5,6-Dihydroxyindole-2-carboxylic acid: a first principles density functional study

We report first principles density functional calculations for 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and several oxidised forms. DHICA and 5,6-dihydroxyindole (DHI) are believed to be the basic building blocks of the eumelanins. Our results show that carboxylation has a significant effect on the physical properties of the molecules. In particular, the relative stabilities and the highest occupied molecular orbital-lowest unoccupied molecular orbital gaps (calculated with the DeltaSCF method) of the various redox forms are strongly affected. We predict that, in contrast to DHI, the density of unpaired electrons, and hence the ESR signal, in DHICA is negligibly small. (C) 2004 Elsevier B.V. All rights reserved.

The effect of cis-5,8,11,14,17-eicosapentaenoic acid upon the contractile mechanisms linked to calcium influx and the mobilisation of intracellular calcium in aortic smooth muscle

Epidemiological studies previously identified cis-5,8,11,14,17-eicosapentaenoic acid (EPA) as the biologically active component of fish oil of benefit to the cardiovascular system. Although clinical investigations demonstrated its usefulness in surgical procedures, its mechanism of action still remained unclear. It was shown in this thesis, that EPA partially blocked the contraction of aortic smooth muscle cells to the vasoactive agents KCl and noradrenaline. The latter effect was likely caused by reducing calcium influx through receptor-operated channels, supporting a recent suggestion by Asano et al (1997). Consistently, EPA decreased noradrenaline-induced contractures in aortic tissue, in support of previous reports (Engler, 1992b). The observed effect of EPA on cell contractions to KCl was not simple due to blocking calcium influx through L-type channels, consistent with a previous suggestion by Hallaq et al (1992). Moreover, EPA caused a transient increase in [Ca2+]i in the absence of extracellular calcium. To resolve this it was shown that EPA increased inositol phosphate formation which, it is suggested, caused the release of calcium from an inositol phosphate-dependent internal binding site, possibly that of an intracellular membrane or superficial sarcoplasmic reticulum, producing the transient increase in [Ca2+]i. As it was shown that the cellular contractile filaments were not desensitised to calcium by EPA, it is suggested that the transient increase in [Ca2+]i subsequently blocks further cell contraction to KCl by activating membrane-associated potassium channels. Activation of potassium channels induces the cellular efflux of potassium ions, thereby hyperpolarising the plasma membrane and moving the membrane potential farther from the activation range for calcium channels. This would prevent calcium influx in the longer term and could explain the initial observed effect of EPA to block cell contraction to KCl.

(Table 5, page 626), Tin and main metal elements composition of ferromanganese concretions (acid-soluble fractions)

Concentrations of tin in sea water decreased from estuarine and shelf (0.02-0.04 µg/kg) to surface Atlantic waters (0.009 µg/kg). Mean contents (ppm) in other materials included: ultramafic rocks, 0.8; basalts, 1.7; silicic rocks, 2.5; red clays, 3.4; amphibolites, 1.2. Oceanic ferromanganese deposits contained from 0.2 to 5.8 ppm; tin and cobalt contents were correlated.

Total synthesis of 3,5-O-dicaffeoylquinic acid and its derivatives

We report the first total synthesis of 3,5-O-dicaffeoylquinic acid and its derivatives, 3,5-O-diferuloylqui- nic acid and 3,5-(3,4-dimethoxycinnamyl)quinic acid, in a nine-step sequence. The key step involves Knoevenagel condensations between vanillin, 3,4-dimethoxybenzaldehyde or 4-hydroxy-3-methoxy- benzaldehyde and the dimalonate ester of quinic acid.

Niobic acid nanoparticle catalysts for the aqueous phase transformation of glucose and fructose to 5-hydroxymethylfurfural

A family of bulk and SBA-15 supported peroxo niobic acid sols were prepared by peptisation of niobic acid precipitates with H2O2 as heterogeneous catalysts for aqueous phase glucose and fructose conversion to 5-hydroxymethylfurfural (5-HMF). Niobic acid nanoparticles possess a high density of Brønsted and Lewis acid sites, conferring good activity towards glucose and fructose conversion, albeit with modest 5-HMF yields under mild reaction conditions (100 °C). Thermally-induced niobia crystallisation suppresses solid acidity and activity. Nanoparticulate niobic acid dispersed over SBA-15 exhibits pure Brønsted acidity and an enhanced Turnover Frequency for fructose dehydration.

3,5,6-trichloro-2-pyridinyloxyacetic acid as effective thinning agent for fruit of 'Montenegrina' mandarin.

2016

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

Background There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. Methods The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. Results The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. Conclusion The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women.

Clinical efficacy and safety of zoledronic acid in osteoporosis and Paget's disease

Osteoporosis and Paget’s bone disease are the most common diseases of the bone. In addition to glucocorticoid treatment, there are many other secondary causes of osteoporosis. Bisphosphonates are used to treat these bone conditions. Zoledronic acid is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least 1 year following a single intravenous administration. The efficacy and safety of zoledronic acid in the treatment of osteoporosis and Paget’s bone disease are reviewed. This article also covers the studies of the effects of zoledronic acid in the bone loss associated with the secondary osteoporosis.

Three-dimensional hydrogen-bonded structures in the 1:1 proton-transfer compounds of L-tartaric acid with the associative-group monosubstituted pyridines 3-minopyridine, 3-carboxypyridine (nicotinic acid) and 2-carboxypyridine (picolinic acid).

The 1:1 proton-transfer compounds of L-tartaric acid with 3-aminopyridine [3-aminopyridinium hydrogen (2R,3R)-tartrate dihydrate, C5H7N2+·C4H5O6-·2H2O, (I)], pyridine-3-carboxylic acid (nicotinic acid) [anhydrous 3-carboxypyridinium hydrogen (2R,3R)-tartrate, C6H6NO2+·C4H5O6-, (II)] and pyridine-2-carboxylic acid [2-carboxypyridinium hydrogen (2R,3R)-tartrate monohydrate, C6H6NO2+·C4H5O6-·H2O, (III)] have been determined. In (I) and (II), there is a direct pyridinium-carboxyl N+-HO hydrogen-bonding interaction, four-centred in (II), giving conjoint cyclic R12(5) associations. In contrast, the N-HO association in (III) is with a water O-atom acceptor, which provides links to separate tartrate anions through Ohydroxy acceptors. All three compounds have the head-to-tail C(7) hydrogen-bonded chain substructures commonly associated with 1:1 proton-transfer hydrogen tartrate salts. These chains are extended into two-dimensional sheets which, in hydrates (I) and (III) additionally involve the solvent water molecules. Three-dimensional hydrogen-bonded structures are generated via crosslinking through the associative functional groups of the substituted pyridinium cations. In the sheet struture of (I), both water molecules act as donors and acceptors in interactions with separate carboxyl and hydroxy O-atom acceptors of the primary tartrate chains, closing conjoint cyclic R44(8), R34(11) and R33(12) associations. Also, in (II) and (III) there are strong cation carboxyl-carboxyl O-HO hydrogen bonds [OO = 2.5387 (17) Å in (II) and 2.441 (3) Å in (III)], which in (II) form part of a cyclic R22(6) inter-sheet association. This series of heteroaromatic Lewis base-hydrogen L-tartrate salts provides further examples of molecular assembly facilitated by the presence of the classical two-dimensional hydrogen-bonded hydrogen tartrate or hydrogen tartrate-water sheet substructures which are expanded into three-dimensional frameworks via peripheral cation bifunctional substituent-group crosslinking interactions.

Fumaric acid monoethyl ester-functionalized poly(D,L-Lactide)/N-vinyl-2- pyrrolidone Resins for the preparation of tissue engineering scaffolds by stereolithography

Polymer networks were prepared by photocross-linking fumaric acid monoethyl ester (FAME) functionalized, three-armed poly(D,L-lactide) oligomers using Af-vinyl-2-pyrrolidone (NVP) as diluent and comonomer. The use of NVP together with FAME-functionalized oligomers resulted in copolymerization at high rates, and networks with gel contents in excess of 90 were obtained. The hydrophilicity of the poly(D,L-lactide) networks increases with increasing amounts of NVP, networks containing 50 wt of NVP absorbed 40 of water. As the amount of NVP was increased from 30 to 50 wt , the Young's modulus after equilibration in water decreased from 0.8 to 0.2 GPa, as opposed to an increase from 1.5 to 2.1 GPa in the dry state. Mouse preosteoblasts readily adhered and spread onto all prepared networks. Using stereolithography, porous structures with a well-defined gyroid architecture were prepared from these novel materials. This allows the preparation of tissue engineering scaffolds with optimized pore architecture and tunable material properties.

Order and disorder in the structures of two crystal polymorphs of the adduct bis(quinolinium-2-carboxylate) DL-malic acid

The structures of two polymorphs of the anhydrous cocrystal adduct of bis(quinolinium-2-carboxylate) DL-malic acid, one triclinic the other monoclinic and disordered, have been determined at 200 K. Crystals of the triclinic polymorph 1 have space group P-1, with Z = 1 in a cell with dimensions a = 4.4854(4), b = 9.8914(7), c = 12.4670(8)Å, α = 79.671(5), β = 83.094(6), γ = 88.745(6)deg. Crystals of the monoclinic polymorph 2 have space group P21/c, with Z = 2 in a cell with dimensions a = 13.3640(4), b = 4.4237(12), c = 18.4182(5)Å, β = 100.782(3)deg. Both structures comprise centrosymmetric cyclic hydrogen-bonded quinolinic acid zwitterion dimers [graph set R2/2(10)] and 50% disordered malic acid molecules which lie across crystallographic inversion centres. However, the oxygen atoms of the malic acid carboxylic groups in 2 are 50% rotationally disordered whereas in 1 these are ordered. There are similar primary malic acid carboxyl O-H...quinaldic acid hydrogen-bonding chain interactions in each polymorph, extended into two-dimensional structures but in l this involves centrosymmetric cyclic head-to-head malic acid hydroxyl-carboxyl O-H...O interactions [graph set R2/2(10)] whereas in 2 the links are through single hydroxy-carboxyl hydrogen bonds.

The conversion of lignocellulosics to levulinic acid

Biomass represents an abundant and relatively low cost carbon resource that can be utilized to produce platform chemicals such as levulinic acid. Current processing technology limits the cost-effective production of levulinic acid in commercial quantities from biomass. The key to improving the yield and effi ciency of levulinic acid production from biomass lies in the ability to optimize and isolate the intermediate products at each step of the reaction pathway and reduce re-polymerization and side reactions. New technologies (including the use of microwave irradiation and ionic liquids) and the development of highly selective catalysts would provide the necessary step change for the optimization of key reactions. A processing environment that allows the use of biphasic systems and/or continuous extraction of products would increase reaction rates, yields and product quality. This review outlines the chemistry of levulinic acid synthesis and discusses current and potential technologies for producing levulinic acid from lignocellulosics.

Oral intake and serum levels of ascorbic acid in continuous ambulatory peritoneal dialysis patients

Oral intake of ascorbic acid is essential for optimum health in human beings. Continuous ambulatory peritoneal dialysis (CAPD) patients have an increased need for ascorbic acid, because of increased loss through dialysate, reduced intake owing to nausea and loss of appetite, and increased oxidative stress. However, optimum intake is still controversial. We studied 50 clinically stable patients to determine the relationship between oral ascorbic acid intake and serum ascorbic acid (SAA) level. Total oral intake ranged from 28 mg daily to 412 mg daily. Only one patient had an oral intake of ascorbic acid below 60 mg per day. The SAA levels ranged from 1 mg/L to 36.17 mg/L. Although a strong correlation existed between intake and SAA (p < 0.001, R2 = 0.47), the variation in SAA at any given intake level was wide. Of the studied patients, 62% had an SAA < 8.7 mg/L, 40% had an SAA < 5.1 mg/L (below the level in a healthy population), and 12% had a level below 2 mg/L (scorbutic). None of the patients demonstrated clinical manifestations of scurvy. Our results show that, in CAPD patients, ascorbic acid deficiency can be reliably detected only with SAA measurements, and oral intake may influence SAA level. To maintain ascorbic acid in the normal range for healthy adults, daily oral intake needs to be increased above the U.S. recommended dietary allowance to 80-140 mg.

A free weekly iron-folic acid supplementation and regular deworming program is associated with improved hemoglobin and iron status indicators in Vietnamese women

Background Anemia due to iron deficiency is recognized as one of the major nutritional deficiencies in women and children in developing countries. Daily iron supplementation for pregnant women is recommended in many countries although there are few reports of these programs working efficiently or effectively. Weekly iron-folic acid supplementation (WIFS) and regular deworming treatment is recommended for non-pregnant women living in areas with high rates of anemia. Following a baseline survey to assess the prevalence of anemia, iron deficiency and soil transmitted helminth infections, we implemented a program to make WIFS and regular deworming treatment freely and universally available for all women of reproductive age in two districts of a province in northern Vietnam over a 12 month period. The impact of the program at the population level was assessed in terms of: i) change in mean hemoglobin and iron status indicators, and ii) change in the prevalence of anemia, iron deficiency and hookworm infections. Method Distribution of WIFS and deworming were integrated with routine health services and made available to 52,000 women. Demographic data and blood and stool samples were collected in baseline, and three and 12-month post-implementation surveys using a population-based, stratified multi-stage cluster sampling design. Results The mean Hb increased by 9.6 g/L (95% CI, 5.7, 13.5, p < 0.001) during the study period. Anemia (Hb<120 g/L) was present in 131/349 (37.5%, 95% CI 31.3, 44.8) subjects at baseline, and in 70/363 (19.3%, 95% CI 14.0, 24.6) after twelve months. Iron deficiency reduced from 75/329 (22.8%, 95% CI 16.9, 28.6) to 33/353 (9.3%, 95% CI 5.7, 13.0) by the 12-mnth survey, and hookworm infection from 279/366 (76.2%,, 95% CI 68.6, 83.8) to 66/287 (23.0%, 95% CI 17.5, 28.5) over the same period. Conclusion A free, universal WIFS program with regular deworming was associated with reduced prevalence and severity of anemia, iron deficiency and ho