Dual action of sulforaphane in the regulation of thioredoxin reductase and thioredoxin in human HepG2 and Caco-2 cells

We have previously demonstrated that sulforaphane is a potent inducer for thioredoxin reductase in HepG2 and MCF-7 cells (Zhang et al. Carcinogenesis 2003, 24, 497-503; Wang et al. J. Agric. Food Chem. 2005, 53, 1417-1421). In this study, we have shown that sulforaphane is not only an inducer for thioredoxin reductase but also an inducer for its substrate, thioredoxin in HepG2, and undifferentiated Caco-2 cells. Sulforaphane acts at two levels in the regulation of thioredoxin reductase/thioredoxin system by the upregulation of the expression of both the enzyme and the substrate. In human hepatoma HepG2 cells, sulforaphane induced thioredoxin reductase mRNA and protein by 4- and 2-fold, respectively, whereas thioredoxin mRNA was induced 2.9-fold and thioredoxin protein was unchanged in whole cell extracts, but an increase in nuclear accumulation (1.8-fold) was observed. Moreover, the induction of thioredoxin reductase was found faster than that of thioredoxin. The effects of PI3K and MAPK kinase inhibitors, LY294002, PD98059, SP600125, and SB202190, have been investigated on the sulforaphane-induced expression of thioredoxin reductase and thioredoxin. PD98059 abrogates the sulforaphane-induced thioredoxin reductase at both mRNA and protein levels in HepG2 cells, although other inhibitors were found less effective. However, both PD98059 and LY294002 significantly decrease thioredoxin mRNA expression in HepG2 cells. None of the inhibitors tested were able to modulate the level of expression of either thioredoxin reductase mRNA or protein in Caco-2 cells suggesting that there are cell-specific responses to sulforaphane. In summary, the dietary isothiocyanate, sulforaphane, is important in the regulation of thioredoxin reductase/thioredoxin redox system in cells.     

Trends in fruit, vegetable and salad intakes in 9-10-year-old schoolchildren living in Liverpool, 2000-2005

OBJECTIVE: To report on the fruit, vegetable and salad intakes of Liverpool schoolchildren aged 9-10 years over a 5-year period (2000-2005). DESIGN: Cross-sectional observational study. SETTING: Between 75 and 100 Liverpool primary schools took part in each survey year. SUBJECTS: Subjects consisted of five separate cohorts of 9-10-year-old children from all areas of the city. MAIN OUTCOME MEASURES: Number and proportion of boys and girls who reported eating fruit, vegetables and salad on the previous day. RESULTS: There was an upward trend in the reported intake of fruit between 2002 and 2005. Girls were more likely than boys to report eating fruit (P < 0.001). The trend in salad intake was positive. Between 2000 and 2005 there were significant increases in the number of boys (chi2 = 17.57, P = 0.001) and girls (chi2 = 80.56, P = 0.001) eating salad. Girls were significantly more likely to eat salad than boys in all years (chi2 = 58.75, P = 0.001). Trends in vegetable intake were similar to those for salad, with both sexes reporting yearly increases over the 5-year period. The increase in the number of boys who reported eating vegetables between 2000 and 2005 was 23.5% (chi2 = 32.9, P = 0.000). In girls there was a 44.8% increase over the same period (chi2 = 110.3, P < 0.000). CONCLUSIONS: The data reveal positive trends in the fruit, vegetable and salad intakes of Liverpool schoolchildren between 2000 and 2005. Further research is needed to elucidate the specific factors that have enabled the changes to take place.     

Changes in consumption of sugars by English adolescents over 20 years

OBJECTIVE: Dietary surveys of 11- to 12-year-old Northumbrian children in 1980 and 1990 revealed that consumption of non-milk extrinsic sugars (NMES) was 16-17% of energy intake. This study reports dietary sugars consumption in 2000 and compares it with data collected in 1980 and 1990, using identical methods. DESIGN: A repeat cross-sectional dietary survey of children aged 1-12 years attending the same schools as in the 1980 and 1990 surveys. SETTING: Seven middle schools in south Northumberland. SUBJECTS: All children aged 11-12 years old attending the seven schools. METHOD: Food consumption was recorded using two 3-day diet diaries. Food composition tables were used to calculate energy and nutrient intakes. NMES, and milk and intrinsic sugars were calculated using previously described methods. RESULTS: The numbers of children completing the surveys in 1980, 1990 and 2000 were 405, 379 and 424, respectively; approximately 60-70% of eligible children. Total sugars provided 22% of energy consistently over the three surveys. NMES consumption in 2000 provided 16% of energy compared with 16% in 1980 and 17% in 1990. Sources of NMES changed over the three surveys. NMES from soft drinks doubled from 15 to 31 g day(-1), and from breakfast cereals increased from 2 to 7 g day(-1) over the 20 years. Confectionery and soft drinks provided 61% of NMES. Over 20 years, the proportion of energy from fat decreased by 5% and from starch increased by 4%, creating a welcome tilt in the fat-starch see-saw, without an adverse effect on sugars intake. CONCLUSIONS: Consumption of NMES in 2000 was substantially higher than recommended, and there has been little change over 20 years. Continued and coordinated efforts are required at a national, community and individual level to reduce the intake of NMES.     

Serum alkaline phosphatase isoenzyme activities in canine malignant mammary neoplasms with and without osseous transformation

BACKGROUND: Increased serum activity of total alkaline phosphatase (TALP) has been found in dogs with mammary neoplasms, especially malignant mixed tumors. We hypothesized that the bone isoenzyme of alkaline phosphatase (BALP), a specific indicator of osteoblastic activity and bone formation, may contribute to increased TALP in dogs with mammary neoplasms with osseous transformation. OBJECTIVE: The purpose of this study was to compare serum TALP, BALP, and other ALP isoenzyme activities in dogs with mammary malignant neoplasms with and without osseous transformation. METHODS: Twenty-one female dogs with malignant mammary neoplasms were compared with 21 clinically healthy, age-matched female control dogs. Physical, clinicopathologic (including preprandial and postprandial serum bile acids, ACTH stimulation, and low-dose dexamethasone suppression tests), radiographic, and ultrasonographic examinations were performed on all dogs with tumors to assess coexisting conditions. On the basis of histologic examination of excised tumors, dogs were further classified as having epithelial (n = 11) or mesenchymal/mixed (epithelial-mesenchymal) (n = 10) neoplasms, the latter of which had histologic and radiologic evidence of bone formation. Serum TALP, BALP, liver alkaline phosphatase (LALP), and corticosteroid-induced alkaline phosphatase (CALP) activities were measured using biochemical methods. RESULTS: Dogs with malignant mammary tumors had significantly higher (P < .05) median serum TALP (170 U/L), BALP (59 U/L), LALP (49 U/L), and CALP (24 U/L) activities, compared with control dogs (81, 32, 37, and 5 U/L, respectively). Significantly higher activities of BALP and LALP were found in dogs with epithelial neoplasms; whereas, only CALP activity was higher in dogs with mesenchymal/mixed neoplasms. There was no significant difference in TALP or isoenzyme activitities between epithelial and mesenchymal/mixed groups. CONCLUSION: BALP activity is increased in some dogs with malignant mammary tumors but does not account for the increase in TALP in dogs with neoplasms that have osseous transformation.     

Antioxidant Activity of Phenolics Compounds From Sugar Cane (Saccharum officinarum L.) Juice

Phenolic compounds in sugar cane (Saccharum officinarum L.) juice were identified and quantified by analytical high performance liquid chromatography and photodiode array detection, showing the predominance of flavones (apigenin, luteolin and tricin derivatives), among flavonoids, and of hydroxycinnamic, caffeic and sinapic acids, among phenolic acids, representing a total content of around 160 mg/L. A tricin derivative was present in the highest proportion (>10% of the total). The phenolic extract obtained from sugar cane juice showed a protective effect against in vivo MeHgCl intoxication and potent inhibition of ex vivo lipoperoxidation of rat brain homogenates, indicating a potential use for beneficial health effects and/or therapeutic applications.     

New therapeutic approaches for equine protozoal myeloencephalitis: pharmacokinetics of diclazuril sodium salts in horses

Diclazuril is a triazine-based antiprotozoal agent which may have clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, the use of the sodium salt diclazuril to increase the apparent bioavailability of diclazuril for the treatment and prophylaxis of EPM and various other Apicomplexan mediated diseases is described. In this study, diclazuril sodium salt was synthesized and administered to horses as diclazuril sodium salt formulations. The absorption, distribution, and clearance of diclazuril sodium salt in the horse are described. Diclazuril was rapidly absorbed, with peak plasma concentrations occurring at 8-24 hours following an oral mucosal administration of diclazuril sodium salt. The mean oral bioavailability of diclazuril as Clinacox was 9.5% relative to oral mucosal administration of diclazuril sodium salt. Additionally, diclazuril in DMSO administered orally was 50% less bioavailable than diclazuril sodium salt following an oral mucosal administration. It was also shown that diclazuril sodium salt has the potential to be used as a feed additive for the treatment and prophylaxis of EPM and various other Apicomplexan mediated diseases.     

Antioxidant activity of diterpenes and polyphenols from Ophryosporus heptanthus

The antioxidant activity of 14 compounds (1-14) isolated from the ether and butanolic extracts of the aerial parts of Ophryosporus heptanthus has been assayed using a beta-carotene bleaching method and the DPPH technique. Compounds 1 and 13 showed the most potent antioxidant activity. Their structures have been established by spectroscopic techniques (mainly NMR). Compounds 7 and 12 are new natural products, and their structures have been confirmed by chemical synthesis.