Celecoxib concentration predicts decrease in prostaglandin E\u3csub\u3e2\u3c/sub\u3e concentrations in nipple aspirate fluid from high risk women

BACKGROUND: Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E2 concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE2 response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE2 concentrations from baseline to end of treatment, and 2) whether menopausal status influenced circulating levels of celecoxib. METHODS: Matched NAF and plasma were collected from 46 high risk women who were administered celecoxib twice daily for two weeks, 20 subjects receiving 200 mg and 26 subjects 400 mg of the agent. NAF and plasma samples were collected before and 2 weeks after taking celecoxib. RESULTS: In women taking 400 mg bid celecoxib, plasma concentrations of the agent correlated inversely with the change in NAF PGE2 levels from pre- to posttreatment. Nonsignificant trends toward higher celecoxib levels were observed in post- compared to premenopausal women. There was a significant decrease in NAF but not plasma PGE2 concentrations in postmenopausal women who took 400 mg celecoxib (p = 0.03). CONCLUSION: In high risk women taking 400 mg celecoxib twice daily, plasma concentrations of celecoxib correlated with downregulation of PGE2 production by breast tissue. Strategies synergistic with celecoxib to downregulate PGE2 are of interest, in order to minimize the celecoxib dose required to have an effect

Fumonisin B-Glucose Reaction Products Are Less Toxic When Fed to Swine

The effects of fumonisin B-glucose reaction products in swine diets was examined. Pigs were fed diets containing 528 µmol of total fumonisin B/kg (FB), 528 µmol of total FB-glucose adducts/kg (FB-G, 122 µmol of unreacted FB/kg), or 0 µmol of total FB/kg for 15 days to test the efficacy of the FB-G reaction products in detoxifying FB. Weight gain in FB pigs was lower than in FB-G or controls, which was correlated with feed intake reduction in FB pigs. Serum aspartate aminotransferase, γ-glutamyltransferase, and total bilirubin in FB pigs were higher than in FB-G or control pigs. Serum sphinganine/shingosine ratios in FB pigs were higher than in FB-G or control pigs. Microscopic examination of tissues from FB pigs showed generalized liver necrosis and apoptosis with marked cellular pleomorphism and disorganized hepatic cords. The liver and kidneys in the FB-G group appeared to be normal. Tissues of controls were free of lesions. Results suggest that dietary FB-G products are less toxic to swine and may provide an detoxification approach in instances of widespread FB grain contamination (p \u3c 0.05)

Do Plant Secondary Metabolite‐Containing Forages Influence Soil Processes in Pasture Systems?

Grazed pastures are susceptible to N loss from urine/manure additions, which increases eutrophication, affecting the global N cycle. Plant secondary metabolites (PSM), such as condensed tannins (CT) and terpenes, influence silviculture soil dynamics by generally decreasing N mineralization. We investigated whether cattle‐grazed pastures of non‐traditional grass and legume forage monoculture strips including CT‐containing sainfoin (Onobrychis viciifolia Scop.) and tall fescue (TF) [Schedonorus arundinaceus (Schreb.) Dumort.] influenced soil dynamics compared with traditional grass and legume forage monoculture strips of alfalfa (Medicago sativa L.), without tannins, and TF. Throughout the study, CT in sainfoin averaged 58.9 g kg−1 whereas alfalfa saponins averaged 5.7 g kg−1. We observed greater soil microbial respiration (p = .01) in TF strips than legume strips, indicating greater microbial activity, and between legumes we found greater soil NO3 (p = .01) in alfalfa than in sainfoin, although aboveground biomass and N differences were negligible. We also conducted a laboratory soil‐feces incubation study to determine if feces from cattle foraging diets of legumes with or without CT influenced soil dynamics. Both feces treatments showed lower NO3 (p \u3c .001) than without feces, suggesting microbial inhibition. Dehydrogenase activity (DHEA) was lower (p = .03) in sainfoin than alfalfa feces, suggesting CT from sainfoin inhibit DHEA. To our knowledge this study is the first considering whether CT‐containing sainfoin and saponin‐containing alfalfa influence soil dynamics by assessing general differences in soil parameters. More research is needed to determine whether specific PSM mitigate N loss in pasture systems by slowing N mineralization

Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women1

We hypothesized that soy isoflavones would have dose related estrogenic and methylation effects. 34 healthy premenopausal women were prospectively enrolled and randomized in double-blind fashion to receive either 40 mg or 140 mg isoflavones daily through one menstrual cycle. Breast specific (NAF) and systemic (serum) estrogenic effects were assessed measuring the estrogenic marker complement (C)3 and changes in cytology, while methylation effects were evaluated in mammary ductoscopy (MD) specimens using methylation specific PCR assessment of five genes (p16, RASSF1A, RARβ2, ER, and CCND2) associated with breast carcinogenesis. Serum genistein significantly increased post treatment in women consuming both isoflavone doses. Neither NAF nor MD cytology significantly changed after either low or high dose isoflavones. Serum C3 levels post treatment were inversely related to change in serum genistein (r= -0.76, p=0.0045) in women consuming low dose isoflavones. RARβ2 hypermethylation increased post treatment correlated with the post treatment level of genistein among all subjects (r=0.67, p=0.0017) and in women receiving high dose isoflavones (r=0.68, p=0.021). At the low dose, CCND2 hypermethylation increase correlated with post treatment genistein levels (r=0.79, p=0.011). The inverse correlation between C3 and genistein suggests an antiestrogenic effect. Isoflavones induced dose specific changes in RARβ2 and CCND2 gene methylation which correlated with genistein levels. This work provides novel insights into estrogenic and methylation effects of dietary isoflavones.

Simultaneous Determination of the Predominant Hyperforins and Hypericins in St. John's Wort (Hypericum perforatum L.) by Liquid Chromatography

Hypericin and hyperforin are believed to be among the active constituents in common St. John's wort (Hypericum perforatum L.). Presently, dietary supplements are generally standardized to contain specified levels of hypericin and hyperforin, and the related compounds, pseudohypericin and adhyperforin. A rapid method was developed for simultaneous determination of these 4 active constituents by liquid chromatography (LC). A 1 g portion of dried, finely ground leaf/flower sample is extracted with 20 mL methanol for 2 h. A 0.6 mL aliquot of the crude extract is combined with 5.4 mL acetonitrile-methanol (9 + 1) and passed through a mixed solid-phase cleanup column. The eluate is examined by LC for hyperforin, adhyperforin, hypericin, and pseudohypericin on a Hypersil reversed-phase column by using simultaneous ultraviolet (284 nm) and fluorescence detection (excitation, 470 nm; emission, 590 nm). The compounds are easily separated isocratically within 8 min with a mobile phase of acetonitrile-aqueous 0.1M triethylammonium acetate (8 + 2). Average recoveries of hyperforin and adhyperforin were 101.9 and 98.4%, respectively, for 3 sample mixtures containing concentrations ranging from approximately 0.2 to 1.5% combined hyperforins per gram dry weight. Average relative standard deviation (RSD) values for hyperforin and adhyperforin for all 3 mixtures were 18.9 and 18.0%, respectively. Average recoveries of hypericin and pseudohypericin were 88.6 and 93.3% respectively, from 3 sample mixtures containing concentrations ranging from approximately 0.2 to 0.4% combined hypericins per gram dry weight. Average RSD values for hypericin and pseudohypericin for all 3 mixtures were 3.8 and 4.2%, respectively. C ommon St. John's wort (Hypericum perforatum L.) is a perennial species of the Hypericaceae family, native to Europe. Dietary supplements and other herbal preparations produced from the leaves and flowers of St. John's wort have gained popularity in the United States in recent years (1, 2). A recent overview of 23 controlled clinical trials concluded that St. John's wort was more effective than a placebo for the treatment of mild depression (3). Commercial extracts from the leaves and flowers are also being investigated for anticancer and antiviral activities (4). The predominant napthodianthrone derivatives, hypericin and pseudohypericin, and the phloroglucine derivatives, hyperforin and adhyperforin, are among the compounds presently being investigated for their biological activities. Standardized dietary supplements of St. John's wort currently contain from 0.3 to 0.5% hypericin(s), and/or approximately 3.0% hyperforin(s). In 1998, St. John's wort herbal products showed exceptional sales growth, increasing nearly 3000% from 1997 to 1998 (2). Several recent papers on the chemical analysis of St. John's wort have provided the means to measure many of the predominant chemical constituents from diluted, crude extracts (5-12). In general, samples were extracted and filtered, or liquid-liquid extraction was used to remove chlorophylls and other pigments. The use of mixed solid-phase (MSP) cleanup columns has been reported recently in the literature. Wilson and Romer (13) developed a proprietary cleanup column consisting of a mixture of reversed-phase, ion-exclusion, and ion-exchange packing materials used for cleanup of extracts of corn, cottonseed, rice, mixed feeds, and a variety of nuts in the determination of aflatoxins. Similarly, Tacke and Casper (14) developed a C 18 -alumina (1 + 3) MSP cleanup column for wheat extracts in the determination of deoxynivalenol. The following method was developed to provide a rapid, inexpensive, MSP cleanup with simultaneous determination of the 4 compounds of greatest current interest, hypericin, hyperforin, pseudohypericin, and adhyperforin from flower and leaf mixtures of St. John's wort

Bisphenol A in Thermal Paper Receipts: Taylor et al. Respond

We agree with Schwartz and Landrigan that there is a need for change in the regulatory system for chemicals used in products in the United States. Bisphenol A (BPA) is one of thousands of chemicals of concern, but it provides a striking example of what happens when there is no requirement for premarket testing

T-2 toxin adsorption by hectorite

The adsorption of T-2 toxin by the natural smectite mineral – hectorite at pH 3.0, 7.0 and 9.0 was investigated. The results of T-2 toxin adsorption on hectorite showed that the T-2 adsorption capacity decreased with increasing concentration of adsorbent in the suspension for all the investigated pH values. From the adsorption isotherms, an increase in T-2 toxin adsorption with increasing initial T-2 toxin concentration was observed for all the investigated pH values. The T-2 toxin adsorption by hectorite followed a non-linear (Langmuir) type of isotherm at pH 3.0, 7.0 and 9.0, with correlation coefficients (r2) of 0.943 at pH 3.0, 0.919 at pH 7.0 and 0.939 at pH 9.0. The estimated maximum T-2 toxin adsorption by hectorite based on the Langmuir fit to the data (9.178 mg/g at pH 3.0, 9.930 mg/g at pH 7.0, and 19.341 mg/g at pH 9.0), indicated that the adsorption of T-2 toxin by hectorite is pH dependent. The obtained data suggest the existence of specific active sites in hectorite onto which the T-2 toxin is adsorbed

Zearalenone and ochratoxin A: adsorption by kaolin modified with surfactant

Octadecyldimethylbenzyl ammonium chloride (OA) was used as a surfactant for the preparation of organokaolin. The natural kaolin (from a plant for production of quartz sand in Rgotina, Serbia) was modified with a surfactant in amount equal to 90% of the kaolin cation exchange capacity (CEC). FTIR spectroscopy was used for characterization of the new product. FTIR spectra confirmed the presence of OA ions at the kaolin surface. Adsorption of mycotoxins – zearalenone (ZEN) and ochratoxin A (OCHRA) was studied by organokaolin at different amounts of adsorbent and pHs. Results showed that the presence of organic cations in the kaolin structure increased adsorption of both ZEN and OCHRA. Adsorption of the mycotoxins by organokaolin increased with increasing amounts of adsorbent and, at the lowest amount of solids in suspension, adsorption of ZEN and OCHRA was slightly higher at pH 7 and 9