Carbanucleosides: synthesis of both enantiomers of 2-(6-chloro-purin-9-yl)-3,5-bishydroxymethyl cyclopentanol from D-glucose

The key intermediate 1,2:5,6-di-O-isopropylidene-3-deoxy-3 beta-allyl-alpha-D-glucofuranose (8) could be conveniently prepared through radical induced allyl substitution at C-3 of appropriate 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose derivatives (7a,b) and used to synthesize enantiomeric bishydroxymethyl aminocyclopentanols 13 and 19 by the application of a 1,3-dipolar nitrone cycloaddition reaction involving the C-5 or C-1 aldehyde functionality. The products were subsequently transformed into carbanucleoside enantiomers 15 and 21. The diastercomeric isoxazolidinocyclopentane derivative 20 was similarly converted to carbanucleoside 22. (c) 2006 Elsevier Ltd. All rights reserved.

Reaction of 4-phenylbut-3-en-2-one with cyanoacetamide in 2:1 ratio

The reaction of 4-phenylbut-3-en-2-one with cyanoacetamide is not confined to a 1 : 1 reaction [which results in formation of 3-cyano-6-methyl-4-phenylpyridin-2(1H)-one]. The reaction of 2 mole equivalents of 4-phenylbut-3-en-2-one with one of cyanoacetamide also takes place, the products being 1-cyano-6-hydroxy-6-methyl-4-methylene-8,9-diphenyl-3-azabicyclo[3.3.1]nonan-2-one and 3-cyano-6-methyl-3-(3-oxo-1-phenylbutyl)-4-phenyl-3,4-dihydropyridin-2(1H)-one. The latter compound cyclises in acid medium to form 6-acetyl-4-cyano-1-methyl-5,8-diphenyl-2-azabicyclo[2.2.2]octan-3-one. X-Ray crystal structures of the 3-azabicyclo[3.3.1]nonan-2-one and the 3-azabicyclo[2.2.2]octan-2-one derivatives are described.

Synthesis and evaluation of novel boron-containing complexes of potential use for the selective treatment of malignant melanoma

Boron-containing complexes that have the potential to irreversibly accumulate in melanoma cells have been prepared by reaction of amino acids with 9-methoxy-9-borabicyclo[3.3.1]nonane. The ability of each complex to act as a substrate for tyrosinase has been probed by oximetry. Increased uptake of the lead candidate in a tyrosinase-rich cell line, compared with a tyrosinase-absent cell line, is reported, with results correlating well with that for a drug currently approved for BNCT.

Atmospheric chemistry of C4F9OC2H5 (HFE-7200), C4F9OCH3 (HFE-7100), C3F7OCH3 (HFE-7000) and C3F7CH2OH: temperature dependence of the kinetics of their reactions with OH radicals, atmospheric lifetimes and global warming potentials

The atmospheric chemistry of several gases used in industrial applications, C4F9OC2H5 (HFE-7200), C4F9OCH3 (HFE-7100), C3F7OCH3 (HFE-7000) and C3F7CH2OH, has been studied. The discharge flow technique coupled with mass-spectrometric detection has been used to study the kinetics of their reactions with OH radicals as a function of temperature. The infrared spectra of the compounds have also been measured. The following Arrhenius expressions for the reactions were determined (in units of cm3 molecule-1 s-1): k(OH + HFE-7200) = (6.9+2.3-1.7) × 10-11 exp(-(2030 ± 190)/T); k(OH + HFE-7100) = (2.8+3.2-1.5) × 10-11 exp(-(2200 ± 490)/T); k(OH + HFE-7000) = (2.0+1.2-0.7) × 10-11 exp(-(2130 ± 290)/T); and k(OH + C3F7CH2OH) = (1.4+0.3-0.2) × 10-11 exp(-(1460 ± 120)/T). From the infrared spectra, radiative forcing efficiencies were determined and compared with earlier estimates in the literature. These were combined with the kinetic data to estimate 100-year time horizon global warming potentials relative to CO2 of 69, 337, 499 and 36 for HFE-7200, HFE-7100, HFE-7000 and CF3CF2CF2CH2OH, respectively.

Changes in light intensity during the rearing period can influence egg production in domestic fowl

1. A total of 240 Shaver White and 240 ISA Brown pullets that had been reared in multi-bird cages on a 10-h photoperiod, and maintained at a light intensity of 3 or 25 lux, or changed from 3 to 25 lux or from 25 to 3 lux at 9 or 16 weeks of age, were moved into individual-bird cages at 20 weeks and transferred to 15-h photoperiods at 25 lux. 2. In both breeds, birds transferred from 3 to 25 lux at 16 or 20 weeks laid significantly more eggs than birds maintained on the brighter intensity from one day or increased to it at 9 weeks. 3. Mean egg weight, shell deformation, albumen height, feed intake and body weight gain in lay were not significantly affected by the light intensity treatments during the rearing period. There was, however, a small, but significant, negative correlation of egg numbers with mean egg weight, although this only partially explained the difference in egg numbers. The differences in egg production were unrelated to rate of sexual maturation.

The effect of ram replacement and sex ratio on the sexual response of anoestrous ewes

It is accepted that an important source of variation in the response of anoestrous ewes, to the introduction of rams, is the intensity of male stimulation. The aim of this study was to investigate strategies capable of increasing the impact and transmission of the ram stimuli. In Experiment 1, two groups of seven ewes (Bluefaced Leicester male x Swaledale female) were individually penned with one ram and for the next 6 h the rams either remained in the pen or were replaced hourly. Blood samples revealed no difference in the pattern of plasma LH secretion. In Experiment 2, three groups of 16 ewes were either introduced to one ram, individually (H) or in groups of 8 (L), or remained isolated. Ram introduction increased the plasma LH pulsatility (P < 0.001). H ewes displayed more (nine versus six) male-induced LH pulses (pulses occurring within the first 45 min) and more pulses per 8 h intervals than the L group of ewes (1.9 +/- 0.3 versus 1.3 +/- 0.3), but these differences were not significant. It was concluded that (i) frequent replacement of rams within a few hours following ram introduction to ewes does not further improve the response of ewes, especially if the ram:ewe ratio is high; (ii) the characterization of the plasma LH secretion parameters during a period of 6-8 h does not seem to be an effective method to detect small differences in the intensity of stimulation received by the ewes when exposed to rams; (iii) North Country Mule ewes (Bluefaced Leicester male x Swaledale female) in the UK respond to the presence of rams in spring (late oestrous/early anoestrous season) with an elevation in plasma LH secretion. (c) 2005 Elsevier B.V. All rights reserved.

Changes in the flavonoid and phenolic acid contents and antioxidant activity of red leaf lettuce (Lollo Rosso) due to cultivation under plastic films varying in ultraviolet transparency

Red leaf lettuce (Lollo Rosso) was grown under three types of plastic films that varied in transparency to UV radiation (designated as UV block, UV low, and UV window). Flavonoid composition was determined by high-performance liquid chromatography (HPLC), total phenolics by the Folin-Ciocalteu assay, and antioxiclant capacity by the oxygen radical absorbance capacity (ORAC) assay. Exposure to increased levels of UV radiation during cultivation caused the leaves to redden and increased concentrations of total phenols and the main flavonoids, quercetin and cyanidin glycosides, as well as luteolin conjugates and phenolic acids. The total phenol content increased from 1.6 mg of gallic acid equivalents (GAE)/g of fresh weight (FW) for lettuce grown under UV block film to 2.9 and 3.5 mg of GAE/g of FW for lettuce grown under the UV low and UV window films. The antioxiclant activity was also higher in lettuce exposed to higher levels of UV radiation with ORAC values of 25.4 and 55.1 mu mol of Trolox equivalents/g of FW for lettuce grown under the UV block and UV window films, respectively. The content of phenolic acids, quantified as caffeic acid, was also different, ranging from 6.2 to 11.1 mu mol/g of FW for lettuce cultivated under the lowest and highest UV exposure plastic films, respectively. Higher concentrations of the flavonoid glycosides were observed with increased exposure to UV radiation, as demonstrated by the concentrations of aglycones after hydrolysis, which were cyanidin (ranging from 165 to 793 mu g/g), quercetin (ranging from 196 to 880,mu g/g), and luteolin (ranging from 19 to 152 mu g/g). The results demonstrate the potential of the use of UV-transparent plastic as a means of increasing beneficial flavonoid content of red leaf lettuce when the crop is grown in polytunnels.

Changes in the flavonoid and phenolic acid contents and antioxidant activity of red leaf lettuce (Lollo Rosso) due to cultivation under plastic films varying in ultraviolet transparency

Red leaf lettuce (Lollo Rosso) was grown under three types of plastic films that varied in transparency to UV radiation (designated as UV block, UV low, and UV window). Flavonoid composition was determined by high-performance liquid chromatography (HPLC), total phenolics by the Folin-Ciocalteu assay, and antioxiclant capacity by the oxygen radical absorbance capacity (ORAC) assay. Exposure to increased levels of UV radiation during cultivation caused the leaves to redden and increased concentrations of total phenols and the main flavonoids, quercetin and cyanidin glycosides, as well as luteolin conjugates and phenolic acids. The total phenol content increased from 1.6 mg of gallic acid equivalents (GAE)/g of fresh weight (FW) for lettuce grown under UV block film to 2.9 and 3.5 mg of GAE/g of FW for lettuce grown under the UV low and UV window films. The antioxiclant activity was also higher in lettuce exposed to higher levels of UV radiation with ORAC values of 25.4 and 55.1 mu mol of Trolox equivalents/g of FW for lettuce grown under the UV block and UV window films, respectively. The content of phenolic acids, quantified as caffeic acid, was also different, ranging from 6.2 to 11.1 mu mol/g of FW for lettuce cultivated under the lowest and highest UV exposure plastic films, respectively. Higher concentrations of the flavonoid glycosides were observed with increased exposure to UV radiation, as demonstrated by the concentrations of aglycones after hydrolysis, which were cyanidin (ranging from 165 to 793 mu g/g), quercetin (ranging from 196 to 880,mu g/g), and luteolin (ranging from 19 to 152 mu g/g). The results demonstrate the potential of the use of UV-transparent plastic as a means of increasing beneficial flavonoid content of red leaf lettuce when the crop is grown in polytunnels.

Comparative study of oestrogenic properties of eight phytoestrogens in MCF7 human breast cancer cells

Previous studies have compared the oestrogenic properties of phytoestrogens in a wide variety of disparate assays. Since not all phytoestrogens have been tested in each assay, this makes inter-study comparisons and ranking oestrogenic potency difficult. In this report, we have compared the oestrogen agonist and antagonist activity of eight phytoestrogens (genistein, daidzein, equol, miroestrol, deoxymiroestrol, 8-prenylnaringenin, coumestrol and resveratrol) in a range of assays all based within the same receptor and cellular context of the MCF7 human breast cancer cell line. The relative binding of each phytoestrogen to oestrogen receptor (ER) of MCF7 cytosol was calculated from the molar excess needed for 50 % inhibition of [H-3]oestradiol binding (IC50), and was in the order coumestrol (35x)/8-prenylnaringenin (45 x)/deoxymiroestrol (50 x) > miroestrol (260x) > genistein (1000x) > equol (4000x) > daidzein (not achieved: 40 % inhibition at 10(4)-fold molar excess) > resveratrol (not achieved: 10 % inhibition at 10(5)-fold molar excess). For cell-based assays, the rank order of potency (estimated in terms of the concentration needed to achieve a response equivalent to 50 % of that found with 17 beta-oestradiol (IC50)) remained very similar for all the assays whether measuring ligand ability to induce a stably transfected oestrogen-responsive ERE-CAT reporter gene, cell growth in terms of proliferation rate after 7 days or cell growth in terms of saturation density after 14 days. The IC50 values for these three assays in order were for 17 beta-oestradiol (1 x 10-(11) M, 1 x 10-(11) M, 2 x 10(-11) M), and in rank order of potency for the phytoestrogens, deoxymiroestrol (1 x 10(-10) M, 3 x 10(-11) M, 2 x 10(-11) M) > miroestrol (3 x 10(-10) M, 2 x 10(-11) M, 8 x 10(-11) M) > 8-prenylnaringenin (1 x 10(-9) M, 3 x 10(-10) M, 3 x 10(-10) M) > cournestrol (3 x 10(-8) M, 2 x 10(-8) M, 3 x 10(-8) M) > genistein (4 x 10(-8) M, 2 x 10(-8) M, 1 x 10(-8) M)/equol (1 x 10(-7) M, 3 x 10(-8) M, 2 x 10(-8) M) > daidzein (3 x 10(-7) M, 2 x 10(-7) M, 4 x 10(-8) M) > resveratrol (4 x 10(-6) M, not achieved, not achieved). Despite using the same receptor context of the MCF7 cells, this rank order differed from that determined from receptor binding. The most marked difference was for cournestrol and 8-prenylnaringenin which both displayed a relatively potent ability to displace [3H]oestradiol from cytosolic ER compared with their much lower activity in the cell-based assays. Albeit at varying concentrations, seven of the eight phytoestrogens (all except resveratrol) gave similar maximal responses to that given by 17 beta-oestradiol in cell-based assays which makes them full oestrogen agonists. We found no evidence for any oestrogen antagonist action of any of these phytoestrogens at concentrations of up to 10(-6) M on either reporter gene induction or on stimulation of cell growth. (c) 2005 Elsevier Ltd. All rights reserved.

Fracture incidence in relation to the pattern of use of hormone therapy in postmenopausal women

Context: Evidence is limited on the effects of different patterns of use of postmenopausal hormone therapy on fracture incidence and particularly on the effects of ceasing use. Objective: To investigate the effect of different patterns of hormone therapy use on fracture incidence. Design, Setting, and Participants: Prospective study of 138737 postmenopausal women aged 50 to 69 years recruited from the UK general population in 19961998 (the Million Women Study) and followed up for 1.9 to 3.9 years (average, 2.8 years) for fracture incidence. Main Outcome Measure: Adjusted relative risk (RR) for incident fracture (except fracture of the fingers, toes, and ribs) in hormone therapy users compared with never users at baseline. Results: A total of 5197 women (3.7%) reported 1 or more fractures, 79% resulting from falls. Current users of hormone therapy at baseline had a significantly reduced incidence of fracture (RR, 0.62; 95% confidence interval [CI], 0.58-0.66; P<.001). This protection was evident soon after hormone therapy began, and the RR decreased with increasing duration of use (P=.001). Among current users at baseline the RR of fracture did not vary significantly according to whether estrogen-only, estrogen-progestin, or other types of hormones were used (RR [95% CI], 0.64 [0.58-0.71], 0.58 [0.53-0.64], and 0.67 [0.56-0.80], respectively; P=19), nor did it vary significantly according to estrogen dose or estrogen or progestin constituents. The RR associated with current use of hormone therapy did not vary significantly according to 11 personal characteristics of study participants, including their age at menopause, body mass index, and physical activity. Past users of hormone therapy at baseline experienced no significant protection against fractures (RR, 1.07; 95% CI, 0.99-1.15); incidence rates returned to those of never-users within about a year of ceasing use. Conclusions: All types of hormone therapy studied confer substantial protection against fracture while they are used. This protection appears rapidly after use commences and wears off rapidly after use ceases. The older women are, the greater is their absolute reduction in fracture incidence while using hormone therapy.

Stereochemically non-rigid helical mercury(II) complexes

Reactions of the 1: 2 condensate (L) of benzil dihydrazone and 2-acetylpyridine with Hg(ClO4)(2) center dot xH(2)O and HgI2 yield yellow [HgL2](ClO4)(2) (1) and HgLI2 (2), respectively. Homoleptic 1 is a 8-coordinate double helical complex with a Hg(II)N-8 core crystallising in the space group Pbca with cell dimensions: a = 16.2250(3), b = 20.9563(7), c = 31.9886(11) angstrom. Complex 2 is a 4-coordinate single helical complex having a Hg(II)N2I2 core crystallising in the space group P2(1)/n with cell dimensions a = 9.8011(3), b = 17.6736(6), c = 16.7123(6) angstrom and b = 95.760(3). In complex 1, the N-donor ligand L uses all of its binding sites to act as tetradentate. On the other hand, it acts as a bidentate N-donor ligand in 2 giving rise to a dangling part. From variable temperature H-1 NMR studies both the complexes are found to be stereochemically non-rigid in solution. In the case of 2, the solution process involves wrapping up of the dangling part of L around the metal. (C) 2008 Elsevier B.V. All rights reserved.

Wheat glutenin proteins assemble into a nanostructure with unusual structural features

The proteins of wheat have a known propensity to aggregate into a variety of forms. We report here a novel nanostructure from wheat proteins, derived from a crude extract of high molecular weight glutenins. The structure was characterised by a significant thioflavin T (ThT) fluorescence and a fibrillar morphology by transmission electron microscopy (TEM). The ThT fluorescence and TEM data are suggestive of an amyloid structure, but the X-ray fibre diffraction data show a reflection pattern (4.02, 4.2-4.3, 4.6, 12.9,19.3 and 38.7 angstrom) inconsistent with both the classic amyloid form and the previously described beta-helix structure. The 4.6 angstrom reflection is consistent with that predicted for the amyloid inter-beta-strand, and the absence of the inter-beta-sheet distance at approximate to 10-11 angstrom is not unprecedented in amyloid-like structures. However, our observed X-ray reflection pattern has not been previously reported and suggests a novel wheat glutenin nanostructure. (C) 2008 Elsevier Ltd. All rights reserved.

Differential induction of apoptosis in human colonic carcinoma cells (Caco-2) by Atopobium, and commensal, probiotic and enteropathogenic bacteria: mediation by the mitochondrial pathway

The induction of apoptosis in mammalian cells by bacteria is well reported. This process may assist infection by pathogens whereas for non-pathogens apoptosis induction within carcinoma cells protects against colon cancer. Here, apoptosis induction by a major new gut bacterium, Atopobium minutum, was compared with induction by commensal (Escherichia coli K-12 strains), probiotic (Lactobacillus rhamnosus, Bifidobacterium latis) and pathogenic (E. coli: EPEC and VTEC) gut bacteria within the colon cancer cell line, Caco-2. The results show a major apoptotic effect for the pathogens, mild effects for the probiotic strains and A. minutum, but no effect for commensal E. coli. The mild apoptotic effects observed are consistent with the beneficial roles of probotics in protection against colon cancer and suggest, for the first time, that A. minutum possesses similar advantageous, anti-cancerous activity. Although bacterial infection increased Caco-2 membrane FAS levels, caspase-8 was not activated indicating that apoptosis is FAS independent. Instead, in all cases, apoptosis was induced through the mitochondrial pathway as indicated by BAX translocation, cytorchrome c release, and caspase-9 and -3 cleavage. This suggests that an intracellular stimulus initiates the observed apoptosis responses.

Kinetic studies of reactions of the nitrate radical (NO3) with peroxy radicals (RO2): an indirect source of OH at night?

A discharge-flow system, coupled to cavity-enhanced absorption spectroscopy (CEAS) detection systems for NO3 at lambda = 662 nm and NO2 at lambda = 404 nm, was used to investigate the kinetics of the reactions of NO3 with eight peroxy radicals at P similar to 5 Torr and T similar to 295 K. Values of the rate constants obtained were (k/10(-12) cm(3) molecule(-1) s(-1)): CH3O2 (1.1 +/- 0.5), C2H5O2 (2.3 +/- 0.7), CH2FO2 (1.4 +/- 0.9), CH2ClO2 (3.8(-2.6)(+1.4)), c-C5H9O2 (1.2(-0.5)(+1.1)), c-C6H11O2 (1.9 +/- 0.7), CF3O2 (0.62 +/- 0.17) and CF3CFO2CF3 (0.24 +/- 0.13). We explore possible relationships between k and the orbital energies of the reactants. We also provide a brief discussion of the potential impact of the reactions of NO3 with RO2 on the chemistry of the night-time atmosphere.