be developed from laboratory toxicity tests based on exposure estimates utilizing techniques that measure the bioavailable fraction of chemicals in soil, not total chemical concentrations. ?? 2003 Elsevier Inc. All rights reserved.

  11. DNA Methylation Targets Influenced by Bisphenol A and/or Genistein Are Associated with Survival Outcomes in Breast Cancer Patients

    Science.gov (United States)

    Jadhav, Rohit R.; Santucci-Pereira, Julia; Wang, Yao V.; Liu, Joseph; Nguyen, Theresa D.; Wang, Jun; Jenkins, Sarah; Russo, Jose; Huang, Tim H.-M.; Jin, Victor X.; Lamartiniere, Coral A.

    2017-01-01

    Early postnatal exposures to Bisphenol A (BPA) and genistein (GEN) have been reported to predispose for and against mammary cancer, respectively, in adult rats. Since the changes in cancer susceptibility occurs in the absence of the original chemical exposure, we have investigated the potential of epigenetics to account for these changes. DNA methylation studies reveal that prepubertal BPA exposure alters signaling pathways that contribute to carcinogenesis. Prepubertal exposure to GEN and BPA + GEN revealed pathways involved in maintenance of cellular function, indicating that the presence of GEN either reduces or counters some of the alterations caused by the carcinogenic properties of BPA. We subsequently evaluated the potential of epigenetic changes in the rat mammary tissues to predict survival in breast cancer patients via the Cancer Genomic Atlas (TCGA). We identified 12 genes that showed strong predictive values for long-term survival in estrogen receptor positive patients. Importantly, two genes associated with improved long term survival, HPSE and RPS9, were identified to be hypomethylated in mammary glands of rats exposed prepuberally to GEN or to GEN + BPA respectively, reinforcing the suggested cancer suppressive properties of GEN. PMID:28505145

  12. Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers

    Science.gov (United States)

    Cai, Limei; Yu, Rufen; Hao, Xi; Ding, Xiangcui

    2017-08-01

    In this study, novel folic acid-conjugated chitosan nanoparticle was formulated for specific delivery of bioflavonoid, Genistein (GEN), to the cervical cancer cells. The prepared GEN-loaded chitosan nanoparticles (GCN) and folic acid-conjugated GCN (FGCN) showed smaller size with a controlled drug release profile. FGCN exhibited enhanced internalization potential in HeLa cells than that of GCN. The specific internalization of FGCN was mainly due to the affinity of folic acid (FA) with FRs-α which is present in large numbers in HeLa cells. The results revealed that FGCN has a specific affinity towards HeLa cells that will contribute to the better treatment. Folic acid-tagged nanoformulations exhibited a superior cytotoxic effect compared to that of non-targeted formulations. Consistently, IC50 value of GEN decreased from 33.8 to 14.6 μg/ml when treated with FGCN after 24 h incubation. The apoptosis studies indicated that the FGCN nanoparticles were then either GCN or free GEN in terms of anticancer activity. Overall, results revealed that folate conjugation to the delivery system might have great effect on the survival of cervical cancers that will be beneficial for overall cancer treatment.

  13. Distribution and bioavailability of cadmium in ornithogenic coral-sand sediments of the Xisha archipelago, South China Sea

    International Nuclear Information System (INIS)

    Liu Xiaodong; Lou Chuangneng; Xu Liqiang; Sun Liguang

    2012-01-01

    Total cadmium (Cd) concentrations in four ornithogenic coral-sand sedimentary profiles displayed a strong positive correlation with guano-derived phosphorus, but had no correlation with plant-originated organic matter in the top sediments. These results indicate that the total Cd distributions were predominantly controlled by guano input. Bioavailable Cd and zinc (Zn) had a greater input rate in the top sediments with respect to total Cd and total Zn, and a positive correlation with total organic carbon (TOC) derived from plant humus. Multi-regression analysis showed that the total Cd and TOC explained over 80% of the variation of bioavailable Cd, suggesting that both guano and plant inputs could significantly influence the distribution of bioavailable Cd, and that plant biocycling processes contribute more to the recent increase of bioavailable Cd. A pollution assessment indicates that the Yongle archipelago is moderately to strongly polluted with guano-derived Cd. - Guano and plant biocycling processes can exert different influences on the distributions of total Cd and bioavailable Cd in coral-sand ornithogenic sediments.

  14. Bioavailability of diclofenac potassium at low doses

    Science.gov (United States)

    Hinz, Burkhard; Chevts, Julia; Renner, Bertold; Wuttke, Henrike; Rau, Thomas; Schmidt, Andreas; Szelenyi, Istvan; Brune, Kay; Werner, Ulrike

    2005-01-01

    Aim Diclofenac-K has been recently launched at low oral doses in different countries for over-the-counter use. However, given the considerable first-pass metabolism of diclofenac, the degree of absorption of diclofenac-K at low doses remained to be determined. The aim of this study was to determine the bioavailability of low-dose diclofenac-K. Methods A randomized, three-way, cross-over study was performed in 10 subjects. Each received diclofenac-K, 22.5 mg via short-term i.v. infusion and orally at single doses of 12.5 mg and 25 mg. Results Mean (± SD) times to maximal plasma concentration (tmax) of diclofenac were 0.48 ± 0.28 h (12.5 mg) and 0.93 ± 0.96 h (25 mg). The absolute bioavailability of diclofenac-K after oral administration did not differ significantly in the 12.5-mg and 25-mg dose group (63.1 ± 12.6% vs. 65.1 ± 19.4%, respectively). The 90% confidence intervals for the AUC∞ and AUCt ratios for the two oral regimes were 82.6, 103.4% (point estimate 92.4%) and 86.2, 112.9% (point estimate 98.6%), respectively. These values were within the acceptance criteria for bioequivalence (80–125%). Conclusions Our data indicate that diclofenac-K is rapidly and well absorbed at low dose, and are consistent with a rapid onset of action of the drug. Abbreviations AUC, area under plasma concentraton-time curve; Cmax, peak plasma concentration; CI, confidence interval; COX, cyclooxygenase; D, dose; F, absolute bioavailability; tmax, time to reach Cmax. PMID:15606444

  15. Atovaquone oral bioavailability enhancement using electrospraying technology.

    Science.gov (United States)

    Darade, Aditya; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

    2018-01-01

    Atovaquone in combination with proguanil hydrochloride, marketed as Malarone® tablets by GlaxoSmithKline (GSK), is prescribed for the treatment of malaria. High dose and poor bioavailability are the main hurdles associated with atovaquone oral therapy. The present study reports development of atovaquone nanoparticles, using in house designed and fabricated electrospraying equipment, and the assessment of bioavailability and therapeutic efficacy of the nanoparticles after oral administration. Solid nanoparticles of atovaquone were successfully produced by electrospraying and were characterized for particle size and flow properties. Differential Scanning Calorimetry, X-ray Diffraction, Fourier Transform Infrared Spectroscopy studies were also carried out. Atovaquone nanoparticles along with proguanil hydrochloride and a suitable wetting agent were filled in size 2 hard gelatin capsules. The formulation was compared with Malarone® tablets (GSK) and Mepron® suspension (GSK) in terms of in vitro release profile and in vivo pharmacokinetic studies. It showed 2.9-fold and 1.8-fold improved bioavailability in rats compared to Malarone® tablets and Mepron® suspension respectively. Therapeutic efficacy of the formulation was determined using modified Peter's 4-day suppressive tests and clinical simulation studies using Plasmodium berghei ANKA infected Swiss mice and compared to Malarone®. The developed formulation showed a 128-fold dose reduction in the modified Peter's 4-day suppressive tests and 32-fold dose reduction in clinical simulation studies. Given that only one capsule a day of developed formulation is required to be administered orally compared to 4 Malarone® tablets once a day and that too at a significantly reduced dose, this nanoparticle formulation will definitely reduce the side-effects of the treatment and is also likely to increase patient compliance. Copyright © 2017. Published by Elsevier B.V.

  16. Bioavailability of omega-3 long-chain polyunsaturated fatty acids from foods

    DEFF Research Database (Denmark)

    Mu, Huiling

    2008-01-01

    Increasing recognition of the importance of the omega-3 long chain polyunsaturated fatty acids (LCPUFA) has caused greater attention about dietary intake of these fatty acids. Fatty fish is the major dietary source of these fatty acids. Because of the low intake of fish at many places, foods...... enriched with omega-3 LCPUFA can be good alternatives to improve the intake of these fatty acids. Effects of lipid structures and food matrices on bioavailability of omega-3 LCPUFA have been investigated. Short term studies showed that both lipid structure and food matrix affect the bioavailability...... of these fatty acids, whereas diverse results have been reported from long-term studies. Therefore more studies are encouraged to clarify the long-term effects....

  17. Eudragit L/HPMCAS blend enteric-coated lansoprazole pellets: enhanced drug stability and oral bioavailability.

    Science.gov (United States)

    Fang, Yu; Wang, Guozheng; Zhang, Rong; Liu, Zhihua; Liu, Zhenghua; Wu, Xiaohui; Cao, Deying

    2014-06-01

    The objectives of the present work were to use blends of Eudragit L and hydroxypropyl methylcellulose acetate succinate (HPMCAS) as enteric film coatings for lansoprazole (LSP) pellets. The enteric-coated pellets were prepared with a fluid-bed coater. The influence of the blend ratio, type of plasticizer, plasticizer level, coating level, and curing conditions on gastric stability in vitro drug release and drug stability was evaluated. Furthermore, the bioavailability of the blend-coated pellets in beagle dogs was also performed. The blend-coated pellets exhibited significant improvement of gastric stability and drug stability compared to the pure polymer-coated pellets. Moreover, the AUC values of blend-coated pellets were greater than that of the pure polymer-coated pellets. It was concluded that the using blends of Eudragit L and HPMCAS as enteric film coatings for LSP pellets improved the drug stability and oral bioavailability.

  18. Extraction, bioavailability, and bioefficacy of capsaicinoids.

    Science.gov (United States)

    Lu, Muwen; Ho, Chi-Tang; Huang, Qingrong

    2017-01-01

    Capsaicinoids are active constituents responsible for the pungent and spicy flavor in chili peppers. During the past few decades, various extraction methods of capsaicinoids from peppers have been developed with high yields. Through biological studies, pharmacological benefits have been reported such as pain relief, antiinflammation, anticancer, cardio-protection, as well as weight loss. In this paper, the extraction methods and bioavailability of capsaicinoids are reviewed and discussed. In addition, the pharmacological effects and their underlying mechanisms are also studied. Copyright © 2016. Published by Elsevier B.V.

  19. Animal bioavailability of defined xenobiotic lignin metabolites

    International Nuclear Information System (INIS)

    Sandermann, H. Jr.; Arjmand, M.; Gennity, I.; Winkler, R.; Struble, C.B.; Aschbacher, P.W.

    1990-01-01

    Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U- 14 C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U- 14 C]chloroaniline/lignin metabolites

  20. Enhanced Bioavailable Contaminant Stripping (EBCS: metal bioavailability for evaluation of phytoextraction success

    Directory of Open Access Journals (Sweden)

    Petruzzelli G.

    2013-04-01

    Full Text Available Phytoextraction may be applied at field scale when the removal of bioavailable metals is the specific target of the technology. Residual metals in soil can be considered substantially inert or to be evaluated by site specific risk analysis.

  1. In utero and lactational exposure to low-dose genistein-vinclozolin mixture affects the development and growth factor mRNA expression of the submandibular salivary gland in immature female rats.

    Science.gov (United States)

    Kouidhi, Wided; Desmetz, Catherine; Nahdi, Afef; Bergès, Raymond; Cravedi, Jean-Pierre; Auger, Jacques; El May, Michèle; Canivenc-Lavier, Marie Chantal

    2012-06-01

    It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex-dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor α was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67-positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor α expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures.

  2. Combinatorial effects of genistein and sex-steroids on the level of cystic fibrosis transmembrane regulator (CFTR), adenylate cyclase (AC) and cAMP in the cervix of ovariectomised rats.

    Science.gov (United States)

    Salleh, Naguib; Ismail, Nurain; Muniandy, Sekaran; Korla, Praveen Kumar; Giribabu, Nelli

    2015-12-01

    The combinatorial effects of genistein and estrogen (E) or estrogen plus progesterone (E+P) on CFTR, AC and cAMP levels in cervix were investigated. Ovariectomised adult female rats received 50 or 100mg/kg/day genistein with E or E followed by E+P [E+(E+P)] for seven consecutive days. Cervixes were harvested and analyzed for CFTR mRNA levels by Real-time PCR. Distribution of AC and CFTR proteins in endocervix were observed by immunohistochemistry. Levels of cAMP were measured by enzyme-immunoassay. Molecular docking predicted interaction between genistein and AC. Our results indicate that levels of CFTR, AC and cAMP in cervix of rats receiving genistein plus E were higher than E-only treatment (pcervix of E and E+(E+P)-treated rats by genistein could affect the cervical secretory function which could influence the female reproductive processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Waste management in Greater Vancouver

    Energy Technology Data Exchange (ETDEWEB)

    Carrusca, K. [Greater Vancouver Regional District, Burnaby, BC (Canada); Richter, R. [Montenay Inc., Vancouver, BC (Canada)]|[Veolia Environmental Services, Vancouver, BC (Canada)

    2006-07-01

    An outline of the Greater Vancouver Regional District (GVRD) waste-to-energy program was presented. The GVRD has an annual budget for solid waste management of $90 million. Energy recovery revenues from solid waste currently exceed $10 million. Over 1,660,00 tonnes of GVRD waste is recycled, and another 280,000 tonnes is converted from waste to energy. The GVRD waste-to-energy facility combines state-of-the-art combustion and air pollution control, and has processed over 5 million tonnes of municipal solid waste since it opened in 1988. Its central location minimizes haul distance, and it was originally sited to utilize steam through sales to a recycle paper mill. The facility has won several awards, including the Solid Waste Association of North America award for best facility in 1990. The facility focuses on continual improvement, and has installed a carbon injection system; an ammonia injection system; a flyash stabilization system; and heat capacity upgrades in addition to conducting continuous waste composition studies. Continuous air emissions monitoring is also conducted at the plant, which produces a very small percentage of the total air emissions in metropolitan Vancouver. The GVRD is now seeking options for the management of a further 500,000 tonnes per year of solid waste, and has received 23 submissions from a range of waste energy technologies which are now being evaluated. It was concluded that waste-to-energy plants can be located in densely populated metropolitan areas and provide a local disposal solution as well as a source of renewable energy. Other GVRD waste reduction policies were also reviewed. refs., tabs., figs.

  4. Influence of lifestyle on vitamin bioavailability.

    Science.gov (United States)

    van den Berg, Henk; van der Gaag, Martijn; Hendriks, Henk

    2002-01-01

    In this review the effects of lifestyle factors, especially alcohol consumption, on vitamin bioavailability are summarized and discussed. Alcohol effects are clearly dose-dependent. Excessive chronic alcohol intake is generally associated with vitamin deficiency (especially folate, thiamine, and vitamin B6) due to malnutrition, malabsorption, and ethanol toxicity. Effects of moderate alcohol use are mainly explained by a lower vitamin intake. In the case of vitamin A and beta-carotene, effects on post-absorptive (lipoprotein) metabolism have been demonstrated. In one diet-controlled crossover study, alcohol consumption resulted in an increase in the plasma vitamin B6 (PLP) content, especially after beer consumption (containing vitamin B6), but also after wine and spirit consumption (not containing vitamin B6). Smoking is also associated with a lower dietary vitamin intake. In the case of vitamin C, B12, folate, and beta-carotene, evidence has been presented for effects on postabsorptive metabolism, due to smoke-induced oxidative stress and/or vitamin inactivation. For vitamin E a direct effect of smoking on absorption has been demonstrated. There is no convincing evidence that low-fat diets negatively affect fat-soluble vitamin absorption, but cholesterol-lowering compounds (diets), or unabsorbable fat substitutes, may do so. Vitamin bioavailability may be compromised from certain vegetables (particularly raw), and/or from high-fiber foods, because of limited digestion and inefficient release of vitamins from the food matrix.

  5. Solubility and bioavailability improvement of pazopanib hydrochloride.

    Science.gov (United States)

    Herbrink, Maikel; Groenland, Stefanie L; Huitema, Alwin D R; Schellens, Jan H M; Beijnen, Jos H; Steeghs, Neeltje; Nuijen, Bastiaan

    2018-06-10

    The anti-cancer drug pazopanib hydrochloride (PZH) has a very low aqueous solubility and a variable oral bioavailability. A new pharmaceutical formulation with an improved solubility may enhance the bioavailability and reduce the variability. A broad selection of polymer excipients was tested for their compatibility and solubilizing properties by conventional microscopic, thermal and spectrometric techniques. A wet milling and mixing technique was used to produce homogenous powder mixtures. The dissolution properties of the formulation were tested by a pH-switch dissolution model. The final formulation was tested in vivo in cancer patient following a dose escalation design. Of the tested mixture formulations, the one containing the co-block polymer Soluplus® in a 8:1 ratio with PZH performed best in terms of in vitro dissolution properties. The in vivo results indicated that 300 mg of the developed formulation yields similar exposure and a lower variability (379 μg/mL∗h (36.7% CV)) than previously reported values for the standard PZH formulation (Votrient®) at the approved dose of 800 mg. Furthermore, the expected plasma-C through levels (27.2 μg/mL) exceeds the defined therapeutic efficacy threshold of 20 μg/mL. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Estimating Lead (Pb) Bioavailability In A Mouse Model

    Science.gov (United States)

    Children are exposed to Pb through ingestion of Pb-contaminated soil. Soil Pb bioavailability is estimated using animal models or with chemically defined in vitro assays that measure bioaccessibility. However, bioavailability estimates in a large animal model (e.g., swine) can be...

  7. Protein and amino acid bioavailability estimates for canine foods

    NARCIS (Netherlands)

    Hendriks, W.H.; Bakker, E.J.; Bosch, G.

    2015-01-01

    Estimates of nutrient bioavailability are required for establishing dietary nutrient requirements and to evaluate the nutritional value of food ingredients or foods that are exposed to processing or extended storage. This study aimed to generate estimates for the bioavailability of dietary CP and AA

  8. The bioavailability of oxalate from Oca (Oxalis tuberosa).

    Science.gov (United States)

    Albihn, P B; Savage, G P

    2001-08-01

    It is believed that soluble oxalate has higher bioavailability than insoluble oxalate. Oca (Oxalis tuberosa) is moderately high in oxalate and contains oxalate in soluble form only. We estimated the bioavailability of oxalate in oca based on the urinary excretion of oxalate after oxalate loading with oca to estimate the bioavailability of oxalate in oca. We also clarified whether bioavailability differs in various oxalate loads from the same food source and studied the effect of an additional calcium source on the bioavailability of oxalate from oca. Four men and 4 women ingested 50, 100 and 150 gm. oca as well as 100 gm. oca with 100 gm. sour cream. Oxalate was measured in a 6-hour urine sample from each volunteer. The mean bioavailability of oxalate from oca plus or minus standard deviation was 1.44% +/- 1.31% during the 6-hour period after intake. There was no significant difference in oxalate bioavailability among oxalate intake levels in this study, although oca consumption with sour cream significantly decreased the uptake of oxalate (p oca appears to be similar to that in spinach. However, bioavailability varies among individuals and depends on other constituents of a combined meal.

  9. Computational modeling of human oral bioavailability: what will be next?

    Science.gov (United States)

    Cabrera-Pérez, Miguel Ángel; Pham-The, Hai

    2018-06-01

    The oral route is the most convenient way of administrating drugs. Therefore, accurate determination of oral bioavailability is paramount during drug discovery and development. Quantitative structure-property relationship (QSPR), rule-of-thumb (RoT) and physiologically based-pharmacokinetic (PBPK) approaches are promising alternatives to the early oral bioavailability prediction. Areas covered: The authors give insight into the factors affecting bioavailability, the fundamental theoretical framework and the practical aspects of computational methods for predicting this property. They also give their perspectives on future computational models for estimating oral bioavailability. Expert opinion: Oral bioavailability is a multi-factorial pharmacokinetic property with its accurate prediction challenging. For RoT and QSPR modeling, the reliability of datasets, the significance of molecular descriptor families and the diversity of chemometric tools used are important factors that define model predictability and interpretability. Likewise, for PBPK modeling the integrity of the pharmacokinetic data, the number of input parameters, the complexity of statistical analysis and the software packages used are relevant factors in bioavailability prediction. Although these approaches have been utilized independently, the tendency to use hybrid QSPR-PBPK approaches together with the exploration of ensemble and deep-learning systems for QSPR modeling of oral bioavailability has opened new avenues for development promising tools for oral bioavailability prediction.

  10. ASSESSING SOIL ARSENIC BIOAVAILABILITY IN THE LABORATORY MOUSE

    Science.gov (United States)

    Variation among soils in the bioavailability of arsenic can be a critical determinant of the risk posed by exposure to these soils. Although in vitro techniques can provide vital data on aspects of bioavailability of metals and metalloids from soils, these results must be valida...

  11. In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.

    Science.gov (United States)

    El Sheikh Saad, H; Toullec, A; Vacher, S; Pocard, M; Bieche, I; Perrot-Applanat, M

    2013-02-01

    Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspring mammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells during mammary gland morphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles.

  12. The influence of particles on bioavailability and toxicity of pesticides in surface water.

    Science.gov (United States)

    Knauer, Katja; Homazava, Nadzeya; Junghans, Marion; Werner, Inge

    2017-07-01

    Environmental risk assessment is an essential part of the approval process for pesticides. Exposure concentrations are compared with ecotoxicological data obtained from standardized laboratory studies and, if available, from field studies to determine the risk of a substance or formulation for aquatic communities. Predicted concentrations in surface waters are derived using, for example, the European FOrum for the Co-ordination of pesticide fate models and their USe (FOCUS) or the German Exposit models, which distinguish between exposure to dissolved and particle-associated pesticide concentrations, because the dissolved concentration is thought to be the best predictor of bioavailability and toxicity. Water and particle-associated concentrations are estimated based on the organic carbon-water partitioning coefficient (K OC ). This review summarizes published information on the influence of natural suspended solids on bioavailability and toxicity of pesticides to aquatic organisms (algae, invertebrates and fish), and the value of log K OC and log K OW (octanol-water coefficient) as sole predictors of the bioavailable fraction is discussed. The information showed that: 1) the quality and origin of suspended solids played an important role in influencing pesticide bioavailability and toxicity; 2) a decrease in toxicity due to the presence of suspended solids was shown only for pyrethroid insecticides with log K OW greater than 5, but the extent of this reduction depended on particle concentration and size, and potentially also on the ecotoxicological endpoint; 3) for pesticides with a log K OW less than 3 (e.g., triazines, carbamates, and organophosphates), the impact of particles on bioavailability and toxicity is small and species dependent; and 4) pesticide bioavailability is greatly influenced by the test species and their physiology (e.g., feeding behavior or digestion). We conclude that exposure of aquatic organisms to pesticides and environmental risk of many

  13. Bioavailability of magnetic nanoparticles to the brain

    International Nuclear Information System (INIS)

    Huang, B.-R.; Chen, P.-Y.; Huang, C.-Y.; Jung, S.-M.; Ma, Y.-H.; Wu, Tony; Chen, J.-P.; Wei, K.-C.

    2009-01-01

    This study investigates the bioavailability of carboxymethyl dextran-coated magnetic nanoparticles (CMD-MNP) to the brain. The cytotoxicity of CMD-MNP was assessed by co-culture with C6, a rat glioma cell line. To investigate the effects of an external magnetic field on the biodistribution of nanoparticles in a rat model, a magnet of 0.3 Tesla was applied externally over the cranium and the particles injected via the external jugular vein. Nanoparticles were also injected into rats implanted with C6 tumor cells. Staining of histological samples with Prussian blue to detect iron particles revealed that the external magnetic field enhanced the aggregation of nanoparticles in the rat brain; this enhancement was even more pronounced in the tumor region.

  14. Biodisponibilidade do licopeno Bioavailability of lycopene

    Directory of Open Access Journals (Sweden)

    Bettina Moritz

    2006-04-01

    Full Text Available Esta revisão procura reunir diversos estudos que avaliam os fatores que influenciam a biodisponibilidade do licopeno, bem como os alimentos fontes e a recomendação de ingestão desse carotenóide. Para tanto, foi realizado um levantamento bibliográfico, mediante consulta às bases de dados Medline (National Library of Medicine, USA e Lilacs (Bireme, Brasil nas quais foram selecionadas publicações científicas em português e inglês, nos últimos quinze anos, que utilizaram os temas: licopeno, carotenóides e/ou biosponibilidade. O licopeno é um carotenóide sem atividade de pró-vitamina A, mas um potente antioxidante, sendo essa função possivelmente associada à redução do risco da ocorrência do câncer e certas doenças crônicas. Esse nutriente é encontrado em um número limitado de alimentos, e, além disso, o organismo não é capaz de sintetizá-lo; dessa forma, o licopeno é obtido exclusivamente por meio da dieta alimentar. A quantidade sugerida de ingestão de licopeno varia de 4 a 35mg/dia. Estudos mostram que existem vários fatores que podem interferir na biodisponibilidade do licopeno, tais como absorção intestinal, quantidade de licopeno no alimento fonte, formas de apresentação (isômeros e sintéticos, presença da matriz alimentar, presença de outros nutrientes na refeição (como gordura, fibra, outros carotenóides, entre outros, ingestão de drogas, processamento do alimento, além da individualidade biológica e do estado nutricional do indivíduo. Estudos da biodisponibilidade do licopeno têm sido desenvolvidos a partir do tomate e seus produtos, por esse ser a fonte mais comumente consumida. O desenvolvimento do estudo enfatizou a importância da melhor forma de absorção desse nutriente, relevante que é para a prevenção de inúmeras doenças.This review collets several papers that evaluated the factors that influence the bioavailability of licopene, as well as the food sources of this nutrient and

  15. Bioavailability of magnetic nanoparticles to the brain

    Energy Technology Data Exchange (ETDEWEB)

    Huang, B.-R. [Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fushing Street, Kweishan, Taoyuan 333, Taiwan (China); Chen, P.-Y. [Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fushing Street, Kweishan, Taoyuan 333, Taiwan (China); Graduate Institute of Biomedical Sciences, Chang-Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Taoyuan 333, Taiwan (China); Huang, C.-Y. [Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fushing Street, Kweishan, Taoyuan 333, Taiwan (China); Jung, S.-M. [Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fushing Street, Kweishan, Taoyuan 333, Taiwan (China); Ma, Y.-H. [Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan (China); Wu, Tony [Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 5 Fushing Street, Kweishan, Taoyuan 333, Taiwan (China); Chen, J.-P. [Department of Chemical and Material Engineering, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan (China)], E-mail: jpchen@mail.cgu.edu.tw; Wei, K.-C. [Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 5 Fushing Street, Kweishan, Taoyuan 333, Taiwan (China)], E-mail: kuochenwei@adm.cgmh.org.tw

    2009-05-15

    This study investigates the bioavailability of carboxymethyl dextran-coated magnetic nanoparticles (CMD-MNP) to the brain. The cytotoxicity of CMD-MNP was assessed by co-culture with C6, a rat glioma cell line. To investigate the effects of an external magnetic field on the biodistribution of nanoparticles in a rat model, a magnet of 0.3 Tesla was applied externally over the cranium and the particles injected via the external jugular vein. Nanoparticles were also injected into rats implanted with C6 tumor cells. Staining of histological samples with Prussian blue to detect iron particles revealed that the external magnetic field enhanced the aggregation of nanoparticles in the rat brain; this enhancement was even more pronounced in the tumor region.

  16. In vitro and in vivo evaluation of capsaicin-loaded microemulsion for enhanced oral bioavailability.

    Science.gov (United States)

    Zhu, Yuan; Zhang, Jiajia; Zheng, Qianfeng; Wang, Miaomiao; Deng, Wenwen; Li, Qiang; Firempong, Caleb Kesse; Wang, Shengli; Tong, Shanshan; Xu, Ximing; Yu, Jiangnan

    2015-10-01

    Capsaicin, as a food additive, has attracted worldwide concern owing to its pungency and multiple pharmacological effects. However, poor water solubility and low bioavailability have limited its application. This study aims to develop a capsaicin-loaded microemulsion to enhance the oral bioavailability of the anti-neuropathic-pain component, capsaicin, which is poorly water soluble. In this study, the microemulsion consisting of Cremophor EL, ethanol, medium-chain triglycerides (oil phase) and water (external phase) was prepared and characterized (particle size, morphology, stability and encapsulation efficiency). The gastric mucosa irritation test of formulated capsaicin was performed in rats to evaluate its oral feasibility, followed by the pharmacokinetic study in vivo. Under these conditions, the encapsulated capsaicin revealed a faster capsaicin release in vitro coupled with a greater absorption in vivo when compared to the free capsaicin. The oral bioavailability of the formulated capsaicin-loaded microemulsions was 2.64-fold faster than that of free capsaicin. No significant irritation was observed on the mucosa from the pathological section of capsaicin-loaded microemulsion treated stomach. These results indicate that the developed microemulsion represents a safe and orally effective carrier for poorly soluble substances. The formulation could be used for clinical trials and expand the application of capsaicin. © 2014 Society of Chemical Industry.

  17. Enhanced oral bioavailability and controlled release of dutasteride by a novel dry elixir.

    Science.gov (United States)

    Jang, Dong-Jin; Kim, Sung Tae; Oh, Euichaul; Ban, Eunmi

    2014-01-01

    To develop a solid dosage form of dutasteride for improving its oral bioavailability, a novel dry elixir (DE) system was fabricated. DEs incorporating dextrin and/or xanthan gum were prepared using spray-drying and evaluated by morphology, ethanol content, crystallinity, dissolution and oral bioavailability. DEs were spherical with a smooth surface and had an average particle size of 20-25 μm. The ethanol content could be easily varied by controlling the spray-drying temperature. The dissolution profiles of dutasteride from each DE proved to be much faster than that of dutasteride powder due to the amorphous state and a high amount of incorporated ethanol. In particular, the pharmacokinetic profiles of dutasteride were significantly altered depending on the proportions of dextrin and xanthan gum. Blood concentrations of dutasteride from DE formulations were similar to those of market products and much greater than those of native dutasteride. Interestingly, the dissolution and pharmacokinetic profiles were easily controlled by changing the ratio of dextrin to xanthan gum. The data suggests that a DE using dextrin and/or xanthan gum could provide an applicable solid dosage form to improve the dissolution and bio-availability of dutasteride as well as to modulate its pharmacokinetics.

  18. Coamorphous Loratadine-Citric Acid System with Enhanced Physical Stability and Bioavailability.

    Science.gov (United States)

    Wang, Jin; Chang, Ruimiao; Zhao, Yanan; Zhang, Jiye; Zhang, Ting; Fu, Qiang; Chang, Chun; Zeng, Aiguo

    2017-10-01

    Coamorphous systems using citric acid as a small molecular excipient were studied for improving physical stability and bioavailability of loratadine, a BCS class II drug with low water solubility and high permeability. Coamorphous loratadine-citric acid systems were prepared by solvent evaporation technique and characterized by differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy. Solid-state analysis proofed that coamorphous loratadine-citric acid system (1:1) was amorphous and homogeneous, had a higher T g over amorphous loratadine, and the intermolecular hydrogen bond interactions between loratadine and citric acid exist. The solubility and dissolution of coamorphous loratadine-citric acid system (1:1) were found to be significantly greater than those of crystalline and amorphous form. The pharmacokinetic study in rats proved that coamorphous loratadine-citric acid system (1:1) could significantly improve absorption and bioavailability of loratadine. Coamorphous loratadine-citric acid system (1:1) showed excellently physical stability over a period of 3 months at 25°C under 0% RH and 25°C under 60% RH conditions. The improved stability of coamorphous loratadine-citric acid system (1:1) could be related to an elevated T g over amorphous form and the intermolecular hydrogen bond interactions between loratadine and citric acid. These studies demonstrate that the developed coamorphous loratadine-citric acid system might be a promising oral formulation for improving solubility and bioavailability of loratadine.

  19. Bioavailability of the Nano-Unit 14C-Agrochemicals Under Various Water Potential.

    Science.gov (United States)

    Jung, S C; Kim, H G; Kuk, Y I; Ahn, H G; Senseman, S A; Lee, D J

    2015-08-01

    The study was conducted to investigate the effects of water potential on bioavailability of the nano-unit 14C-cafenstrole, 14C-pretilachlor, 14C-benfuresate, 14C-simetryn and 14C-oxyfluorfen applied with or without dimepiperate or daimuron under various water potential conditions. The highest bioavailable concentration in soil solution (BCSS) was found at 60% soil moisture, while the lowest occurred at 50% soil moisture for soil-applied alone or in combination. All water potential conditions differed significantly from each other with variations in total bioavailable amount in soil solution (TBSS) when either dimepiperate or daimuron were added to the soil, and changes were directly proportional to variations in water potential. Across all treatments, TBSS at 80% soil moisture was three to four times greater than that at 50% soil moisture when applied alone or in combination with dimepiperate or daimuron. Cafenstrole and simetryn had distribution coefficient (Kd) values <64 ml g-1 and a TBSS ranging from 10 to 44 ng g-1 soil, regardless of water potential conditions applied alone or in combination. Pretilachlor and benfuresate had Kd values <15 ml g-1 and a TBSS range of 38 to 255 ng g-1 soil when applied with or without dimepiperate or daimuron.

  20. Gender differences on bioavailability of ofloxacin

    International Nuclear Information System (INIS)

    Hassan, Z.U.; Naseer, R.

    2008-01-01

    The fluoroquinolones are currently enjoying extensive worldwide clinical applications because of their good bioavailability and pharmacokinetic profile. Investigation into several aspects of the pharmacokinetic of all clinically relevant fluoroquinolones, have been carried out notably in Europe, USA and Japan. In view of the geonetical (geographical influences on genetics-pharmacogenetics) differences, it is important that for the optimal therapeutic outcome, biodisposition studies on drugs are better conducted in the population and environments where wide and extensive use of the drug is anticipated. The Objectives of study were to see the pharmacokinetic parameters in healthy young male and female volunteers. This comparative study was conducted King Edward Medical University, Lahore, Pakistan, from July 2005 to December 2005. In Pakistan where the use of antibiotics is more frequent by the general practitioners it is important to elucidate certain dose parameters it is also noticed that side effects are more in females than males so present study is conducted to calculate any differences in bioavailability on the basis of sex. The pharmacokinetic parameters of ofloxacin were determined in each of the clinically health eight young girls and boys (mean age 23.9 and 25.1 years, respectively) following a single oral dose of 400 mg tablet. The method adopted was microbiological assay. The blood samples collected at predetermined time intervals after drug administration revealed almost twice as high concentration of the drug in plasma of the girls than that in the boys. The pharmacokinetic parameters revealed significantly (p<0.01) higher values for area under curve (AUC) and Cmax, and lower total body clearance (TBC) and volume of distribution in the girls than in the boys. The gender differences in pharmacokinetic parameters indicate that the dose adjustment should be considered in male and female. (author)

  1. Assessing the bioavailability and risk from metal-contaminated ...

    Science.gov (United States)

    Exposure to contaminated soil and dust is an important pathway in human health risk assessment. Physical and chemical characteristics, as well as biological factors, determine the bioaccessibility/bioavailability of soil and dust contaminants. Within a single sample, contamination may arise from multiple sources of toxic elements that may exist as different forms (species) which impact bioavailability. In turn, the bioaccessibility/bioavailability of soil and dust contaminants has a direct impact on human health risk assessment and risk management practices. Novel research efforts focusing on development and application of in vitro and in vivo methods to measure the bioaccessibility/bioavailability of metal contaminated soils have advanced in the past few years. The objective of this workshop was to focus on recent developments in assessing the bioaccessibility/bioavailability of arsenic contaminated soils, metal contamination in urban residences in Canada and potential children’s exposures to toxic elements in house dust, a community-based study known as the West Oakland Residential Lead Assessment , studies of the bioavailability of soil cadmium, chromium, nickel and mercury and human exposures to contaminated Brownfield soils. These presentations covered issues related to human health and bioavailability along with the most recent studies on community participation in assessing metal contamination, studies of exposures to residential contamination, and

  2. Bioavailability of zinc, copper, and manganese from infant diets

    International Nuclear Information System (INIS)

    Bell, J.G.

    1987-01-01

    A series of trace element absorption experiments were performed using the Sprague-Dawley suckling rat put and infant rhesis monkey (Macaca mulatta) with extrinsic radiolabeling to assess the bioavailability of Zn, Cu, and Mn from infant diets and to examine specific factors that affect absorption of these essential nutrients. Bioavailability of Cu as assessed by 6 h liver uptake (% of 64 Cu dose) was highest from human milk and cow milk based formula and significantly lower from cow milk and soy based formula. Copper bioavailability from infant cereal products as assessed by whole body uptake (% of 64 Cu dose) in d 20 rats, 9 h postintubation, was low compared to the bioavailability from cow milk or human milk alone. 65 Zn uptake in d 20 rats, 9 h postintubation, was significantly lower from cereals fed alone or in combination with cow or human milk as compared to the uptake from the milks fed alone. Zn bioavailability varied among cereal diets, (lowest from cereals containing phytate and highest from cereal/fruit products). Mn bioavailability from infant diets was assessed using a modified suckling rat pup model. Bioavailability (24 h whole body retention of 54 Mn) was high from all milks and commercial formulas tested

  3. Bioavailability and soil-to-crop transfer of heavy metals in farmland soils: A case study in the Pearl River Delta, South China.

    Science.gov (United States)

    Zhang, Jingru; Li, Huizhen; Zhou, Yongzhang; Dou, Lei; Cai, Limei; Mo, Liping; You, Jing

    2018-04-01

    Soil-bound heavy metals are of great concern for human health due to the potential exposure via food chain transfer. In the present study, the occurrence, the bioavailability and the soil-to-crop transfer of heavy metals in farmland soils were investigated based on data from two agricultural areas, i.e. Sihui and Shunde in South China. Six heavy metals (As, Cu, Hg, Mn, Ni and Pb) were quantified in the farmland soils. The mean single pollution level indices (PI) were all lower than 1 except for Hg in soils from Shunde (PI = 1.51 ± 0.46), suggesting the farmland soils were within clean and slightly polluted by heavy metals. As, Cu, Ni and Pb were found to be mostly present in the non-bioavailable form. The majority of Hg was considered potentially bioavailable, and Mn was found to be largely bioavailable. Soil pH was an important factor influencing bioavailability of soil-bound heavy metals. The concentrations of heavy metals in vegetables from Sihui and Shunde were within the food hygiene standards, while the rice grain from Sihui was polluted by Pb (PI = 10.3 ± 23.4). Total soil concentrations of heavy metals were not correlated to their corresponding crop concentrations, instead, significant correlations were observed for bioavailable concentrations in soil. The results supported the notion that the bioavailability of the investigated heavy metals in the soil was largely responsible for their crop uptake. The soil-to-crop transfer factors based on bioavailable concentrations suggested that Cu, As and Hg in soils of the study area had greater tendency to be accumulated in the vegetables than other heavy metals, calling for further human health assessment by consuming the contaminated crops. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The effect of dietary factors on strawberry anthocyanins oral bioavailability.

    Science.gov (United States)

    Xiao, Di; Sandhu, Amandeep; Huang, Yancui; Park, Eunyoung; Edirisinghe, Indika; Burton-Freeman, Britt M

    2017-11-15

    Strawberries are a dietary source of anthocyanins, particularly pelargonidin glycosides. Dietary anthocyanins have received increasing attention among researchers and consumers due to their health benefits. The oral bioavailability of anthocyanins is reported to be low and various dietary factors may influence their oral bioavailability further. Milk is suggested to reduce (poly)phenols' oral bioavailability. However, the effect of milk on anthocyanin oral bioavailability remains uncertain. Likewise, mixed nutrient meals may influence the oral bioavailability of anthocyanins. Therefore, the purpose of this study was to assess the effect of milk on the oral bioavailability and other pharmacokinetic (PK) variables of strawberry anthocyanins consumed with and without a meal. Nine healthy participants consumed a strawberry beverage prepared in milk or water with a standard meal on two occasions. On two additional occasions, the beverages were given to a subset (n = 4) of participants to determine the impact of the meal on anthocyanin PK variables, including oral bioavailability. Independent of the meal, beverages prepared in milk significantly reduced the peak plasma concentrations (C max ) of pelargonidin-3-O-glucoside (P-3-G), pelargonidin-glucuronide (PG) and pelargonidin-3-O-rutinoside (P-3-R), as well as the PG and P-3-R area under the curve (AUC) (p bioavailability of pelargonidin anthocyanins under meal conditions; however, the oral relative bioavailability of pelargonidin anthocyanins was reduced by ∼50% by milk under without meal conditions (p < 0.05). Consuming strawberry beverages made with milk and consuming those made with water with and without a meal influenced different aspects of strawberry anthocyanin PKs. The significance of this effect on clinical efficacy requires additional research.

  5. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy.

    Science.gov (United States)

    Rein, Maarit J; Renouf, Mathieu; Cruz-Hernandez, Cristina; Actis-Goretta, Lucas; Thakkar, Sagar K; da Silva Pinto, Marcia

    2013-03-01

    Bioavailability is a key step in ensuring bioefficacy of bioactive food compounds or oral drugs. Bioavailability is a complex process involving several different stages: liberation, absorption, distribution, metabolism and elimination phases (LADME). Bioactive food compounds, whether derived from various plant or animal sources, need to be bioavailable in order to exert any beneficial effects. Through a better understanding of the digestive fate of bioactive food compounds we can impact the promotion of health and improvement of performance. Many varying factors affect bioavailability, such as bioaccessibility, food matrix effect, transporters, molecular structures and metabolizing enzymes. Bioefficacy may be improved through enhanced bioavailability. Therefore, several technologies have been developed to improve the bioavailability of xenobiotics, including structural modifications, nanotechnology and colloidal systems. Due to the complex nature of food bioactive compounds and also to the different mechanisms of absorption of hydrophilic and lipophilic bioactive compounds, unravelling the bioavailability of food constituents is challenging. Among the food sources discussed during this review, coffee, tea, citrus fruit and fish oil were included as sources of food bioactive compounds (e.g. (poly)phenols and polyunsaturated fatty acids (PUFAs)) since they are examples of important ingredients for the food industry. Although there are many studies reporting on bioavailability and bioefficacy of these bioactive food components, understanding their interactions, metabolism and mechanism of action still requires extensive work. This review focuses on some of the major factors affecting the bioavailability of the aforementioned bioactive food compounds. © 2012 Nestec S. A.. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  6. On definition and use of the term bioavailability.

    Science.gov (United States)

    Rescigno, A; Thakur, A K; Marzo, A

    1994-10-01

    In common usage, the rate of absorption of an active ingredient or its therapeutic moiety is generally not mentioned in the context of bioavailability. In this communication it is shown that exclusion of the rate of absorption may have serious consequence on the interpretation of bioavailability depending on the underlying model for the system under study. In the case of endogenous substances, the term "bioavailability" is ambiguous unless one specifies whether it refers to availability of the exogenous substance only or the sum total of the exogenous and endogenous substances.

  7. In vitro effects of diethylstilbestrol, genistein, 4-tert-butylphenol, and 4-tert-octylphenol on steroidogenic activity of isolated immature rat ovarian follicles

    International Nuclear Information System (INIS)

    Myllymaeki, Sari; Haavisto, Tapio; Vainio, Minna; Toppari, Jorma; Paranko, Jorma

    2005-01-01

    Isolated rat ovarian follicles grow and produce steroid hormones in vitro and so provide a good model for studying the effects of hormonally active compounds on follicular steroidogenesis. We have evaluated the effects of diethylstilbestrol (DES), genistein (GEN) and two alkylphenols, 4-tert-butylphenol (BP) and 4-tert-octylphenol (OP) on the growth, survival, and steroid hormone and cAMP production by isolated 14-day-old rat (Sprague-Dawley) ovarian follicles. During a 5-day culture, FSH was obligatory for follicle growth and increased estradiol and testosterone secretion in a dose-dependent manner. DES (10 -6 M) caused the strongest decline in estradiol and testosterone levels but did not have detectable effects on either cAMP production or aromatase enzyme activity. GEN caused a prominent decrease in cAMP and testosterone levels without significant changes in secreted estradiol. The latter, apparently, was due to a dose-dependent stimulation of aromatase enzyme activity in the presence of genistein. Both BP and OP decreased estradiol and testosterone secretion in a dose-dependent manner while no effect on aromatase activity was observed. OP, unlike BP, decreased forskolin-induced cAMP levels. Xenoestrogens at the used concentrations did not interfere with the growth and survival of the follicles. The results indicate that isolated ovarian follicles representing intact morphological and functional units offer a sensitive model system for elucidating the female-specific reproductive effects of environmental chemicals

  8. Amyloid beta(1-40-induced astrogliosis and the effect of genistein treatment in rat: a three-dimensional confocal morphometric and proteomic study.

    Directory of Open Access Journals (Sweden)

    Maryam Bagheri

    Full Text Available Astrocytes are highly involved in regulation and homeostasis of the extracellular environment in the healthy brain. In pathological conditions, these cells play a major role in the inflammatory response seen in CNS tissues, which is called reactive astrogliosis and includes hypertrophy and proliferation of astrocytes. Here, we performed 3D confocal microscopy to evaluate the morphological response of reactive astrocytes positive for glial fibrillary acidic protein (GFAP in rats, to the presence of Aβ(1-40 in the rat brain before and after treatment with genistein. In 50 astrocytes per animal, we measured the volume and surface area for the nucleus, cell body, the entire cell, the tissue covered by single astrocytes and quantified the number and length of branches, the density of the astrocytes and the intensity of GFAP immunoreactivity. Injecting Aβ(1-40 into the brain of rats caused astrogliosis indicated by increased values for all measured parameters. Mass spectrometric analysis of hippocampal tissue in Aβ(1-40-injected brain showed decreased amounts of tubulins, enolases and myelin basic protein, and increased amounts of dihydropyrimidinase-related protein 2. In Aβ(1-40-injected rats pretreated with genistein, GFAP intensity was decreased to the sham-operated group level, and Aβ(1-40-induced astrogliosis was significantly ameliorated.

  9. Chronic dietary exposure to a low-dose mixture of genistein and vinclozolin modifies the reproductive axis, testis transcriptome, and fertility.

    Science.gov (United States)

    Eustache, Florence; Mondon, Françoise; Canivenc-Lavier, Marie Chantal; Lesaffre, Corinne; Fulla, Yvonne; Berges, Raymond; Cravedi, Jean Pierre; Vaiman, Daniel; Auger, Jacques

    2009-08-01

    The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood. We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility. Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays. The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the "neuroactive ligand-receptor interactions" family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production. Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose-albeit not environmental-of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility.

  10. Genistein, a general kinase inhibitor, as a potential antiviral for arenaviral hemorrhagic fever as described in the Pirital virus-Syrian golden hamster model.

    Science.gov (United States)

    Vela, Eric M; Knostman, Katherine A; Mott, Jason M; Warren, Richard L; Garver, Jennifer N; Vela, Lela Johnson; Stammen, Rachelle L

    2010-09-01

    Arenaviruses are rodent-borne negative strand RNA viruses and infection of these viruses in humans may result in disease and hemorrhagic fever. To date, supportive care, ribavirin, and in some cases immune plasma remain the foremost treatment options for arenaviral hemorrhagic fever. Research with the hemorrhagic fever causing-arenaviruses usually requires a Biosafety level (BSL)-4 environment; however, surrogate animal model systems have been developed to preliminarily study and screen various vaccines and antivirals. The Syrian golden hamster-Pirital virus (PIRV) surrogate model of hemorrhagic fever provides an opportunity to test new antivirals in an ABSL-3 setting. Thus, we challenged hamsters, implanted with telemetry, with PIRV and observed viremia and tissue viral titers, and changes in core body temperature, hematology, clinical chemistry, and coagulation parameters. Physical signs of disease of the PIRV-infected hamsters included weight loss, lethargy, petechial rashes, epistaxis, ocular orbital and rectal hemorrhage, and visible signs of neurologic disorders. However, treating animals with genistein, a plant derived isoflavone and general kinase inhibitor, resulted in increased survival rates and led to an improved clinical profile. In all, the results from this study demonstrate the potential of a general kinase inhibitor genistein as an antiviral against arenaviral hemorrhagic fever. 2010 Elsevier B.V. All rights reserved.

  11. Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability.

    Science.gov (United States)

    Parikh, Ankit; Kathawala, Krishna; Song, Yunmei; Zhou, Xin-Fu; Garg, Sanjay

    2018-05-29

    Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.

  12. Accumulation of genistein and daidzein, soybean isoflavones implicated in promoting human health, is significantly elevated by irrigation.

    Science.gov (United States)

    Bennett, John O; Yu, Oliver; Heatherly, Larry G; Krishnan, Hari B

    2004-12-15

    late-planted soybeans as much as 2.5-fold. Accumulation of individual isoflavones, daidzein and genistein, was also elevated by irrigation. Because this cultural practice improves the quality traits of seeds, ESPS provides an opportunity for enhancing the quality of soybean.

  13. Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl phthalate and genistein

    Directory of Open Access Journals (Sweden)

    Lian-Dong Zhang

    2013-01-01

    Full Text Available Studies of developmental effects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive effects of the co-administration of di-2-(ethylhexyl phthalate (DEHP and genistein (GEN during pregnancy and lactation were studied in male rat offspring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg/kg body weight (bwyday, GEN 50 mg/kg bwday, GEN 400 mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday + GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday. The outcomes studied were general morphometry (weight, AGD, testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coefficient, AGD / body weight1/3 י, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bwday, GEN(50mg/kg bwday or GEN(400mg/kg bwday alone were not significantly different from the control group. When exposed to (DEHP 250mg/kg bwday +GEN 50mg/kg bwday together during pregnancy and lactation, serum testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA expression significantly decreased compared to the control and GEN(50mg/kg bwday. When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday together during pregnancy and lactation, AGD / body weight1/3 י, serum testosterone concentration, testis and epididymis coefficient and Star, Cypal17a1 mRNA expression appeared significantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most significant alterations in the neonate, especially with GEN at high dose, although the effect of the DEHP

  14. Food synergies for improving bioavailability of micronutrients from plant foods.

    Science.gov (United States)

    Nair, K Madhavan; Augustine, Little Flower

    2018-01-01

    Plant foods are endowed with micronutrients but an understanding of bioavailability is essential in countries primarily dependent on plant based foods. Bioavailability depends majorly on food synergies. This review examines the nature of certain food synergies and methods to screen and establish it as a strategy to control micronutrient deficiency in the populations. Strong evidence on the synergistic effect of inclusion of vitamin C rich fruits and non-vegetarian foods in enhancing the bioavailability of iron has been demonstrated. Fat is found to be synergistic for vitamin A absorption. Red wine and protein have been explored for zinc absorption and effect of fat has been studied for vitamin D. Methods for screening of bioavailability, and biomarkers to demonstrate the synergistic effects of foods are required. Translation of food synergy as a strategy requires adaptation to the context and popularization of intelligent food synergies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Development of Bioavailability Adjustment Factors: A Feasibility Study

    National Research Council Canada - National Science Library

    Rembish, Steve

    2000-01-01

    The primary purpose of this effort is to investigate the feasibility of developing and using bioavailability adjustment factors to modify intake assumptions used in risk assessments on a site-specific basis...

  16. From bioavailability science to regulation of organic chemicals

    NARCIS (Netherlands)

    Ortega-Calvo, J.J.; Harmsen, J.; Parsons, J.R.; Semple, K.T.; Aitkin, M.D.; Ajao, C.; Eadsforth, C.; Galay-Burgos, M.; Naidu, R.; Oliver, R.; Peijnenburg, W.J.G.M.; Römbke, J.; Streck, G.; Versonnen, B.

    2015-01-01

    The bioavailability of organic chemicals in soil and sediment is an important area of scientific investigation for environmental scientists, although this area of study remains only partially recognized by regulators and industries working in the environmental sector. Regulators have recently

  17. Flavanol plasma bioavailability is affected by metabolic syndrome in rats

    NARCIS (Netherlands)

    Margalef, M.; Pons, Z.; Iglesias-Carres, L.; Bravo, F.I.; Muguerza, B.; Arola-Arnal, A.

    2017-01-01

    Flavanols, which exert several health benefits, are metabolized after ingestion. Factors such as the host physiological condition could affect the metabolism and bioavailability of flavanols, influencing their bioactivities. This study aimed to qualitatively evaluate whether a pathological state

  18. Candesartan cilexetil loaded nanodelivery systems for improved oral bioavailability.

    Science.gov (United States)

    Dudhipala, Narendar; Veerabrahma, Kishan

    2017-02-01

    Candesartan cilexetil (CC), an antihypertensive drug, has low oral bioavailability due to poor solubility and hepatic first-pass metabolism. These are major limitations in oral delivery of CC. Several approaches are known to reduce the problems of solubility and improve the bioavailability of CC. Among various approaches, nanotechnology-based delivery of CC has potential to overcome the challenges associated with the oral administration. This review focuses on various nano-based delivery systems available and tried for improving the aqueous solubility, dissolution and consequently bioavailability of CC upon oral administration. Of all, solid lipid nanoparticles appear to be promising delivery system, based on current reported results, for delivery of CC, as this system improved the oral bioavailability and possessed prolonged pharmacodynamic effect.

  19. Marine lipids and the bioavailability of omega-3 fatty acids

    DEFF Research Database (Denmark)

    Mu, Huiling; Müllertz, Anette

    2015-01-01

    of omega-3 fatty acids has been reported to be affected by several factors; among the important factors were the digestion and absorption processes of omega-3 containing lipids in the gastrointestinal tract. Both lipid structures and food structures can affect the bioavailability of omega-3 fatty acids....... In vitro studies provided a mechanistic understanding on the varied bioavailability caused by different lipid structures, the lower relative bioavailability of omega-3 fatty acids from FAEE formulation was closely related to the slower digestion rate of FAEE. Microencapsulated fish oil has often been used...... as a food additive because of its better chemical stability; studies showed that microencapsulation did not affect the bioavailability significantly. Even though food structures also affect the digestion and absorption of omega-3 containing lipids, several studies have shown that long-term intake of fish...

  20. Iron bioavailability: UK Food Standards Agency workshop report.

    Science.gov (United States)

    Singh, Mamta; Sanderson, Peter; Hurrell, Richard F; Fairweather-Tait, Susan J; Geissler, Catherine; Prentice, Ann; Beard, John L

    2006-11-01

    The UK Food Standards Agency convened a group of expert scientists to review current research investigating factors affecting iron status and the bioavailability of dietary iron. Results presented at the workshop show menstrual blood loss to be the major determinant of body iron stores in premenopausal women. In the presence of abundant and varied food supplies, the health consequences of lower iron bioavailability are unclear and require further investigation.

  1. Bioavailability of syrup and tablet formulations of cefetamet pivoxil.

    Science.gov (United States)

    Ducharme, M P; Edwards, D J; McNamara, P J; Stoeckel, K

    1993-12-01

    Two studies examining the bioavailability of cefetamet pivoxil in healthy male subjects were conducted. In the first, the bioavailabilities of the 250-mg (M250) and M500 tablet formulations of cefetamet pivoxil to be marketed were compared with that of a tablet used in clinical trials. All products were given with food at a dose of 500 mg. In the second study, the bioavailability of the syrup formulation was evaluated under both fasting and nonfasting conditions and compared with that of the M500 tablet formulation given with food. The absolute bioavailabilities of the M500 and M250 tablets (55.0% +/- 8.0% and 55.7% +/- 7.0%, respectively) were not significantly different from that of the clinical-trial formulation (49.8% +/- 8.5%). The newer tablet formulations exhibited faster absorption as evidenced by higher peak concentrations (3.8 [M500] and 3.9 [M250] mg/liter compared with 3.2 mg/liter for the clinical-trial formulation), a shorter time to peak concentration, and a shorter mean absorption time. The syrup formulation was found to have significantly lower absolute bioavailability (37.9% +/- 6.0%) compared with that of the M500 tablet (58.4% +/- 9.0%) when both were given with food. Food had no significant effect on the bioavailability of the syrup, which averaged 34.0% +/- 8.6% under fasting conditions, although absorption was delayed by food (mean absorption time increased from 2.2 to 3.9 h). This contrasts with the results of previous studies documenting significant increases in tablet bioavailability with food. Despite the lower bioavailability of the syrup, unbound-cefetamet concentrations are expected to remain above the MICs for 90% of the strains tested for susceptible organisms for approximately 10 h of the usual 12-h dosing interval with both syrup and tablet formulations of cefetamet pivoxil given with food.

  2. Bioaccessibility tests accurately estimate bioavailability of lead to quail

    Science.gov (United States)

    Beyer, W. Nelson; Basta, Nicholas T; Chaney, Rufus L.; Henry, Paula F.; Mosby, David; Rattner, Barnett A.; Scheckel, Kirk G.; Sprague, Dan; Weber, John

    2016-01-01

    Hazards of soil-borne Pb to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, we measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from five Pb-contaminated Superfund sites had relative bioavailabilities from 33%-63%, with a mean of about 50%. Treatment of two of the soils with phosphorus significantly reduced the bioavailability of Pb. Bioaccessibility of Pb in the test soils was then measured in six in vitro tests and regressed on bioavailability. They were: the “Relative Bioavailability Leaching Procedure” (RBALP) at pH 1.5, the same test conducted at pH 2.5, the “Ohio State University In vitro Gastrointestinal” method (OSU IVG), the “Urban Soil Bioaccessible Lead Test”, the modified “Physiologically Based Extraction Test” and the “Waterfowl Physiologically Based Extraction Test.” All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the RBALP pH 2.5 and OSU IVG tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter (24%), or present as Pb sulfate (18%). Additional Pb was associated with P (chloropyromorphite, hydroxypyromorphite and tertiary Pb phosphate), and with Pb carbonates, leadhillite (a lead sulfate carbonate hydroxide), and Pb sulfide. The formation of chloropyromorphite reduced the bioavailability of Pb and the amendment of Pb-contaminated soils with P may be a thermodynamically favored means to sequester Pb.

  3. Evaluation of Iodine Bioavailability in Seaweed Using in Vitro Methods.

    Science.gov (United States)

    Domínguez-González, M Raquel; Chiocchetti, Gabriela M; Herbello-Hermelo, Paloma; Vélez, Dinoraz; Devesa, Vicenta; Bermejo-Barrera, Pilar

    2017-09-27

    Due to the high levels of iodine present in seaweed, the ingestion of a large amount of this type of food can produce excessive intake of iodine. However, the food after ingestion undergoes different chemistry and physical processes that can modify the amount of iodine that reaches the systemic circulation (bioavailability). Studies on the bioavailability of iodine from food are scarce and indicate that the bioavailable amount is generally lower than ingested. Iodine in vitro bioavailability estimation from different commercialized seaweed has been studied using different in vitro approaches (solubility, dialyzability, and transport and uptake by intestinal cells). Results indicate that iodine is available after gastrointestinal digestion for absorption (bioaccessibility: 49-82%), kombu being the seaweed with the highest bioaccessibility. The incorporation of dialysis cell cultures to elucidate bioavailability modifies the estimation of the amount of iodine that may reach the systemic circulation (dialysis, 5-28%; cell culture, ≤3%). The paper discusses advantages and drawbacks of these methodologies for iodine bioavailability in seaweed.

  4. Bioavailability enhancement of atovaquone using hot melt extrusion technology.

    Science.gov (United States)

    Kate, Laxman; Gokarna, Vinod; Borhade, Vivek; Prabhu, Priyanka; Deshpande, Vinita; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

    2016-04-30

    Emerging parasite resistance and poor oral bioavailability of anti-malarials are the two cardinal issues which hinder the clinical success of malaria chemotherapy. Atovaquone-Proguanil is a WHO approved fixed dose combination used to tackle the problem of emerging resistance. However, Atovaquone is a highly lipophilic drug having poor aqueous solubility (less than 0.2 μg/ml) thus reducing its oral bioavailability. The aim of the present investigation was to explore hot melt extrusion (HME) as a solvent-free technique to enhance solubility and oral bioavailability of Atovaquone and to develop an oral dosage form for Atovaquone-Proguanil combination. Solid dispersion of Atovaquone was successfully developed using HME. The solid dispersion was characterized for DSC, FTIR, XRD, SEM, and flow properties. It was filled in size 2 hard gelatin capsules. The formulation showed better release as compared to Malarone® tablets, and 3.2-fold and 4.6-fold higher bioavailability as compared to Malarone® tablets and Atovaquone respectively. The enhanced bioavailability also resulted in 100% anti-malarial activity in murine infection model at 1/8(th) therapeutic dose. Thus the developed methodology shows promising potential to solve the problems associated with Atovaquone therapy, namely its high cost and poor oral bioavailability, resulting in increased therapeutic efficacy of Atovaquone. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Bioaccumulation and bioavailability of polybrominated diphynel ethers (PBDEs) in soil

    International Nuclear Information System (INIS)

    Liang Xianwei; Zhu Shuzhen; Chen Peng; Zhu Lingyan

    2010-01-01

    Earthworms were exposed to artificially contaminated soils of DE-71 and DE-79 to investigate the bioaccumulation and bioavailability of PBDEs in soil. All major congeners were bioavailable to earthworms. The uptake and elimination rate coefficients of PBDEs decreased with their logK ow s. The biota soil accumulation factors of PBDEs also declined with logK ow . These may be due to the large molecular size and the high affinity of PBDEs to soil particles. The concentrations extracted by Tenax for 6 h correlated very well with those found in earthworms, suggesting that the bioavailability of PBDEs in soil is related to the fraction of rapid desorption from soil. This also indicates that 6 h Tenax extraction is a good proxy for the bioavailability of PBDEs to earthworms in soil. The BSAFs of PBDEs in aged soil decreased 22-84% compared to freshly spiked soil, indicating that aging may diminish the bioavailability of PBDEs in soil significantly. - PBDEs are bioavailable to earthworms in soil and the uptake and elimination rate coefficients and BSAFs declined with their logK ow s.

  6. Bioaccumulation and bioavailability of polybrominated diphynel ethers (PBDEs) in soil

    Energy Technology Data Exchange (ETDEWEB)

    Liang Xianwei; Zhu Shuzhen; Chen Peng [College of Environmental Science and Engineering, Nankai University, Weijin Road 94, Tianjin 300071 (China); Key Laboratory of Pollution Processes and Environmental Criteria (Nankai University), Ministry of Education, Tianjin 300071 (China); Tianjin Key Laboratory of Urban Ecology Environmental Remediation and Pollution Control, Nankai University, Tianjin 300071 (China); Zhu Lingyan, E-mail: zhuly@nankai.edu.c [College of Environmental Science and Engineering, Nankai University, Weijin Road 94, Tianjin 300071 (China); Key Laboratory of Pollution Processes and Environmental Criteria (Nankai University), Ministry of Education, Tianjin 300071 (China); Tianjin Key Laboratory of Urban Ecology Environmental Remediation and Pollution Control, Nankai University, Tianjin 300071 (China)

    2010-07-15

    Earthworms were exposed to artificially contaminated soils of DE-71 and DE-79 to investigate the bioaccumulation and bioavailability of PBDEs in soil. All major congeners were bioavailable to earthworms. The uptake and elimination rate coefficients of PBDEs decreased with their logK{sub ow}s. The biota soil accumulation factors of PBDEs also declined with logK{sub ow}. These may be due to the large molecular size and the high affinity of PBDEs to soil particles. The concentrations extracted by Tenax for 6 h correlated very well with those found in earthworms, suggesting that the bioavailability of PBDEs in soil is related to the fraction of rapid desorption from soil. This also indicates that 6 h Tenax extraction is a good proxy for the bioavailability of PBDEs to earthworms in soil. The BSAFs of PBDEs in aged soil decreased 22-84% compared to freshly spiked soil, indicating that aging may diminish the bioavailability of PBDEs in soil significantly. - PBDEs are bioavailable to earthworms in soil and the uptake and elimination rate coefficients and BSAFs declined with their logK{sub ow}s.

  7. Endogenous estrogen status, but not genistein supplementation, modulates 7,12-dimethylbenz[a]anthracene-induced mutation in the liver cII gene of transgenic big blue rats.

    Science.gov (United States)

    Chen, Tao; Hutts, Robert C; Mei, Nan; Liu, Xiaoli; Bishop, Michelle E; Shelton, Sharon; Manjanatha, Mugimane G; Aidoo, Anane

    2005-06-01

    A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12-dimethylbenz[a]anthracene (DMBA)-induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical-specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA-induced mutagenesis in either intact or ovariectomized rats.

  8. Enhancement of Curcumin Bioavailability Using Nanocellulose Reinforced Chitosan Hydrogel

    Directory of Open Access Journals (Sweden)

    Thennakoon M. Sampath Udeni Gunathilake

    2017-02-01

    Full Text Available A unique biodegradable, superporous, swellable and pH sensitive nanocellulose reinforced chitosan hydrogel with dynamic mechanical properties was prepared for oral administration of curcumin. Curcumin, a less water-soluble drug was used due to the fact that the fast swellable, superporous hydrogel could release a water-insoluble drug to a great extent. CO2 gas foaming was used to fabricate hydrogel as it eradicates using organic solvents. Field emission scanning electron microscope images revealed that the pore size significantly increased with the formation of widely interconnected porous structure in gas foamed hydrogels. The maximum compression of pure chitosan hydrogel was 25.9 ± 1 kPa and it increased to 38.4 ± 1 kPa with the introduction of 0.5% cellulose nanocrystals. In vitro degradation of hydrogels was found dependent on the swelling ratio and the amount of CNC of the hydrogel. All the hydrogels showed maximum swelling ratios greater than 300%. The 0.5% CNC-chitosan hydrogel showed the highest swelling ratio of 438% ± 11%. FTIR spectrum indicated that there is no interaction between drug and ingredients present in hydrogels. The drug release occurred in non-Fickian (anomalous manner in simulated gastric medium. The drug release profiles of hydrogels are consistent with the data obtained from the swelling studies. After gas foaming of the hydrogel, the drug loading efficiency increased from 41% ± 2.4% to 50% ± 2.0% and release increased from 0.74 to 1.06 mg/L. The drug release data showed good fitting to Ritger-Peppas model. Moreover, the results revealed that the drug maintained its chemical activity after in vitro release. According to the results of this study, CNC reinforced chitosan hydrogel can be suggested to improve the bioavailability of curcumin for the absorption from stomach and upper intestinal tract.

  9. Assessing arsenic bioavailability through the use of bioassays

    Science.gov (United States)

    Diesel, E.; Nadimpalli, M.; Hull, M.; Schreiber, M. E.; Vikesland, P.

    2009-12-01

    Various methods have been used to characterize the bioavailability of a contaminant, including chemical extractions from soils, toxicity tests, bioaccumulation measurements, estimation from soil properties, in vitro/in vivo tests, and microbial biossays. Unfortunately, these tests are all unique (i.e. they measure bioavailability through different mechanisms) and it is difficult to compare measurements collected using one method to those collected from another. Additionally, there are fundamental aspects of bioavailability research that require further study. In particular, changes in bioavailability over time are not well understood, as well as what the geochemical controls are on changes in bioavailability. In addition, there are no studies aimed at the integration of bioavailability measurements and potential geochemical controls. This research project seeks to find a standard set of assays and sensors that can be used to assess arsenic bioavailability at any field site, as well as to use these tools and techniques to better understand changes in, and controls on, arsenic bioavailability. The bioassays to be utilized in this research are a bioluminescent E. coli assay and a Corbicula fluminea (Asian clam) assay. Preliminary experiments to determine the suitability of the E. coli and C. fluminea assays have been completed. The E. coli assay can be utilized to analyze As(III) and As(V) with a linear standard curve between 5 and 200 ppb for As(III) and 100 ppb and 5 ppm for As(V); no bioluminescent response above background was elicited in the presence of Roxarsone, an organoarsenical. The C. fluminea assay is capable of bioaccumulating As(III), As(V), Roxarsone, and MSMA, with As(III) being the most readily accumulated, followed by As(V), Roxarsone and MSMA, respectively. Additional research will include assessing bioavailability of various arsenic species adsorbed to natural colloidal materials (i.e. clays, iron oxides, NOM) to the E. coli and C. fluminea assays

  10. Aggregation, sedimentation, dissolution and bioavailability of ...

    Science.gov (United States)

    To understand their fate and transport in estuarine systems, the aggregation, sedimentation, and dissolution of CdSe quantum dots (QDs) in seawater were investigated. Hydrodynamic size increased from 40 to 60 nm to >1 mm within 1 h in seawater, and the aggregates were highly polydispersed. Their sedimentation rates in seawater were measured to be 4–10 mm/day. Humic acid (HA), further increased their size and polydispersity, and slowed sedimentation. Light increased their dissolution and release of dissolved Cd. The ZnS shell also slowed release of Cd ions. With sufficient light, HA increased the dissolution of QDs, while with low light, HA alone did not change their dissolution. The benthic zone in estuarine systems is the most probable long-term destination of QDs due to aggregation and sedimentation. The bioavailability of was evaluated using the mysid Americamysis bahia. The 7-day LC50s of particulate and dissolved QDs were 290 and 23 μg (total Cd)/L, respectively. For mysids, the acute toxicity appears to be from Cd ions; however, research on the effects of QDs should be conducted with other organisms where QDs may be lodged in critical tissues such as gills or filtering apparatus and Cd ions may be released and delivered directly to those tissues. Because of their increasing use and value to society, cadmium-based quantum dots (QDs) will inevitably find their way into marine systems. In an effort to understand the fate and transport of CdSe QDs in estuar

  11. Selenium bioavailability of infant milk diets

    International Nuclear Information System (INIS)

    Raghib, H.; Chan, W.Y.; Rennert, O.M.

    1986-01-01

    The effects of age, types of milk diet and chemical forms of SE on its bioavailability were studied using suckling rats as a model. Human milk, bovine milk and infant formula (regular Similac) extrinsically labeled with either ( 75 Se) selenite or ( 75 Se) selenomethionine were fed by gastric intubation to 8, 10, 15 and 20 (or 30)-day-old rats. Retention of 75 Se in gut free carcass and liver was measured 3 hours after feeding. At any given age the corresponding absorption of 75 Se from the 3 diets was similar except at 15 days of age when significantly more ( 75 Se) selenomethionine was absorbed from human milk (83%) than from bovine milk or formula (72%). Much higher amount of ( 75 Se) selenomethionine was absorbed by any age group from the 3 milk diets compared to ( 75 Se) selenite. An age related change in both ( 75 Se) selenite and ( 75 Se) selenomethionine absorption was noticed in all 3 diets. Gut free carcass ( 75 Se) selenite absorption was 32% in 8-d-old rats and increased to 46% in 20-d-old rats. The corresponding liver 75 Se retention was 7.5 and 19.5%. On the other hand, ( 75 Se) selenomethionine retention by the gut free carcass decreased with age from an average of 83% in 8-d-old rats to 72% in 20-d-old rats. The corresponding 75 Se incorporation into the liver increased from 15.5% in 8-d-old rats to 21.9% in 20-d-old rats. It is concluded that twice as much 75 Se) selenite and an age related change in 75 Se absorption was noticed between the 2 chemical forms of Se and between human milk and the other 2 milk diets

  12. Comparative bioavailability of two formulations of sibutramine.

    Science.gov (United States)

    Franco Spínola, A C; Almeida, S; Filipe, A; Neves, R; Abolfathi, Z; Yritia, M; Anctil, D

    2009-10-01

    This study was conducted in order to compare the bioavailability of two capsule formulations containing 15 mg of sibutramine, N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N,N-dimethylamine hydrochloride monohydrate, 84485-00-7 CAS registry number. 62 healthy subjects were enrolled in a single-center, randomized, single-dose, open-label, 2-way crossover study, with a minimum washout period of 14 days. Plasma samples were collected up to 72.0 hours post-dosing. R-sibutramine, S-sibutramine, N-mono-desmethyl-sibutramine (M1) and N-di-desmethyl-sibutramine (M2) levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection, LC/MS/MS method. Pharmacokinetic parameters used for bioequivalence assessment were the area under the concentration-time curve from time zero to time of last non-zero concentration (AUC0-t) and the maximum observed concentration (Cmax). These parameters were determined from sibutramine enantiomers as well from M1 and M2 concentration data using non-compartmental analysis. The 90% confidence intervals obtained by analysis of variance were 89.25 - 122.88% for Cmax, 90.37 - 123.18% for AUC0-t and 91.20 - 122.38% for AUCinf for R-sibutramine and 88.27 - 124.08% for Cmax, 86.15 - 121.78% for AUC0-t and 88.02 - 120.96% for AUCinf for S-sibutramine. These results were all within the range of 80.00 - 125.00% established by regulatory requirements. Bioequivalence between formulations was concluded both in terms of rate and extent of absorption.

  13. Effects of biochar and the earthworm Eisenia fetida on the bioavailability of polycyclic aromatic hydrocarbons and potentially toxic elements

    International Nuclear Information System (INIS)

    Gomez-Eyles, Jose L.; Sizmur, Tom; Collins, Chris D.; Hodson, Mark E.

    2011-01-01

    Polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) were monitored over 56 days in calcareous contaminated-soil amended with either or both biochar and Eisenia fetida. Biochar reduced total (449 to 306 mg kg -1 ) and bioavailable (cyclodextrin extractable) (276 to 182 mg kg -1 ) PAHs, PAH concentrations in E. fetida (up to 45%) but also earthworm weight. Earthworms increased PAH bioavailability by >40%. Combined treatment results were similar to the biochar-only treatment. Earthworms increased water soluble Co (3.4 to 29.2 mg kg -1 ), Cu (60.0 to 120.1 mg kg -1 ) and Ni (31.7 to 83.0 mg kg -1 ) but not As, Cd, Pb or Zn; biochar reduced water soluble Cu (60 to 37 mg kg -1 ). Combined treatment results were similar to the biochar-only treatment but gave a greater reduction in As and Cd mobility. Biochar has contaminated land remediation potential, but its long-term impact on contaminants and soil biota needs to be assessed. - Research highlights: → Biochar reduced total and bioavailable PAH concentrations. → Biochar was less effective at immobilising PTEs, due to its low cation exchange capacity. → E. fetida increased PAH bioavailability and PTE mobility. → When used in combination biochar reduced the concentration of PTEs mobilised by E. fetida. → Biochar had a negative effect on E. fetida in terms of weight loss. - Biochar decreased PAH biovailability but was less effective at reducing PTE mobility, whilst E. fetida increased both PAH and PTE bioavailability.

  14. Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

    Directory of Open Access Journals (Sweden)

    Sun J

    2012-11-01

    Full Text Available Jiao Sun,1 Fan Wang,1,2 Yue Sui,1 Zhennan She,1 Wenjun Zhai,1 Chunling Wang,1 Yihui Deng11College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; 2Beijing Zhijianjinrui Applied Pharmaceutical Science Inc, Beijing, ChinaAbstract: In this paper work, four naked nanocrystals (size range 80–700 nm were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q10 increased as particle size decreased. The bioavailability of coenzyme Q10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold.Keywords: particle size, solubility, dissolution, nanocrystal, bioavailability, coenzyme Q10

  15. Effects of biochar and the earthworm Eisenia fetida on the bioavailability of polycyclic aromatic hydrocarbons and potentially toxic elements

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Eyles, Jose L., E-mail: j.l.gomezeyles@reading.ac.u [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom); Sizmur, Tom; Collins, Chris D.; Hodson, Mark E. [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom)

    2011-02-15

    Polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) were monitored over 56 days in calcareous contaminated-soil amended with either or both biochar and Eisenia fetida. Biochar reduced total (449 to 306 mg kg{sup -1}) and bioavailable (cyclodextrin extractable) (276 to 182 mg kg{sup -1}) PAHs, PAH concentrations in E. fetida (up to 45%) but also earthworm weight. Earthworms increased PAH bioavailability by >40%. Combined treatment results were similar to the biochar-only treatment. Earthworms increased water soluble Co (3.4 to 29.2 mg kg{sup -1}), Cu (60.0 to 120.1 mg kg{sup -1}) and Ni (31.7 to 83.0 mg kg{sup -1}) but not As, Cd, Pb or Zn; biochar reduced water soluble Cu (60 to 37 mg kg{sup -1}). Combined treatment results were similar to the biochar-only treatment but gave a greater reduction in As and Cd mobility. Biochar has contaminated land remediation potential, but its long-term impact on contaminants and soil biota needs to be assessed. - Research highlights: Biochar reduced total and bioavailable PAH concentrations. Biochar was less effective at immobilising PTEs, due to its low cation exchange capacity. E. fetida increased PAH bioavailability and PTE mobility. When used in combination biochar reduced the concentration of PTEs mobilised by E. fetida. Biochar had a negative effect on E. fetida in terms of weight loss. - Biochar decreased PAH biovailability but was less effective at reducing PTE mobility, whilst E. fetida increased both PAH and PTE bioavailability.

  16. ABSORPTION AND BIOAVAILABILITY OF THE MINERALS IN THE MULTI-MIXTURE FOOD SUPPLEMENT: BIOLOGICAL ASSAY IN RATS

    Directory of Open Access Journals (Sweden)

    E. HELBIG

    2008-12-01

    Full Text Available

    The absorption and bioavailability of the minerals Ca, Fe and Zn in balanced and mineral restricted diets with the addition of the food supplement multi-mixture (MM, was evaluated. A biological assay was carried out for 28 days with recently weaned Wistar rats, using 3 treatments and 8 animals in each group. The diets offered to each group were distributed as follows: CD – Control Diet (AIN-93G; CcD/MM – Control Diet + Supplement 5% MM; DRMIXc/MM – Control Diet with Mineral Restricted + Supplement 5% MM. The animals were monitored for weight; amount of diet consumed and amount of faeces excreted. They were sacrifi ced at the end of the experimental period and the pair of femurs, pancreas and liver removed for the determination of Ca, Fe and Zn. The CcD/MM diet presented absorption of Ca and Fe and bioavailability of Ca, Fe and Zn equal to that of CD, showing no statistical difference between the treatments. However the DRMIXcD/MM diet presented an increase in Ca absorption, equal absorption of Fe and an increase in the bioavailability of Ca, Fe and Zn when compared to CD. It was concluded that when fed on a balanced diet supplemented with 5% MM, there was no increase in the bioavailability of Ca, Fe or Zn, whereas when fed on a mineral defi cient diet, the group of animals that received supplementation with 5% MM, presented greater absorption and bioavailability of these minerals.

  17. Mesoporous carbon with spherical pores as a carrier for celecoxib with needle-like crystallinity: Improve dissolution rate and bioavailability

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Wenquan; Zhao, Qinfu; Sun, Changshan [Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang (China); Zhang, Zhiwen [Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203 (China); Jiang, Tongying; Sun, Jin [Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang (China); Li, Yaping [Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203 (China); Wang, Siling, E-mail: silingwang@syphu.edu.cn [Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang (China)

    2014-06-01

    The purposes of this investigation are to design mesoporous carbon (MC) with spherical pore channels and incorporate CEL to it for changing its needlelike crystal form and improving its dissolution and bioavailability. A series of solid-state characterization methods, such as SEM, TEM, DSC and XRD, were employed to systematically investigate the existing status of celecoxib (CEL) within the pore channels of MC. The pore size, pore volume and surface area of samples were characterized by nitrogen physical absorption. Gastric mucosa irritation test was carried out to evaluate the safety of mesoporous carbon as a drug carrier. Dissolution tests and in vivo pharmacokinetic studies were conducted to confirm the improvement in drug dissolution kinetics and oral bioavailability. Uptake experiments were conducted to investigate the mechanism of the improved oral bioavailability. The results of solid state characterization showed that MC was prepared successfully and CEL was incorporated into the mesoporous channels of the MC. The crystallinity of CEL in MC was affected by different loading methods, which involve evaporation method and melting method. The dissolution rate of CEL from MC was found to be significantly higher than that of pure CEL, which attributed to reduced crystallinity of CEL. The gastric mucosa irritation test indicated that the MC caused no harm to the stomach and produced a protective effect on the gastric mucosa. Uptake experiments indicated that MC enhanced the amount of CEL absorbed by Caco-2 cells. Moreover, oral bioavailability of CEL loaded within the MC was approximately 1.59-fold greater than that of commercial CEL. In conclusion, MC was a safe carrier to load water insoluble drug by controlling the crystallinity or crystal form with improvement in drug dissolution kinetics and oral bioavailability. - Highlights: • Mesoporous carbon with spherical pore structure was prepared according to the needlelike crystalline of celecoxib. • The

  18. Mesoporous carbon with spherical pores as a carrier for celecoxib with needle-like crystallinity: Improve dissolution rate and bioavailability

    International Nuclear Information System (INIS)

    Zhu, Wenquan; Zhao, Qinfu; Sun, Changshan; Zhang, Zhiwen; Jiang, Tongying; Sun, Jin; Li, Yaping; Wang, Siling

    2014-01-01

    The purposes of this investigation are to design mesoporous carbon (MC) with spherical pore channels and incorporate CEL to it for changing its needlelike crystal form and improving its dissolution and bioavailability. A series of solid-state characterization methods, such as SEM, TEM, DSC and XRD, were employed to systematically investigate the existing status of celecoxib (CEL) within the pore channels of MC. The pore size, pore volume and surface area of samples were characterized by nitrogen physical absorption. Gastric mucosa irritation test was carried out to evaluate the safety of mesoporous carbon as a drug carrier. Dissolution tests and in vivo pharmacokinetic studies were conducted to confirm the improvement in drug dissolution kinetics and oral bioavailability. Uptake experiments were conducted to investigate the mechanism of the improved oral bioavailability. The results of solid state characterization showed that MC was prepared successfully and CEL was incorporated into the mesoporous channels of the MC. The crystallinity of CEL in MC was affected by different loading methods, which involve evaporation method and melting method. The dissolution rate of CEL from MC was found to be significantly higher than that of pure CEL, which attributed to reduced crystallinity of CEL. The gastric mucosa irritation test indicated that the MC caused no harm to the stomach and produced a protective effect on the gastric mucosa. Uptake experiments indicated that MC enhanced the amount of CEL absorbed by Caco-2 cells. Moreover, oral bioavailability of CEL loaded within the MC was approximately 1.59-fold greater than that of commercial CEL. In conclusion, MC was a safe carrier to load water insoluble drug by controlling the crystallinity or crystal form with improvement in drug dissolution kinetics and oral bioavailability. - Highlights: • Mesoporous carbon with spherical pore structure was prepared according to the needlelike crystalline of celecoxib. • The

  19. Sex and nitric oxide bioavailability interact to modulate interstitial PO2 in healthy rat skeletal muscle.

    Science.gov (United States)

    Craig, Jesse C; Colburn, Trenton D; Hirai, Daniel M; Schettler, Michael J; Musch, Timothy I; Poole, David C

    2018-01-25

    Pre-menopausal women express reduced blood pressure and risk of cardiovascular disease relative to age-matched men. This purportedly relates to elevated estrogen levels increasing nitric oxide synthase (NOS) activity and NO-mediated vasorelaxation. We tested the hypotheses that female rat skeletal muscle would: 1) evince higher O 2 delivery-to-utilization ratio (Q̇O 2 /V̇O 2 ) during contractions; and 2) express greater modulation of Q̇O 2 /V̇O 2 with changes to NO bioavailability, compared to males. The spinotrapezius muscle of Sprague-Dawley rats (females (♀)=8, males (♂)=8) was surgically exposed and electrically-stimulated (180s, 1Hz, 6V). OxyphorG4 was injected into the muscle and phosphorescence quenching employed to determine the temporal profile of interstitial PO 2 (PO 2is , determined by Q̇O 2 /V̇O 2 ). This was performed under three conditions: control (CON), 300 µM sodium nitroprusside (SNP; NO donor), and 1.5 mM L-arginine methyl ester (L-NAME; NOS blockade) superfusion. No sex differences were found for the PO 2is kinetics parameters in CON or L-NAME (p>0.05), but females elicited a lower baseline following SNP (♂:42{plus minus}3 vs ♀:36{plus minus}2 mmHg, p0.05). The total NO effect (SNP minus L-NAME) on PO 2is was not different between sexes. However, the spread across both conditions was shifted to a lower absolute range for females (reduced SNP baseline and greater reduction following L-NAME). These data support that females have a greater reliance on basal NO bioavailability and males have greater responsiveness to exogenous NO and less responsiveness to reduced endogenous NO.

  20. 13C CP MAS NMR and GIAO-CHF/DFT calculations of flavonoids: Morin, kaempferol, tricin, genistein, formononetin and 3,7-dihydroxyflavone

    Science.gov (United States)

    Zielińska, Agnieszka; Paradowska, Katarzyna; Jakowski, Jacek; Wawer, Iwona

    2008-02-01

    13C CP MAS NMR spectra of the flavonoids: morin, kaempferol, 3,7-dihydroxyflavone, tricin and isoflavones: genistein and formononetin were recorded to characterize solid-state conformations. Intramolecular hydrogen bonds forming five-, six- and seven-membered rings are present in the two morin molecules in the crystals - their 13C resonances have been assigned with the aid of the calculated shielding constants. Linear relationships between the calculated shielding constants σDFT (ppm) and chemical shifts ( δCPMAS, ppm) were obtained for all studied compounds. Higher correlation coefficients suggest that the conformation with "clockwise" orientation of both OH groups is more probable in the solid 3,7-dihydroxyflavone, whereas in the solid formononetin the OH and OCH 3 substituents are directed "anticlockwise". The barrier to the rotation of phenyl ring B decreases in the order: morin (2'-OH, 3-OH) > kaempferol (3-OH) > tricin.

  1. Speciation and bioavailability of lead in complementary medicines

    International Nuclear Information System (INIS)

    Bolan, S.; Naidu, R.; Kunhikrishnan, A.; Seshadri, B.; Ok, Y.S.; Palanisami, T.; Dong, M.; Clark, I.

    2016-01-01

    Complementary medicines have associated risks which include toxic heavy metal(loid) and pesticide contamination. The objective of this study was to examine the speciation and bioavailability of lead (Pb) in selected complementary medicines. Six herbal and six ayurvedic medicines were analysed for: (i) total heavy metal(loid) contents including arsenic (As), cadmium (Cd), Pb and mercury (Hg); (ii) speciation of Pb using sequential fractionation and extended x-ray absorption fine structure (EXAFS) techniques; and (iii) bioavailability of Pb using a physiologically-based in vitro extraction test (PBET). The daily intake of Pb through the uptake of these medicines was compared with the safety guidelines for Pb. The results indicated that generally ayurvedic medicines contained higher levels of heavy metal(loid)s than herbal medicines with the amount of Pb much higher than the other metal(loid)s. Sequential fractionation indicated that while organic-bound Pb species dominated the herbal medicines, inorganic-bound Pb species dominated the ayurvedic medicines. EXAFS data indicated the presence of various Pb species in ayurvedic medicines. This implies that Pb is derived from plant uptake and inorganic mineral input in herbal and ayurvedic medicines, respectively. Bioavailability of Pb was higher in ayurvedic than herbal medicines, indicating that Pb added as a mineral therapeutic input is more bioavailable than that derived from plant uptake. There was a positive relationship between soluble Pb fraction and bioavailability indicating that solubility is an important factor controlling bioavailability. The daily intake values for Pb as estimated by total and bioavailable metal(loid) contents are likely to exceed the safe threshold level in certain ayurvedic medicines. This research demonstrated that Pb toxicity is likely to result from the regular intake of these medicines which requires further investigation. - Highlights: • Pb species in complementary medicines was

  2. 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.

  3. Bacterial metal resistance genes and metal bioavailability in contaminated sediments

    International Nuclear Information System (INIS)

    Roosa, Stéphanie; Wattiez, Ruddy; Prygiel, Emilie; Lesven, Ludovic; Billon, Gabriel; Gillan, David C.

    2014-01-01

    In bacteria a metal may be defined as bioavailable if it crosses the cytoplasmic membrane to reach the cytoplasm. Once inside the cell, specific metal resistance systems may be triggered. In this research, specific metal resistance genes were used to estimate metal bioavailability in sediment microbial communities. Gene levels were measured by quantitative PCR and correlated to metals in sediments using five different protocols to estimate dissolved, particle-adsorbed and occluded metals. The best correlations were obtained with czcA (a Cd/Zn/Co efflux pump) and Cd/Zn adsorbed or occluded in particles. Only adsorbed Co was correlated to czcA levels. We concluded that the measurement of czcA gene levels by quantitative PCR is a promising tool which may complement the classical approaches used to estimate Cd/Zn/Co bioavailability in sediment compartments. - Highlights: • Metal resistance genes were used to estimate metal bioavailability in sediments. • Gene levels were correlated to metals using 5 different metal extraction protocols. • CzcA gene levels determined by quantitative PCR is a promising tool for Cd/Zn/Co. - Capsule Bacterial czcA is a potential biomarker of Cd, Zn and Co bioavailability in aquatic sediments as shown by quantitative PCR and sequential metal extraction

  4. Assessing the bioavailability and bioaccessibility of metals and metalloids.

    Science.gov (United States)

    Ng, Jack C; Juhasz, Albert; Smith, Euan; Naidu, Ravi

    2015-06-01

    Bioavailability (BA) determines the potential harm of a contaminant that exerts on the receptor. However, environmental guidelines for site contamination assessment are often set assuming the contaminant is 100 % bioavailable. This conservative approach to assessing site risk may result in the unnecessary and expensive remediation of a contaminated site. The National Environmental Protection Measures in Australia has undergone a statutory 5-year review that recommended that contaminant bioavailability and bioaccessibility (BAC) measures be adopted as part of the contaminated site risk assessment process by the National Environment Protection Council. We undertook a critical review of the current bioavailability and bioaccessibility approaches, methods and their respective limitations. The 'gold' standard to estimate the portion of a contaminant that reaches the system circulatory system (BA) of its receptor is to determine BA in an in vivo system. Various animal models have been utilised for this purpose. Because of animal ethics issues, and the expenses associated with performing in vivo studies, several in vitro methods have been developed to determine BAC as a surrogate model for the estimation of BA. However, few in vitro BAC studies have been calibrated against a reliable animal model, such as immature swine. In this review, we have identified suitable methods for assessing arsenic and lead BAC and proposed a decision tree for the determination of contaminant bioavailability and bioaccessibility for health risk assessment.

  5. The bioavailability of Chernobyl accident products

    International Nuclear Information System (INIS)

    Lujaniene, G.; Lujans, V.

    1995-01-01

    Full text: Following the Chernobyl NPP accident a great quantity of radionuclides was emitted to the atmosphere. A diverse fallout of radioactive pollutants to the earth's surface was conditioned by various factors. And this is testified by the distinctions in radionuclide composition and physicochemical forms of their carriers were measured in different regions. The study of physicochemical properties of radionuclides is necessary for the evaluation of their biological availability and for understanding and predicting their behavior in the environment. The physicochemical forms of radioactive nuclide carriers collected on April 28-20 and May 9-10 were investigated. In those samples the water soluble fractions of 137 Cs and 90 Sr carriers were 9 and 30%, respectively. The main part of these nuclides was bound to the exchangeable fraction of the carriers. For 137 Cs marked concentrations were provided by the from bound to organic (13%) and acid-soluble (12%) substances and for 90 Sr a considerable amount consisted of the organic (14%) and the fixed in crystal lattice (13%) forms. The investigation of the state of water soluble 137 Cs and 90 Sr shows that nuclides completely were of the cationic form. The dialysable fractions of both nuclides were about 90%. The bioavailability of 137 Cs and 90 Sr was about 60-70%. The fraction of water-soluble increased after the breakdown reactor was covered by an inert material. The radionuclide carrier properties greatly depend on the type of source and under the influence of various factors the radionuclide physicochemical forms are able to change and at the same time their biological availability changes as well. The influence of the source nature is confirmed by the analysis of aerosol samples brought to Lithuania following dust storms in Ukraine, where 94% of 134,137 Cs was observed in the residue, i. e. nuclide was bound to particles with penetration into crystal lattice. And also, following forest and peat-bog fires in

  6. Greater trochanteric pain syndrome diagnosis and treatment.

    Science.gov (United States)

    Mallow, Michael; Nazarian, Levon N

    2014-05-01

    Lateral hip pain, or greater trochanteric pain syndrome, is a commonly seen condition; in this article, the relevant anatomy, epidemiology, and evaluation strategies of greater trochanteric pain syndrome are reviewed. Specific attention is focused on imaging of this syndrome and treatment techniques, including ultrasound-guided interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Permeability enhancers dramatically increase zanamivir absolute bioavailability in rats: implications for an orally bioavailable influenza treatment.

    Directory of Open Access Journals (Sweden)

    Eric H Holmes

    Full Text Available We have demonstrated that simple formulations composed of the parent drug in combination with generally regarded as safe (GRAS permeability enhancers are capable of dramatically increasing the absolute bioavailability of zanamivir. This has the advantage of not requiring modification of the drug structure to promote absorption, thus reducing the regulatory challenges involved in conversion of an inhaled to oral route of administration of an approved drug. Absolute bioavailability increases of up to 24-fold were observed when Capmul MCM L8 (composed of mono- and diglycerides of caprylic/capric acids in glycerol was mixed with 1.5 mg of zanamivir and administered intraduodenally to rats. Rapid uptake (t(max of 5 min and a C(max of over 7200 ng/mL was achieved. Variation of the drug load or amount of enhancer demonstrated a generally linear variation in absorption, indicating an ability to optimize a formulation for a desired outcome such as a targeted C(max for enzyme saturation. No absorption enhancement was observed when the enhancer was given 2 hr prior to drug administration, indicating, in combination with the observed tmax, that absorption enhancement is temporary. This property is significant and aligns well with therapeutic applications to limit undesirable drug-drug interactions, potentially due to the presence of other poorly absorbed polar drugs. These results suggest that optimal human oral dosage forms of zanamivir should be enteric-coated gelcaps or softgels for intraduodenal release. There continues to be a strong need and market for multiple neuraminidase inhibitors for influenza treatment. Creation of orally available formulations of inhibitor drugs that are currently administered intravenously or by inhalation would provide a significant improvement in treatment of influenza. The very simple GRAS formulation components and anticipated dosage forms would require low manufacturing costs and yield enhanced convenience. These results

  8. Enhanced oral bioavailability of felodipine by novel solid self-microemulsifying tablets.

    Science.gov (United States)

    Jing, Boyu; Wang, Zhiyuan; Yang, Rui; Zheng, Xia; Zhao, Jia; Tang, Si; He, Zhonggui

    2016-01-01

    The novel self-microemulsifying (SME) tablets were developed to enhance the oral bioavailability of a poor water-soluble drug felodipine (FDP). Firstly, FDP was dissolved in the optimized liquid self-microemusifying drug delivery systems (SMEDDS) containing Miglyol® 812, Cremophor® RH 40, Tween 80 and Transcutol® P, and the mixture was solidified with porous silicon dioxide and crospovidone as adsorbents. Then after combining the solidified powders with other excipients, the solid SME tablets were prepared by wet granulation-compression method. The prepared tablets possessed satisfactory characterization; the droplet size of the SME tablets following self-emulsification in water was nearly equivalent to the liquid SMEDDS (68.4 ± 14.0 and 64.4 ± 12.0 nm); differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) analysis demonstrated that FDP in SME tablets had undergone a polymorphism transition from a crystal form to an amorphous state, which was further confirmed by transmission electron microscopy (TEM). A similar dissolution performance of SME tablets and liquid SMEDDS was also obtained under the sink condition (85% within 10 min), both significantly higher than commercial tablets. The oral bioavailability was evaluated for the SME tablets, liquid SMEDDS and commercial conventional tablets in the fasted beagle dogs. The AUC of FDP from the SME tablets was about 2-fold greater than that of conventional tablets, but no significant difference was found when compared with the liquid SMEDDS. Accordingly, these preliminary results suggest that this formulation approach offers a useful large-scale producing method to prepare the solid SME tablets from the liquid SMEDDS for oral bioavailability equivalent enhancement of poorly soluble FDP.

  9. Influence of dispersants on petroleum bioavailability in a marine food chain

    International Nuclear Information System (INIS)

    Wolfe, M.; Tjeerdema, R.

    1995-01-01

    When crude oil is accidentally released into the ocean it threatens many levels of marine life. Intervention, in the form of chemical dispersing agents, may alter the normal behavior of petroleum hydrocarbons (PH) by increasing their functional water solubility and the extent of their exposure to sub-surface marine organisms. Further, the dispersing agent may modify bioavailability as a result of altered interactions between dispersed PH droplets and organismal cell membranes, To date, little information exists on the sub-lethal effects of dispersants and factors modifying their role in the bioavailability and disposition of PH in marine food chains. The objective of the current research was to determine the impact of dispersing agents on PH bioavailability to primary levels of a marine food chain. Uptake, bioaccumulation, deputation, and metabolic transformation of a model PH, 14 C-naphthalene, were measured and compared for dispersed Prudhoe Bay Crude Oil (PBCO) vs. undispersed preparations of the water-accommodated fractions (WAF) of PBCO at two salinities (22 and 34 ppt) employing Isochrysis galbana, a primary producer, and Brachionus plicatilis, a primary consumer. Fractionation and identification of metabolites was done by HPLC co-chromatography with analytical standards, and quantitation was done by liquid scintillation counting. GC-FID characterization of WAF and dispersed oil preparations shows higher concentrations of petroleum hydrocarbons and a greater number of individual constituents in the dispersed oil preparations. However, short term (eight hour) and long term (two week) static exposure studies indicate the uptake of 14 C-naphthalene from WAF preparations is inhibited by up to 50% from dispersed oil preparations. Results of comparative static and flow-through chamber exposure studies will be presented

  10. Influence of dispersants on petroleum bioavailability in a marine food chain

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, M.; Tjeerdema, R. [Univ. of California, Santa Cruz, CA (United States). Dept. of Chemistry and Biochemistry; Sowby, M. [California Dept. of Fish and Game, Sacramento, CA (United States)

    1995-12-31

    When crude oil is accidentally released into the ocean it threatens many levels of marine life. Intervention, in the form of chemical dispersing agents, may alter the normal behavior of petroleum hydrocarbons (PH) by increasing their functional water solubility and the extent of their exposure to sub-surface marine organisms. Further, the dispersing agent may modify bioavailability as a result of altered interactions between dispersed PH droplets and organismal cell membranes, To date, little information exists on the sub-lethal effects of dispersants and factors modifying their role in the bioavailability and disposition of PH in marine food chains. The objective of the current research was to determine the impact of dispersing agents on PH bioavailability to primary levels of a marine food chain. Uptake, bioaccumulation, deputation, and metabolic transformation of a model PH, {sup 14}C-naphthalene, were measured and compared for dispersed Prudhoe Bay Crude Oil (PBCO) vs. undispersed preparations of the water-accommodated fractions (WAF) of PBCO at two salinities (22 and 34 ppt) employing Isochrysis galbana, a primary producer, and Brachionus plicatilis, a primary consumer. Fractionation and identification of metabolites was done by HPLC co-chromatography with analytical standards, and quantitation was done by liquid scintillation counting. GC-FID characterization of WAF and dispersed oil preparations shows higher concentrations of petroleum hydrocarbons and a greater number of individual constituents in the dispersed oil preparations. However, short term (eight hour) and long term (two week) static exposure studies indicate the uptake of{sup 14}C-naphthalene from WAF preparations is inhibited by up to 50% from dispersed oil preparations. Results of comparative static and flow-through chamber exposure studies will be presented.

  11. Determination of genkwanin in rat plasma by liquid chromatography-tandem mass spectrometry: application to a bioavailability study.

    Science.gov (United States)

    Song, Yanqing; Zhang, Sixi; Liu, Hong; Jin, Xiangqun

    2013-10-01

    We developed and validated a sensitive, rapid, and specific liquid chromatography tandem mass spectrometry method to determine genkwanin in rat plasma. Genistein was used as the internal standard. After liquid-liquid extraction with ethyl acetate, the chromatographic separation of genkwanin was achieved by using a reversed-phase HPLC using Agela Venusil MP-C18 analytical column (2.1 mm × 50 mm, 5 μm particles) with a mobile phase of methanol (A)-water (B) (65:35, v/v) containing 5mM ammonium acetate and 0.1% formic acid. The detection was performed by negative ion electrospray ionization in multiple-reaction monitoring mode by using transitions of m/z 283.1→268.1 and m/z 269.1→133.0 for genkwanin and IS, respectively. Good linearity was observed in the concentration range of 3.84 ng/ml to 3,840 ng/ml (r(2)>0.99), and the lower limit of quantification was 3.84 ng/ml in 100 μl of rat plasma. The intra- and inter-day accuracy and precision of genkwanin were both within acceptable limits. This present method was successfully applied to a pharmacokinetic study of genkwanin in rats following oral (50mg/kg) and intravenous (5mg/kg) administration. For the oral administration group, the maximum mean concentration of genkwanin in plasma (Cmax, 36.9 ± 9.4 ng/ml) was achieved at 3.83 ± 1.33 h (Tmax), and the area under the plasma concentration versus time curve from 0 h to 12h (AUC0-12h) was 218 ± 40 ngh/ml. For the intravenous administration group, essential pharmacokinetic parameters such as Cmax (1,755 ± 197 ng/ml) and AUC0-12h (2,349 ± 573 ngh/ml) were shown. The result showed that the compound was poorly absorbed with an absolute bioavailability of approximately 1.1%. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  12. Considering bioavailability in the remediation of heavy metal contaminated sites

    Directory of Open Access Journals (Sweden)

    Leita L.

    2013-04-01

    Full Text Available Many years of research have demonstrated that instead of the total concentration of metals in soil, bioavailability is the key to understand the environmental risk derived by metals, since adverse effects are related only to the biologically available forms of these elements. The knowledge of bioavailability can decrease the uncertainties in evaluating exposure in human and ecological risk assessment. At the same time, the efficiency of remediation treatments could be greatly influenced by availability of the contaminants. Consideration of the bioavailability processes at contaminated sites could be useful in site-specific risk assessment: the fraction of mobile metals, instead of total content should be provided as estimates of metal exposure. Moreover, knowledge of the chemical forms of heavy metals in soils is a critical component in the evaluation of applicability of different remediation technologies such as phytoremdiation or soil washing.

  13. Bioavailability of lead in rats fed human diets

    International Nuclear Information System (INIS)

    Kostial, K.; Kello, D.

    1979-01-01

    The bioavailability of lead was studied in rats fed various baby foods (Babymix-turkey, Babymix-vegetables, Frutolino-fruit, Frutamix-bananas, Babyron-S-26, Truefood), cow's milk, bread, liver and standard rat diet. Lead absorption was determined by measuring the whole body retention of 203 Pb 6 days after a single oral application. Highest absorption values ranging from 17 to 20% were obtained in animals fed cow's milk and fruit foods. Rats on other human diets absorbed between 3 and 8% of the radioactive lead dose. Only in animals on rat diet lead absorption was below 1%. It is concluded that rats fed human diets show absorption values similar to those in humans. This might indicate that the bioavailability of lead is primarily dependent on dietary habits. This experimental model, if confirmed by further work, might be useful for obtaining preliminary data on the bioavailability of metals from various foods

  14. Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

    Science.gov (United States)

    Jonkman, Kelly; Duma, Andreas; Olofsen, Erik; Henthorn, Thomas; van Velzen, Monique; Mooren, René; Siebers, Liesbeth; van den Beukel, Jojanneke; Aarts, Leon; Niesters, Marieke; Dahan, Albert

    2017-10-01

    Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.

  15. A Review of Mercury Bioavailability in Humans and Fish

    Directory of Open Access Journals (Sweden)

    Mark A. Bradley

    2017-02-01

    Full Text Available To estimate human exposure to methylmercury (MeHg, risk assessors often assume 95%–100% bioavailability in their models. However, recent research suggests that assuming all, or most, of the ingested mercury (Hg is absorbed into systemic circulation may be erroneous. The objective of this paper is to review and discuss the available state of knowledge concerning the assimilation or bioavailability of Hg in fish and humans. In fish, this meant reviewing studies on assimilation efficiency, that is the difference between ingested and excreted Hg over a given period of time. In humans, this meant reviewing studies that mostly investigated bioaccessibility (digestive processes rather than bioavailability (cumulative digestive + absorptive processes, although studies incorporating absorption for a fuller picture of bioavailability were also included where possible. The outcome of this review shows that in a variety of organisms and experimental models that Hg bioavailability and assimilation is less than 100%. Specifically, 25 studies on fish were reviewed, and assimilation efficiencies ranged from 10% to 100% for MeHg and from 2% to 51% for Hg(II. For humans, 20 studies were reviewed with bioaccessibility estimates ranging from 2% to 100% for MeHg and 0.2% to 94% for Hg(II. The overall absorption estimates ranged from 12% to 79% for MeHg and 49% to 69% for Hg(II, and were consistently less than 100%. For both fish and humans, a number of cases are discussed in which factors (e.g., Hg source, cooking methods, nutrients are shown to affect Hg bioavailability. The summaries presented here challenge a widely-held assumption in the Hg risk assessment field, and the paper discusses possible ways forward for the field.

  16. A Review of Mercury Bioavailability in Humans and Fish.

    Science.gov (United States)

    Bradley, Mark A; Barst, Benjamin D; Basu, Niladri

    2017-02-10

    To estimate human exposure to methylmercury (MeHg), risk assessors often assume 95%-100% bioavailability in their models. However, recent research suggests that assuming all, or most, of the ingested mercury (Hg) is absorbed into systemic circulation may be erroneous. The objective of this paper is to review and discuss the available state of knowledge concerning the assimilation or bioavailability of Hg in fish and humans. In fish, this meant reviewing studies on assimilation efficiency, that is the difference between ingested and excreted Hg over a given period of time. In humans, this meant reviewing studies that mostly investigated bioaccessibility (digestive processes) rather than bioavailability (cumulative digestive + absorptive processes), although studies incorporating absorption for a fuller picture of bioavailability were also included where possible. The outcome of this review shows that in a variety of organisms and experimental models that Hg bioavailability and assimilation is less than 100%. Specifically, 25 studies on fish were reviewed, and assimilation efficiencies ranged from 10% to 100% for MeHg and from 2% to 51% for Hg(II). For humans, 20 studies were reviewed with bioaccessibility estimates ranging from 2% to 100% for MeHg and 0.2% to 94% for Hg(II). The overall absorption estimates ranged from 12% to 79% for MeHg and 49% to 69% for Hg(II), and were consistently less than 100%. For both fish and humans, a number of cases are discussed in which factors (e.g., Hg source, cooking methods, nutrients) are shown to affect Hg bioavailability. The summaries presented here challenge a widely-held assumption in the Hg risk assessment field, and the paper discusses possible ways forward for the field.

  17. Bioavailability of autochthonous dissolved organic nitrogen in marine plankton communities

    DEFF Research Database (Denmark)

    Knudsen, Helle; Markager, Svend Stiig; Søndergaard, Morten

    The purpose of this study was to investigate the bioavailability of dissolved organic nitrogen (DON) produced during a phytoplankton bloom. The experiments were conducted with natural plankton communities as batch growth experiments over approximately 30 days with nitrogen limitation. Five to six...... times during the exponential and stationary phases of each experimental bloom the bioavailability of DON was measured over 60 days together with DOC and oxygen consumption. The overall aim was to quantify remineralization of the added nitrate. The results showed that maximum 33 % of the added nitrate...

  18. Bioavailability of four oral Coenzyme Q formulations in healthy volunteers

    DEFF Research Database (Denmark)

    Weis, M.; Mortensen, S.A.; Rassing, M.R.

    1994-01-01

    The bioavailability of four different Coenzyme Q (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatine capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatine capsules containing......Q (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o.administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile....

  19. Bioavailability of sediment-bound contaminants to marine organisms

    Energy Technology Data Exchange (ETDEWEB)

    Brown, B. [Battelle/Marine Sciences Lab., Sequim, WA (United States)]|[Colby Coll., Waterville, ME (United States); Neff, J. [Battelle/Marine Sciences Lab., Sequim, WA (United States)]|[Battelle Ocean Sciences, Duxbury, MA (United States)

    1993-09-01

    The bioavailability of sediment-bound contaminants to marine organisms indicates that there exists a potential for transfer of these contaminants through marine food webs to commercial fisheries products consumed by humans. However, there has been relatively little effort to combine and synthesize data on chemical/biological interactions between benthic animals and seagrasses and the sediments in which they reside on the one hand, and on the chemistry of bioaccumulation on the other. This report provides a conceptual basis for an approach to bioavailability and biomagnification of sediment-bound contaminants that reviews biological and chemical approaches.

  20. Assessment of Bioavailability Limitations During Slurry Biodegradation of Petroleum Hydrocarbons in Aged Soils

    International Nuclear Information System (INIS)

    Huesemann, Michael H.; Hausmann, Tom S.; Fortman, Timothy J.

    2003-01-01

    In an effort to determine whether bioavailability limitations are responsible for the slow or incomplete hydrocarbon biodegradation in aged soils, both the rate of desorption (rdes) and biodegradation (rbio) was measured for n-alkanes and polynuclear aromatic hydrocarbons (PAHs) at different times during the slurry biotreatment of six different soils. While all n-alkanes were biodegraded to various degrees depending on their respective carbon number and the soil organic matter content, none of them were desorbed to a significant extent indicating that these saturated hydrocarbons do not need to be transferred from the soil particles into the aqueous phase in order to be metabolized by microorganisms. Most 2 and 3 ring PAHs biodegraded as fast as they were desorbed (rbio=rdes), i.e., desorption rates controlled biodegradation rates. By contrast, the biodegradation kinetics of 4, 5, and 6 ring PAHs was limited by microbial factors during the initial phase (rbio > 0) but was more likely caused by microbial factors such as the absence of specific PAH degraders or cometabolic substrates. Consequently, PAHs that are found to be microbially recalcitrant in aged soils may not be so because of limited bioavailability and thus could pose a greater risk to the environment than previously thought

  1. A new biocompatible microemulsion increases extraction yield and bioavailability of Andrographis paniculata.

    Science.gov (United States)

    Liu, Xiao-Yan; Niu, Xin; Feng, Qian-Jin; Yang, Xue-Zhi; Wang, Dan-Wei; Zhao, Tong; Li, Lei; DU, Hong

    2016-09-01

    The purpose of this study was to design and prepare a biocompatible microemulsion of Andrographis paniculata (BMAP) containing both fat-soluble and water-soluble constituents. We determined the contents of active constituents of BMAP and evaluated its bioavailability. The biocompatible microemulsion (BM), containing lecithin and bile salts, was optimized in the present study, showing a good physical stability. The mean droplet size was 19.12 nm, and the average polydispersity index (PDI) was 0.153. The contents of andrographolide and dehydroandrographolide in BMAP, as determined by high performance liquid chromatography (HPLC), were higher than that in ethanol extraction. The pharmacokinetic results of BMAP showed that the AUC0-7 and AUC0→∞ values of BMAP were 2.267 and 27.156 μg·mL(-1)·h(-1), respectively, and were about 1.41-fold and 6.30-fold greater than that of ethanol extraction, respectively. These results demonstrated that the bioavailability of and rographolide extracted by BMAP was significantly higher than that extracted by ethanol. In conclusion, the BMAP preparation displayed ann improved dose form for future clinical applications. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  2. Enhanced uridine bioavailability following administration of a triacetyluridine-rich nutritional supplement.

    Directory of Open Access Journals (Sweden)

    Melissa E Weinberg

    Full Text Available BACKGROUND: Uridine is a therapy for hereditary orotic aciduria and is being investigated in other disorders caused by mitochondrial dysfunction, including toxicities resulting from treatment with nucleoside reverse transcriptase inhibitors in HIV. Historically, the use of uridine as a therapeutic agent has been limited by poor bioavailability. A food supplement containing nucleosides, NucleomaxX®, has been reported to raise plasma uridine to supraphysiologic levels. METHODOLOGY/PRINCIPAL FINDINGS: Single- and multi-dose PK studies following NucleomaxX® were compared to single-dose PK studies of equimolar doses of pure uridine in healthy human volunteers. Product analysis documented that more than 90% of the nucleoside component of NucleomaxX® is in the form of triacetyluridine (TAU. Single and repeated dosing with NucleomaxX® resulted in peak plasma uridine concentrations 1-2 hours later of 150.9 ± 39.3 µM and 161.4 ± 31.5 µM, respectively, levels known to ameliorate mitochondrial toxicity in vitro. C(max and AUC were four-fold higher after a single dose of NucleomaxX® than after uridine. No adverse effects of either treatment were observed. CONCLUSIONS/SIGNIFICANCE: NucleomaxX®, containing predominantly TAU, has significantly greater bioavailability than pure uridine in human subjects and may be useful in the management of mitochondrial toxicity.

  3. Bioavailability of zinc in two zinc sulfate by-products of the galvanizing industry.

    Science.gov (United States)

    Edwards, H M; Boling, S D; Emmert, J L; Baker, D H

    1998-10-01

    Two Zn depletion/repletion assays were conducted with chicks to determine the relative bioavailability (RBV) of Zn from two new by-products of the galvanizing industry. Using a soy concentrate-dextrose diet, slope-ratio methodology was employed to evaluate two different products: Fe-ZnSO4 x H2O with 20.2% Fe and 13.0% Zn, and Zn-FeSO4 x H2O with 14.2% Fe and 20.2% Zn. Feed-grade ZnSO4 x H2O was used as a standard. Weight gain, tibia Zn concentration, and total tibia Zn responded linearly (P 0.10) from the ZnSO4 standard (100%). Slope-ratio calculations based on total tibia Zn established average Zn RBV values of 126% for Fe-ZnSO4 x H2O and 127% for Zn-FeSO4 x H2O, and these values were greater (P < 0.01) than those of the ZnSO4 standard (100%). It is apparent that both mixed sulfate products of Fe and Zn are excellent sources of bioavailable Zn.

  4. The oleic acid esterification of policosanol increases its bioavailability and hypocholesterolemic action in rats

    Energy Technology Data Exchange (ETDEWEB)

    Hain, D.; Valenzuela, A.; Branes, M. C.; Fuenzalida, M.; Videla, L. A.

    2012-07-01

    Policosanol comprises a mixture of long-chain aliphatic alcohols from sugarcane wax. More than 50 studies indicate that policosanol decreases serum cholesterol, while others failed to reproduce this effect. The objective of this investigation was to assess the bioavailability of esterified policosanol and non-esterified policosanol (NEP), in relation to their hypocholesterolemic effects. Sprague Dawley rats were given a daily oral dose of 100 mg/kg of NEP, 117 mg kg1 of butyric acid esterified policosanol (BAEP), or 164 mg kg1 of oleic acid esterified policosanol (OAEP). Policosanol absorption was evaluated in plasma between 0 and 3 hours after ingestion. To assess changes in total cholesterol, LDL-cholesterol, HDLcholesterol and triacylglycerols in plasma and liver 3-hydroxy- 3-methylglutaryl coenzyme A reductase (HMG- CoA red) phosphorylation, the rats were supplemented with nonesterified or esterified policosanol for 5 weeks. The results indicate that policosanol absorption was significantly greater in OAEP-treated rats than in those subjected to NEP or BAEP administration. OAEP significantly reduced plasma total and LDL-cholesterol in rats, in addition to a 5.6-fold increase (P < 0.05) in the hepatic content of phosphorylated HMG-CoA red over the control values. In conclusion, esterification of policosanol with oleic acid enhances policosanol bioavailability, and significantly improves the serum lipid profile in normocholesterolemic rats in association with the inactivation of HMG-CoA red controlling cholesterogenesis. (Author) 49 refs.

  5. Critically Ill Children Have Low Vitamin D–Binding Protein, Influencing Bioavailability of Vitamin D

    Science.gov (United States)

    Feldman, Henry A.; Chun, Rene F.; Smith, Ellen M.; Sullivan, Ryan M.; Agan, Anna A.; Keisling, Shannon M.; Panoskaltsis-Mortari, Angela; Randolph, Adrienne G.

    2015-01-01

    Rationale: Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25[OH]D) interquartile range, 108–221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age <1 year, nonwhite race, being previously healthy, 25(OH)D <20 ng/ml and greater illness severity. In the subgroup that was genotyped, GC haplotype had the strongest association with VDBP level; carriage of one additional copy of GC1S was associated with a 37.5% higher level (95% confidence interval, 31.9–44.8; P < 0.001). Bioavailable 25(OH)D was also inversely associated with illness severity (r = −0.24, P < 0.001), and ratio to measured total 25(OH)D was variable and related to haplotype. Conclusions: Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower VDBP levels increase bioavailability. Treatment studies conducted on the basis of total 25(OH)D level, without consideration of VDBP concentration and genotype, may increase the risk of falsely negative results. PMID:26356094

  6. Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Zhao L

    2013-10-01

    -time curve value of BAN-1 was 1.8-fold and 7-fold greater than those of BAN-2 and free baicalin suspension after oral administration at a dose of 100 mg/kg. In conclusion, these results demonstrated that the baicalin-loaded nanoemulsion formulation, in particular BAN-1, was very effective for improving the oral bioavailability of baicalin and exhibited great potential for future clinical application.Keywords: nanoemulsion, baicalin, oral bioavailability, pharmacokinetics

  7. The potential bioavailability of mineral-associated organic nitrogen in the rhizosphere.

    Science.gov (United States)

    Jilling, A.; Grandy, S.; Keiluweit, M.

    2017-12-01

    Nitrogen (N) transformations and bioavailability limit both plant productivity and N losses in most ecosystems. Recent research has focused on the mineralization path that N takes—from polymeric to monomeric and finally inorganic forms—and how these pools and processes influence the bioavailability of soil N. By contrast, there has been inadequate exploration of the N-sources that dominate the production of bioavailable N. In a new conceptual framework, we propose that mineral-associated organic matter (MAOM) is an overlooked, but critical, source of organic N, especially in the rhizosphere. We hypothesize that root-deposited low molecular weight exudates enhance the direct and indirect (via microbial communities) destabilization, solubilization, and subsequent bioavailable of MAOM. To test this conceptual framework, we conducted a laboratory incubation to examine the capacity for MAOM to supply N and to determine whether the soil-microbial response to root exudates facilitates the release and subsequent degradation of mineral-bound N. We isolated silt and clay organic matter fractions from two agricultural soils and added sterile sand to create a soil in which MAOM was the sole source of organic N. We applied three solution treatments: 13C-labelled glucose, to stimulate microbial activity and potentially the production of extracellular enzymes capable of liberating N; 13C-labelled oxalic acid, which has been demonstrated to dissolve metal-organic bonds and possibly destabilize mineral-bound and N-rich organic matter; and water, to serve as a control. Over the 12-day incubation, we observed an increase in enzyme activities and C- and N-cycling rates following glucose additions. Oxalic acid additions initially suppressed microbial activity, but eventually favored a slower-growing community with greater oxidative enzyme potential. Results suggest that C additions stimulate a microbial SOM-mining response. We will further assess the abiotic effect of organic acids

  8. Electron emission and biological consequences of hormones in polar media, studied on testosterone, progesterone, 17 beta-Estradiol and Genistein

    International Nuclear Information System (INIS)

    Schittl, H.

    2011-01-01

    In recent years, a rapid increase of breast and prostate cancer incidence was observed in the Western countries. Besides lifestyle factors like nutrition etc., sexual hormones and their role in the initiation and progression of cancer development became a centre of interest, especially the action of their individual metabolites. Recently, it was proven that the sex hormones 17β-estradiol (E2) and progesterone (P4) are able to eject electrons (e-aq) in polar media, when excited in their singlet state. The originating hormone transients are subsequently forming metabolites, some of which can initiate neoplastic processes. Therefore, it is of interest to investigate other sex hormones in this respect and to examine the fate of the resulting transients. Now, testosterone (T) is found for the first time to eject electrons in a solvent mixture of 60% ethanol and 40% triply-distilled water, when excited to its singlet state by UV-irradiation with monochromatic light of 254 nm wavelength. The phytoestrogen genistein (GEN), which contributes to the compartively low breast cancer incidence in Asian countries, emits electrons from its excited singlet state, as well. The resulting hormone products can likewise eject e-aq, but with lower quantum yields of solvated electrons, Q(e-aq), as can be seen by the observed 2nd and 3rd maxima of electron emission. Due to the formation of hormone associates, Q(e-aq) is decreasing with increasing concentration of hormones. As T and GEN are able to emit and to consume electrons, they are classified as 'electron mediators'. Comparing the electron emission of T and P4, Q(e-aq) from T turns out to be 3.6 times higher. This fact is due to the different molecular structures of the hormones at position 17 of ring D: T carries a hydroxyl group favouring the electron emission, and P4 a carbonyl group, which consumes a part of the emitted e-aq from T, leading to a partial regeneration of T. Using vitamin C (vitC) as representative for potent

  9. Saccharides enhance iron bioavailability to Southern Ocean phytoplankton

    NARCIS (Netherlands)

    Hassler, C.S.; Schoemann, V.; Nichols, C.M.; Butler, E.C.V.; Boyd, P.W.; Nichols, C.M.

    2011-01-01

    Iron limits primary productivity in vast regions of the ocean. Given that marine phytoplankton contribute up to 40% of global biological carbon fixation, it is important to understand what parameters control the availability of iron (iron bioavailability) to these organisms. Most studies on iron

  10. Incorporating Contaminant Bioavailability into Sediment Quality Assessment Frameworks

    Science.gov (United States)

    The recently adopted sediment quality assessment framework for evaluating bay and estuarine sediments in the State of California incorporates bulk sediment chemistry as a key line of evidence(LOE) but does not address the bioavailability of measured contaminants. Thus, the chemis...

  11. Improved oral bioavailability of probucol by dry media-milling.

    Science.gov (United States)

    Li, Jia; Yang, Yan; Zhao, Meihui; Xu, Hui; Ma, Junyuan; Wang, Shaoning

    2017-09-01

    The polymer/probucol co-milled mixtures were prepared to improve drug dissolution rate and oral bioavailability. Probucol, a BCS II drug, was co-milled together with Copovidone (Kollidon VA64, VA64), Soluplus, or MCC using the dry media-milling process with planetary ball-milling equipment. The properties of the milled mixtures including morphology, crystal form, vitro drug dissolution and in vivo oral bioavailability in rats were evaluated. Probucol existed as an amorphous in the matrix of the co-milled mixtures containing VA64, which helped to enhance drug dissolution. The ternary mixture composed of VA64, RH40, and probucol showed increased dissolution rates in both sink and non-sink conditions. It also had a higher oral bioavailability compared to the reference formulation. Dry-media milling of binary or ternary mixtures composed of drug, polymer and surfactant possibly have wide applications to improve dissolution rate and oral bioavailability of water-insoluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Mobility, bioavailability, and toxic effects of cadmium in soil samples

    International Nuclear Information System (INIS)

    Prokop, Z.; Cupr, P.; Zlevorova-Zlamalikova V.; Komarek, J.; Dusek, L.; Holoubek, I.

    2003-01-01

    Total concentration is not a reliable indicator of metal mobility or bioavailability in soils. The physicochemical form determines the behavior of metals in soils and hence the toxicity toward terrestrial biota. The main objectives of this study were the application and comparison of three approaches for the evaluation of cadmium behavior in soil samples. The mobility and bioavailability of cadmium in five selected soil samples were evaluated using equilibrium speciation (Windermere humic aqueous mode (WHAM)), extraction procedures (Milli-Q water, DMSO, and DTPA), and a number of bioassays (Microtox, growth inhibition test, contact toxicity test, and respiration). The mobility, represented by the water-extractable fraction corresponded well with the amount of cadmium in the soil solution, calculate using the WHAM (r 2 =0.96, P<0.001). The results of the ecotoxicologica evaluation, which represent the bioavailable fraction of cadmium, correlated well with DTPA extractability and also with the concentration of free cadmium ion, which is recognized as the most bioavailable metal form. The results of the WHAM as well as the results of extraction experiments showed a strong binding of cadmium to organic matter and a weak sorption of cadmium to clay minerals

  13. Dynamic speciation analysis and bioavailability of metals in aquatic systems

    NARCIS (Netherlands)

    Leeuwen, van H.P.; Town, R.M.; Buffle, J.; Cleven, R.F.M.J.; Davison, W.; Puy, J.; Riemsdijk, van W.H.; Sigg, L.

    2005-01-01

    Dynamic metal speciation analysis in aquatic ecosystems is emerging as a powerful basis for development of predictions of bioavailability and reliable risk assessment strategies. A given speciation sensor is characterized by an effective time scale or kinetic window that defines the measurable metal

  14. Prediction of Petroleum Hydrocarbon Bioavailability in Contaminated Soils and Sediments

    NARCIS (Netherlands)

    Cuypers, M.P.; Clemens, R.; Grotenhuis, J.T.C.; Rulkens, W.H.

    2001-01-01

    Recently, several laboratory methods have been developed for the prediction of contaminant bioavailability. So far, none of these methods has been extensively tested for petroleum hydrocarbons. In the present study we investigated solid-phase extraction and persulfate oxidation for the prediction of

  15. Bioavailability of metals-trace in sediments: a review

    International Nuclear Information System (INIS)

    Rodrigues, Rafaela E. de A.V.; Souza, Vivianne Lucia Bormann; Lima, Vanessa Lemos de; Hazin, Clovis Abrahao

    2014-01-01

    The chemical association of metals in sediments provides an indication of its release by physical, chemical and biological processes, with toxic effects under certain environmental conditions. Knowing about their chemical bonds in sediments, can recognize specific sources of pollution, and speciation of trace metals is important for bioavailability and toxicity to animals and plants. The accumulation of these particles in the sediment occur by the following mechanisms: a) adsorption to the finest particles; b) precipitating of the element in the form of compounds; c) co-precipitating of the element with iron and manganese oxides; d) complexation with organic matter; e) incorporation into the crystal lattice of minerals. Currently, five phases are considered when studying the bioavailability of trace elements in sediments: a) the exchangeable phase, MgCl 2 (causes saltiness change); b) leachable phase, (acetic acid causes pH change); c) reducible phase (hydroxylamine hydrochloride causes release of the bound metals linked to Fe and Mn oxides); d) oxidized phase, the peroxide hydrogen (cause the degradation of organic matter); e) the residual pseudo-phase, the aqua regia (cause release of metals associated to minerals). The first three phases are considered the most bioavailable. In the last two fractions, the metals are linked to sediment constituents and not bioavailable. The organic phase is relatively stable and the metal present therein are removed under oxidative conditions. Metals present in the pseudo-phase residual measure the degree of environmental pollution, since great amount of metals at this stage indicates a lower degree of pollution

  16. The efficacy of urine data in comparative bioavailability of proguanil ...

    African Journals Online (AJOL)

    The bioavailability of proguanil formulated as suppository, was compared to the tablet formulation in a bid to evaluate the utility of the suppository dosage form as means of administering proguanil in children and high-risk groups, such as sickle cell patients, who may not tolerate oral route of administration. The study was a ...

  17. Effect of antacids in didanosine tablet on bioavailability of isoniazid.

    OpenAIRE

    Gallicano, K; Sahai, J; Zaror-Behrens, G; Pakuts, A

    1994-01-01

    The antacids in two didanosine placebo tablets had no significant effect on the plasma pharmacokinetics of a single oral dose of 300 mg of isoniazid administered to 12 healthy volunteers. These results suggest that isoniazid bioavailability will be unaffected by the antacids in didanosine tablets when the two medications are administered simultaneously to human immunodeficiency virus-seropositive patients.

  18. Effect of antacids in didanosine tablet on bioavailability of isoniazid.

    Science.gov (United States)

    Gallicano, K; Sahai, J; Zaror-Behrens, G; Pakuts, A

    1994-04-01

    The antacids in two didanosine placebo tablets had no significant effect on the plasma pharmacokinetics of a single oral dose of 300 mg of isoniazid administered to 12 healthy volunteers. These results suggest that isoniazid bioavailability will be unaffected by the antacids in didanosine tablets when the two medications are administered simultaneously to human immunodeficiency virus-seropositive patients.

  19. Rapid persulfate oxidation predicts PAH bioavailability in soils and sediments

    NARCIS (Netherlands)

    Cuypers, M.P.; Grotenhuis, J.T.C.; Joziasse, J.; Rulkens, W.H.

    2000-01-01

    Persulfate oxidation was validated as a method to predict polycyclic aromatic hydrocarbon (PAH) bioavailability in soils and sediments. It was demonstrated for 14 field contaminated soils and sediments that residual PAH concentrations after a short (3 h) persulfate oxidation correspond well to

  20. USE OF PELLETED LETTUCE SEEDS IN BIOAVAILABILITY STUDIES

    Science.gov (United States)

    Lettuce (Latuca sativa L., cv. Buttercrunch) is one of the most common and sensitive test organisms, among plants, used in toxicology and bioavailability studies. Much of the available lettuce seeds in commercial channels are pelleted to allow for precision machine planting. Th...

  1. Bioavailability of folate from processed spinach in humans

    NARCIS (Netherlands)

    Castenmiller, J.J.M.; Poll, van de C.J.; West, C.E.; Brouwer, I.A.; Thomas, C.M.G.; Dusseldorp, van M.

    2000-01-01

    The effect of the food matrix and dietary fibre on the bioavailability of folate is not known. In a controlled, 3-week dietary intervention study, 28 men and 42 women were divided into six groups to receive either a control diet (n = 10), or the control diet plus 20 g/MJ per day (n = 12 per group)

  2. Induction of interleukin-6 by coal containing bioavailable iron is ...

    Indian Academy of Sciences (India)

    Coal mining causes health problems, such as pneumoconiosis. We have previously shown that prevalence of pneumoconiosis in workers from various coalmine regions positively correlates with levels of bioavailable iron (BAI) in the coals from that region. In the present study, the nature of reactive oxygen species formed ...

  3. Rumen microorganisms decrease bioavailability of inorganic selenium supplements

    Science.gov (United States)

    Despite the availaility of selenium (Se)-enriched trace mineral supplements, we have observed low Se status in cattle and sheep offered traditional inorganic Se supplements. Reasons for this may include inadequate intake or low bioavailability of inorganic Se sources. The objective of this study w...

  4. Bioavailability and stability of mercury sulfide in Armuchee (USA) soil

    International Nuclear Information System (INIS)

    Han, Fengxiang; Shiyab, Safwan; Su, Yi; Monts, David L.; Waggoner, Charles A.; Matta, Frank B.

    2007-01-01

    Because of the adverse effects of elemental mercury and mercury compounds upon human health, the U.S. Department of Energy (DOE) is engaged in an on-going effort to monitor and remediate mercury-contaminated DOE sites. In order to more cost effectively implement those extensive remediation efforts, it is necessary to obtain an improved understanding of the role that mercury and mercury compounds play in the ecosystem. We have conducted pilot scale experiments to study the bioavailability of mercury sulfide in an Armuchee (eastern US ) soil. The effects of plants and incubation time on chemical stability and bioavailability of HgS under simulated conditions of the ecosystem have been examined, as has the dynamics of the dissolution of mercury sulfide by various extractants. The results show that mercury sulfide in contaminated Armuchee soil was still to some extent bioavailable to plants. After planting, soil mercury sulfide is more easily dissolved by both 4 M and 12 M nitric acid than pure mercury sulfide reagent. Dissolution kinetics of soil mercury sulfide and pure chemical reagent by nitric acid are different. Mercury release by EDTA from HgS-contaminated soil increased with time of reaction and soil mercury level. Chelating chemicals increase the solubility and bioavailability of mercury in HgS-contaminated soil. (authors)

  5. Bioavailability of contaminants estimated from uptake rates into soil invertebrates

    International Nuclear Information System (INIS)

    Straalen, N.M. van; Donker, M.H.; Vijver, M.G.; Gestel, C.A.M. van

    2005-01-01

    It is often argued that the concentration of a pollutant inside an organism is a good indicator of its bioavailability, however, we show that the rate of uptake, not the concentration itself, is the superior predictor. In a study on zinc accumulation and toxicity to isopods (Porcellio scaber) the dietary EC 50 for the effect on body growth was rather constant and reproducible, while the internal EC 50 varied depending on the accumulation history of the animals. From the data a critical value for zinc accumulation in P. scaber was estimated as 53 μg/g/wk. We review toxicokinetic models applicable to time-series measurements of concentrations in invertebrates. The initial slope of the uptake curve is proposed as an indicator of bioavailability. To apply the dynamic concept of bioavailability in risk assessment, a set of representative organisms should be chosen and standardized protocols developed for exposure assays by which suspect soils can be evaluated. - Sublethal toxicity of zinc to isopods suggests that bioavailability of soil contaminants is best measured by uptake rates, not by body burdens

  6. BIOAVAILABILITY AND PHARMACOKINETICS OF NORFLOXACIN AFTER INTRAMUSCULAR ADMINISTRATION IN GOATS

    Directory of Open Access Journals (Sweden)

    WAJEEHA, F. H. KHAN AND I. JAVED

    2006-01-01

    Full Text Available Bioavailability and pharmacokinetics of two commercially available preparations of norfloxacin i.e. A (imported and B (locally prepared were determined in six healthy female goats after single intramuscular administration @ 5 mg/kg b.wt following crossover study design. The blood samples collected at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8 and 12 hours postmedication were also analysed for drug concentration by microbiological assay. Results revealed that preparation A showed higher (p<0.05 plasma drug levels than the preparation B at 1, 3, 6 and 8 hours after medication. Among bioavailability parameters AUC (g.h/ml and relative bioavailability (F% were higher for preparation A than the preparation B, while other parameters did not differ between the two preparations. Similarly, various pharmacokinetic parameters did not show any statistical difference between preparation A and B. The study revealed comparable elimination kinetics but different bioavailability of two commercial preparations of norfloxacin. It is concluded from the study that for optimal dosage regimen of drugs, the bioequivalence studies and kinetic behavior of the drugs are of paramount importance.

  7. In vitro evaluation of dietary compounds to reduce mercury bioavailability.

    Science.gov (United States)

    Jadán-Piedra, Carlos; Vélez, Dinoraz; Devesa, Vicenta

    2018-05-15

    Mercury in foods, in inorganic form [Hg(II)] or as methylmercury (CH 3 Hg), can have adverse effects. Its elimination from foods is not technologically viable. To reduce human exposure, possible alternatives might be based on reducing its intestinal absorption. This study evaluates the ability of 23 dietary components to reduce the amount of mercury that is absorbed and reaches the bloodstream (bioavailability). We determined their effect on uptake of mercury in Caco-2 cells, a model of intestinal epithelium, exposed to Hg(II) and CH 3 Hg standards and to swordfish bioaccessible fractions. Cysteine, homocysteine, glutathione, quercetin, albumin and tannic reduce bioavailability of both mercury species. Fe(II), lipoic acid, pectin, epigallocatechin and thiamine are also effective for Hg(II). Some of these strategies also reduce Hg bioavailability in swordfish (glutathione, cysteine, homocysteine). Moreover, extracts and supplements rich in these compounds are also effective. This knowledge may help to define dietary strategies to reduce in vivo mercury bioavailability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Speciation and bioavailability of copper in Lake Tjeukemeer

    NARCIS (Netherlands)

    Verweij, W.

    1991-01-01

    Chapter 1: introduction

    In this thesis an account is given of a research project dealing with the chemical speciation and bioavailability of copper in Lake Tjeukemeer, a lake in the north of the Netherlands. The reason for the initiation of this project was a lack of

  9. Iron bioavailability of maize hemoglobin in a Caco-2 cell culture model

    Science.gov (United States)

    Maize is an important staple crop in many parts of the world but has low iron bioavailability, in part due to its high phytate content. Hemoglobin is a form of iron that is highly bioavailable and its bioavailability is not inhibited by phytate. We hypothesize that maize hemoglobin is a highly bioav...

  10. Effect of dose increase or cimetidine co-administration on albendazole bioavailability

    NARCIS (Netherlands)

    Schipper, H. G.; Koopmans, R. P.; Nagy, J.; Butter, J. J.; Kager, P. A.; van Boxtel, C. J.

    2000-01-01

    The low bioavailability of albendazole affects the therapeutic response in patients with echinococcosis. Cimetidine co-administration is reported to improve bioavailability. To analyze the assumed dose-dependent bioavailability of albendazole, we administered 5 to 30 mg/kg albendazole to 6 male

  11. Simultaneous bilateral isolated greater trochanter fracture

    Directory of Open Access Journals (Sweden)

    Maruti Kambali

    2013-01-01

    Full Text Available A 48-year-old woman sustained simultaneous isolated bilateral greater trochanteric fracture, following a road traffic accident. The patient presented to us 1 month after the injury. She presented with complaints of pain in the left hip and inability to walk. Roentgenograms revealed displaced comminuted bilateral greater trochanter fractures. The fracture of the left greater trochanter was reduced and fixed internally using the tension band wiring technique. The greater trochanter fracture on the right side was asymptomatic and was managed conservatively. The patient regained full range of motion and use of her hips after a postoperative follow-up of 6 months. Isolated fractures of the greater trochanter are unusual injuries. Because of their relative rarity and the unsettled controversy regarding their etiology and pathogenesis, several methods of treatment have been advocated. Furthermore, the reports of this particular type of injury are not plentiful and the average textbook coverage afforded to this entity is limited. In our study we discuss the mechanism of injury and the various treatment options available.

  12. Processing ‘Ataulfo’ Mango into Juice Preserves the Bioavailability and Antioxidant Capacity of Its Phenolic Compounds

    Directory of Open Access Journals (Sweden)

    Ana Elena Quirós-Sauceda

    2017-09-01

    Full Text Available The health-promoting effects of phenolic compounds depend on their bioaccessibility from the food matrix and their consequent bioavailability. We carried out a randomized crossover pilot clinical trial to evaluate the matrix effect (raw flesh and juice of ‘Ataulfo’ mango on the bioavailability of its phenolic compounds. Twelve healthy male subjects consumed a dose of mango flesh or juice. Blood was collected for six hours after consumption, and urine for 24 h. Plasma and urine phenolics were analyzed by electrochemical detection coupled to high performance liquid chromatography (HPLC-ECD. Five compounds were identified and quantified in plasma. Six phenolic compounds, plus a microbial metabolite (pyrogallol were quantified in urine, suggesting colonic metabolism. The maximum plasma concentration (Cmax occurred 2–4 h after consumption; excretion rates were maximum at 8–24 h. Mango flesh contributed to greater protocatechuic acid absorption (49%, mango juice contributed to higher chlorogenic acid absorption (62%. Our data suggests that the bioavailability and antioxidant capacity of mango phenolics is preserved, and may be increased when the flesh is processed into juice.

  13. Uranium Speciation and Bioavailability in Aquatic Systems: An Overview

    Directory of Open Access Journals (Sweden)

    Scott J. Markich

    2002-01-01

    Full Text Available The speciation of uranium (U in relation to its bioavailability is reviewed for surface waters (fresh- and seawater and their sediments. A summary of available analytical and modeling techniques for determining U speciation is also presented. U(VI is the major form of U in oxic surface waters, while U(IV is the major form in anoxic waters. The bioavailability of U (i.e., its ability to bind to or traverse the cell surface of an organism is dependent on its speciation, or physicochemical form. U occurs in surface waters in a variety of physicochemical forms, including the free metal ion (U4+ or UO22+ and complexes with inorganic ligands (e.g., uranyl carbonate or uranyl phosphate, and humic substances (HS (e.g., uranyl fulvate in dissolved, colloidal, and/or particulate forms. Although the relationship between U speciation and bioavailability is complex, there is reasonable evidence to indicate that UO22+ and UO2OH+ are the major forms of U(VI available to organisms, rather than U in strong complexes (e.g., uranyl fulvate or adsorbed to colloidal and/or particulate matter. U(VI complexes with inorganic ligands (e.g., carbonate or phosphate and HS apparently reduce the bioavailability of U by reducing the activity of UO22+ and UO2OH+. The majority of studies have used the results from thermodynamic speciation modeling to support these conclusions. Time-resolved laser-induced fluorescence spectroscopy is the only analytical technique able to directly determine specific U species, but is limited in use to freshwaters of low pH and ionic strength. Nearly all of the available information relating the speciation of U to its bioavailability has been derived using simple, chemically defined experimental freshwaters, rather than natural waters. No data are available for estuarine or seawater. Furthermore, there are no available data on the relationship between U speciation and bioavailability in sediments. An understanding of this relationship has been

  14. Influence of hardness on the bioavailability of silver to a freshwater snail after waterborne exposure to silver nitrate and silver nanoparticles

    Science.gov (United States)

    Stoiber, Tasha L.; Croteau, Marie-Noele; Romer, Isabella; Tejamaya, Mila; Lead, Jamie R.; Luoma, Samuel N.

    2015-01-01

    The release of Ag nanoparticles (AgNPs) into the aquatic environment is likely, but the influence of water chemistry on their impacts and fate remains unclear. Here, we characterize the bioavailability of Ag from AgNO3 and from AgNPs capped with polyvinylpyrrolidone (PVP AgNP) and thiolated polyethylene glycol (PEG AgNP) in the freshwater snail, Lymnaea stagnalis, after short waterborne exposures. Results showed that water hardness, AgNP capping agents, and metal speciation affected the uptake rate of Ag from AgNPs. Comparison of the results from organisms of similar weight showed that water hardness affected the uptake of Ag from AgNPs, but not that from AgNO3. Transformation (dissolution and aggregation) of the AgNPs was also influenced by water hardness and the capping agent. Bioavailability of Ag from AgNPs was, in turn, correlated to these physical changes. Water hardness increased the aggregation of AgNPs, especially for PEG AgNPs, reducing the bioavailability of Ag from PEG AgNPs to a greater degree than from PVP AgNPs. Higher dissolved Ag concentrations were measured for the PVP AgNPs (15%) compared to PEG AgNPs (3%) in moderately hard water, enhancing Ag bioavailability of the former. Multiple drivers of bioavailability yielded differences in Ag influx between very hard and deionized water where the uptake rate constants (kuw, l g-1 d-1 ± SE) varied from 3.1 ± 0.7 to 0.2 ± 0.01 for PEG AgNPs and from 2.3 ± 0.02 to 1.3 ± 0.01 for PVP AgNPs. Modeling bioavailability of Ag from NPs revealed that Ag influx into L. stagnalis comprised uptake from the NPs themselves and from newly dissolved Ag.

  15. Origins and bioavailability of dissolved organic matter in groundwater

    Science.gov (United States)

    Shen, Yuan; Chapelle, Francis H.; Strom, Eric W.; Benner, Ronald

    2015-01-01

    Dissolved organic matter (DOM) in groundwater influences water quality and fuels microbial metabolism, but its origins, bioavailability and chemical composition are poorly understood. The origins and concentrations of dissolved organic carbon (DOC) and bioavailable DOM were monitored during a long-term (2-year) study of groundwater in a fractured-rock aquifer in the Carolina slate belt. Surface precipitation was significantly correlated with groundwater concentrations of DOC, bioavailable DOM and chromophoric DOM, indicating strong hydrological connections between surface and ground waters. The physicochemical and biological processes shaping the concentrations and compositions of DOM during its passage through the soil column to the saturated zone are conceptualized in the regional chromatography model. The model provides a framework for linking hydrology with the processes affecting the transformation, remineralization and microbial production of DOM during passage through the soil column. Lignin-derived phenols were relatively depleted in groundwater DOM indicating substantial removal in the unsaturated zone, and optical properties of chromophoric DOM indicated lower molecular weight DOM in groundwater relative to surface water. The prevalence of glycine, γ-aminobutyric acid, and d-enantiomers of amino acids indicated the DOM was highly diagenetically altered. Bioassay experiments were used to establish DOC-normalized yields of amino acids as molecular indicators of DOM bioavailability in groundwater. A relatively small fraction (8 ± 4 %) of DOC in groundwater was bioavailable. The relatively high yields of specific d-enantiomers of amino acids indicated a substantial fraction (15–34 %) of groundwater DOC was of bacterial origin.

  16. Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

    Science.gov (United States)

    Putcha, Lakshmi; Flynn, Chris; Paloski, W. H. (Technical Monitor)

    2000-01-01

    Space Motion Sickness (SMS) is often treated in space with promethazine (PMZ). Anecdotal reports indicate that the common side effects of drowsiness and decrements in cognitive performance that are associated with PMZ administration (50 mg IM on the ground, are absent or less pronounced in space suggesting I that-the bioavailability and/or pharmacodynamic behavior of PMZ may be altered during space flight. There are limited flight opportunities available for clinical research in space, the NRA-99, therefore, solicits research required to improve, or answer specific questions about in-flight diagnosis, therapy, and post-flight rehabilitation. We propose here, to establish a noninvasive method for pharmacodynamic and therapeutic assessment of PMZ. The specific objectives of the proposed research are to, 1. Establish a saliva to plasma ratio of PMZ after administration, 2. Estimate the relative bioavailability of the three flight-specific dosage forms of PMZ, and 3. Establish the dose-response relationship of PMZ. We will estimate the bioavailability of intramuscular injection (IM), oral tablets and rectal suppositories in normal subjects during ambulatory and antiorthostatic; bed rest (ABR) conditions using novel stable isotope techniques. Drowsiness, cognitive performance and salivary flow rate will be measured as a function of circulating drug concentrations after administration of three IM doses of PMZ. We will compare and contrast the bioavailability of PMZ during normal and ABR conditions to examine whether or not ABR can simulate changes in drug, absorption and availability similar to those anticipated in a microgravity environment. Results of this study will validate methods for an approved study with this medication awaiting a flight opportunity for manifestation. These data will also provide the much needed information on the dynamics and therapeutic index. of this medication and their implications on crew fatigue and performance in space. Key words

  17. Phase behavior and oral bioavailability of amorphous Curcumin.

    Science.gov (United States)

    Pawar, Yogesh B; Shete, Ganesh; Popat, Dharmesh; Bansal, Arvind K

    2012-08-30

    Amorphous form has been used as a means to improve aqueous solubility and oral bioavailability of poorly water soluble drugs. The objective of present study was to characterize thermodynamic and kinetic parameters of amorphous form of Curcumin (CRM-A). CRM-A was found to be a good glass former with glass transition temperature (T(g)) of 342.64K and critical cooling rate below 1K/min. CRM-A had a moderate tendency of crystallization and exhibited Kauzmann temperature (T(KS)) of 294.23 K. CRM-A was found to be fragile in nature as determined by T(m)/T(g) (1.32), C(p)(1 iq):C(p)(glass) (1.22), strength parameter (D75), T(K)/T(g) (0.85), and T(g)-T(K) (48.41). Theoretically predicted aqueous solubility advantage of 43.15-folds, was reduced to 17-folds under practical conditions. This reduction in solubility was attributed to water induced devitrification, as evident through PXRD and SEM analysis. Further, oral bioavailability study of CRM-A was undertaken to investigate bioavailability benefits, if any. C(max) was improved by 1.97-folds (statistically significant difference over control). However, oral bioavailability (AUC(0-)(∞)) was improved by 1.45-folds (statistically non significant difference over control). These observations pointed towards role of rapid devitrification of CRM-A in GIT milieu, thus limiting its oral bioavailability advantage. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Bioavailability of copper to rats from various foodstuffs and in the presence of different carbohydrates

    International Nuclear Information System (INIS)

    Johnson, P.E.; Stuart, M.A.; Bowman, T.D.

    1988-01-01

    Copper bioavailability was studied in rats using an extrinsic Cu label. Copper absorption from sunflower seeds (46%), peanuts (41%), cooked shrimp (50%), and cooked beef (40%) was as good or better than copper sulfate (46%). Copper from plant foods (sunflower seeds, garbanzo beans, peanuts) was absorbed equally as well as copper from animal foods (beef, shrimp, chicken liver), 39 +/- 7% vs 43 +/- 7%, P greater than 0.05. There was no significant difference in percentage Cu absorption between intrinsically labeled chicken liver and extrinsically labeled chicken liver. In a second experiment, Cu absorption was measured in the presence of glucose, fructose, sucrose, or cornstarch. There were no significant differences in Cu absorption due to different carbohydrates in a single meal

  19. Bioavailability of ginsenosides from white and red ginsengs in the simulated digestion model.

    Science.gov (United States)

    Kim, Eun Ok; Cha, Kwang Hyun; Lee, Eun Ha; Kim, Sang Min; Choi, Sang Won; Pan, Cheol-Ho; Um, Byung-Hun

    2014-10-15

    This study aims to investigate the bioavailability of ginsenosides during simulated digestion of white (WG) and red (RG) ginseng powders. Stability, bioaccessibility, and permeability of ginsenosides present in WG and RG were studied in a Caco-2 cell culture model coupled with oral, gastric, and small intestinal simulated digestion. Most ginsenosides in WG and RG were stable (>90%) during the simulated digestion. Bioaccessibilities of total ginsenosides during in vitro digestion of WG and RG were similar at approximately 85%. However, the bioaccessibility of protopanaxatriol type ginsenosides in the early food phase was greater than that of the protopanaxadiol type. The less polar RG ginsenosides were released later following the jejunum phase. Ginsenosides had low permeability (digestion and that ginsenosides are poorly absorbed in humans.

  20. Reduction in bioavailability of arsenic in contaminated irrigated soil using zinc and organic manure

    International Nuclear Information System (INIS)

    Batool, S.Q.

    2012-01-01

    The experiments were conducted to reduce the bioavailability of arsenic with application of organic and inorganic materials from contaminated soils irrigated with arsenic contaminated water. The results showed that the amount of extractable arsenic increased with submergence and decreased with application of organic material. However, amount of such decrease altered with inorganic material i.e. zinc and decrease was greater with As5Zn10 (0.17 to 0.0 mg/kg) where zinc was applied at the rate of 10 mg/kg. Among the different organic materials, arsenic content in soil remarkably decreased with application of farmyard manure. The decrease in arsenic content was less than upper toxic limit of arsenic in soil i.e.10mg/kg for paddy soils. Other manures also showed decrease in arsenic concentration but with desorption after half interval of treatment. Best remediating agents used for arsenic retention was zinc sulphate> organic compost >farmyard manure. (author)

  1. Formulation, optimization, and in vitro/in vivo evaluation of furosemide nanosuspension for enhancement of its oral bioavailability

    Science.gov (United States)

    Sahu, Bhanu P.; Das, Malay K.

    2014-04-01

    Furosemide is a poorly soluble diuretic used for treatment of hypertension and edema. It has very poor or variable oral bioavailability due to its reduced solubility in gastric fluid and reduced permeability in intestinal fluid. The aim of this study was to prepare nanosuspension of furosemide to enhance its oral bioavailability by increasing its dissolution in stomach where it has better permeability. Full factorial design was used for a systematic approach of formulation and optimization. The nanosuspensions were prepared by precipitation with ultrasonication method. Polyvinyl acetate was used for sterically stabilizing the nanosuspensions. The diffusing drug concentration and stabilizer were used as the factors and the particle size, polydispersity index, and drug release were selected as dependent variables and characterized. The effect of nanoprecipitation on enhancement of oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption studies in rats and compared to pure drug. Quality by design using full factorial design provided a systematic approach in optimizing nanosuspensions to produce products with desired quality. Stable nanosuspension were obtained with average size range of the precipitated nanoparticles between 150 and 300 nm and were found to be homogenous showing a narrow polydispersity index of 0.3 ± 0.1. The in vivo studies on rats revealed a significant increase in the oral absorbtion of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and C max values of nanosuspension were approximately 1.38- and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06 ± 0.02 % decrease in systolic blood pressure compared to 13.37 + 0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamic effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results

  2. Solid dispersion of dutasteride using the solvent evaporation method: Approaches to improve dissolution rate and oral bioavailability in rats.

    Science.gov (United States)

    Choi, Jin-Seok; Lee, Sang-Eun; Jang, Woo Suk; Byeon, Jong Chan; Park, Jeong-Sook

    2018-09-01

    The aim of this study was to develop a dutasteride (DUT) solid dispersion (SD) using hydrophilic substances to enhance its dissolution (%) and oral bioavailability in rats. DUT-SD formulations were prepared with various co-polymers using a solvent evaporation method. The physical properties of DUT-SD formulations were confirmed using field emission scanning electron microscopy (FE-SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy. The toxicity and oral bioavailability of DUT-SD formulations were evaluated. Tocopheryl polyethylene glycol-1000-succinate (TPGS) was chosen as the solubilizer; and methylene chloride, and Aerosil® 200 or microcrystalline cellulose (MCC) were chosen as the solvent and carrier, respectively, based on a solubility test and pre-dissolution study. The dissolution levels of DUT-SD formulations were 86.3 ± 2.3% (F15) and 95.1 ± 1.9% (F16) after 1 h, which were higher than those of the commercial product, i.e., Avodart® (75.8 ± 1.5%) in 0.1 N HCl containing 1% (w/v) sodium lauryl sulfate (SLS). The F16 formulation was found to be stable, after assessing its dissolution (%) and drug content (%) for 6 months. The DUT-SD formulations resulted in relative bioavailability (BA) values of 126.4% (F15) and 132.1% (F16), which were enhanced compared to that of Avodart®. Dissolution (%) and relative BA values were both increased by hydrogen interaction between TPGS and DUT. This study might contribute to a new formulation (powder) whose oral bioavailability is greater than that of Avodart® (soft capsule), which could facilitate to the use of the SD system during the production process. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Accounting for both local aquatic community composition and bioavailability in setting site-specific quality standards for zinc.

    Science.gov (United States)

    Peters, Adam; Simpson, Peter; Moccia, Alessandra

    2014-01-01

    Recent years have seen considerable improvement in water quality standards (QS) for metals by taking account of the effect of local water chemistry conditions on their bioavailability. We describe preliminary efforts to further refine water quality standards, by taking account of the composition of the local ecological community (the ultimate protection objective) in addition to bioavailability. Relevance of QS to the local ecological community is critical as it is important to minimise instances where quality classification using QS does not reconcile with a quality classification based on an assessment of the composition of the local ecology (e.g. using benthic macroinvertebrate quality assessment metrics such as River InVertebrate Prediction and Classification System (RIVPACS)), particularly where ecology is assessed to be at good or better status, whilst chemical quality is determined to be failing relevant standards. The alternative approach outlined here describes a method to derive a site-specific species sensitivity distribution (SSD) based on the ecological community which is expected to be present at the site in the absence of anthropogenic pressures (reference conditions). The method combines a conventional laboratory ecotoxicity dataset normalised for bioavailability with field measurements of the response of benthic macroinvertebrate abundance to chemical exposure. Site-specific QSref are then derived from the 5%ile of this SSD. Using this method, site QSref have been derived for zinc in an area impacted by historic mining activities. Application of QSref can result in greater agreement between chemical and ecological metrics of environmental quality compared with the use of either conventional (QScon) or bioavailability-based QS (QSbio). In addition to zinc, the approach is likely to be applicable to other metals and possibly other types of chemical stressors (e.g. pesticides). However, the methodology for deriving site-specific targets requires

  4. Systems biological approach of molecular descriptors connectivity: optimal descriptors for oral bioavailability prediction.

    Science.gov (United States)

    Ahmed, Shiek S S J; Ramakrishnan, V

    2012-01-01

    Poor oral bioavailability is an important parameter accounting for the failure of the drug candidates. Approximately, 50% of developing drugs fail because of unfavorable oral bioavailability. In silico prediction of oral bioavailability (%F) based on physiochemical properties are highly needed. Although many computational models have been developed to predict oral bioavailability, their accuracy remains low with a significant number of false positives. In this study, we present an oral bioavailability model based on systems biological approach, using a machine learning algorithm coupled with an optimal discriminative set of physiochemical properties. The models were developed based on computationally derived 247 physicochemical descriptors from 2279 molecules, among which 969, 605 and 705 molecules were corresponds to oral bioavailability, intestinal absorption (HIA) and caco-2 permeability data set, respectively. The partial least squares discriminate analysis showed 49 descriptors of HIA and 50 descriptors of caco-2 are the major contributing descriptors in classifying into groups. Of these descriptors, 47 descriptors were commonly associated to HIA and caco-2, which suggests to play a vital role in classifying oral bioavailability. To determine the best machine learning algorithm, 21 classifiers were compared using a bioavailability data set of 969 molecules with 47 descriptors. Each molecule in the data set was represented by a set of 47 physiochemical properties with the functional relevance labeled as (+bioavailability/-bioavailability) to indicate good-bioavailability/poor-bioavailability molecules. The best-performing algorithm was the logistic algorithm. The correlation based feature selection (CFS) algorithm was implemented, which confirms that these 47 descriptors are the fundamental descriptors for oral bioavailability prediction. The logistic algorithm with 47 selected descriptors correctly predicted the oral bioavailability, with a predictive accuracy

  5. Greater trochanteric fracture with occult intertrochanteric extension.

    Science.gov (United States)

    Reiter, Michael; O'Brien, Seth D; Bui-Mansfield, Liem T; Alderete, Joseph

    2013-10-01

    Proximal femoral fractures are frequently encountered in the emergency department (ED). Prompt diagnosis is paramount as delay will exacerbate the already poor outcomes associated with these injuries. In cases where radiography is negative but clinical suspicion remains high, magnetic resonance imaging (MRI) is the study of choice as it has the capability to depict fractures which are occult on other imaging modalities. Awareness of a particular subset of proximal femoral fractures, namely greater trochanteric fractures, is vital for both radiologists and clinicians since it has been well documented that they invariably have an intertrochanteric component which may require surgical management. The detection of intertrochanteric or cervical extension of greater trochanteric fractures has been described utilizing MRI but is underestimated with both computed tomography (CT) and bone scan. Therefore, if MRI is unavailable or contraindicated, the diagnosis of an isolated greater trochanteric fracture should be met with caution. The importance of avoiding this potential pitfall is demonstrated in the following case of an elderly woman with hip pain and CT demonstrating an isolated greater trochanteric fracture who subsequently returned to the ED with a displaced intertrochanteric fracture.

  6. Butterfly valves: greater use in power plants

    International Nuclear Information System (INIS)

    McCoy, M.

    1975-01-01

    Improvements in butterfly valves, particularly in the areas of automatic control and leak tightness are described. The use of butterfly valves in nuclear power plants is discussed. These uses include service in component cooling, containment cooling, and containment isolation. The outlook for further improvements and greater uses is examined. (U.S.)

  7. Greater Somalia, the never-ending dream?

    DEFF Research Database (Denmark)

    Zoppi, Marco

    2015-01-01

    This paper provides an historical analysis of the concept of Greater Somalia, the nationalist project that advocates the political union of all Somali-speaking people, including those inhabiting areas in current Djibouti, Ethiopia and Kenya. The Somali territorial unification project of “lost...

  8. Dietary genistein supplementation in laying broiler breeder hens alters the development and metabolism of offspring embryos as revealed by hepatic transcriptome analysis.

    Science.gov (United States)

    Lv, Zengpeng; Fan, Hao; Zhang, Beibei; Ning, Chao; Xing, Kun; Guo, Yuming

    2018-03-08

    Genistein (GEN) is a type of isoflavone mainly derived from soy products. In this experiment, we added 40 and 400 mg/kg GEN to the diet of laying broiler breeder hens to clarify the maternal effects of GEN on the development and metabolism of chick embryos. GEN treatment at 40 mg/kg increased embryonic length, weight, and liver index, as well as the width of the proliferative zone in the tibial growth plate of chick embryos. Gene ontology (GO) cluster analysis of the hepatic transcriptome showed that GEN treatment promoted embryonic development and cell proliferation. Low-dose GEN treatment increased insulin growth factor-binding protein (IGFBP)3 mRNA expression in the embryonic liver, whereas high-dose GEN treatment increased IGFBP5 expression and activated the apoptosis and protein tyrosine kinase signaling pathways. Furthermore, adding supplemental GEN to the diet of hens promoted the glycolysis process in the embryonic liver through the insulin-signaling pathway, upregulated target genes (phosphoglucomutase-2, hexokinase 1, dihydroxyacetone phosphate by aldolase, phosphofructokinase, platelet, and enolase 2), and enhanced the transport of carboxylic acids and cholesterol and the synthesis of unsaturated fatty acid (arachidonic acid) in the embryonic liver through upregulation of liver X receptor, sterol regulatory element-binding protein 1, and patatin-like phospholipase A. Additionally, GEN treatment increased fatty acid β-oxidation and Na + /K + -ATPase activity in the embryonic liver through activation of peroxisome proliferator-activated receptors (PPARs; PPARα and PPARδ) and the AMPK signaling pathway, which could provide energy for embryonic development. In addition, GEN treatment in hens increased superoxide dismutase activity and metallothionein expression in the chick embryonic liver and promoted lymphocyte proliferation through upregulation of mRNA expression of CDKN1A, IL12RB1, Sox11, PRKAR1A, PRKCQ, and TCF3. The improved immunity and antioxidant

  9. Estrogen, progesterone, and genistein differentially regulate levels of expression of α-, β-, and γ-epithelial sodium channel (ENaC) and α-sodium potassium pump (Na⁺/K⁺-ATPase) in the uteri of sex steroid-deficient rats.

    Science.gov (United States)

    Chinigarzadeh, Asma; Muniandy, Sekaran; Salleh, Naguib

    2015-10-01

    Estrogen, progesterone, and genistein could induce changes in uterine fluid volume and Na(+) concentration. Progesterone upregulates expression of epithelial sodium channel (ENaC) and Na(+)/K(+)-ATPase which contributed toward these changes. However, effects of estrogen and genistein were unknown. This study therefore investigated changes in expression of these proteins in the uterus under estrogen, progesterone, and genistein influences to further understand mechanisms underlying sex steroids and phytoestrogen effects on uterine fluid Na(+) regulation. In this study, uteri of ovariectomized female rats receiving 7-day treatment with genistein (25, 50, and 100 mg/kg/day), estrogen (0.8 × 10(-4) mg/kg/day), or progesterone (4 mg/kg/day) were harvested, and expression levels of α-, β-, and γ-ENaC proteins and messenger RNAs (mRNAs) and α-Na(+)/K(+)-ATPase protein were determined by Western blotting (proteins) and real-time polymerase chain reaction (mRNA). Meanwhile, distribution of α-, β-, and γ-ENaC and α-Na(+)/K(+)-ATPase proteins in the uterus was identified by immunohistochemistry. Our findings indicated that expression of α-, β-, and γ-ENaC proteins and mRNAs and α-Na(+)/K(+)-ATPase protein were enhanced under progesterone influence. Lower expressions were noted under estrogen and genistein influences compared to progesterone. Under estrogen, progesterone, and genistein influences, α- and β-ENaC were distributed at apical membrane and γ-ENaC was distributed at apical and basolateral membranes of uterine luminal epithelia. Under progesterone influence, α-Na(+)/K(+)-ATPase was highly expressed at basolateral membrane. In conclusion, high expression of α-, β-, and γ-ENaC and α-Na(+)/K(+)-ATPase under progesterone influence would contribute toward increased uterine fluid Na(+) reabsorption, whereas lesser expression of these proteins under estrogen and genistein influences would contribute toward lower reabsorption of uterine fluid Na

  10. Importance of M2-M3 loop in governing properties of genistein at the α7 nicotinic acetylcholine receptor inferred from α7/5-HT3A chimera.

    Science.gov (United States)

    Grønlien, Jens Halvard; Ween, Hilde; Thorin-Hagene, Kirsten; Cassar, Steven; Li, Jinhe; Briggs, Clark A; Gopalakrishnan, Murali; Malysz, John

    2010-11-25

    Genistein and 5-hydroxyindole (5-HI) potentiate the α7 nicotinic acetylcholine receptor current by primarily increasing peak amplitude, a property of type I α7 positive allosteric modulation. In this study, the effects of these two compounds were investigated at two different α7/5-HT(3) chimeras (chimera 1, comprising of extracellular α7 N-terminus fused to the remainder of 5-HT(3A), and chimera 2 containing an additional α7 encoded M2-M3 loop), and wild-type α7 and 5-HT(3A) receptors. Agonist-evoked responses, examined by expression of the chimeras in Xenopus laevis oocytes or HEK-293 cells, revealed that currents decayed slower and compounds {rank order: N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987)~2-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-5-phenyl-1,3,4-oxadiazole (NS6784)>acetylcholine>choline} were more potent in chimera 2 than chimera 1 or α7 receptors. In chimera 2, genistein and 5-HI potentiated agonist-evoked responses (EC(50): 4-5 μM for genistein and 300-500 μM for 5-HI) and at higher concentrations evoked current directly consistent with ago-allosteric modulation. At chimera 1 and 5-HT(3A) receptors, neither compound directly evoked any current and 5-HI, only at chimera 1, was able to potentiate agonist-evoked responses. Genistein and 5-HI did not inhibit the binding of the α7 agonist [(3)H](1S,4S)-2,2-dimethyl-5-(6-phenylpyridazin-3-yl)-5-aza-2-azoniabicyclo[2.2.1] heptane ([(3)H]A-585539) to rat brain or chimera 2. In summary, this study supports the role of the M2-M3 loop being critical for the positive allosteric effect of genistein, but not 5-HI, and in agonist-evoked response fine-tuning. The identification of distinct α7 receptor modulatory sites offers unique opportunities for developing CNS therapeutics and understanding its pharmacology. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Utilization of wind energy in greater Hanover

    International Nuclear Information System (INIS)

    Sahling, U.

    1993-01-01

    Since the beginning of the Eighties, the association of communities of Greater Hanover has dealt intensively with energy and ecopolitical questions in the scope of regional planning. Renewable energy sources play a dominant role in this context. This brochure is the third contribution to the subject ''Energy policy and environmental protection''. Experts as well as possibly interested parties are addressed especially. For all 8 contributions contained, separate entries have been recorded in this database. (BWI) [de

  12. Small cities face greater impact from automation

    OpenAIRE

    Frank, Morgan R.; Sun, Lijun; Cebrian, Manuel; Youn, Hyejin; Rahwan, Iyad

    2017-01-01

    The city has proven to be the most successful form of human agglomeration and provides wide employment opportunities for its dwellers. As advances in robotics and artificial intelligence revive concerns about the impact of automation on jobs, a question looms: How will automation affect employment in cities? Here, we provide a comparative picture of the impact of automation across U.S. urban areas. Small cities will undertake greater adjustments, such as worker displacement and job content su...

  13. The Greater Sekhukhune-CAPABILITY outreach project.

    Science.gov (United States)

    Gregersen, Nerine; Lampret, Julie; Lane, Tony; Christianson, Arnold

    2013-07-01

    The Greater Sekhukhune-CAPABILITY Outreach Project was undertaken in a rural district in Limpopo, South Africa, as part of the European Union-funded CAPABILITY programme to investigate approaches for capacity building for the translation of genetic knowledge into care and prevention of congenital disorders. Based on previous experience of a clinical genetic outreach programme in Limpopo, it aimed to initiate a district clinical genetic service in Greater Sekhukhune to gain knowledge and experience to assist in the implementation and development of medical genetic services in South Africa. Implementing the service in Greater Sekhukhune was impeded by a developing staff shortage in the province and pressure on the health service from the existing HIV/AIDS and TB epidemics. This situation underscores the need for health needs assessment for developing services for the care and prevention of congenital disorders in middle- and low-income countries. However, these impediments stimulated the pioneering of innovate ways to offer medical genetic services in these circumstances, including tele-teaching of nurses and doctors, using cellular phones to enhance clinical care and adapting and assessing the clinical utility of a laboratory test, QF-PCR, for use in the local circumstances.

  14. Operational technology for greater confinement disposal

    International Nuclear Information System (INIS)

    Dickman, P.T.; Vollmer, A.T.; Hunter, P.H.

    1984-12-01

    Procedures and methods for the design and operation of a greater confinement disposal facility using large-diameter boreholes are discussed. It is assumed that the facility would be located at an operating low-level waste disposal site and that only a small portion of the wastes received at the site would require greater confinement disposal. The document is organized into sections addressing: facility planning process; facility construction; waste loading and handling; radiological safety planning; operations procedures; and engineering cost studies. While primarily written for low-level waste management site operators and managers, a detailed economic assessment section is included that should assist planners in performing cost analyses. Economic assessments for both commercial and US government greater confinement disposal facilities are included. The estimated disposal costs range from $27 to $104 per cubic foot for a commercial facility and from $17 to $60 per cubic foot for a government facility. These costs are based on average site preparation, construction, and waste loading costs for both contact- and remote-handled wastes. 14 figures, 22 tables

  15. Effect of Genistein and 17-β Estradiol on the Viability and Apoptosis of Human Hepatocellular Carcinoma HepG2 cell line

    Directory of Open Access Journals (Sweden)

    Masumeh Sanaei

    2017-01-01

    Full Text Available Background: One of the most lethal cancers is hepatocellular carcinoma (HCC. Genistein (GE is a choice compound for treatment of certain types of cancer. Phytoestrogens are plant derivatives that bear a structural similarity to 17-β estradiol (E2 and act in a similar manner. They are a group of lipophillic plant compounds with tumorigenic and antitumorigenic effects. E2 has stimulatory and inhibitory effects on cancer cell lines. This study was designed to investigate the antiproliferative and apoptotic effects of GE and E2 on the HCC HepG2 cell line. Materials and Methods: HepG2 cells were cultured and treated with various concentrations of GE and E2 and then 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromideand flow cytometry assay were performed to determine cell viability and apoptosis. Results: GE and E2 induced apoptosis and inhibited cell growth significantly. Reduction of cell viability by 50% required 20 μM E2 for E2-treatment groups and 20 μMGE for GE-treatment groups. The percentage of the GE-treated apoptotic cells was reduced by about 35%, 42%, and 47% (P < 0.001 and that of E2-treated groups 34%, 39%, and 42% (P < 0.001 after 24, 48, and 72 h, respectively. Conclusions: Our experimental work clearly demonstrated that GE and E2 exhibited significant antiproliferative and apoptotic effects on human HCC HepG2 cells.

  16. Development and In Vitro Evaluation of Vitamin E-Enriched Nanoemulsion Vehicles Loaded with Genistein for Chemoprevention Against UVB-Induced Skin Damage.

    Science.gov (United States)

    Brownlow, Bill; Nagaraj, Vinay J; Nayel, Amy; Joshi, Megha; Elbayoumi, Tamer

    2015-10-01

    There is a great need for effective protection against cutaneous pathologies arising from chronic exposure to harmful solar UVB radiations. A promising pharmaceutical strategy to improve the efficacy of chemotherapeutic/preventative natural compounds (e.g., soy isoflavone Genistein, Gen) is to enhance their dermal delivery using nanoemulsion (NE) formulations. This report investigates the development of nanoemulsified tocotrienol(T3)-rich fraction of red palm oil (Tocomin®), to yield an optimal NE delivery system for dermal photoprotection (z-average size vitamin E TPGS (TPGS) as cosurfactant was significantly superior to formulations that utilized Lutrol® F68 (LF68) as the cosurfactant. A ratio of 60:40 of SHS15-TPGS-NE was further identified as lead Tocomin® NE topical platform using in vitro pharmaceutical skin reactivity studies that assess cutaneous irritancy and cytotoxicity. Prototype Tocomin® NE loaded with the antiphotocarcinogenic molecule Gen (Gen-Tocomin® NE) showed slow-release profile in both liquid and cream forms. Gen-Tocomin® NE also showed excellent biocompatibility, and provided substantial UVB protection to cultured subcutaneous L929 fibroblasts, indicating the great potential of our Tocomin® NE warranting further prototype development as topical pharmaceutical platform for skin photoprotection applications. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. A Longitudinal Study of the Effect of Genistein on Bone in Two Different Murine Models of Diminished Estrogen-Producing Capacity

    Directory of Open Access Journals (Sweden)

    Susan Reinwald

    2010-01-01

    Full Text Available This experiment was designed to assess the capacity of dietary genistein (GEN, to attenuate bone loss in ovariectomized (OVX and ovary-intact VCD-treated mice. Pretreatment of mice with 4-vinylcyclohexene diepoxide (VCD gradually and selectively destroys ovarian follicles whilst leaving ovarian androgen-producing cells largely intact. VCD induces a perimenopause-like condition prior to the onset of reproductive acyclicity. Sixteen-week-old C57BL/6J mice were randomized to five treatment groups: sham(SHM, OVX, SHM + VCD, OVX + GEN, and SHM + VCD + GEN. In vivo, blood samples were drawn for hormone and isoflavone analyses, estrous cycles were monitored, and X-ray imaging was performed to assess changes in bone parameters. Following sacrifice, ovaries were assessed histologically, bone microarchitecture was evaluated via microcomputed tomography, and bone mechanical properties were measured. Some effects of GEN were observed in OVX mice, but GEN effects were not able to be evaluated in VCD-treated mice due to the subtle diminution of bone during the 4 months of this experiment.

  18. Perinatal exposure to genistein, a soy phytoestrogen, improves spatial learning and memory but impairs passive avoidance learning and memory in offspring.

    Science.gov (United States)

    Kohara, Yumi; Kuwahara, Rika; Kawaguchi, Shinichiro; Jojima, Takeshi; Yamashita, Kimihiro

    2014-05-10

    This study investigated the effects of perinatal genistein (GEN) exposure on the central nervous system of rat offspring. Pregnant dams orally received GEN (1 or 10 mg/kg/day) or vehicle (1 ml/kg/day) from gestation day 10 to postnatal day 14. In order to assess the effects of GEN on rat offspring, we used a battery of behavioral tests, including the open-field, elevated plus-maze, MAZE and step-through passive avoidance tests. MAZE test is an appetite-motivation test, and we used this mainly for assessing spatial learning and memory. In the MAZE test, GEN groups exhibited shorter latency from start to goal than the vehicle-treated group in both sexes. On the other hand, performances in the step-through passive avoidance test were non-monotonically inhibited by GEN in both sexes, and a significant difference was observed in low dose of the GEN-treated group compared to the vehicle-treated group in female rats. Furthermore, we found that perinatal exposure to GEN did not significantly alter locomotor activity or emotionality as assessed by the open-field and elevated-plus maze tests. These results suggest that perinatal exposure to GEN improved spatial learning and memory of rat offspring, but impaired their passive avoidance learning and memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin.

    Science.gov (United States)

    Ji, Hongyu; Tang, Jingling; Li, Mengting; Ren, Jinmei; Zheng, Nannan; Wu, Linhua

    2016-01-01

    The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin. The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin. The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p curcumin for SLNs was significantly improved (p curcumin solution. Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.

  20. Copper availability and bioavailability are controlled by rhizosphere pH in rape grown in an acidic Cu-contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    Chaignon, Valerie; Quesnoit, Marie [INRA, UMR 1222 Eco and Sols Ecologie fonctionnelle and Biogeochimie des Sols (INRA-IRD-SupAgro), Place Viala, F-34060 Montpellier (France); Hinsinger, Philippe, E-mail: philippe.hinsinger@supagro.inra.f [INRA, UMR 1222 Eco and Sols Ecologie fonctionnelle and Biogeochimie des Sols (INRA-IRD-SupAgro), Place Viala, F-34060 Montpellier (France)

    2009-12-15

    We evaluated how root-induced changes in rhizosphere pH varied and interacted with Cu availability and bioavailability in an acidic soil. Rape was grown on a Cu-contaminated acidic soil, which had been limed at 10 rates. Soil Cu bioavailability was not influenced by liming. However, liming significantly decreased CaCl{sub 2}-extracted Cu for pH between 3.7 and 5.1. Little effect was found for pH above 5.1. For soil pH < 4.4, CaCl{sub 2}-Cu contents were smaller in rhizosphere than uncropped soil. Rhizosphere alkalisation occurred at pH < 4.8, while acidification occurred at greater pH. This explained the changes of CaCl{sub 2}-Cu in the rhizosphere at low pH and the absence of pH dependency of Cu bioavailability to rape. In addition, apoplastic Cu in roots increased with increasing soil pH, most probably as a result of increased dissociation and affinity of cell wall compounds for Cu. - Root-induced increase in pH reduces Cu availability in the rhizosphere and Cu bioavailability to rape.

  1. Effects of the amendment of biochars and carbon nanotubes on the bioavailability of hexabromocyclododecanes (HBCDs) in soil to ecologically different species of earthworms.

    Science.gov (United States)

    Li, Bing; Zhu, Hongkai; Sun, Hongwen; Xu, Jiayao

    2017-03-01

    Biochar is a promising material used in soil amendment and carbon nanotubes may enter soil due to its increasing application. These carbonaceous materials may change the bioavailability of pollutants in soil. In this concern, 0.5% w/w multi-walled carbon nanotubes (MWCNTs) and 3 corn-straw biochars acquired at different pyrolyzing temperatures were used in soil amendment and their influences on the bioavailability of hexabromocyclododecanes (HBCDs), a brominated flame retardant, to 2 ecologically different earthworm species were studied. The amendment of 4 carbonaceous materials all reduced the bioaccumulation of HBCDs in earthworms by 18.2%-67.3%, which varied depending on the type of carbonaceous materials and the pyrolyzing temperature of biochars. The reduction in HBCDs uptake by Eisenia fetida (an epigeic species) was greater than by Metaphire guillelmi (an anecic species). The 2 earthworm species both showed bioaccumulative selectivity on certain HBCD diastereoisomer and enantiomer in the amended soils, which was similar to that in the control soil. Moreover, Tenax-assisted HBCDs desorption test was carried out for the simulation of their bioavailability. The rapid desorption fraction (F rap ), total desorption (15 d), and 24 h desorption all correlated well with the uptake of HBCDs in the earthworms, suggesting that the 24 h-desorption, due to its easy availability, can be a good proxy to predict the bioavailability of HBCDs to earthworms in soil. Copyright © 2016. Published by Elsevier Ltd.

  2. Acetylated Hyaluronic Acid: Enhanced Bioavailability and Biological Studies

    Directory of Open Access Journals (Sweden)

    Carmela Saturnino

    2014-01-01

    Full Text Available Hyaluronic acid (HA, a macropolysaccharidic component of the extracellular matrix, is common to most species and it is found in many sites of the human body, including skin and soft tissue. Not only does HA play a variety of roles in physiologic and in pathologic events, but it also has been extensively employed in cosmetic and skin-care products as drug delivery agent or for several biomedical applications. The most important limitations of HA are due to its short half-life and quick degradation in vivo and its consequently poor bioavailability. In the aim to overcome these difficulties, HA is generally subjected to several chemical changes. In this paper we obtained an acetylated form of HA with increased bioavailability with respect to the HA free form. Furthermore, an improved radical scavenging and anti-inflammatory activity has been evidenced, respectively, on ABTS radical cation and murine monocyte/macrophage cell lines (J774.A1.

  3. Bioavailability in rats of metal adsorbed to soils

    International Nuclear Information System (INIS)

    Rubenstein, R.; Griffin, S.; Irene, S.; DeRosa, C.; Choudhury, H.

    1990-01-01

    The toxicity of metals to humans and animals has been well documented, however little data are available on the physiological bioavailability of metals from various soil types. These studies were designed to assess the bioavailability of sodium 75 selenate (NaS), 63 nickel chloride (NiCl) and 109 cadmium chloride (CdCl) adsorbed to sand or clay loam in rats. Each test compound was administered in seven dose groups: Group 1 - intravenously, Group 2 and 3 - oral aqueous solution by gavage, Groups 4-7 - aqueous suspension adsorbed to each soil type by gavage. Blood was collected from the jugular vein at intervals up to 48 hours post dosing and analyzed for radio-activity. Both NiCl and CdCl were poorly adsorbed from the soils. Approximately 3% of the CdCl bound to sand and 1.5% of the NiCl bound to clay loam were absorbed into the bloodstream. Approximately 0.5% and 0.1% of the CdCl bound to sand and clay, respectively were absorbed. NaS was well absorbed following oral administration with approximately 85% of the compound bound to sand and 94% bound to clay being absorbed into the blood. Bioavailability of metals from soil appears to be primarily affected by the ionic state of the metal. Anions, such as selenium, are more mobile in an acid environment and may leach more readily from soil. Cations, such as Ni and Cd may bind to soil more tightly, thus soil type becomes a factor affecting bioavailability

  4. Bioavailability of trans-resveratrol from red wine in humans.

    Science.gov (United States)

    Vitaglione, Paola; Sforza, Stefano; Galaverna, Gianni; Ghidini, Cristiana; Caporaso, Nicola; Vescovi, Pier Paolo; Fogliano, Vincenzo; Marchelli, Rosangela

    2005-05-01

    Many in vitro studies demonstrated significant biological effects of trans-resveratrol. Thus, understanding the rate of intestinal absorption and metabolization in vivo of trans-resveratrol is the prerequisite to evaluate its potential health impact. Bioavailability studies mainly in animals or in humans using the pure compound at very high doses were performed. In this work, trans-resveratrol bioavailability from a moderate consumption of red wine in 25 healthy humans has been studied by three different experiments. The wine ingestion was associated to three different dietary approaches: fasting, a standard meal, a meal with high and low amount of lipids. Trans-resveratrol 3- and 4'-glucuronides were synthesized, purified, and characterized as pure standards. Bioavailability data were obtained by measuring the concentration of free, 3-glucuronide and 4'-glucuronide trans-resveratrol by high-performance liquid chromatography (HPLC), both with ultraviolet (UV) and mass spectrometry (MS) detection, in serum samples taken at different times after red wine administration. Free trans-resveratrol was found, in trace amounts, only in some serum samples collected 30 min after red wine ingestion while after longer times resveratrol glucuronides predominated. Trans-resveratrol bioavailability was shown to be independent from the meal or its lipid content. The finding in human serum of trans-resveratrol glucuronides, rather than the free form of the compound, with a high interindividual variability, raises some doubts about the health effects of dietary resveratrol consumption and suggests that the benefits associated to red wine consumption could be probably due to the whole antioxidant pool present in red wine.

  5. Bioavailability of two oral formulations of triazolam using radioreceptor assay

    Energy Technology Data Exchange (ETDEWEB)

    Lapka, R; Cepelakova, H; Rejholec, V; Franc, Z

    1986-04-01

    The radioreceptor assay (RRA) was used to quantitate plasma triazolam concentration in eight female volunteers following single 0.5 mg doses of two tablet formulations in a cross-over study. Bioavailability in terms of area under the plasma concentration versus time curve, maximum plasma concentration, time to maximum, and mean residence time was not statistically significantly different from one formulation to the other.

  6. Relative bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension.

    Science.gov (United States)

    Clemens, Pamela L; Cloyd, James C; Kriel, Robert L; Remmel, Rory P

    2007-01-01

    Maintenance of effective drug concentrations is essential for adequate treatment of epilepsy. Some antiepileptic drugs can be successfully administered rectally when the oral route of administration is temporarily unavailable. Oxcarbazepine is a newer antiepileptic drug that is rapidly converted to a monohydroxy derivative, the active compound. This study aimed to characterise the bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension using a randomised, crossover design in ten healthy volunteers. Two subjects received 300 mg doses of oxcarbazepine suspension via rectal and oral routes and eight received 450 mg doses. A washout period of at least 2 weeks elapsed between doses. The rectal dose was diluted 1:1 with water. Blood samples and urine were collected for 72 hours post-dose. Adverse effects were assessed at each blood collection time-point using a self-administered questionnaire. Plasma was assayed for oxcarbazepine and monohydroxy derivative; urine was assayed for monohydroxy derivative and monohydroxy derivative-glucuronide. Maximum plasma concentration (C(max)) and time to reach C(max) (t(max)) were obtained directly from the plasma concentration-time curves. The areas under the concentration-time curve (AUCs) were determined via non-compartmental analysis. Relative bioavailability was calculated and the C(max) and AUCs were compared using Wilcoxon signed-rank tests. Mean relative bioavailability calculated from plasma AUCs was 8.3% (SD 5.5%) for the monohydroxy derivative and 10.8% (SD 7.3%) for oxcarbazepine. Oxcarbazepine and monohydroxy derivative C(max) and AUC values were significantly lower following rectal administration (p effects were headache and fatigue with no discernible differences between routes. Monohydroxy derivative bioavailability following rectal administration of oxcarbazepine suspension is significantly lower than following oral administration, most likely because of poor oxcarbazepine water

  7. Antimalarial Bioavailability and Disposition of Artesunate in Acute Falciparum Malaria

    OpenAIRE

    Newton, Paul; Suputtamongkol, Yupin; Teja-Isavadharm, Paktiya; Pukrittayakamee, Sasithon; Navaratnam, V; Bates, Imelda; White, Nicholas

    2000-01-01

    The pharmacokinetic properties of oral and intravenous artesunate (2 mg/kg of body weight) were studied in 19 adult patients with acute uncomplicated Plasmodium falciparum malaria by using a randomized crossover design. A sensitive bioassay was used to measure the antimalarial activity in plasma which results from artesunate and its principal metabolite, dihydroartemisinin. The oral study was repeated with 15 patients during convalescence. The mean absolute oral bioavailability of the antimal...

  8. Solubility and bioavailability of stabilized amorphous calcium carbonate.

    Science.gov (United States)

    Meiron, Oren E; Bar-David, Elad; Aflalo, Eliahu D; Shechter, Assaf; Stepensky, David; Berman, Amir; Sagi, Amir

    2011-02-01

    Since its role in the prevention of osteoporosis in humans was proven some 30 years ago, calcium bioavailability has been the subject of numerous scientific studies. Recent technology allowing the production of a stable amorphous calcium carbonate (ACC) now enables a bioavailability analysis of this unique form of calcium. This study thus compares the solubility and fractional absorption of ACC, ACC with chitosan (ACC-C), and crystalline calcium carbonate (CCC). Solubility was evaluated by dissolving these preparations in dilute phosphoric acid. The results demonstrated that both ACC and ACC-C are more soluble than CCC. Fractional absorption was evaluated by intrinsically labeling calcium carbonate preparations with (45)Ca, orally administrated to rats using gelatin capsules. Fractional absorption was determined by evaluating the percentage of the administrated radioactive dose per milliliter that was measured in the serum, calcium absorption in the femur, and whole-body retention over a 34-hour period. Calcium serum analysis revealed that calcium absorption from ACC and ACC-C preparations was up to 40% higher than from CCC, whereas retention of ACC and ACC-C was up to 26.5% higher than CCC. Absorbed calcium in the femurs of ACC-administrated rats was 30% higher than in CCC-treated animals, whereas 15% more calcium was absorbed following ACC-C treatment than following CCC treatment. This study demonstrates the enhanced solubility and bioavailability of ACC over CCC. The use of stable ACC as a highly bioavailable dietary source for calcium is proposed based on the findings of this study. Copyright © 2011 American Society for Bone and Mineral Research.

  9. In Vitro Bioavailability Study of an Antiviral Compound Enisamium Iodide

    OpenAIRE

    Eleonore Haltner-Ukomadu; Svitlana Gureyeva; Oleksii Burmaka; Andriy Goy; Lutz Mueller; Grygorii Kostyuk; Victor Margitich

    2018-01-01

    An investigation into the biopharmaceutics classification and a study of the in vitro bioavailability (permeability and solubility) of the antiviral compound enisamium iodide (4-(benzylcarbamoyl)-1-methylpyridinium iodide) were carried out. The solubility of enisamium iodide was determined in four different buffers. Apparent intestinal permeability (Papp) of enisamium iodide was assessed using human colon carcinoma (Caco-2) cells at three concentrations. The solubility of enisamium iodide in ...

  10. Stable isotope studies of nicotine kinetics and bioavailability

    International Nuclear Information System (INIS)

    Benowitz, N.L.; Jacob, P. III; Denaro, C.; Jenkins, R.

    1991-01-01

    The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine

  11. Bioavailability of phosphorus from composts and struvite in acid soils

    Directory of Open Access Journals (Sweden)

    Carmo Horta

    Full Text Available ABSTRACT The objective of this study was to assess the type and fractions of phosphorus (P forms in composts and struvite and how these P forms affect the bioavailability of P in the soil. P fertilization was performed with compost from sewage sludge (CSS, compost from poultry litter (CPL and struvite (SV and compared with single superphosphate (SSP. P forms were quantified through a sequential fractionation scheme. The first extraction was performed with H2O, the second with 0.5 M NaHCO3, the third with 0.1 M NaOH and the fourth with 1 M HCl. The release of P over time, after soil P fertilization, was assessed by incubating the fertilizers with a low-P acid soil. P bioavailability was assessed through a micro-pot experiment with the incubated soils in a growth chamber using rye plants (Secale cereale L.. Inorganic P forms in the first two fractions represented ~50% (composts, 32% (SV and 86% (SSP of the total P; and in the HCl fraction, ~40% (composts, 26% (SV and 13% (SSP of the total P. Despite the variability of the P form fractions in the composts and struvite, the P release and bioavailability were similar among the fertilized treatments. The acidic nature of the soil, which improve solubility of Ca-P forms, and the high efficiency of rye, which favors P uptake, were factors that contributed to these results.

  12. Influence of ageing on zinc bioavailability in soils

    Energy Technology Data Exchange (ETDEWEB)

    Lock, K.; Janssen, C.R

    2003-12-01

    Currently, soil quality criteria or soil risk assessments of metals are based on laboratory toxicity tests which are carried out in soils freshly spiked with metal salts. With these data, species sensitivity distributions are fitted, from which hazardous concentrations and predicted no effect concentrations are derived. However, due to long-term processes, called ageing, soil metal availability decreases with time. Here we show that pH is the most important parameter determining the effect of ageing on zinc partitioning in soils, with the effect of ageing becoming more important with increasing pH. Furthermore, zinc bioavailability, expressed as the internal zinc concentrations in red clover (Trifolium pratense) is closely related to pore water zinc concentration. In addition, there is a clear dose-response relationship between the survival of the earthworm Eisenia fetida and the calcium chloride-extracted zinc fraction. These results indicate that zinc partitioning can be used to predict zinc bioavailability to terrestrial organisms. However, the use of spiked soils in toxicity assays can result in an over-estimation of the effects of zinc, especially at a high pH. - Zn ageing is affected by pH, while Zn partitioning can be used to predict its bioavailability.

  13. Bioavailability and stability of erythromycin delayed release tablets.

    Science.gov (United States)

    Ogwal, S; Xide, T U

    2001-12-01

    Erythromycin is available as the free base, ethylsuccinate, estolate, stearate, gluceptate, and lactobionate derivatives. When given orally erythromycin and its derivatives except the estolate are inactivated to some extent by the gastric acid and poor absorption may result. To establish whether delayed release erythromycin tablets meet the bioequivalent requirement for the market. Sectrophotometric analysis was used to determine the dissolution percentage of the tablets in vitro. High performance liquid chromatography and IBM/XT microcomputer was used to determine the bioavailability and pharmacokinetic parameters in vivo. Dissolution percentage in thirty minutes reached 28.9% and in sixty minutes erythromycin was completely released. The parameters of the delayed release tablets were Tlag 2.3 hr, Tmax.4.5 hr, and Cmax 2.123 g/ml Ka 0.38048 hr(-1) T (1/2) 1.8 hr, V*C/F 49.721 AUC 12.9155. The relative bioavailability of erythromycin delayed release tablet to erythromycin capsules was 105.31% The content, appearance, and dissolution bioavailability of delayed release erythromycin tablets conforms to the United States pharmacopoeia standards. The tablets should be stored in a cool and dry place in airtight containers and the shelf life is temporarily assigned two years.

  14. Nanoemulsifying drug delivery system to improve the bioavailability of piroxicam.

    Science.gov (United States)

    Motawea, Amira; Borg, Thanaa; Tarshoby, Manal; Abd El-Gawad, Abd El-Gawad H

    2017-05-01

    The aim of this study is to develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of piroxicam in liquid and solid forms to improve its dissolution, absorption and therapeutic efficacy. The generation of liquid SNEDDS (L-SNEDDS) was composed of soybean or coconut oil/Tween 80/Transcutol HP (12/80/8%w/w) and it was selected as the optimized formulation based on the solubility study and pseudo-ternary phase diagram. Optimized L-SNEDDS and liquid supersaturatable SNEDDS (L-sSNEDDS) preparations were then adsorbed onto adsorbents and formulated as directly compressed tablets. The improved drug dissolution rate in the solid supersaturatable preparation (S-sSNEDDS) may be due to the formation of a nanoemulsion and the presence of drug in an amorphous state with hydrogen bond interaction between the drug and SNEDDS components. In vivo pharmacokinetic studies on eight healthy human volunteers showed a significant improvement in the oral bioavailability of piroxicam from S-sSNEDDS (F12) compared with both the pure drug (PP) and its commercial product (Feldene ® ) (commercial dosage form (CD)). The relative bioavailability of S-sSNEDDS (F12) relative to PP or CD was about 151.01 and 98.96%, respectively. The obtained results ratify that S-sSNEDDS is a promising drug delivery system to enhance the oral bioavailability of piroxicam.

  15. Excipient Nanoemulsions for Improving Oral Bioavailability of Bioactives

    Directory of Open Access Journals (Sweden)

    Laura Salvia-Trujillo

    2016-01-01

    Full Text Available The oral bioavailability of many hydrophobic bioactive compounds found in natural food products (such as vitamins and nutraceuticals in fruits and vegetables is relatively low due to their low bioaccessibility, chemical instability, or poor absorption. Most previous research has therefore focused on the design of delivery systems to incorporate isolated bioactive compounds into food products. However, a more sustainable and cost-effect approach to enhancing the functionality of bioactive compounds is to leave them within their natural environment, but specifically design excipient foods that enhance their bioavailability. Excipient foods typically do not have functionality themselves but they have the capacity to enhance the functionality of nutrients present in natural foods by altering their bioaccessibility, absorption, and/or chemical transformation. In this review article we present the use of excipient nanoemulsions for increasing the bioavailability of bioactive components from fruits and vegetables. Nanoemulsions present several advantages over other food systems for this application, such as the ability to incorporate hydrophilic, amphiphilic, and lipophilic excipient ingredients, high physical stability, and rapid gastrointestinal digestibility. The design, fabrication, and application of nanoemulsions as excipient foods will therefore be described in this article.

  16. Nicotianamine, a novel enhancer of rice iron bioavailability to humans.

    Directory of Open Access Journals (Sweden)

    Luqing Zheng

    Full Text Available BACKGROUND: Polished rice is a staple food for over 50% of the world's population, but contains little bioavailable iron (Fe to meet human needs. Thus, biofortifying the rice grain with novel promoters or enhancers of Fe utilization would be one of the most effective strategies to prevent the high prevalence of Fe deficiency and iron deficiency anemia in the developing world. METHODOLOGY/PRINCIPAL FINDINGS: We transformed an elite rice line cultivated in Southern China with the rice nicotianamine synthase gene (OsNAS1 fused to a rice glutelin promoter. Endosperm overexpression of OsNAS1 resulted in a significant increase in nicotianamine (NA concentrations in both unpolished and polished grain. Bioavailability of Fe from the high NA grain, as measured by ferritin synthesis in an in vitro Caco-2 cell model that simulates the human digestive system, was twice as much as that of the control line. When added at 1:1 molar ratio to ferrous Fe in the cell system, NA was twice as effective when compared to ascorbic acid (one of the most potent known enhancers of Fe bioavailability in promoting more ferritin synthesis. CONCLUSIONS: Our data demonstrated that NA is a novel and effective promoter of iron utilization. Biofortifying polished rice with this compound has great potential in combating global human iron deficiency in people dependent on rice for their sustenance.

  17. Topical bioavailability of diclofenac from locally-acting, dermatological formulations.

    Science.gov (United States)

    Cordery, S F; Pensado, A; Chiu, W S; Shehab, M Z; Bunge, A L; Delgado-Charro, M B; Guy, R H

    2017-08-30

    Assessment of the bioavailability of topically applied drugs designed to act within or beneath the skin is a challenging objective. A number of different, but potentially complementary, techniques are under evaluation. The objective of this work was to evaluate in vitro skin penetration and stratum corneum tape-stripping in vivo as tools with which to measure topical diclofenac bioavailability from three approved and commercialized products (two gels and one solution). Drug uptake into, and its subsequent clearance from, the stratum corneum of human volunteers was used to estimate the input rate of diclofenac into the viable skin layers. This flux was compared to that measured across excised porcine skin in conventional diffusion cells. Both techniques clearly demonstrated (a) the superiority in terms of drug delivery from the solution, and (b) that the two gels performed similarly. There was qualitative and, importantly, quantitative agreement between the in vitro and in vivo measurements of drug flux into and beyond the viable skin. Evidence is therefore presented to support an in vivo - in vitro correlation between methods to assess topical drug bioavailability. The potential value of the stratum corneum tape-stripping technique to quantify drug delivery into (epi)dermal and subcutaneous tissue beneath the barrier is demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Bioavailability of mercury in East Fork Poplar Creek soils

    International Nuclear Information System (INIS)

    Barnett, M.O.; Turner, R.R.

    1995-05-01

    The initial risk assessment for the East Fork Poplar Creek (EFPC) floodplain in Oak Ridge, Tennessee, a superfund site heavily contaminated with mercury, was based upon a reference dose for mercuric chloride, a soluble mercury compound not expected to be present in the floodplain, which is frequently saturated with water. Previous investigations had suggested mercury in the EFPC floodplain was less soluble and therefore less bioavailable than mercuric chloride, possibly making the results of the risk assessment unduly conservative. A bioavailability study, designed to measure the amount of mercury available for absorption in a child's digestive tract, the most critical risk endpoint and pathway, was performed on twenty soils from the EFPC floodplain. The average percentage of mercury released during the study for the twenty soils was 5.3%, compared to 100% of the compound mercuric chloride subjected to the same conditions. Alteration of the procedure to test additional conditions possible during soil digestion did not appreciably alter the results. Therefore, use of a reference dose for mercuric chloride in the EFPC risk assessment without inclusion of a corresponding bioavailability factor may be unduly conservative

  19. Hologram QSAR model for the prediction of human oral bioavailability.

    Science.gov (United States)

    Moda, Tiago L; Montanari, Carlos A; Andricopulo, Adriano D

    2007-12-15

    A drug intended for use in humans should have an ideal balance of pharmacokinetics and safety, as well as potency and selectivity. Unfavorable pharmacokinetics can negatively affect the clinical development of many otherwise promising drug candidates. A variety of in silico ADME (absorption, distribution, metabolism, and excretion) models are receiving increased attention due to a better appreciation that pharmacokinetic properties should be considered in early phases of the drug discovery process. Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects. In the present work, hologram quantitative structure-activity relationships (HQSAR) were performed on a training set of 250 structurally diverse molecules with known human oral bioavailability. The most significant HQSAR model (q(2)=0.70, r(2)=0.93) was obtained using atoms, bond, connection, and chirality as fragment distinction. The predictive ability of the model was evaluated by an external test set containing 52 molecules not included in the training set, and the predicted values were in good agreement with the experimental values. The HQSAR model should be useful for the design of new drug candidates having increased bioavailability as well as in the process of chemical library design, virtual screening, and high-throughput screening.

  20. Recycled water sources influence the bioavailability of copper to earthworms.

    Science.gov (United States)

    Kunhikrishnan, Anitha; Bolan, Nanthi S; Naidu, Ravi; Kim, Won-Il

    2013-10-15

    Re-use of wastewaters can overcome shortfalls in irrigation demand and mitigate environmental pollution. However, in an untreated or partially treated state, these water sources can introduce inorganic contaminants, including heavy metals, to soils that are irrigated. In this study, earthworms (Eisenia fetida) have been used to determine copper (Cu) bioavailability in two contrasting soils irrigated with farm dairy, piggery and winery effluents. Soils spiked with varying levels of Cu (0-1,000 mg/kg) were subsequently irrigated with recycled waters and Milli-Q (MQ) water and Cu bioavailability to earthworms determined by mortality and avoidance tests. Earthworms clearly avoided high Cu soils and the effect was more pronounced in the absence than presence of recycled water irrigation. At the highest Cu concentration (1,000 mg/kg), worm mortality was 100% when irrigated with MQ-water; however, when irrigated with recycled waters, mortality decreased by 30%. Accumulation of Cu in earthworms was significantly less in the presence of recycled water and was dependent on CaCl2-extractable free Cu(2+) concentration in the soil. Here, it is evident that organic carbon in recycled waters was effective in decreasing the toxic effects of Cu on earthworms, indicating that the metal-organic complexes decreased Cu bioavailability to earthworms. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Greater happiness for a greater number: Is that possible in Austria?

    NARCIS (Netherlands)

    R. Veenhoven (Ruut)

    2011-01-01

    textabstractWhat is the final goal of public policy? Jeremy Bentham (1789) would say: greater happiness for a greater number. He thought of happiness as subjective enjoyment of life; in his words as “the sum of pleasures and pains”. In his time the happiness of the great number could not be measured

  2. Greater happiness for a greater number: Is that possible? If so how? (Arabic)

    NARCIS (Netherlands)

    R. Veenhoven (Ruut); E. Samuel (Emad)

    2012-01-01

    textabstractWhat is the final goal of public policy? Jeremy Bentham (1789) would say: greater happiness for a greater number. He thought of happiness as subjective enjoyment of life; in his words as “the sum of pleasures and pains”. In his time, the happiness of the great number could not be

  3. Greater happiness for a greater number: Is that possible in Germany?

    NARCIS (Netherlands)

    R. Veenhoven (Ruut)

    2009-01-01

    textabstractWhat is the final goal of public policy? Jeremy Bentham (1789) would say: greater happiness for a greater number. He thought of happiness as subjective enjoyment of life; in his words as “the sum of pleasures and pains”. In his time the Happiness of the great number could not be measured

  4. Oral bioavailability of heavy metals and organic compounds from soil ; too complicated to absorb? An inventarisation of factors affecting bioavailability of environmental contaminants from soil

    NARCIS (Netherlands)

    Sips AJAM; Eijkeren JCH van; LBO

    1996-01-01

    Bioavailability plays an important role in risk assessment of environmental contaminants from soil. It is one of the determinants in the assessment of intervention values. In present risk assessment, bioavailability from soil is supposed to be 100% due to a paucity of reliable information. However,

  5. Search for greater stability in nuclear regulation

    International Nuclear Information System (INIS)

    Asselstine, J.K.

    1985-01-01

    The need for greater stability in nuclear regulation is discussed. Two possible approaches for dealing with the problems of new and rapidly changing regulatory requirements are discussed. The first approach relies on the more traditional licensing reform initiatives that have been considered off and on for the past decade. The second approach considers a new regulator philosophy aimed at the root causes of the proliferation of new safety requirements that have been imposed in recent years. For the past few years, the concepts of deregulation and regulatory reform have been in fashion in Washington, and the commercial nuclear power program has not remained unaffected. Many look to these concepts to provide greater stability in the regulatory program. The NRC, the nuclear industry and the administration have all been avidly pursuing regulatory reform initiatives, which take the form of both legislative and administrative proposals. Many of these proposals look to the future, and, if adopted, would have little impact on currently operating nuclear power plants or plants now under construction

  6. Greater Sudbury fuel efficient driving handbook

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-12-15

    Reducing the amount of fuel that people use for personal driving saves money, improves local air quality, and reduces personal contributions to climate change. This handbook was developed to be used as a tool for a fuel efficient driving pilot program in Greater Sudbury in 2009-2010. Specifically, the purpose of the handbook was to provide greater Sudbury drivers with information on how to drive and maintain their personal vehicles in order to maximize fuel efficiency. The handbook also provides tips for purchasing fuel efficient vehicles. It outlines the benefits of fuel maximization, with particular reference to reducing contributions to climate change; reducing emissions of air pollutants; safe driving; and money savings. Some tips for efficient driving are to avoid aggressive driving; use cruise control; plan trips; and remove excess weight. Tips for efficient winter driving are to avoid idling to warm up the engine; use a block heater; remove snow and ice; use snow tires; and check tire pressure. The importance of car maintenance and tire pressure was emphasized. The handbook also explains how fuel consumption ratings are developed by vehicle manufacturers. refs., figs.

  7. Women at greater risk of HIV infection.

    Science.gov (United States)

    Mahathir, M

    1997-04-01

    Although many people believe that mainly men get infected with HIV/AIDS, women are actually getting infected at a faster rate than men, especially in developing countries, and suffer more from the adverse impact of AIDS. As of mid-1996, the Joint UN Program on AIDS estimated that more than 10 million of the 25 million adults infected with HIV since the beginning of the epidemic are women. The proportion of HIV-positive women is growing, with almost half of the 7500 new infections daily occurring among women. 90% of HIV-positive women live in a developing country. In Asia-Pacific, 1.4 million women have been infected with HIV out of an estimated total 3.08 million adults from the late 1970s until late 1994. Biologically, women are more vulnerable than men to infection because of the greater mucus area exposed to HIV during penile penetration. Women under age 17 years are at even greater risk because they have an underdeveloped cervix and low vaginal mucus production. Concurrent sexually transmitted diseases increase the risk of HIV transmission. Women's risk is also related to their exposure to gender inequalities in society. The social and economic pressures of poverty exacerbate women's risk. Prevention programs are discussed.

  8. Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide

    Directory of Open Access Journals (Sweden)

    Cha KH

    2012-10-01

    Full Text Available Kwang-Ho Cha,1,3 Kyung-Jin Cho,3 Min-Soo Kim,4 Jeong-Soo Kim,3 Hee Jun Park,1,3 Junsung Park,1,3 Wonkyung Cho,1,3 Jeong-Sook Park,3 Sung-Joo Hwang1,21Yonsei Institute of Pharmaceutical Sciences, 2College of Pharmacy, Yonsei University, Incheon, Republic of Korea; 3College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 4Department of Pharmaceutical Engineering, Inje University, Gimhae, Republic of KoreaBackground: The aim of this study was to enhance the bioavailability of fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with supercritical CO2.Methods: Fenofibrate was loaded onto Neusilin® UFL2 at different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using supercritical CO2. For comparison, fenofibrate-loaded Neusilin UFL2 was prepared by solvent evaporation and hot melt-adsorption methods. The fenofibrate formulations prepared were characterized by differential scanning calorimetry, powder x-ray diffractometry, specific surface area, pore size distribution, scanning electron microscopy, and energy-dispersive x-ray spectrometry. In vitro dissolution and in vivo bioavailability were also investigated.Results: Fenofibrate was distributed into the pores of Neusilin UFL2 and showed reduced crystal formation following adsorption. Supercritical CO2 facilitated the introduction of fenofibrate into the pores of Neusilin UFL2. Compared with raw fenofibrate, fenofibrate from the prepared powders showed a significantly increased dissolution rate and better bioavailability. In particular, the area under the drug concentration-time curve and maximal serum concentration of the powders prepared using supercritical CO2 were 4.62-fold and 4.52-fold greater than the corresponding values for raw fenofibrate.Conclusion: The results of this study highlight the usefulness of the melt-adsorption method using supercritical CO2 for improving the bioavailability of fenofibrate.Keywords: fenofibrate

  9. pH-dependent solubility and permeability profiles: A useful tool for prediction of oral bioavailability.

    Science.gov (United States)

    Sieger, P; Cui, Y; Scheuerer, S

    2017-07-15

    pH-dependent solubility - permeability profiles offer a simple way to predict bioavailability after oral application, if bioavailability is only solubility and permeability driven. Combining both pH-dependent solubility and pH-dependent permeability in one diagram provides a pH-window (=ΔpH sol-perm ) from which the conditions for optimal oral bioavailability can be taken. The size of this window is directly proportional to the observed oral bioavailability. A set of 21 compounds, with known absolute human oral bioavailability, was used to establish this correlation. Compounds with ΔpH sol-perm bioavailability (bioavailability typically by approximately 25%. For compounds where ΔpH sol-perm ≥3 but still showing poor bioavailability, most probably other pharmacokinetic aspects (e.g. high clearance), are limiting exposure. Interestingly, the location of this pH-window seems to have a negligible influence on the observed oral bioavailability. In scenarios, where the bioavailability is impaired by certain factors, like for example proton pump inhibitor co-medication or food intake, the exact position of this pH-window might be beneficial for understanding the root cause. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Food effect on the bioavailability of two distinct formulations of megestrol acetate oral suspension

    Directory of Open Access Journals (Sweden)

    Benoit Deschamps

    2009-09-01

    Full Text Available Benoit Deschamps1, Naomi Musaji2, John A Gillespie21SFBC Anapharm, Montreal, Canada; 2Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc., Woodcliff Lake, NJ, USAObjective: Megestrol acetate oral suspension (MAOS is an appetite stimulant indicated for cachexia in patients with AIDS. It is available in its original formulation, Megace® (MAOS, and as a nanocrystal dispersion, Megace® ES (MA-ES. Three studies were conducted to evaluate the pharmacokinetic properties of these formulations under fed and fasting conditions.Methods: An open-label, crossover trial was conducted in 24 healthy males randomized to MA-ES 625 mg/5 mL given with a high-calorie, high-fat meal, or after an overnight fast. Blood samples were drawn at multiple time points and pharmacokinetic parameters were determined. Two separate, open-label reference studies evaluated MAOS 800 mg/20 mL in 40 fed or 40 fasting healthy male volunteers.Results: In fasting MA-ES subjects, the average maximum concentration (Cmax was 30% less than the fed Cmax value. For MAOS, fasting Cmax was 86% less than fed Cmax. In fasting subjects, the area under the curve was 12,095 ng⋅h/mL for MA-ES, and 8,942 ng⋅h/mL for MAOS. In fed subjects, the absorption of the two formulations was comparable.Conclusion: Bioavailability and absorption are greater for MA-ES than MAOS in fasting subjects. MA-ES may be a preferred formulation of megestrol acetate when managing cachectic patients whose caloric intake is reduced.Keywords: megestrol acetate, bioavailability, cachexia, nanocrystal technology, appetite stimulant

  11. Small cities face greater impact from automation.

    Science.gov (United States)

    Frank, Morgan R; Sun, Lijun; Cebrian, Manuel; Youn, Hyejin; Rahwan, Iyad

    2018-02-01

    The city has proved to be the most successful form of human agglomeration and provides wide employment opportunities for its dwellers. As advances in robotics and artificial intelligence revive concerns about the impact of automation on jobs, a question looms: how will automation affect employment in cities? Here, we provide a comparative picture of the impact of automation across US urban areas. Small cities will undertake greater adjustments, such as worker displacement and job content substitutions. We demonstrate that large cities exhibit increased occupational and skill specialization due to increased abundance of managerial and technical professions. These occupations are not easily automatable, and, thus, reduce the potential impact of automation in large cities. Our results pass several robustness checks including potential errors in the estimation of occupational automation and subsampling of occupations. Our study provides the first empirical law connecting two societal forces: urban agglomeration and automation's impact on employment. © 2018 The Authors.

  12. Small cities face greater impact from automation

    Science.gov (United States)

    Sun, Lijun; Cebrian, Manuel; Rahwan, Iyad

    2018-01-01

    The city has proved to be the most successful form of human agglomeration and provides wide employment opportunities for its dwellers. As advances in robotics and artificial intelligence revive concerns about the impact of automation on jobs, a question looms: how will automation affect employment in cities? Here, we provide a comparative picture of the impact of automation across US urban areas. Small cities will undertake greater adjustments, such as worker displacement and job content substitutions. We demonstrate that large cities exhibit increased occupational and skill specialization due to increased abundance of managerial and technical professions. These occupations are not easily automatable, and, thus, reduce the potential impact of automation in large cities. Our results pass several robustness checks including potential errors in the estimation of occupational automation and subsampling of occupations. Our study provides the first empirical law connecting two societal forces: urban agglomeration and automation's impact on employment. PMID:29436514

  13. Planning for greater-confinement disposal

    International Nuclear Information System (INIS)

    Gilbert, T.L.; Luner, C.; Meshkov, N.K.; Trevorrow, L.E.; Yu, C.

    1984-01-01

    This contribution is a progress report for preparation of a document that will summarize procedures and technical information needed to plan for and implement greater-confinement disposal (GCD) of low-level radioactive waste. Selection of a site and a facility design (Phase I), and construction, operation, and extended care (Phase II) will be covered in the document. This progress report is limited to Phase I. Phase I includes determination of the need for GCD, design alternatives, and selection of a site and facility design. Alternative designs considered are augered shafts, deep trenches, engineered structures, high-integrity containers, hydrofracture, and improved waste form. Design considerations and specifications, performance elements, cost elements, and comparative advantages and disadvantages of the different designs are covered. Procedures are discussed for establishing overall performance objectives and waste-acceptance criteria, and for comparative assessment of the performance and cost of the different alternatives. 16 references

  14. Greater confinement disposal of radioactive wastes

    International Nuclear Information System (INIS)

    Trevorrow, L.E.; Gilbert, T.L.; Luner, C.; Merry-Libby, P.A.; Meshkov, N.K.; Yu, C.

    1985-01-01

    Low-level radioactive waste (LLW) includes a broad spectrum of different radionuclide concentrations, half-lives, and hazards. Standard shallow-land burial practice can provide adequate protection of public health and safety for most LLW. A small volume fraction (approx. 1%) containing most of the activity inventory (approx. 90%) requires specific measures known as greater-confinement disposal (GCD). Different site characteristics and different waste characteristics - such as high radionuclide concentrations, long radionuclide half-lives, high radionuclide mobility, and physical or chemical characteristics that present exceptional hazards - lead to different GCD facility design requirements. Facility design alternatives considered for GCD include the augered shaft, deep trench, engineered structure, hydrofracture, improved waste form, and high-integrity container. Selection of an appropriate design must also consider the interplay between basic risk limits for protection of public health and safety, performance characteristics and objectives, costs, waste-acceptance criteria, waste characteristics, and site characteristics

  15. Planning for greater-confinement disposal

    International Nuclear Information System (INIS)

    Gilbert, T.L.; Luner, C.; Meshkov, N.K.; Trevorrow, L.E.; Yu, C.

    1984-01-01

    This contribution is a progress report for preparation of a document that will summarize procedures and technical information needed to plan for and implement greater-confinement disposal (GCD) of low-level radioactive waste. Selection of a site and a facility design (Phase I), and construction, operation, and extended care (Phase II) will be covered in the document. This progress report is limited to Phase I. Phase I includes determination of the need for GCD, design alternatives, and selection of a site and facility design. Alternative designs considered are augered shafts, deep trenches, engineered structures, high-integrity containers, hydrofracture, and improved waste form. Design considerations and specifications, performance elements, cost elements, and comparative advantages and disadvantages of the different designs are covered. Procedures are discussed for establishing overall performance objecties and waste-acceptance criteria, and for comparative assessment of the performance and cost of the different alternatives. 16 refs

  16. Increased iron bioavailability from lactic-fermented vegetables is likely an effect of promoting the formation of ferric iron (Fe(3+)).

    Science.gov (United States)

    Scheers, Nathalie; Rossander-Hulthen, Lena; Torsdottir, Inga; Sandberg, Ann-Sofie

    2016-02-01

    Lactic fermentation of foods increases the availability of iron as shown in a number of studies throughout the years. Several explanations have been provided such as decreased content of inhibitory phytate, increased solubility of iron, and increased content of lactic acid in the fermented product. However, to our knowledge, there are no data to support that the bioavailability of iron is affected by lactic fermentation. The objective of the present study was to investigate whether the bioavailability of iron from a vegetable mix was affected by lactic fermentation and to propose a mechanism for such an event, by conducting human and cell (Caco-2, HepG2) studies and iron speciation measurements (voltammetry). We also investigated whether the absorption of zinc was affected by the lactic fermentation. In human subjects, we observed that lactic-fermented vegetables served with both a high-phytate and low-phytate meal increased the absorption of iron, but not zinc. In vitro digested fermented vegetables were able to provoke a greater hepcidin response per ng Fe than fresh vegetables, indicating that Fe in the fermented mixes was more bioavailable, independent on the soluble Fe content. We measured that hydrated Fe(3+) species were increased after the lactic fermentation, while there was no significant change in hydrated Fe(2+). Furthermore, lactate addition to Caco-2 cells did not affect ferritin formation in response to Fe nor did lactate affect the hepcidin response in the Caco-2/HepG2 cell system. The mechanism for the increased bioavailability of iron from lactic-fermented vegetables is likely an effect of the increase in ferric iron (Fe(3+)) species caused by the lactic fermentation. No effect on zinc bioavailability was observed.

  17. Bioavailability of zinc and copper in biosolids compared to their soluble salts

    International Nuclear Information System (INIS)

    Heemsbergen, Diane A.; McLaughlin, Mike J.; Whatmuff, Mark; Warne, Michael St.J.; Broos, Kris; Bell, Mike; Nash, David; Barry, Glenn; Pritchard, Deb; Penney, Nancy

    2010-01-01

    For essential elements, such as copper (Cu) and zinc (Zn), the bioavailability in biosolids is important from a nutrient release and a potential contamination perspective. Most ecotoxicity studies are done using metal salts and it has been argued that the bioavailability of metals in biosolids can be different to that of metal salts. We compared the bioavailability of Cu and Zn in biosolids with those of metal salts in the same soils using twelve Australian field trials. Three different measures of bioavailability were assessed: soil solution extraction, CaCl 2 extractable fractions and plant uptake. The results showed that bioavailability for Zn was similar in biosolid and salt treatments. For Cu, the results were inconclusive due to strong Cu homeostasis in plants and dissolved organic matter interference in extractable measures. We therefore recommend using isotope dilution methods to assess differences in Cu availability between biosolid and salt treatments. - Metals in biosolids are not necessarily less bioavailable than their soluble salt.

  18. Research progress on berberine with a special focus on its oral bioavailability.

    Science.gov (United States)

    Liu, Chang-Shun; Zheng, Yu-Rong; Zhang, Ying-Feng; Long, Xiao-Ying

    2016-03-01

    The natural product berberine (BBR) has become a potential drug in the treatment of diabetes, hyperlipidemia, and cancer. However, the oral delivery of BBR is challenged by its poor bioavailability. It is necessary to improve the oral bioavailability of BBR before it can be used in many clinical applications. Understanding the pharmacokinetic characteristics of BBR will enable the development of suitable formulas that have improved oral bioavailability. The key considerations for BBR are how to enhance the drug absorption and to avoid the intestinal first-pass effect. This review summarizes the pharmacological activities of BBR and analyzes the factors that lead to its poor oral bioavailability. In particular, the therapeutic potential of BBR in new indications from the aspect of oral bioavailability is discussed. In conclusion, BBR is a promising drug candidate for metabolic disorders and cancer but faces considerable challenges due to its poor oral bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Bioavailability of zinc and copper in biosolids compared to their soluble salts

    Energy Technology Data Exchange (ETDEWEB)

    Heemsbergen, Diane A., E-mail: diane.heemsbergen@csiro.a [Centre for Environmental Contaminants Research, CSIRO Land and Water, PMB 2, Glen Osmond, Adelaide, SA 5064 (Australia); McLaughlin, Mike J., E-mail: mike.mclaughlin@csiro.a [Centre for Environmental Contaminants Research, CSIRO Land and Water, PMB 2, Glen Osmond, Adelaide, SA 5064 (Australia); School of Earth and Environmental Sciences, University of Adelaide, Adelaide, SA 5064 (Australia); Whatmuff, Mark, E-mail: mark.whatmuff@csiro.a [Centre for Environmental Contaminants Research, CSIRO Land and Water, PMB 2, Glen Osmond, Adelaide, SA 5064 (Australia); NSW Department of Primary Industries, Locked Bag 4 Richmond, NSW 2753 (Australia); Warne, Michael St.J., E-mail: michael.warne@csiro.a [Centre for Environmental Contaminants Research, CSIRO Land and Water, PMB 2, Glen Osmond, Adelaide, SA 5064 (Australia); Broos, Kris, E-mail: kris.broos@vito.b [Centre for Environmental Contaminants Research, CSIRO Land and Water, PMB 2, Glen Osmond, Adelaide, SA 5064 (Australia); Bell, Mike, E-mail: Mike.Bell@dpi.qld.gov.a [Department of Primary Industries, Kingaroy, Queensland 4610 (Australia); Nash, David, E-mail: David.Nash@dpi.vic.gov.a [Department of Primary Industries, Ellinbank, Victoria 3821 (Australia); Barry, Glenn, E-mail: Glenn.Barry@nrw.qld.gov.a [Department of Natural Resources and Mines, Indooroopilly, Queensland 4068 (Australia); Pritchard, Deb, E-mail: D.Pritchard@curtin.edu.a [Curtin University of Technology, Muresk Institute, Northam, Western Australia 6401 (Australia); Penney, Nancy, E-mail: Nancy.Penney@WaterCorporation.com.a [Water Corporation of Western Australia, Leederville, Western Australia 6001 (Australia)

    2010-05-15

    For essential elements, such as copper (Cu) and zinc (Zn), the bioavailability in biosolids is important from a nutrient release and a potential contamination perspective. Most ecotoxicity studies are done using metal salts and it has been argued that the bioavailability of metals in biosolids can be different to that of metal salts. We compared the bioavailability of Cu and Zn in biosolids with those of metal salts in the same soils using twelve Australian field trials. Three different measures of bioavailability were assessed: soil solution extraction, CaCl{sub 2} extractable fractions and plant uptake. The results showed that bioavailability for Zn was similar in biosolid and salt treatments. For Cu, the results were inconclusive due to strong Cu homeostasis in plants and dissolved organic matter interference in extractable measures. We therefore recommend using isotope dilution methods to assess differences in Cu availability between biosolid and salt treatments. - Metals in biosolids are not necessarily less bioavailable than their soluble salt.

  20. In vivo and in vitro testing for selenium and selenium compounds bioavailability assessment in foodstuff.

    Science.gov (United States)

    Moreda-Piñeiro, Jorge; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar

    2017-03-04

    The assessment of selenium and selenium species bioavailability in foodstuff is of special concern on the context of human nutrition. In vivo (human and animal), and in vitro tests are important approaches for estimating the bioavailability of toxic and essential compounds to humans. An overview on in vivo and in vitro bioavailability assays for releasing selenium and selenium species in foodstuffs is summarized. Se and Se species content in a foodstuff critically influence Se bioavailability and bioactivity to humans and animals. Se bioavailability is affected by foodstuff-matrix major composition and minor components. Foodstuffs processing and/or treatments could enhancement or decrease Se bioavailability. Experimental conditions such as the selection of healthy status of examined people (in in vivo humans approaches), the selection of animal model (in vivo animals approaches), or the selection of GI conditions (in in vitro tests) could determines the results. Thus, international standardized protocol for in vivo and in vitro approaches assessment is mandatory.

  1. Bioavailability of isoflavones from soy products in equol producers and non-producers in Japanese women

    OpenAIRE

    Ayako Miura; Chitose Sugiyama; Hiroyuki Sakakibara; Kayoko Simoi; Toshinao Goda

    2016-01-01

    Background: The estimated intake of soy isoflavones from a meal has been based on the content in a food, but the health effects of soy isoflavones are possibly affected by their bioavailability. In this study we have evaluated the isoflavone bioavailability after the intake of three kinds of soy foods and a commercial soy isoflavone supplement, and examined whether the isoflavone bioavailability is different between equol producers and non-producers. Methods: Healthy female subjects (n = 2...

  2. Urban acid deposition in Greater Manchester

    Energy Technology Data Exchange (ETDEWEB)

    Lee, D.S.; Longhurst, J.W.S.; Gee, D.R.; Hare, S.E. (Manchester Polytechnic, Manchester (UK). Acid Rain Information Centre)

    1989-08-01

    Data are presented from a monitoring network of 18 bulk precipitation collectors and one wet-only collector in the urban area of Greater Manchester, in the north west of England. Weekly samples were analysed for all the major ions in precipitation along with gaseous nitrogen dioxide concentrations from diffusion tubes. Statistical analysis of the data shows significant spatial variation of non marine sulphate, nitrate, ammonium, acidity and calcium concentrations, and nitrogen dioxide concentrations. Calcium is thought to be responsible for the buffering of acidity and is of local origin. Wet deposition is the likely removal process for calcium in the atmosphere and probably by below cloud scavenging. Nitrate and ammonium concentrations and depositions show close spatial, temporal and statistical association. Examination of high simultaneous episodes of nitrate and ammonium deposition shows that these depositions cannot be explained in terms of trajectories and it is suggested that UK emissions of ammonia may be important. Statistical analysis of the relationships between nitrate and ammonium depositions, concentrations and precipitation amount suggest that ammonia from mesoscale sources reacts reversibly with nitric acid aerosol and is removed by below cloud scavenging. High episodes of the deposition of non marine sulphate are difficult to explain by trajectory analysis alone, perhaps suggesting local sources. In a comparison between wet deposition and bulk deposition, it was shown that only 15.2% of the non marine sulphur was dry deposited to the bulk precipitation collector. 63 refs., 86 figs., 31 tabs.

  3. Using deuterated PAH amendments to validate chemical extraction methods to predict PAH bioavailability in soils

    International Nuclear Information System (INIS)

    Gomez-Eyles, Jose L.; Collins, Chris D.; Hodson, Mark E.

    2011-01-01

    Validating chemical methods to predict bioavailable fractions of polycyclic aromatic hydrocarbons (PAHs) by comparison with accumulation bioassays is problematic. Concentrations accumulated in soil organisms not only depend on the bioavailable fraction but also on contaminant properties. A historically contaminated soil was freshly spiked with deuterated PAHs (dPAHs). dPAHs have a similar fate to their respective undeuterated analogues, so chemical methods that give good indications of bioavailability should extract the fresh more readily available dPAHs and historic more recalcitrant PAHs in similar proportions to those in which they are accumulated in the tissues of test organisms. Cyclodextrin and butanol extractions predicted the bioavailable fraction for earthworms (Eisenia fetida) and plants (Lolium multiflorum) better than the exhaustive extraction. The PAHs accumulated by earthworms had a larger dPAH:PAH ratio than that predicted by chemical methods. The isotope ratio method described here provides an effective way of evaluating other chemical methods to predict bioavailability. - Research highlights: → Isotope ratios can be used to evaluate chemical methods to predict bioavailability. → Chemical methods predicted bioavailability better than exhaustive extractions. → Bioavailability to earthworms was still far from that predicted by chemical methods. - A novel method using isotope ratios to assess the ability of chemical methods to predict PAH bioavailability to soil biota.

  4. Role of organic acids on the bioavailability of selenium in soil: A review.

    Science.gov (United States)

    Dinh, Quang Toan; Li, Zhe; Tran, Thi Anh Thu; Wang, Dan; Liang, Dongli

    2017-10-01

    Organic Acids (OAs) are important components in the rhizosphere soil and influence Se bioavailability in soil. OAs have a bidirectional contrasting effect on Se bioavailability. Understanding the interaction of OAs with Se is essential to assessing Se bioavailability in soil and clarifying the role of OAs in controlling the behavior and fate of Se in soil. This review examines the mechanisms for the (im)mobilization of Se by OAs and discusses the practical implications of these mechanisms in relation to sequestration and bioavailability of Se in soil. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. From conceptual model to remediation: bioavailability, a key to clean up heavy metal contaminated soils.

    Science.gov (United States)

    Petruzzelli, Gianniantonio; Pedron, Francesca; Pezzarossa, Beatrice

    2013-04-01

    Processes of metal bioavailability in the soil To know the bioavailability processes at site specific levels is essential to understand in detail the risks associated with pollution, and to support the decision-making process, i.e. description of the conceptual model and choice of clean up technologies. It is particularly important to assess how chemical, physical and biological processes in the soil affect the reactions leading to adsorption, precipitation or release of contaminants. The measurement of bioavailability One of the main difficulties in the practical application of the bioavailability concept in soil remediation is the lack of consensus on the method to be used to measure bioavailability. The best strategy is to apply a series of tests to assess bioavailability, since no applicable method is universally valid under all conditions. As an example, bioavailability tests for phytotechnology application should consider two distinct aspects: a physico-chemical driven solubilization process and a physiologically driven uptake process. Soil and plant characteristics strongly influence bioavailability. Bioavailability as a tool in remediation strategies Bioavailability can be used at all stages in remediation strategies: development of the conceptual model, evaluation of risk assessment, and selection of the best technology, considering different scenarios and including different environmental objectives. Two different strategies can be followed: the reduction and the increase of bioavailability. Procedures that reduce bioavailability aim to prevent the movement of pollutants from the soil to the living organisms, essentially by: i) removal of the labile phase of the contaminant, i.e. the fraction which is intrinsic to the processes of bioavailability (phytostabilization); ii) conversion of the labile fraction into a stable fraction (precipitation or adsorption); iii) increase of the resistance to mass transfer of the contaminants (inertization). Procedures

  6. Sorption, transport and biodegradation - An insight into bioavailability of persistent organic pollutants in soil.

    Science.gov (United States)

    Ren, Xiaoya; Zeng, Guangming; Tang, Lin; Wang, Jingjing; Wan, Jia; Liu, Yani; Yu, Jiangfang; Yi, Huan; Ye, Shujing; Deng, Rui

    2018-01-01

    Contamination of soils with persistent organic pollutants (POPs), such as organochlorine pesticide, polybrominated diphenyl ethers, halohydrocarbon, polycyclic aromatic hydrocarbons (PAHs) is of increasing concern. Microbial degradation is potential mechanism for the removal of POPs, but it is often restricted by low bioavailability of POPs. Thus, it is important to enhance bioavailability of POPs in soil bioremediation. A series of reviews on bioavailability of POPs has been published in the past few years. However, bioavailability of POPs in relation to soil organic matter, minerals and soil microbes has been little studied. To fully understand POPs bioavailability in soil, research on interactions of POPs with soil components and microbial responses in bioavailability limitation conditions are needed. This review focuses on bioavailability mechanisms of POPs in terms of sorption, transport and microbial adaptation, which is particularly novel. In consideration of the significance of bioavailability, further studies should investigate the influence of various bioremediation strategies on POPs bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Using deuterated PAH amendments to validate chemical extraction methods to predict PAH bioavailability in soils

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Eyles, Jose L., E-mail: j.l.gomezeyles@reading.ac.uk [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom); Collins, Chris D.; Hodson, Mark E. [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom)

    2011-04-15

    Validating chemical methods to predict bioavailable fractions of polycyclic aromatic hydrocarbons (PAHs) by comparison with accumulation bioassays is problematic. Concentrations accumulated in soil organisms not only depend on the bioavailable fraction but also on contaminant properties. A historically contaminated soil was freshly spiked with deuterated PAHs (dPAHs). dPAHs have a similar fate to their respective undeuterated analogues, so chemical methods that give good indications of bioavailability should extract the fresh more readily available dPAHs and historic more recalcitrant PAHs in similar proportions to those in which they are accumulated in the tissues of test organisms. Cyclodextrin and butanol extractions predicted the bioavailable fraction for earthworms (Eisenia fetida) and plants (Lolium multiflorum) better than the exhaustive extraction. The PAHs accumulated by earthworms had a larger dPAH:PAH ratio than that predicted by chemical methods. The isotope ratio method described here provides an effective way of evaluating other chemical methods to predict bioavailability. - Research highlights: > Isotope ratios can be used to evaluate chemical methods to predict bioavailability. > Chemical methods predicted bioavailability better than exhaustive extractions. > Bioavailability to earthworms was still far from that predicted by chemical methods. - A novel method using isotope ratios to assess the ability of chemical methods to predict PAH bioavailability to soil biota.

  8. Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat

    Directory of Open Access Journals (Sweden)

    Wei-Lun Hung

    2018-04-01

    Full Text Available Tangeretin, 4′,5,6,7,8-pentamethoxyflavone, is one of the major polymethoxyflavones (PMFs existing in citrus fruits, particularly in the peels of sweet oranges and mandarins. Tangeretin has been reported to possess several beneficial bioactivities including anti-inflammatory, anti-proliferative and neuroprotective effects. To achieve a thorough understanding of the biological actions of tangeretin in vivo, our current study is designed to investigate the pharmacokinetics, bioavailability, distribution and excretion of tangeretin in rats. After oral administration of 50 mg/kg bw tangeretin to rats, the Cmax, Tmax and t1/2 were 0.87 ± 0.33 μg/mL, 340.00 ± 48.99 min and 342.43 ± 71.27 min, respectively. Based on the area under the curves (AUC of oral and intravenous administration of tangeretin, calculated absolute oral bioavailability was 27.11%. During tissue distribution, maximum concentrations of tangeretin in the vital organs occurred at 4 or 8 h after oral administration. The highest accumulation of tangeretin was found in the kidney, lung and liver, followed by spleen and heart. In the gastrointestinal tract, maximum concentrations of tangeretin in the stomach and small intestine were found at 4 h, while in the cecum, colon and rectum, tangeretin reached the maximum concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered within 48 h after oral administration, concentrations were only 0.0026% and 7.54%, respectively. These results suggest that tangeretin was mainly eliminated as metabolites. In conclusion, our study provides useful information regarding absorption, distribution, as well as excretion of tangeretin, which will provide a good base for studying the mechanism of its biological effects. Keywords: Tangeretin, Oral bioavailability, Pharmacokinetics, Tissue distribution, Excretion

  9. Bioavailability of the antiemetic metopimazine given as a microenema

    DEFF Research Database (Denmark)

    Herrstedt, J.; Jørgensen, M.; Angelo, H.R.

    1996-01-01

    The absorption of the antiemetic metopimazine (MPZ) given as a single dose of (a) 40 mg microenema, (b) 40 mg orally and (c) 10 mg as a 60 min i.v. continuous infusion was investigated in six healthy volunteers. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite ...... were measured. The bioavailability of MPZ given orally and as enemas was 22.3 and 19.5% respectively. Partial avoidance of hepatic first pass metabolism was seen with the enemas, which in contrast to suppositories, seems to represent a reliable form of rectal administration....

  10. Chemical and biological factors affecting bioavailability of contaminants in seawater

    International Nuclear Information System (INIS)

    Knezovich, J.P.

    1992-09-01

    This paper discusses the influence that salinity has on the bioavailability of the two largest classes of contaminants, trace metals and organic compounds will be discussed. Although data on contaminant toxicity will be used to draw inferences about chemical availability, this discussion will focus on the properties that contaminants are likely to exhibit in waters of varying salinities. In addition, information on physiological changes that are affected by salinity will be used to illustrate how biological effects can alter the apparent availability of contaminants

  11. Caco-2 accumulation of lutein is greater from human milk than from infant formula despite similar bioaccessibility.

    Science.gov (United States)

    Lipkie, Tristan E; Banavara, Dattatreya; Shah, Bhavini; Morrow, Ardythe L; McMahon, Robert J; Jouni, Zeina E; Ferruzzi, Mario G

    2014-10-01

    Clinical evidence suggests that the bioavailability of lutein is lower from infant formula than from human milk. The purpose of this study was to assess characteristics of human milk and lutein-fortified infant formula that may impact carotenoid delivery. Carotenoid bioaccessibility and intestinal absorption were modeled by in vitro digestion coupled with Caco-2 human intestinal cell culture. Twelve human milk samples were assessed from 1-6 months postpartum, and 10 lutein-fortified infant formula samples from three lutein sources in both ready-to-use and reconstituted powder forms. The relative bioaccessibility of lutein was not different (p > 0.05) between human milk (29 ± 2%) and infant formula (36 ± 4%). However, lutein delivery was 4.5 times greater from human milk than infant formula when including Caco-2 accumulation efficiency. Caco-2 accumulation of lutein was increasingly efficient with decreasing concentration of lutein from milk. Carotenoid bioaccessibility and Caco-2 accumulation were not affected by lactation stage, total lipid content, lutein source, or form of infant formula (powder vs. liquid). These data suggest that the bioavailability of carotenoids is greater from human milk than infant formula primarily due to intestinal absorptive processes, and that absorption of lutein is potentiated by factors from human milk especially at low lutein concentration. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Long-term fate and bioavailability of sediment associated 2,3,7,8-tetrachlorodibenzofuran in littoral enclosures

    Energy Technology Data Exchange (ETDEWEB)

    Currie, R.S.; Fairchild, W.L.; Holoka, M.H.; Muir, D.C.G.

    2000-06-01

    the fate and bioavailability of 2,3,7,8-tetrachlorodibenzofuran (TCDF; 4,6-tritium labeled) was examined over a 3-year period in littoral enclosures in a small oligotrophic lake in the Experimental Lakes Area. Tetrachlorodibenzofuran was added as a single dose or as five small multiple additions over a 5-d period in a sediment slurry. Tetrachlorodibenzofuran was rapidly redistributed, mainly to bottom sediments reflecting removal on settling particles. Between 0 and 120 d. 80 to 90% of TCDF in the water column was associated with particles (>1 {micro}m). The highest concentration of TCDF in suspended particles was consistently observed in the smallest size fraction (0.22--1 {micro}m) at 326 to 464 d post treatment. Mode of addition had no effect on TCDF concentrations in water or surficial sediments or pore waters throughout the experiment. Mean TCDF concentrations in surficial sediment were 1.830 {+-} 1.180 pg/g whereas they averaged 1.260 {+-} 596 pg/g OC from 318 to 851 d post treatment. Increasing concentrations of TCDE in lower sediment layers at 952 d suggests that TCDF was either diffusing into the sediment or undergoing burial. Fugacity (f) calculations indicated that the TCDF in enclosures shifted from disequilibrium favoring the water column to a disequilibrium with respect to bottom sediments from day 21 onward. Initially, TCDF was more bioavailable to filtering and deposit feeders (mussels, Chironomidae, Hexagenia sp., and zooplankton) in enclosures receiving multiple additions; however, differences were rarely statistically significant. Concentrations of TCDF in all organisms were initially high, and they decreased in later sampling periods. Biota--sediment-accumulation factors (BSAFs) in mussels and crayfish were >1 in the early sampling periods, which reflected greater bioavailability of the added particle-borne TCDF. By 851 d, BSAFs had declined to 0.02 to 0.04, reflecting removal of TCDF from the water column and from surficial sediments.

  13. The influence of dissolved phosphorus molecular form on recalcitrance and bioavailability

    International Nuclear Information System (INIS)

    Li, Bo; Brett, Michael T.

    2013-01-01

    Several studies have shown Soluble Reactive Phosphorus (SRP) analyses provide a poor index of dissolved phosphorus (P) bioavailability in natural systems. We tested 21 inorganic and organic P containing compounds with series of nutrient uptake and bioavailability bioassay experiments and chemical characterizations. Our results show that in 81% of cases, these compounds did not fit the classic assumption that SRP approximately equals Bioavailable P (BAP). Many organic compounds were classified as non-reactive, but had very rapid uptake kinetics and were nearly entirely bioavailable (e.g., several nucleic acids, ATP, RNA, DNA and phosphatidylcholine). Several inorganic compounds also classified as non-reactive but had high bioavailability (i.e., sodium tripolyphosphate and phosphorus pentoxide). Conversely, apatite was operationally classified as reactive, but had low bioavailability. Due to their tendency to alias as SRP, but recalcitrance and very low bioavailability, humic-(Al/Fe)-phosphorus complexes may play an especially important role in the dissolved phosphorus dynamics of natural systems. Highlights: •We tested 21 P containing compounds with bioassay and chemical speciation. •The acid molybdate method does not consistently predict the bioavailability of P compounds. •The P in humic substances was bounded with Al/Fe and could not be taken up by algal. •A new classification scheme divided P species based on bioavailability and chemical speciation. -- SRP is a poor indicator of the bioavailability of many of P containing compounds and much of what is classified as SRP in nature could be associated with humic-metal complexes with low bioavailability

  14. Polymeric Nanoparticles for Increasing Oral Bioavailability of Curcumin

    Directory of Open Access Journals (Sweden)

    Anita Umerska

    2018-03-01

    Full Text Available Despite the promising biological and antioxidant properties of curcumin, its medical applications are limited due to poor solubility in water and low bioavailability. Polymeric nanoparticles (NPs adapted to oral delivery may overcome these drawbacks. Properties such as particle size, zeta potential, morphology and encapsulation efficiency were assessed. Then, the possibility of storing these NPs in a solid-state form obtained by freeze-drying, in vitro curcumin dissolution and cytocompatibility towards intestinal cells were evaluated. Curcumin-loaded Eudragit® RLPO (ERL NPs showed smaller particle diameters (245 ± 2 nm and better redispersibility after freeze-drying than either poly(lactic-co-glycolic acid (PLGA or polycaprolactone (PCL NPs. The former NPs showed lower curcumin encapsulation efficiency (62% than either PLGA or PCL NPs (90% and 99%, respectively. Nevertheless, ERL NPs showed rapid curcumin release with 91 ± 5% released over 1 h. The three curcumin-loaded NPs proposed in this work were also compatible with intestinal cells. Overall, ERL NPs are the most promising vehicles for increasing the oral bioavailability of curcumin.

  15. Polyphenols: Extraction Methods, Antioxidative Action, Bioavailability and Anticarcinogenic Effects

    Directory of Open Access Journals (Sweden)

    Eva Brglez Mojzer

    2016-07-01

    Full Text Available Being secondary plant metabolites, polyphenols represent a large and diverse group of substances abundantly present in a majority of fruits, herbs and vegetables. The current contribution is focused on their bioavailability, antioxidative and anticarcinogenic properties. An overview of extraction methods is also given, with supercritical fluid extraction highlighted as a promising eco-friendly alternative providing exceptional separation and protection from degradation of unstable polyphenols. The protective role of polyphenols against reactive oxygen and nitrogen species, UV light, plant pathogens, parasites and predators results in several beneficial biological activities giving rise to prophylaxis or possibly even to a cure for several prevailing human diseases, especially various cancer types. Omnipresence, specificity of the response and the absence of or low toxicity are crucial advantages of polyphenols as anticancer agents. The main problem represents their low bioavailability and rapid metabolism. One of the promising solutions lies in nanoformulation of polyphenols that prevents their degradation and thus enables significantly higher concentrations to reach the target cells. Another, more practiced, solution is the use of mixtures of various polyphenols that bring synergistic effects, resulting in lowering of the required therapeutic dose and in multitargeted action. The combination of polyphenols with existing drugs and therapies also shows promising results and significantly reduces their toxicity.

  16. Pollutants bioavailability and toxicological risk from microplastics to marine mussels

    International Nuclear Information System (INIS)

    Avio, Carlo Giacomo; Gorbi, Stefania; Milan, Massimo; Benedetti, Maura; Fattorini, Daniele; D'Errico, Giuseppe; Pauletto, Marianna; Bargelloni, Luca; Regoli, Francesco

    2015-01-01

    Microplastics represent a growing environmental concern for the oceans due to their potential of adsorbing chemical pollutants, thus representing a still unexplored source of exposure for aquatic organisms. In this study polyethylene (PE) and polystyrene (PS) microplastics were shown to adsorb pyrene with a time and dose-dependent relationship. Results also indicated a marked capability of contaminated microplastics to transfer this model PAH to exposed mussels Mytilus galloprovincialis; tissue localization of microplastics occurred in haemolymph, gills and especially digestive tissues where a marked accumulation of pyrene was also observed. Cellular effects included alterations of immunological responses, lysosomal compartment, peroxisomal proliferation, antioxidant system, neurotoxic effects, onset of genotoxicity; changes in gene expression profile was also demonstrated through a new DNA microarray platform. The study provided the evidence that microplastics adsorb PAHs, emphasizing an elevated bioavailability of these chemicals after the ingestion, and the toxicological implications due to responsiveness of several molecular and cellular pathways to microplastics. - Highlights: • Polyethylene and polystyrene microplastics efficiently adsorbed pyrene. • Pyrene adsorbed on microplastics was readily bioavailable for mussels. • Microplastics affected several molecular and cellular pathways. • Potential toxicological risk can arise from virgin and contaminated microplastics. - Pyrene adsorbed on microplastics is accumulated in tissues of marine mussels. Transcriptional and cellular responses highlight the potential risk of virgin and contaminated polymers

  17. Influence of estuarine processes on spatiotemporal variation in bioavailable selenium

    Science.gov (United States)

    Stewart, Robin; Luoma, Samuel N.; Elrick, Kent A.; Carter, James L.; van der Wegen, Mick

    2013-01-01

    Dynamic processes (physical, chemical and biological) challenge our ability to quantify and manage the ecological risk of chemical contaminants in estuarine environments. Selenium (Se) bioavailability (defined by bioaccumulation), stable isotopes and molar carbon-tonitrogen ratios in the benthic clam Potamocorbula amurensis, an important food source for predators, were determined monthly for 17 yr in northern San Francisco Bay. Se concentrations in the clams ranged from a low of 2 to a high of 22 μg g-1 over space and time. Little of that variability was stochastic, however. Statistical analyses and preliminary hydrodynamic modeling showed that a constant mid-estuarine input of Se, which was dispersed up- and down-estuary by tidal currents, explained the general spatial patterns in accumulated Se among stations. Regression of Se bioavailability against river inflows suggested that processes driven by inflows were the primary driver of seasonal variability. River inflow also appeared to explain interannual variability but within the range of Se enrichment established at each station by source inputs. Evaluation of risks from Se contamination in estuaries requires the consideration of spatial and temporal variability on multiple scales and of the processes that drive that variability.

  18. Bioavailability of zinc from sweet potato roots and leaves

    International Nuclear Information System (INIS)

    Baiden, H.N.; Ercanli-Huffman, F.G.

    1986-01-01

    Bioavailability of zinc from sweet potato (SP) roots and leaves were determined, by extrinsic labeling technique, in rats fed control and zinc deficient diets. Weanling male Sprague Dawley (SD) rats (60-75g) were divided into 4 groups, and fed laboratory chow, a control diet (ad libitum and pair fed) and a zinc deficient diet, for 4 weeks. Each group then was divided into at least 2 sub groups, containing 6 rats, which were intubated with one of 3 tubing solutions extrinsically labeled with 65 Zn; baked sweet potato roots (BSPR), raw sweet potato leaves (RSPL) and cooked sweet potato leaves (CSPL). Five hours after intubation the rats were sacrificed, blood, liver, testes, spleen, heart, brain, thymus and lungs were removed. Feces, urine, and GI tract contents were collected and their 65 Zn activity was determined in a gamma counter. In all treatment groups zinc bioavailability from BSPR, RSPL or CSPL were not significantly different. Zinc deficient rats absorbed significantly more (P 65 Zn (86-90% of the dose), regardless of type of tubing solution than the pairfed or control animals (35-58% of the dose). The highest retention of 65 Zn was found in the liver (12-20% of absorbed dose), GI tract (6-17% of absorbed dose), kidney (2-8% of absorbed dose), and blood (1-5% of absorbed dose). The lowest retention was found in the brain, heart, thymus and testes. (< 1% of absorbed dose)

  19. Is bioavailability altered in generic versus brand anticonvulsants?

    Science.gov (United States)

    Jankovic, Slobodan M; Ignjatovic Ristic, Dragana

    2015-03-01

    Therapeutic window of anticonvulsants is not a wide one, with phenytoin being one extreme, which can be classified as a narrow therapeutic index drug, since its ratio between the least toxic and the least effective concentration is less than twofold. In order to obtain marketing authorization, a generic anticonvulsant should demonstrate relative bioequivalence with its brand-name counterpart. However, although bioequivalent, generic anticonvulsants still do not have the same bioavailability as brand-name drugs, which may lead to larger fluctuations of steady-state plasma concentrations, and sometimes to loss of seizure control if a patient is switched from brand-name to generic or from generic to generic anticonvulsant. Generic anticonvulsants are effective, safe and affordable drugs for treatment of epilepsy, and patients could be successfully treated with them from the very beginning. It is switching from brand-name to generic anticonvulsant or from one generic anticonvulsant to another that should be avoided in clinical practice, since subtle differences in bioavailability may disturb optimal degree of seizure control to which the patient was previously successfully titrated.

  20. Measurement, analysis and prediction of topical UV filter bioavailability.

    Science.gov (United States)

    Roussel, L; Gilbert, E; Salmon, D; Serre, C; Gabard, B; Haftek, M; Maibach, H I; Pirot, F

    2015-01-30

    The aim of the present study was to objectively quantify and predict bioavailability of three sunscreen agents (i.e., benzophenone-3, 2-ethylhexylsalicylate, and 2 ethylhexyl-4-methoxycinnamate) in epidermis treated by petrolatum and emulsion-based formulations for 7 and 30min on four human volunteers. Profiles of sunscreen agents through stratum corneum (SC), derived from the assessment of chemical amounts in SC layers collected by successive adhesive tape-stripping, were successfully fitted to Fick's second law of diffusion. Therefore, permeability coefficients of sunscreen agents were found lower with petrolatum than with emulsion based formulations confirming the crucial role of vehicle in topical delivery. Furthermore, the robustness of that methodology was confirmed by the linear relationship between the chemical absorption measured after 30min and that predicted from the 7-min exposure experiment. Interestingly, in this dermatopharmacokinetic method, the deconvolution of permeability coefficients in their respective partition coefficients and absorption constants allowed a better understanding of vehicle effects upon topical bioavailability mechanisms and bioequivalence of skin products. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability

    Directory of Open Access Journals (Sweden)

    Annika Tuomela

    2016-05-01

    Full Text Available Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer’s role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro–in vivo correlation with nanocrystalline products, and stabilizers’ effect on higher bioavailability are discussed.

  2. Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron

    Science.gov (United States)

    Shen, Yi; Posavec, Lidija; Bolisetty, Sreenath; Hilty, Florentine M.; Nyström, Gustav; Kohlbrecher, Joachim; Hilbe, Monika; Rossi, Antonella; Baumgartner, Jeannine; Zimmermann, Michael B.; Mezzenga, Raffaele

    2017-07-01

    Iron-deficiency anaemia (IDA) is a major global public health problem. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods, but the most bioavailable fortificants cause adverse organoleptic changes in foods. Iron nanoparticles are a promising solution in food matrices, although their tendency to oxidize and rapidly aggregate in solution severely limits their use in fortification. Amyloid fibrils are protein aggregates initially known for their association with neurodegenerative disorders, but recently described in the context of biological functions in living organisms and emerging as unique biomaterial building blocks. Here, we show an original application for these protein fibrils as efficient carriers for iron fortification. We use biodegradable amyloid fibrils from β-lactoglobulin, an inexpensive milk protein with natural reducing effects, as anti-oxidizing nanocarriers and colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms a stable protein-iron colloidal dispersion that undergoes rapid dissolution and releases iron ions during acidic and enzymatic in vitro digestion. Importantly, this hybrid shows high in vivo iron bioavailability, equivalent to ferrous sulfate in haemoglobin-repletion and stable-isotope studies in rats, but with reduced organoleptic changes in foods. Feeding the rats with these hybrid materials did not result in abnormal iron accumulation in any organs, or changes in whole blood glutathione concentrations, inferring their primary safety. Therefore, these iron-amyloid fibril hybrids emerge as novel, highly effective delivery systems for iron in both solid and liquid matrices.

  3. Dissolution and oral bioavailability enhancement of praziquantel by solid dispersions.

    Science.gov (United States)

    Liu, Yanyan; Wang, Tianzi; Ding, Wenya; Dong, Chunliu; Wang, Xiaoting; Chen, Jianqing; Li, Yanhua

    2018-06-01

    The aim of the present investigation was to enhance the solubility, dissolution, and oral bioavailability of praziquantel (PZQ), a poorly water-soluble BCS II drug (Biopharmaceutical Classification System), using a solid dispersion (SD) technique involving hydrophilic copolymers. The SD formulations were prepared by a solvent evaporation method with PZQ and PEG 4000 (polyethylene glycol 4000), PEG 6000, or P 188 polymers at various weight ratios or a combination of PEG 4000/P 188. The optimized SD formulation, which had the highest solubility in distilled water, was further characterized by its surface morphology, crystallinity, and dissolution in 0.1 M HCl with 0.2% w/v of sodium dodecyl sulfate (SDS). X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) revealed the amorphous form of PZQ in the SDs. Moreover, at an oral dosage of 5 mg/kg PZQ, the SDs had higher C max values and areas under the curve (AUCs) compared to those of commercial PZQ tablets. Preparation of PZQ-loaded SDs using PEG 4000/P 188 is a promising strategy to improve the oral bioavailability of PZQ.

  4. Role of Marine Snows in Microplastic Fate and Bioavailability.

    Science.gov (United States)

    Porter, Adam; Lyons, Brett P; Galloway, Tamara S; Lewis, Ceri

    2018-06-01

    Microplastics contaminate global oceans and are accumulating in sediments at levels thought sufficient to leave a permanent layer in the fossil record. Despite this, the processes that vertically transport buoyant polymers from surface waters to the benthos are poorly understood. Here we demonstrate that laboratory generated marine snows can transport microplastics of different shapes, sizes, and polymers away from the water surface and enhance their bioavailability to benthic organisms. Sinking rates of all tested microplastics increased when incorporated into snows, with large changes observed for the buoyant polymer polyethylene with an increase in sinking rate of 818 m day -1 and for denser polyamide fragments of 916 m day -1 . Incorporation into snows increased microplastic bioavailability for mussels, where uptake increased from zero to 340 microplastics individual -1 for free microplastics to up to 1.6 × 10 5 microplastics individual -1 when incorporated into snows. We therefore propose that marine snow formation and fate has the potential to play a key role in the biogeochemical processing of microplastic pollution.

  5. Vanadium bioavailability in soils amended with blast furnace slag

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, Maja A., E-mail: maja.larsson@slu.se [Department of Soil and Environment, Swedish University of Agricultural Sciences, P.O. Box 7014, 750 07 Uppsala (Sweden); Baken, Stijn, E-mail: stijn.baken@ees.kuleuven.be [Department of Earth and Environmental Sciences, Leuven University, Kasteelpark Arenberg 20 bus 2459, 3001 Leuven (Belgium); Smolders, Erik, E-mail: erik.smolders@ees.kuleuven.be [Department of Earth and Environmental Sciences, Leuven University, Kasteelpark Arenberg 20 bus 2459, 3001 Leuven (Belgium); Cubadda, Francesco, E-mail: francesco.cubadda@iss.it [Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161 (Italy); Gustafsson, Jon Petter, E-mail: jon-petter.gustafsson@slu.se [Department of Soil and Environment, Swedish University of Agricultural Sciences, P.O. Box 7014, 750 07 Uppsala (Sweden); Division of Land and Water Resources Engineering, KTH Royal Institute of Technology, Brinellvägen 28, 100 44 Stockholm (Sweden)

    2015-10-15

    Blast furnace (BF) slags are commonly applied as soil amendments and in road fill material. In Sweden they are also naturally high in vanadium. The aim of this study was to assess the vanadium bioavailability in BF slags when applied to soil. Two soils were amended with up to 29% BF slag (containing 800 mg V kg{sup −1}) and equilibrated outdoors for 10 months before conducting a barley shoot growth assay. Additional soil samples were spiked with dissolved vanadate(V) for which assays were conducted two weeks (freshly spiked) and 10 months (aged) after spiking. The BF slag vanadium was dominated by vanadium(III) as shown by V K-edge XANES spectroscopy. In contrast, results obtained by HPLC-ICP-MS showed that vanadium(V), the most toxic vanadium species, was predominant in the soil solution. Barley shoot growth was not affected by the BF slag additions. This was likely due to limited dissolution of vanadium from the BF slag, preventing an increase of dissolved vanadium above toxic thresholds. The difference in vanadium bioavailability among treatments was explained by the vanadium concentration in the soil solution. It was concluded that the vanadium in BF slag is sparingly available. These findings should be of importance in environmental risk assessment.

  6. In Vitro Bioavailability Study of an Antiviral Compound Enisamium Iodide

    Directory of Open Access Journals (Sweden)

    Eleonore Haltner-Ukomadu

    2018-01-01

    Full Text Available An investigation into the biopharmaceutics classification and a study of the in vitro bioavailability (permeability and solubility of the antiviral compound enisamium iodide (4-(benzylcarbamoyl-1-methylpyridinium iodide were carried out. The solubility of enisamium iodide was determined in four different buffers. Apparent intestinal permeability (Papp of enisamium iodide was assessed using human colon carcinoma (Caco-2 cells at three concentrations. The solubility of enisamium iodide in four buffer solutions from pH 1.2 to 7.5 is about 60 mg/mL at 25 °C, and ranges from 130 to 150 mg/mL at 37 °C, depending on the pH. Based on these results, enisamium iodide can be classified as highly soluble. Enisamium iodide demonstrated low permeability in Caco-2 experiments in all tested concentrations of 10–100 μM with permeability coefficients between 0.2 × 10−6 cm s−1 and 0.3 × 10−6 cm s−1. These results indicate that enisamium iodide belongs to class III of the Biopharmaceutics Classification System (BCS due to its high solubility and low permeability. The bioavailability of enisamium iodide needs to be confirmed in animal and human studies.

  7. Geochemical partitioning of Cu and Ni in mangrove sediments: Relationships with their bioavailability

    International Nuclear Information System (INIS)

    Chakraborty, Parthasarathi; Ramteke, Darwin; Chakraborty, Sucharita

    2015-01-01

    Highlights: • Metal speciation controls bioavailability in mangrove ecosystem. • Bioavailability of Ni was controlled by Fe/Mn-oxyhydroxide and organic phases • Bioavailability of Cu in mangrove roots was controlled by organic phase in the sediments. • Cu interacts more strongly with organic phases than Ni in mangrove sediment. - Abstract: Sequential extraction study was performed to determine the concentrations of non-residual metal-complexes in the mangrove sediments from the Divar Island, (west coast of India). Accumulation of metal in the mangrove roots (from the same location) was determined and used as an indicator of bioavailability of metal. An attempt was made to establish a mechanistic linkage between the non-residual metal complexes and their bioavailability in the mangrove system. The non-residual fractions of Cu and Ni were mainly associated with Fe/Mn oxyhydroxide and organic phases in the sediments. A part of these metal fractions were bioavailable in the system. These two phases were the major controlling factors for Ni speciation and their bioavailability in the studied sediments. However, Cu was found to interact more strongly with the organic phases than Ni in the mangrove sediments. Organic phases in the mangrove sediments acted as buffer to control the speciation and bioavailability of Cu in the system

  8. Bioavailability of Isothiocyanates From Broccoli Sprouts in Protein, Lipid, and Fiber Gels

    NARCIS (Netherlands)

    Oliviero, Teresa; Lamers, Simone; Capuano, Edoardo; Dekker, Matthijs; Verkerk, Ruud

    2018-01-01

    Scope: Optimization of bioavailability of dietary bioactive health-beneficial compounds is as important as increasing their concentration in foods. The aim of this study is to explore the change in bioavailability of isothiocyanates (ITCs) in broccoli sprouts incorporated in protein, fiber, and

  9. 21 CFR 320.25 - Guidelines for the conduct of an in vivo bioavailability study.

    Science.gov (United States)

    2010-04-01

    ... conduct of an in vivo bioavailability study. (a) Guiding principles. (1) The basic principle in an in vivo... not been approved for marketing can be used to measure the following pharmacokinetic data: (i) The bioavailability of the formulation proposed for marketing; and (ii) The essential pharmacokinetic characteristics...

  10. Bioavailability and antioxidant effects of olive oil phenols in humans: a review

    NARCIS (Netherlands)

    Vissers, M.N.; Katan, M.B.; Zock, P.L.

    2004-01-01

    Objective: We reviewed the bioavailability and antioxidant effects of phenols from extra virgin olive oil. Search strategy: We searched the MEDLINE database for the years 1966 - 2002. To review the bioavailability of olive oil phenols, we selected animal and human studies that studied the

  11. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in...

  12. Synthetic and tomato-based lycopene have identical bioavailability in humans

    NARCIS (Netherlands)

    Hoppe, P.P.; Krämer, K.; Berg, H. van den; Steenge, G.; Vliet, T. van

    2003-01-01

    Background: Bioavailability studies with lycopene have focused on natural sources. A synthetic source has recently become available. Aim of the study: To determine the relative bioavailabilities of synthetic and tomato-based lycopene in free living volunteers in a single-blind, randomized,

  13. Measurement of soil lead bioavailability and influence of soil types and properties: A review.

    Science.gov (United States)

    Yan, Kaihong; Dong, Zhaomin; Wijayawardena, M A Ayanka; Liu, Yanju; Naidu, Ravi; Semple, Kirk

    2017-10-01

    Lead (Pb) is a widespread heavy metal which is harmful to human health, especially to young children. To provide a human health risk assessment that is more relevant to real conditions, Pb bioavailability in soils is increasingly employed in the assessment procedure. Both in vivo and in vitro measurements for lead bioavailability are available. In vivo models are time- consuming and expensive, while in vitro models are rapid, economic, reproducible, and reliable while involving more uncertainties. Uncertainties in various measurements create difficulties in accurately predicting Pb bioavailability, resulting in the unnecessary remediation of sites. In this critical review, we utilised available data from in vivo and in vitro studies to identify the key parameters influencing the in vitro measurements, and presented uncertainties existing in Pb bioavailability measurements. Soil type, properties and metal content are reported to influence lead bioavailability; however, the differences in methods for assessing bioavailability and the differences in Pb source limit one's ability to conduct statistical analyses on influences of soil factors on Pb bioavailability. The information provided in the review is fundamentally useful for the measurement of bioavailability and risk assessment practices. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Optimizing Oral Bioavailability in Drug Discovery: An Overview of Design and Testing Strategies and Formulation Options.

    Science.gov (United States)

    Aungst, Bruce J

    2017-04-01

    For discovery teams working toward new, orally administered therapeutic agents, one requirement is to attain adequate systemic exposure after oral dosing, which is best accomplished when oral bioavailability is optimized. This report summarizes the bioavailability challenges currently faced in drug discovery, and the design and testing methods and strategies currently utilized to address the challenges. Profiling of discovery compounds usually includes separate assessments of solubility, permeability, and susceptibility to first-pass metabolism, which are the 3 most likely contributors to incomplete oral bioavailability. An initial assessment of absorption potential may be made computationally, and high throughput in vitro assays are typically performed to prioritize compounds for in vivo studies. The initial pharmacokinetic study is a critical decision point in compound evaluation, and the importance of the effect the dosing vehicle or formulation can have on oral bioavailability, especially for poorly water soluble compounds, is emphasized. Dosing vehicles and bioavailability-enabling formulations that can be used for discovery and preclinical studies are described. Optimizing oral bioavailability within a chemical series or for a lead compound requires identification of the barrier limiting bioavailability, and methods used for this purpose are outlined. Finally, a few key guidelines are offered for consideration when facing the challenges of optimizing oral bioavailability in drug discovery. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. EFFECT OF SOIL PROPERTIES ON LEAD BIOAVAILABILITY AND TOXCITY TO EARTHWORMS

    Science.gov (United States)

    Soil properties are important factors modifying metal bioavailability to ecological receptors. Twenty-one soils with a wide range of soil properties were amended with a single concentration of Pb (2000 mg/kg) to determine the effects of soil properties on Pb bioavailability and ...

  16. Red wine is a poor source of bioavailable flavonols in men

    NARCIS (Netherlands)

    De Vries, Jeanne H M; Hollman, Peter C H; Van Amersfoort, Ingrid; Olthof, Margreet R.; Katan, Martijn B.

    2001-01-01

    Red wine is a source of polyphenolic antioxidants, of which flavonols such as quercetin are representatives. Red wine might therefore prevent LDL oxidation and atherosclerosis. However, data on the bioavailability of flavonols from wine are lacking. Therefore, we compared the bioavailability of

  17. Understanding the nature of atmospheric acid processing of mineral dusts in supplying bioavailable phosphorus to the oceans.

    Science.gov (United States)

    Stockdale, Anthony; Krom, Michael D; Mortimer, Robert J G; Benning, Liane G; Carslaw, Kenneth S; Herbert, Ross J; Shi, Zongbo; Myriokefalitakis, Stelios; Kanakidou, Maria; Nenes, Athanasios

    2016-12-20

    Acidification of airborne dust particles can dramatically increase the amount of bioavailable phosphorus (P) deposited on the surface ocean. Experiments were conducted to simulate atmospheric processes and determine the dissolution behavior of P compounds in dust and dust precursor soils. Acid dissolution occurs rapidly (seconds to minutes) and is controlled by the amount of H + ions present. For H + 10 -4 mol/g of dust, the amount of P (and calcium) released has a direct proportionality to the amount of H + consumed until all inorganic P minerals are exhausted and the final pH remains acidic. Once dissolved, P will stay in solution due to slow precipitation kinetics. Dissolution of apatite-P (Ap-P), the major mineral phase in dust (79-96%), occurs whether calcium carbonate (calcite) is present or not, although the increase in dissolved P is greater if calcite is absent or if the particles are externally mixed. The system was modeled adequately as a simple mixture of Ap-P and calcite. P dissolves readily by acid processes in the atmosphere in contrast to iron, which dissolves more slowly and is subject to reprecipitation at cloud water pH. We show that acidification can increase bioavailable P deposition over large areas of the globe, and may explain much of the previously observed patterns of variability in leachable P in oceanic areas where primary productivity is limited by this nutrient (e.g., Mediterranean).

  18. Bioavailability of zinc from defatted soy flour, soy hulls and whole eggs as determined by intrinsic and extrinsic labeling techniques.

    Science.gov (United States)

    Meyer, N R; Stuart, M A; Weaver, C M

    1983-06-01

    Bioavailability of zinc from diets prepared from intrinsically and extrinsically labeled autoclaved, defatted soy flour and scrambled, freeze-dried egg was investigated in male rats marginally depleted in zinc. In one study, retention of zinc from intrinsically labeled soybean flour (73%) was significantly less than from 65ZnCl2 extrinsically added to a soy flour-based diet (80%). Zinc from intrinsically labeled soybean hulls and from soy flour diets containing 10% soybean hulls extrinsically labeled with 65ZnCl2 was as available as the zinc from the extrinsically labeled soy flour diet. In a second study, extrinsic and intrinsic labeling techniques gave a similar assessment of bioavailability of zinc from egg- and soy flour-based diets when extrinsic labeling was accomplished by thoroughly mixing 65ZnCl2 with the protein source prior to incorporation into the diet. Absorption of 65Zn was greater from egg diets than from soy flour diets and of intermediate value from mixed soy flour and egg (50:50, wt/wt) diets regardless of which protein source was labeled, indicating that the zinc entered a common pool.

  19. Bioavailability of prednisolone in rabbits: Comparison of a highviscosity gel and an aqueous suspension - single- and repeated applications

    DEFF Research Database (Denmark)

    Johansen, Sven; Rask-Pedersen, Eva; Prause, J.U.

    1994-01-01

    Øjenpatologi, carbomer, vehicle, fusidic acid, ophthalmic bioavailability, rabbit, aqueous suspension, prednisolone acetate, sulfacetamide sodium......Øjenpatologi, carbomer, vehicle, fusidic acid, ophthalmic bioavailability, rabbit, aqueous suspension, prednisolone acetate, sulfacetamide sodium...

  20. Bioavailability and Bioaccumulation of Metal-Based Engineered Nanomaterials in Aquatic Environments

    DEFF Research Database (Denmark)

    Luoma, Samuel; Khan, Farhan R.; Croteau, Marie-Noelle

    2014-01-01

    Bioavailability of Me-ENMs to aquatic organisms links their release into the environment to ecological implications. Close examination shows some important differences in the conceptual models that define bioavailability for metals and Me-ENMs. Metals are delivered to aquatic animals from Me......-ENMs via water, ingestion, and incidental surface exposure. Both metal released from the Me-ENM and uptake of the nanoparticle itself contribute to bioaccumulation. Some mechanisms of toxicity and some of the metrics describing exposure may differ from metals alone. Bioavailability is driven by complex...... interaction of particle attributes, environmental transformations, and biological traits. Characterization of Me-ENMs is an essential part of understanding bioavailability and requires novel methodologies. The relative importance of the array of processes that could affect Me-ENM bioavailability remains...

  1. Application of a mer-lux biosensor for estimating bioavailable mercury in soil

    DEFF Research Database (Denmark)

    Rasmussen, Lasse Dam; Sørensen, S. J.; Turner, R. R.

    2000-01-01

    A previously described bioassay using a mer-lux gene fusion for detection of bioavailable mercury was applied for the estimation of the bioavailable fraction of mercury in soil. The bioavailable fraction is defined here as being part of the water leachable fraction. Due to masking of light emission...... responses. The utility of the mer-lux biosensor assay was tested by relating measurements of bioavailable and total mercury to the response of the soil microbial community to mercury exposure. Two different soil types (an agricultural and a beech forest soil) were spiked with 2.5 µg Hg(II) g-1 in microcosms...... in resistance or diversity. This study showed that the bioassay using the mer-lux biosensor is a useful and sensitive tool for estimation of bioavailable mercury in soil....

  2. Biosurfactants and increased bioavailability of sorbed organic contaminants: Measurements using a biosensor

    International Nuclear Information System (INIS)

    Strong-Gunderson, J.M.; Palumbo, A.V.; Applegate, B.; Saylor, G.S.

    1993-01-01

    Bioremediation of sites contaminated with hydrophobic materials that sorb onto the soil matrix is very difficult due to reduced microbial (bio)availability. Following biosurfactant addition, we have measured an increase in contaminant bioavailability by using a lux biosensor. Direct microbial bioavailability was determined by using a genetically engineered microbial bioreporter strain of Pseudomonas putida. This strain was engineered so the lux genes, which code for light production, are transcriptionally fused with genes that code for contaminant degradation and are thus induced in the presence of specific compounds. By using a bioreporter we can quantify the actual microbial bioavailability of the contaminants and compare it to concentrations measured by other analytical methods (e.g. gas chromatograph). It is possible that these values are not equal to each other. Thus, bioremediation rates may not be accurately predicted if bioavailability is not considered

  3. Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

    International Nuclear Information System (INIS)

    Grassi, Tony F.; Silva, Glenda N. da; Bidinotto, Lucas T.; Rossi, Bruna F.; Quinalha, Marília M.; Kass, Laura; Muñoz-de-Toro, Mónica; Barbisan, Luís F.

    2016-01-01

    This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation of the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland development.

  4. Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

    Energy Technology Data Exchange (ETDEWEB)

    Grassi, Tony F. [UNESP – Univ. Estadual Paulista, Botucatu Medical School, Department of Pathology, Botucatu, SP (Brazil); Silva, Glenda N. da [UFOP – Federal University of Ouro Preto, Analysis Clinical Department, Ouro Preto, MG (Brazil); Bidinotto, Lucas T. [Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP (Brazil); Barretos School of Health Sciences, Dr. Paulo Prata - FACISB, Barretos, SP (Brazil); Rossi, Bruna F.; Quinalha, Marília M. [UNESP – Univ. Estadual Paulista, Botucatu Biosciences Institute, Department of Morphology, Botucatu, SP (Brazil); Kass, Laura; Muñoz-de-Toro, Mónica [UNL – Universidad Nacional del Litoral, School of Biochemistry and Biological Sciences, Human Pathology Department, Instituto de Salud y Ambiente del Litoral (ISAL, CONICET-UNL), Santa Fe (Argentina); Barbisan, Luís F., E-mail: barbisan@ibb.unesp.br [UNESP – Univ. Estadual Paulista, Botucatu Biosciences Institute, Department of Morphology, Botucatu, SP (Brazil)

    2016-07-15

    This study aimed to evaluate the modifying effects of dietary genistein (GEN) and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats were treated with BPA25 or 250 μg/kg bw/day from gestational days 10 to 21 with or without dietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day (PND) 21, female offspring from different litters were euthanized for mammary gland development and gene expression analyses. Our results indicated that prenatal exposure to BPA25 and 250 did not modify the ductal elongation of the mammary gland tree or the estrogen receptor alpha (ER-α) expression in terminal end buds (TEBs). However, BPA25-exposed offspring had a higher number of terminal structures (TEBs + TDs) and an increased mammary branching and cell proliferation index in TEBs. Besides that, BPA25 and 250 modulated the expression of several genes in the immature mammary gland that were not changed in a dose dependent manner and involved different clusters of up- and down-regulated genes. Furthermore, BPA25 and BPA250 + I3C-treated groups also had a higher number of enriched functional gene categories. In addition, maternal dietary GEN and I3C in association with BPA exposure produced specific gene expression alterations in the mammary gland and overcome the adverse effect of BPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPA exposure induced both morphological and gene expression modifications on the mammary gland that dietary intake of GEN and I3C reverted on BPA25-exposed animals. - Highlights: • Gestational BPA and its association with GEN and I3C modify gene expression on the early mammary gland development. • GEN and I3C induced a different gene expression signature than lower BPA dose. • Dietary GEN and I3C countered the adverse effect of lower BPA dose on the cell proliferation and mammary gland development.

  5. Chemodynamics of chromium reduction in soils: Implications to bioavailability

    Energy Technology Data Exchange (ETDEWEB)

    Choppala, Girish [Centre for Environmental Risk Assessment and Remediation, Building-X, University of South Australia, Mawson Lakes, South Australia 5095 (Australia); Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, PO Box 486, Salisbury, South Australia 5106 (Australia); Bolan, Nanthi, E-mail: Nanthi.Bolan@unisa.edu.au [Centre for Environmental Risk Assessment and Remediation, Building-X, University of South Australia, Mawson Lakes, South Australia 5095 (Australia); Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, PO Box 486, Salisbury, South Australia 5106 (Australia); Seshadri, Balaji [Centre for Environmental Risk Assessment and Remediation, Building-X, University of South Australia, Mawson Lakes, South Australia 5095 (Australia); Cooperative Research Centre for Contamination Assessment and Remediation of the Environment, PO Box 486, Salisbury, South Australia 5106 (Australia)

    2013-10-15

    Highlights: • Examined the effects of sorption, pH and C sources on Cr(VI) reduction and toxicity. • The rate of Cr(VI) reduction decreased with an increase in Cr(VI) adsorption and pH. • The proton dynamics in Cr(VI) reduction was assessed in relation to remediation. • A novel black carbon showed the highest reduction rate of Cr(VI) in soils. • Black carbon decreased the bioavailability and phytotoxicity of Cr(VI) in soils. -- Abstract: Chromium toxicity in soils can be mitigated by reduction of Cr(VI) to Cr(III) which is influenced by the presence of free Cr(VI) species in soil solution, and the supply of protons and electrons. In this study, the effects of Cr(VI) adsorption (i.e. availability of free Cr(VI) species in soil solution), soil pH (i.e. supply of protons) and three electron donor carbon sources [black carbon (BC), chicken manure biochar (CMB) and cow manure (CM)] on the reduction of Cr(VI) to Cr(III) in soils were investigated. The results indicated that the rate of Cr(VI) reduction decreased with an increase in Cr(VI) adsorption and soil pH, which is attributed to decreased supply of free Cr(VI) ions and protons, respectively. Among the three different amendments tested, BC showed the highest rate of Cr(VI) reduction followed by CM and CMB. Furthermore, addition of BC, CM and CMB decreased the bioavailability of Cr(VI) in contaminated soils. The high efficiency of BC on Cr(VI) reduction was due to the electron donor's functional groups such as phenolic, hydroxyl, carbonyl and amides. The study demonstrated that free form of Cr(VI) ions in soil solution and carbon amendments enriched with acidic functional groups favored the reduction of Cr(VI), thereby mitigating its bioavailability and toxicity in contaminated soils.

  6. Bioavailability of cadmium from infant diets in newborn rats

    International Nuclear Information System (INIS)

    Eklund, G.; Oskarsson, A.; Petersson Grawe, K.

    2001-01-01

    Infants are exposed to higher levels of cadmium (Cd) from infant and follow-on formulas than from breast milk. We studied the bioavailability of 109 CdCl 2 from cows' milk formula, soy formula, wheat/oat/milk formula, wholemeal/milk formula and water in 11-day-old rat pups. The pups received a single oral dose of one diet labelled with 109 Cd, 0.1 or 0.3 mg Cd/kg body weight. After 2 or 24 h or 4, 9 or 12 days the fractional retention of 109 Cd in the whole body, in segments of rinsed small intestine and in tissue was measured in a gamma counter. Pups receiving 109 Cd in water or cows' milk formula had the highest mean whole-body retention. It ranged from 67% of the dose in the water group to 52% in the wholemeal/milk formula group 4 days after dosing. The retention of 109 Cd in the rinsed small intestine was significantly higher in the water group and the cows' milk formula group than in the cereal-based formula groups at 24 h and 4 days after dosing. It was still high in all groups on day 9, ranging from 26 to 11%. Initially most of the 109 Cd was retained in the duodenum but by day 4 it had moved further down into the jejunum. In the liver, the highest and lowest retention on day 4 was 16 permille and 3 permille of the dose in the water group and wholemeal/milk formula group, respectively. In the kidney, 109 Cd was still increasing 12 days after exposure in all groups. Whole-body retention and tissue levels were higher than previously reported in adult animals. The lower bioavailability of 109 Cd from the cereal-based formulas compared to water and cows' milk formula on the longer survival times is most likely explained by Cd binding to dietary fibre and phytic acid in the cereal-based formulas reducing the intestinal binding and decreasing the bioavailability of Cd. The high retention of 109 Cd in the small intestine, leading to a prolonged absorption period, emphasizes the importance of extending studies on neonatal Cd absorption over a long time period in

  7. Bioavailability of cadmium from infant diets in newborn rats

    Energy Technology Data Exchange (ETDEWEB)

    Eklund, G.; Oskarsson, A. [Dept. of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala (Sweden); Petersson Grawe, K. [Toxicology Div., National Food Administration, Uppsala (Sweden)

    2001-11-01

    Infants are exposed to higher levels of cadmium (Cd) from infant and follow-on formulas than from breast milk. We studied the bioavailability of {sup 109}CdCl{sub 2} from cows' milk formula, soy formula, wheat/oat/milk formula, wholemeal/milk formula and water in 11-day-old rat pups. The pups received a single oral dose of one diet labelled with {sup 109}Cd, 0.1 or 0.3 mg Cd/kg body weight. After 2 or 24 h or 4, 9 or 12 days the fractional retention of {sup 109}Cd in the whole body, in segments of rinsed small intestine and in tissue was measured in a gamma counter. Pups receiving {sup 109}Cd in water or cows' milk formula had the highest mean whole-body retention. It ranged from 67% of the dose in the water group to 52% in the wholemeal/milk formula group 4 days after dosing. The retention of {sup 109}Cd in the rinsed small intestine was significantly higher in the water group and the cows' milk formula group than in the cereal-based formula groups at 24 h and 4 days after dosing. It was still high in all groups on day 9, ranging from 26 to 11%. Initially most of the {sup 109}Cd was retained in the duodenum but by day 4 it had moved further down into the jejunum. In the liver, the highest and lowest retention on day 4 was 16 permille and 3 permille of the dose in the water group and wholemeal/milk formula group, respectively. In the kidney, {sup 109}Cd was still increasing 12 days after exposure in all groups. Whole-body retention and tissue levels were higher than previously reported in adult animals. The lower bioavailability of {sup 109}Cd from the cereal-based formulas compared to water and cows' milk formula on the longer survival times is most likely explained by Cd binding to dietary fibre and phytic acid in the cereal-based formulas reducing the intestinal binding and decreasing the bioavailability of Cd. The high retention of {sup 109}Cd in the small intestine, leading to a prolonged absorption period, emphasizes the importance of

  8. Bioavailability and ecotoxicity of arsenic species in solution culture and soil system: implications to remediation.

    Science.gov (United States)

    Bolan, Nanthi; Mahimairaja, Santiago; Kunhikrishnan, Anitha; Seshadri, Balaji; Thangarajan, Ramya

    2015-06-01

    In this work, bioavailability and ecotoxicity of arsenite (As(III)) and arsenate (As(V)) species were compared between solution culture and soil system. Firstly, the adsorption of As(III) and As(V) was compared using a number of non-allophanic and allophanic soils. Secondly, the bioavailability and ecotoxicity were examined using germination, phytoavailability, earthworm, and soil microbial activity tests. Both As-spiked soils and As-contaminated sheep dip soils were used to test bioavailability and ecotoxicity. The sheep dip soil which contained predominantly As(V) species was subject to flooding to reduce As(V) to As(III) and then used along with the control treatment soil to compare the bioavailability between As species. Adsorption of As(V) was much higher than that of As(III), and the difference in adsorption between these two species was more pronounced in the allophanic than non-allophanic soils. In the solution culture, there was no significant difference in bioavailability and ecotoxicity, as measured by germination and phytoavailability tests, between these two As species. Whereas in the As-spiked soils, the bioavailability and ecotoxicity were higher for As(III) than As(V), and the difference was more pronounced in the allophanic than non-allophanic soils. Bioavailability of As increased with the flooding of the sheep dip soils which may be attributed to the reduction of As(V) to As(III) species. The results in this study have demonstrated that while in solution, the bioavailability and ecotoxicity do not vary between As(III) and As(V), in soils, the latter species is less bioavailable than the former species because As(V) is more strongly retained than As(III). Since the bioavailability and ecotoxicity of As depend on the nature of As species present in the environment, risk-based remediation approach should aim at controlling the dynamics of As transformation.

  9. Bioavailability of organically bound Fe to model phytoplankton of the Southern Ocean

    Directory of Open Access Journals (Sweden)

    C. S. Hassler

    2009-10-01

    Full Text Available Iron (Fe is known to be mostly bound to organic ligands and to limit primary productivity in the Southern Ocean. It is thus important to investigate the bioavailability of organically bound Fe. In this study, we used four phytoplankton species of the Southern Ocean (Phaeocystis sp., Chaetoceros sp., Fragilariopsis kerguelensis and Thalassiosira antarctica Comber to measure the influence of various organic ligands on Fe solubility and bioavailability. Short-term uptake Fe:C ratios were inversely related to the surface area to volume ratios of the phytoplankton. The ratio of extracellular to intracellular Fe is used to discuss the relative importance of diffusive supply and uptake to control Fe bioavailability. The effect of excess organic ligands on Fe bioavailability cannot be solely explained by their effect on Fe solubility. For most strains studied, the bioavailability of Fe can be enhanced relative to inorganic Fe in the presence of porphyrin, catecholate siderophore and saccharides whereas it was decreased in presence of hydroxamate siderophore and organic amine. For Thalassiosira, iron bioavailability was not affected by the presence of porphyrin, catecholate siderophore and saccharides. The enhancement of Fe bioavailability in presence of saccharides is presented as the result from both the formation of bioavailable (or chemically labile organic form of Fe and the stabilisation of Fe within the dissolved phase. Given the ubiquitous presence of saccharides in the ocean, these compounds might represent an important factor to control the basal level of soluble and bioavailable Fe. Results show that the use of model phytoplankton is promising to improve mechanistic understanding of Fe bioavailability and primary productivity in HNLC regions of the ocean.

  10. Determination of cadmium relative bioavailability in contaminated soils and its prediction using in vitro methodologies.

    Science.gov (United States)

    Juhasz, Albert L; Weber, John; Naidu, Ravi; Gancarz, Dorota; Rofe, Allan; Todor, Damian; Smith, Euan

    2010-07-01

    In this study, cadmium (Cd) relative bioavailability in contaminated (n = 5) and spiked (n = 2) soils was assessed using an in vivo mouse model following administration of feed containing soil or Cd acetate (reference material) over a 15 day exposure period. Cadmium relative bioavailability varied depending on whether the accumulation of Cd in the kidneys, liver, or kidney plus liver was used for relative bioavailability calculations. When kidney plus liver Cd concentrations were used, Cd relative bioavailability ranged from 10.1 to 92.1%. Cadmium relative bioavailability was higher (14.4-115.2%) when kidney Cd concentrations were used, whereas lower values (7.2-76.5%) were derived when liver Cd concentrations were employed in calculations. Following in vivo studies, four in vitro methodologies (SBRC, IVG, PBET, and DIN), encompassing both gastric and intestinal phases, were assessed for their ability to predict Cd relative bioavailability. Pearson correlations demonstrated a strong linear relationship between Cd relative bioavailability and Cd bioaccessibility (0.62-0.91), however, stronger in vivo-in vitro relationships were observed when Cd relative bioavailability was calculated using kidney plus liver Cd concentrations. Whereas all in vitro assays could predict Cd relative bioavailability with varying degrees of confidence (r(2) = 0.348-0.835), large y intercepts were calculated for a number of in vitro assays which is undesirable for in vivo-in vitro predictive models. However, determination of Cd bioaccessibility using the intestinal phase of the PBET assay resulted in a small y intercept (5.14; slope =1.091) and the best estimate of in vivo Cd relative bioavailability (r(2) = 0.835).

  11. 21 CFR 320.27 - Guidelines on the design of a multiple-dose in vivo bioavailability study.

    Science.gov (United States)

    2010-04-01

    ... vivo bioavailability study. 320.27 Section 320.27 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.27...

  12. Development of a Passive Multisampling Method to Measure Dioxins/Furans and Other Contaminant Bioavailability in Aquatic Sediments

    Science.gov (United States)

    2016-11-01

    FINAL REPORT Development of a Passive Multisampling Method to Measure Dioxins/Furans and Other Contaminant Bioavailability in Aquatic...passive multisampling method to measure Dioxins/Furans 5a. CONTRACT NUMBER and other contaminant bioavailability in aquatic sediments...This also indicates the bioavailability or pressure (fugacity) of contaminants on organisms2 and consequently represents the exposure level for

  13. Bioavailability of energy-effluent materials in coastal ecosystems

    International Nuclear Information System (INIS)

    Hardy, J.T.

    1987-01-01

    An attempt is made to study the long-term effects of effluents from coastal and offshore nuclear power plants. The original intent of the program was to integrate approaches in chemistry, ocean transport, and biological uptake to quantify the variables that regulate biological availability of energy-effluent materials. Initial work was focused on the fate and effects of copper. In later research, the authors examined the basic environmental variables controlling the bioavailability of energy-related contaminants. They investigated how factors such as dissolved organic compounds, suspended particles, and sediment binding affected chemical speciation and how chemical speciation, in turn, influenced the availability of metals and radionuclides to marine invertebrates. They developed a hydrodynamic model to predict sediment and contaminant transport, and they quantified the bioconcentration of synthetic-fuel residuals in plankton

  14. Assessing biochar's ability to reduce bioavailability of aminocyclopyrachlor in soils

    International Nuclear Information System (INIS)

    Rittenhouse, Jennifer L.; Rice, Pamela J.; Spokas, Kurt A.; Koskinen, William C.

    2014-01-01

    Aminocyclopyrachlor is a pyrimidine carboxylic acid herbicide used to control broadleaf weeds and brush. Amending soil with activated charcoal is recommended to prevent off-site transport of aminocyclopyrachlor and non-target plant damage. We used the batch-equilibrium method to determine the concentration of aminocyclopyrachlor in a pseudo-steady state with biochar, soil, and biochar-soil systems ( 5  kg ha −1 –7.27 × 10 5  kg ha −1 ). - Highlights: • Aminocyclopyrachlor is mobile in three Minnesota soils. • Biochar amendments had limited use for aminocyclopyrachlor remediation in soil. • Two biochar amendments consistently reduced the aqueous-phase herbicide. • Biochar inputs would be very high and not feasible for field-scale remediation. - This was the first study to assess the use of biochar as a remediation tool for reducing bioavailable aminocyclopyrachlor in the liquid phase soil systems

  15. Bioavailability and impact of effluents on coastal ecosystems

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    The Bioavailability and Impact of Effluents on Coastal Ecosystems program was initiated in July 1974. The program's major objective was to bring together a multidisciplinary team of researchers to investigate the biogeochemical processes that control the transport, transfer, distribution, biological availability and toxicity of materials found in energy-related effluents. This year has been spent in planning the needed research tasks, assembling the necessary personnel and equipment, and initiating first stage research as defined by the program. The program is centered at the Marine Research Laboratory, Sequim, Washington, and involves scientists located at Sequim and Richland. The operating philosophy is to conduct the program at the Marine Research Laboratory and use equipment and expertise from Richland as a resource for studies that cannot be practically done at Sequim. The research described represents the first year's efforts by the investigators involved in the program

  16. Vitamin D bioavailability in cystic fibrosis: a cause for concern?

    Science.gov (United States)

    Mailhot, Geneviève

    2012-05-01

    Despite the inclusion of extra vitamin D in their regimen of fat-soluble vitamin supplementation, cystic fibrosis patients remain chronically depleted of vitamin D. The persistence of suboptimal vitamin D status is often blamed on the maldigestion and malabsorption of fat. However, the mitigated success of recent clinical trials with high-dose vitamin D supplementation suggests that vitamin D bioavailability might be impaired in these patients. Given the growing understanding of the importance of this vitamin in the regulation of multiple biological functions beyond skeletal health, the present review analyzes the current literature by addressing each step of vitamin D metabolism and action in the context of this life-limiting pathology. In addition, it highlights the importance of vitamin D in relation to organs and or conditions affected by cystic fibrosis. © 2012 International Life Sciences Institute.

  17. Improving oral bioavailability of cyclic peptides by N-methylation.

    Science.gov (United States)

    Räder, Andreas F B; Reichart, Florian; Weinmüller, Michael; Kessler, Horst

    2018-06-01

    The renaissance of peptides in pharmaceutical industry results from their importance in many biological functions. However, low metabolic stability and the lack of oral availability of most peptides is a certain limitation. Whereas metabolic instability may be often overcome by development of small cyclic peptides containing d-amino acids, the very low oral availability of most peptides is a serious limitation for some medicinal applications. The situation is complicated because a twofold optimization - biological activity and oral availability - is required to overcome this problem. Moreover, most simple "rules" for achieving oral availability are not general and are applicable only to limited cases. Many structural modifications for increasing biological activities and metabolic stabilities of cyclic peptides have been described, of which N-alkylation is probably the most common. This mini-review focuses on the effects of N-methylation of cyclic peptides in strategies to optimize bioavailabilities. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Improvement of physico-chemical properties and phenolic compounds bioavailability by concentrating dietary fiber of peach (Prunus persica) juice by-product.

    Science.gov (United States)

    Rodríguez-González, Sarahí; Pérez-Ramírez, Iza F; Castaño-Tostado, Eduardo; Amaya-Llano, Silvia; Rodríguez-García, Mario E; Reynoso-Camacho, Rosalía

    2018-06-01

    This study aimed to concentrate dietary fiber (DF) from peach (Prunus persica) juice by-product (PJBP), to improve its functional properties, and its polyphenols bioavailability. The dietary fiber concentrates (DFCs) were obtained from PJBP using water/ethanol treatments (100:0, 20:80, 50:50, 80:20, and 0:100, v/v) at 1:5 ratio (wet weight/solvent, w/v) for 5 and 20 min at 21 °C. All treatments concentrated condensed tannins, total and insoluble DF, with the highest content found with 100% H 2 O treatment. The major polyphenols of DFC were 4-O-caffeoylquinic, chlorogenic, and 1,5-di-O-caffeoylquinic acids. Water and oil retention capacity and maximum glucose diffusion rate were improved mainly with 100% H 2 O treatment. Healthy rats were fed with a standard diet supplemented with 8% of PJBP, DFC obtained with 100% H 2 O for 5 min, or DFC obtained with 20% EtOH for 5 min. Gastrointestinal digesta weight and viscosity were increased in animals supplemented with 100% H 2 O DFC. Moreover, the urinary excretion of polyphenol metabolites, mainly glucuronide and sulfate conjugates, was increased with this treatment, indicating a greater bioavailability of PJBP polyphenols, which was associated with an increased dietary fiber porosity. Water treatment could be used to potentiate PJBP functional properties and polyphenols bioavailability. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  19. Metabolism, oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats

    Science.gov (United States)

    Barve, Avantika; Chen, Chi; Hebbar, Vidya; Desiderio, Joseph; Saw, Constance Lay-Lay; Kong, Ah-Ng

    2012-01-01

    The purpose of this study was to compare the hepatic and small intestinal metabolism, and examine bioavailability and gastro-intestinal first-pass effects of Kaempferol in the rats. Liver and small intestinal microsomes fortified with either NADPH or UDPGA were incubated with varying concentrations of Kaempferol for upto 120 minutes. Based on the values of the kinetic constants (Km and Vmax), the propensity for UDPGA-dependent conjugation as compared to NADPH-dependent oxidative metabolism was higher for both hepatic and small intestinal microsomes. Male Sprague-Dawley rats were administered Kaempferol intravenously (IV) (10, 25 mg/kg) or orally (100, 250 mg/kg). Gastro-intestinal first pass effects were observed by collecting portal blood after oral administration of 100 mg/kg Kaempferol. Pharmacokinetic parameters were obtained by Noncompartmental analysis using WinNonlin. After IV administration, the plasma concentration-time profiles for 10 and 25 mg/kg were consistent with high clearance (~ 3 L/hr/kg) and large volumes of distribution (8-12 L/kg). The disposition was characterized by a terminal half-life value of 3-4 hours. After oral administration the plasma concentration-time profiles demonstrated fairly rapid absorption (tmax ~ 1-2 hours). The area under the curve (AUC) values after IV and oral doses increased proportional to the dose. The bioavailability (F) was poor at ~ 2%. Analysis of portal plasma after oral administration revealed low to moderate absorption. Taken together, the low F of Kaempferol is attributed in part to extensive first-pass metabolism by glucuronidation and other metabolic pathways in the gut and in the liver. PMID:19722166

  20. Improving maraviroc oral bioavailability by formation of solid drug nanoparticles.

    Science.gov (United States)

    Savage, Alison C; Tatham, Lee M; Siccardi, Marco; Scott, Trevor; Vourvahis, Manoli; Clark, Andrew; Rannard, Steve P; Owen, Andrew

    2018-05-17

    Oral drug administration remains the preferred approach for treatment of HIV in most patients. Maraviroc (MVC) is the first in class co-receptor antagonist, which blocks HIV entry into host cells. MVC has an oral bioavailability of approximately 33%, which is limited by poor permeability as well as affinity for CYP3A and several drug transporters. While once-daily doses are now the favoured option for HIV therapy, dose-limiting postural hypotension has been of theoretical concern when administering doses high enough to achieve this for MVC (particularly during coadministration of enzyme inhibitors). To overcome low bioavailability and modify the pharmacokinetic profile, a series of 70 wt% MVC solid drug nanoparticle (SDN) formulations (containing 30 wt% of various polymer/surfactant excipients) were generated using emulsion templated freeze-drying. The lead formulation contained PVA and AOT excipients ( MVC SDN PVA/AOT ), and was demonstrated to be fully water-dispersible to release drug nanoparticles with z-average diameter of 728 nm and polydispersity index of 0.3. In vitro and in vivo studies of MVC SDN PVA/AOT showed increased apparent permeability of MVC, compared to a conventional MVC preparation, with in vivo studies in rats showing a 2.5-fold increase in AUC (145.33 vs. 58.71 ng h ml -1 ). MVC tissue distribution was similar or slightly increased in tissues examined compared to the conventional MVC preparation, with the exception of the liver, spleen and kidneys, which showed statistically significant increases in MVC for MVC SDN PVA/AOT . These data support a novel oral format with the potential for dose reduction while maintaining therapeutic MVC exposure and potentially enabling a once-daily fixed dose combination product. Copyright © 2018. Published by Elsevier B.V.

  1. How bioavailable is highly weathered Deepwater Horizon oil?

    Science.gov (United States)

    Bostic, J.; Ziolkowski, L. A.; Reddy, C. M.; Aeppli, C.; Swarthout, B.

    2016-02-01

    Oiled sand patties continue to be deposited on northern Gulf of Mexico beaches five years after the Deepwater Horizon (DwH) oil spill. It is known that during the first 18 months post-spill, sand patties from DwH were chemically transformed, both biotically and abiotically, from wellhead release to beach deposition. However, the chemically transformed oil, which appears to become more polar over time, is not well understood in regards to its biodegradation potential. Biodegradation exerts a large control on the fate of spilled oil, representing a major conduit for its removal from the environment. To assess the bioavailability of this weathered oil, sand patties were collected from intertidal and supratidal zones of beaches in Florida, Alabama, and Mississippi in July 2015. Microbial biomarkers of the viable community, phospholipid fatty acids (PLFA), were detected on all samples collected. The PLFA distributions (mostly saturated and branched structures) and abundances (2 - 9 x 1013 cells/g sand patty) were similar across sampling locations. The positive correlation between PLFA abundance and surface area to volume ratios of sand patties indicates that microbes are preferentially inhabiting outside surfaces of the patties. We will present data on the radiocarbon (14C) content of PLFA to assess carbon (C) sources assimilated by microbes. 14C of PLFA is a powerful tool for assessing C sources assimilated in this setting. Oil has no 14C (Δ14C= -1000‰) while modern organic matter has relatively abundant 14C (Δ14C= 0‰). Fingerprinting analysis of biomarker ratios using comprehensive two-dimensional gas chromatography will be presented to ascertain if oil originated from DwH. The extent of the chemical transformation of the oil into more polar compounds will also be measured using thin layer chromatography. Results of this investigation aim to determine the bioavailability and ultimate fate of oiled sand patties that continue to wash ashore on Gulf of Mexico

  2. Detection of a negative correlation between prescription of Chinese herbal products containing coumestrol, genistein or daidzein and risk of subsequent endometrial cancer among tamoxifen-treated female breast cancer survivors in Taiwan between 1998 and 2008: A population-based study.

    Science.gov (United States)

    Hu, Yi-Cheng; Wu, Chien-Tung; Lai, Jung-Nien; Tsai, Yueh-Ting

    2015-07-01

    Tamoxifen users sometimes seek complementary and alternative medicine advice for treatment of a variety of illness and co-administer with phytoestrogen-containing herbs, resulting in an increasing concern of its influence in subsequent endometrial cancer risk. Our study aims to determine the prevalence of Chinese herbal products containing coumestrol, genistein, or daidzein and their association with subsequent endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan. We selected all patients who were newly diagnosed with invasive breast cancer and received tamoxifen treatment between January 1, 1998, and December 31, 2008, from the National Health Insurance Research Database. Among the 26,656 tamoxifen-treated breast cancer survivors, we evaluated the usage, frequency of service, and prescription of Chinese herbal products containing coumestrol, genistein, or daidzein. The logistic regression method was employed to calculate the odds ratios for utilization of those herbal products. Cox proportional hazard regression was set to calculate the hazard ratios of endometrial cancer associated with such usage. Of the patients surveyed, 36.2% (n=9652) of the tamoxifen-treated breast cancer survivors examined in the study had consumed Chinese herbal products containing coumestrol, genistein, or daidzein during the study period. Exposure to Ge Gen(Puerariae Radix) specifically was the most extensive. For it, the population consumed an average cumulative dose of above 180g. Compared to those who had never used Chinese herbal products, breast cancer survivors who had taken Chinese herbal products containing coumestrol, genistein, or daidzein concurrently with tamoxifen treatment did not have a higher hazard ratio for subsequent development of endometrial cancer. Among those tamoxifen-treated female breast cancer survivors in Taiwan, consumption of Chinese herbal products containing coumestrol, genistein, or daidzein is negatively correlated with

  3. Liposomal-encapsulated Ascorbic Acid: Influence on Vitamin C Bioavailability and Capacity to Protect against Ischemia–Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Janelle L. Davis

    2016-01-01

    Full Text Available Intravenous administration of vitamin C has been shown to decrease oxidative stress and, in some instances, improve physiological function in adult humans. Oral vitamin C administration is typically less effective than intravenous, due in part to inferior vitamin C bioavailability. The purpose of this study was to determine the efficacy of oral delivery of vitamin C encapsulated in liposomes. On 4 separate randomly ordered occasions, 11 men and women were administered an oral placebo, or 4 g of vitamin C via oral, oral liposomal, or intravenous delivery. The data indicate that oral delivery of 4 g of vitamin C encapsulated in liposomes (1 produces circulating concentrations of vitamin C that are greater than unencapsulated oral but less than intravenous administration and (2 provides protection from ischemia–reperfusion-mediated oxidative stress that is similar to the protection provided by unencapsulated oral and intravenous administrations.

  4. Recent Warming, Rather than Industrial Emissions of Bioavailable Nutrients, Is the Dominant Driver of Lake Primary Production Shifts across the Athabasca Oil Sands Region.

    Directory of Open Access Journals (Sweden)

    Jamie C Summers

    Full Text Available Freshwaters in the Athabasca Oil Sands Region (AOSR are vulnerable to the atmospheric emissions and land disturbances caused by the local oil sands industry; however, they are also affected by climate change. Recent observations of increases in aquatic primary production near the main development area have prompted questions about the principal drivers of these limnological changes. Is the enhanced primary production due to deposition of nutrients (nitrogen and phosphorus from local industry or from recent climatic changes? Here, we use downcore, spectrally-inferred chlorophyll-a (VRS-chla profiles (including diagenetic products from 23 limnologically-diverse lakes with undisturbed catchments to characterize the pattern of primary production increases in the AOSR. Our aim is to better understand the relative roles of the local oil sands industry versus climate change in driving aquatic primary production trends. Nutrient deposition maps, generated using geostatistical interpolations of spring-time snowpack measurements from a grid pattern across the AOSR, demonstrate patterns of elevated total phosphorus, total nitrogen, and bioavailable nitrogen deposition around the main area of industrial activity. However, this pattern is not observed for bioavailable phosphorus. Our paleolimnological findings demonstrate consistently greater VRS-chla concentrations compared to pre-oil sands development levels, regardless of morphological and limnological characteristics, landscape position, bioavailable nutrient deposition, and dibenzothiophene (DBT-inferred industrial impacts. Furthermore, breakpoint analyses on VRS-chla concentrations across a gradient of DBT-inferred industrial impact show limited evidence of a contemporaneous change among lakes. Despite the contribution of bioavailable nitrogen to the landscape from industrial activities, we find no consistency in the spatial pattern and timing of VRS-chla shifts with an industrial fertilizing signal

  5. Using SPME fibers and Tenax to predict the bioavailability of pyrethroids and chlorpyrifos in field sediments

    International Nuclear Information System (INIS)

    Harwood, Amanda D.; Landrum, Peter F.; Weston, Donald P.; Lydy, Michael J.

    2013-01-01

    The presence of pyrethroids in both urban and agricultural sediments at levels lethal to invertebrates has been well documented. However, variations in bioavailability among sediments make accurate predictions of toxicity based on whole sediment concentrations difficult. A proposed solution to this problem is the use of bioavailability-based estimates, such as solid phase microextraction (SPME) fibers and Tenax beads. This study compared three methods to assess the bioavailability and ultimately toxicity of pyrethroid pesticides including field-deployed SPME fibers, laboratory-exposed SPME fibers, and a 24-h Tenax extraction. The objective of the current study was to compare the ability of these methods to quantify the bioavailable fraction of pyrethroids in contaminated field sediments that were toxic to benthic invertebrates. In general, Tenax proved a more sensitive method than SPME fibers and a correlation between Tenax extractable concentrations and mortality was observed. - Highlights: ► Can use bioavailability-based methods for pyrethroids in sediments. ► Tenax was a more sensitive technique. ► Tenax extractable concentrations relate to invertebrate mortality. - This research provides an important first step in using bioavailability-based techniques for estimating the bioavailability and toxicity of hydrophobic pesticides in field sediments.

  6. Improving the accuracy of effect-directed analysis: the role of bioavailability.

    Science.gov (United States)

    You, Jing; Li, Huizhen

    2017-12-13

    Aquatic ecosystems have been suffering from contamination by multiple stressors. Traditional chemical-based risk assessment usually fails to explain the toxicity contributions from contaminants that are not regularly monitored or that have an unknown identity. Diagnosing the causes of noted adverse outcomes in the environment is of great importance in ecological risk assessment and in this regard effect-directed analysis (EDA) has been designed to fulfill this purpose. The EDA approach is now increasingly used in aquatic risk assessment owing to its specialty in achieving effect-directed nontarget analysis; however, a lack of environmental relevance makes conventional EDA less favorable. In particular, ignoring the bioavailability in EDA may cause a biased and even erroneous identification of causative toxicants in a mixture. Taking bioavailability into consideration is therefore of great importance to improve the accuracy of EDA diagnosis. The present article reviews the current status and applications of EDA practices that incorporate bioavailability. The use of biological samples is the most obvious way to include bioavailability into EDA applications, but its development is limited due to the small sample size and lack of evidence for metabolizable compounds. Bioavailability/bioaccessibility-based extraction (bioaccessibility-directed and partitioning-based extraction) and passive-dosing techniques are recommended to be used to integrate bioavailability into EDA diagnosis in abiotic samples. Lastly, the future perspectives of expanding and standardizing the use of biological samples and bioavailability-based techniques in EDA are discussed.

  7. Use of Tunable Whole-Cell Bioreporters to Assess Bioavailable Cadmium and Remediation Performance in Soils.

    Directory of Open Access Journals (Sweden)

    Youngdae Yoon

    Full Text Available It is important to have tools to measure the bioavailability to assess the risks of pollutants because the bioavailability is defined as the portions of pollutants showing the biological effects on living organisms. This study described the construction of tunable Escherichia coli whole-cell bioreporter (WCB using the promoter region of zinc-inducible operon and its application on contaminated soils. It was verified that this WCB system showed specific and sensitive responses to cadmium rather than zinc in the experimental conditions. It was inferred that Cd(II associates stronger with ZntR, a regulatory protein of zinc-inducible operon, than other metal ions. Moreover, the expression of reporter genes, egfp and mcherry, were proportional to the concentration of cadmium, thereby being a quantitative sensor to monitor bioavailable cadmium. The capability to determine bioavailable cadmium was verified with Cd(II amended LUFA soils, and then the applicability on environmental systems was investigated with field soils collected from smelter area in Korea before and after soil-washing. The total amount of cadmium was decreased after soil washing, while the bioavailability was increased. Consequently, it would be valuable to have tools to assess bioavailability and the effectiveness of soil remediation should be evaluated in the aspect of bioavailability as well as removal efficiency.

  8. Use of Tunable Whole-Cell Bioreporters to Assess Bioavailable Cadmium and Remediation Performance in Soils.

    Science.gov (United States)

    Yoon, Youngdae; Kim, Sunghoon; Chae, Yooeun; Kang, Yerin; Lee, Youngshim; Jeong, Seung-Woo; An, Youn-Joo

    2016-01-01

    It is important to have tools to measure the bioavailability to assess the risks of pollutants because the bioavailability is defined as the portions of pollutants showing the biological effects on living organisms. This study described the construction of tunable Escherichia coli whole-cell bioreporter (WCB) using the promoter region of zinc-inducible operon and its application on contaminated soils. It was verified that this WCB system showed specific and sensitive responses to cadmium rather than zinc in the experimental conditions. It was inferred that Cd(II) associates stronger with ZntR, a regulatory protein of zinc-inducible operon, than other metal ions. Moreover, the expression of reporter genes, egfp and mcherry, were proportional to the concentration of cadmium, thereby being a quantitative sensor to monitor bioavailable cadmium. The capability to determine bioavailable cadmium was verified with Cd(II) amended LUFA soils, and then the applicability on environmental systems was investigated with field soils collected from smelter area in Korea before and after soil-washing. The total amount of cadmium was decreased after soil washing, while the bioavailability was increased. Consequently, it would be valuable to have tools to assess bioavailability and the effectiveness of soil remediation should be evaluated in the aspect of bioavailability as well as removal efficiency.

  9. In Vitro Iron Bioavailability of Brazilian Food-Based by-Products.

    Science.gov (United States)

    Chiocchetti, Gabriela M; De Nadai Fernandes, Elisabete A; Wawer, Anna A; Fairweather-Tait, Susan; Christides, Tatiana

    2018-05-16

    Background : Iron deficiency is a public health problem in many low- and middle-income countries. Introduction of agro-industrial food by-products, as additional source of nutrients, could help alleviate this micronutrient deficiency, provide alternative sources of nutrients and calories in developed countries, and be a partial solution for disposal of agro-industry by-products. Methods : The aim of this study was to determine iron bioavailability of 5 by-products from Brazilian agro-industry (peels from cucumber, pumpkin, and jackfruit, cupuaçu seed peel, and rice bran), using the in vitro digestion/ Caco-2 cell model; with Caco-2 cell ferritin formation as a surrogate marker of iron bioavailability. Total and dialyzable Fe, macronutrients, the concentrations of iron-uptake inhibitors (phytic acid, tannins, fiber) and their correlation with iron bioavailability were also evaluated. Results : The iron content of all by-products was high, but the concentration of iron and predicted bioavailability were not related. Rice bran and cupuaçu seed peel had the highest amount of phytic acid and tannins, and lowest iron bioavailability. Cucumber peels alone, and with added extrinsic Fe, and pumpkin peels with extrinsic added iron, had the highest iron bioavailability. Conclusion : The results suggest that cucumber and pumpkin peel could be valuable alternative sources of bioavailable Fe to reduce iron deficiency in at-risk populations.

  10. Causal inference between bioavailability of heavy metals and environmental factors in a large-scale region

    International Nuclear Information System (INIS)

    Liu, Yuqiong; Du, Qingyun; Wang, Qi; Yu, Huanyun; Liu, Jianfeng; Tian, Yu; Chang, Chunying; Lei, Jing

    2017-01-01

    The causation between bioavailability of heavy metals and environmental factors are generally obtained from field experiments at local scales at present, and lack sufficient evidence from large scales. However, inferring causation between bioavailability of heavy metals and environmental factors across large-scale regions is challenging. Because the conventional correlation-based approaches used for causation assessments across large-scale regions, at the expense of actual causation, can result in spurious insights. In this study, a general approach framework, Intervention calculus when the directed acyclic graph (DAG) is absent (IDA) combined with the backdoor criterion (BC), was introduced to identify causation between the bioavailability of heavy metals and the potential environmental factors across large-scale regions. We take the Pearl River Delta (PRD) in China as a case study. The causal structures and effects were identified based on the concentrations of heavy metals (Zn, As, Cu, Hg, Pb, Cr, Ni and Cd) in soil (0–20 cm depth) and vegetable (lettuce) and 40 environmental factors (soil properties, extractable heavy metals and weathering indices) in 94 samples across the PRD. Results show that the bioavailability of heavy metals (Cd, Zn, Cr, Ni and As) was causally influenced by soil properties and soil weathering factors, whereas no causal factor impacted the bioavailability of Cu, Hg and Pb. No latent factor was found between the bioavailability of heavy metals and environmental factors. The causation between the bioavailability of heavy metals and environmental factors at field experiments is consistent with that on a large scale. The IDA combined with the BC provides a powerful tool to identify causation between the bioavailability of heavy metals and environmental factors across large-scale regions. Causal inference in a large system with the dynamic changes has great implications for system-based risk management. - Causation between the

  11. Lutein and zeaxanthin: Role as macular pigment and factors that control bioavailability from egg yolks and nanoemulsions

    Science.gov (United States)

    Vishwanathan, Rohini

    Lutein and zeaxanthin, two oxygenated carotenoids, exclusively accumulate in the macula, protecting the underlying photoreceptors and retinal pigment epithelial cells from da