Effect of dietary supplementation of vitamins A, D-3, E, and C on yearling rice field eel, Monopterus albus: Serum indices, gonad development, and metabolism of calcium and phosphorus

The objective of this study was to determine the effect of dietary vitamins A, D-3, E, and C on the gonad development, lipid peroxidation, and immune response of yearling rice field eel, Monopterus albus. A 6-wk feeding trial was designed according to an L-16(4(5)) orthogonal design, in which four vitamins, each at four supplementation levels, were arranged. Sixteen diets were mixed with the different vitamin levels and randomly assigned to 16 groups of fish. Increasing dietary vitamin E supplementation level significantly (P <= 0.05) increased the gonadosomatic index and lowered the serum content of malondialdehyde of rice field eel. Increasing dietary vitamin A and C levels also showed similar effect, but the differences were not statistically significant. Serum immunoglobulin M content increased significantly (P <= 0.01) as dietary vitamin C supplementation levels increased. The concentrations of calcium in bones showed significant (P <= 0.05) trend with vitamin D-3 and A supplementation levels, but the bone phosphorus content was not affected by the dietary vitamin levels.

Optimization of GaInNAs(Sb)/GaAs quantum wells at 1.3-1.55 mu m grown by molecular beam epitaxy

The InGaNAs(Sb)/(GaNAs)/GaAs quantum wells (QWs) emitting at 1.3-1.55 mu m have been grown by molecular beam epitaxy (MBE). The parameters of the radio frequency (RF) such as RF power and flow rate are optimized to reduce the damages from the ions or energetic species. The growth temperature is carefully controlled to prevent the phase segregation and strain relaxation. The effects of Sb on the wavelength and quality are investigated. The GaNAs barrier is used to extend the wavelength and reduce the strain. A 1.5865 mu m InGaNAs(Sb)/GaNAs SQW edge emitting laser lasing at room temperature at continuous wave operation mode is demonstrated. (c) 2006 Elsevier B.V. All rights reserved.

Metamorphic InGaAs quantum wells for light emission at 1.3-1.6 mu m

Metamorphic InGaAs quantum well structures grown on GaAs reveal strong light emission at 1.3-1.6 mu m, smooth surface with an average roughness below 2 nm. and good rectifying I-V characteristics. Dark line defects are found in the QW Post growth thermal annealing further improves the luminescence efficiency but does not remove those dark line defects. Some challenges of epitaxial growth using this method for laser applications are discussed. (c) 2006 Elsevier B.V. All rights reserved.

Electrolummescence from (5)Do -> F-7(J) and D-5(1) -> F-7(J) (J=0-4) transitions with a europium complex as emitter

Electroluminescence (EL) devices with Eu(HTH)(3)phen [HTH: 4,4,5,5,6,6,6-heptafluoro-1-(2-thienyl)-1,3-hexanedione, phen: I 10-phenanthroline] as an emissive centre were fabricated using vacuum evaporation. In addition to the Eu3+ 5D0 --> F-7(J) (J = 0-4) lines that were visible in the photoluminescence signal, the device also showed strong emission from the D-5(1) --> F-7(J) (J = 0-4) transitions. The enhanced emission from the D-5(1) F-7(J) (J = 0-4) transitions was attributed to the increased excitation intensity in the EL device. The luminescence lifetimes of the 5 D, and 5 Do levels were measured to be 0.6 mus and 866 mus, respectively.

Crystal structure and DFT studies of a triazole derivative: 4-(2-hydrobenzylideneamino)-3-(1,2,4-triazol-4-yl-methyl) 1H-1,2,4-triazole-5 (4H)-thione

A novel triazole derivative 4-(2-hydrobenzylideneamino)-3-(1, 2, 4-triazol-4-ylmethyl)-1H-1, 2, 4-triazole-5 (4H)-thione(1) was synthesized and characterized using elemental analysis, MR, and H-1 NMR, and its crystal structure was determined via X-ray single crystal diffraction analysis. Crystal data: monoclinic, P2 (1)/c, a = 0.83335 (9) nm, b = 1. 49777 (16) run, c = 1. 14724 (12) nm, beta = 107. 990 (2)degrees, D = 1. 470 Mg/m(3), and Z = 4. The geometries and the vibrational frequencies were determined using the density functional theory(DFT) method at the B3LYP/6-31G* level. To demonstrate the accuracy of the reaction route of compound 1, one of the important intermediates was also tested using the same method. The structural parameters of the two compounds calculated using the DFT study are close to those of the crystals, and the harmonic vibrations of the two compounds computed via the DFT method are in good agreement with those in the observed IR spectral data. The thermodynamic properties of the title compound were calculated, and the compound shows a good structural stability at normal temperature. The test results of biological activities show that it has a certain bactericidal ability.

2-(2-Phenyl-1H-phenanthro-[9,10-d]imidazole-1-yl)-acetic acid (PPIA) and its application for determination of amines by high performance liquid chromatography with fluorescence detection and identification with mass spectroscopy/atmospheric pressure chemical ionization

A simple, sensitive, and mild method for the determination of amino compounds based on a condensation reaction with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC-HCI) as the dehydrant with fluorescence detection has been developed. Amines were derivatized to their acidamides with labeling reagent 2-(2-phenyl-1H-phenanthro-[9,10-d]imidazole-1-yl)-acetic acid (PPIA). Studies on derivatization conditions indicated that the coupling reaction proceeded rapidly and smoothly in the presence of a base catalyst in acetonitrile to give the corresponding sensitively fluorescent derivatives with an excitation maximum at lambda(ex) 260nm and an emission maximum at lambda(em) 380nm. The labeled derivatives exhibited high stability and were enough to be efficiently analyzed by high-performance liquid chromatography. Identification of derivatives was carried out by online post-column mass spectrometry (LC/APCI-MS/MS) and showed an intense protonated molecular ion corresponding m/z [MH](+) under APCI in positive-ion mode. At the same time, the fluorescence properties of derivatives in various solvents or at different temperature were investigated. The method, in conjunction with a gradient elution, offered a baseline resolution of the common amine derivatives on a reversed-phase Eclipse XDB-C-8 column. LC separation for the derivatized amines showed good reproducibility with acetonitrile-water as mobile phase. Detection limits calculated from 0.78 pmol injection, at a signal-to-noise ratio of 3, were 3.1-18.2 fmol. The mean intra- and inter-assay precision for all amine levels were < 3.85% and 2.11%, respectively. Excellent linear responses were observed with coefficients of > 0.9996. The established method for the determination of aliphatic amines from real wastewater and biological samples was satisfactory. (c) 2006 Elsevier B.V. All rights reserved.

A importância clínica da vitamina D

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Vitamin D status and requirements during pregnancy and lactation

Vitamin D deficiency during pregnancy, lactation, and early infancy has been widely reported. Current understanding of vitamin D metabolism during pregnancy and lactation is incomplete, and to date, experimental data to support vitamin D requirements for these life stages are scarce. There is a shortage of nationally representative data and appropriate reference ranges for serum 25-hydroxyvitamin D (25OHD) during pregnancy, lactation and infancy, including in umbilical cord blood. This thesis described concentrations of total 25OHD and individual metabolites including 25OHD3, 25OHD2, and 3-epi-25OHD3 at 15 weeks’ gestation in a large seasonally balanced pregnancy cohort study (n 1768), carried out in Cork, Ireland (52oN). The prevalence of low 25OHD concentrations in pregnant women was higher than published reports in other Caucasian women, and was highest among non-users of vitamin D-containing supplements during winter. A longitudinal pregnancy study was included which suggested gestational stages had an impact on the total serum 25OHD concentration. This thesis incorporated a randomized controlled trial carried out among 100 women across 3 intervention groups using 20 μg/day of vitamin D3 with or without 500 mg calcium, or placebo, over 12-weeks of lactation to investigate the vitamin D requirement for lactating mothers and the vitamin D content of human milk. A daily intake of 25 μg/day was suggested to meet the requirement of lactating women to maintain a 25OHD levels above 50 nmol/L in 97.5% of the population at 52oN all year around. However, vitamin D content in human milk did not increase in response to supplementation. Serum 25OHD concentration has been used as a predictor of a number of health outcomes. This thesis reported large differences in serum 25OHD concentrations using different methods in 86 umbilical cord samples. The need for international standardization of serum 25OHD measurements was re-emphasized in this thesis.

Vitamin D deficiency and insufficiency in pregnant women: a longitudinal study.

Maternal vitamin D insufficiency is associated with childhood rickets and longer-term problems including schizophrenia and type 1 diabetes. Whilst maternal vitamin D insufficiency is common in mothers with highly pigmented skin, little is known about vitamin D status of Caucasian pregnant women. The aim was to investigate vitamin D status in healthy Caucasian pregnant women and a group of age-matched non-pregnant controls living at 54–55°N. In a longitudinal study, plasma 25-hydroxyvitamin D (25(OH)D) was assessed in ninety-nine pregnant women at 12, 20 and 35 weeks of gestation, and in thirty-eight non-pregnant women sampled concurrently. Plasma 25(OH)D concentrations were lower in pregnant women compared to non-pregnant women (P < 0·0001). Of the pregnant women, 35, 44 and 16 % were classified as vitamin D deficient (25(OH)D < 25 nmol/l), and 96, 96 and 75 % were classified as vitamin D insufficient (25(OH)D < 50 nmol/l) at 12, 20 and 35 weeks gestation, respectively. Vitamin D status was higher in pregnant women who reported taking multivitamin supplements at 12 (P < 0·0001), 20 (P = 0·001) and 35 (P = 0·001) weeks gestation than in non-supplement users. Vitamin D insufficiency is evident in pregnant women living at 54–55°N. Women reporting use of vitamin D-containing supplements had higher vitamin D status, however, vitamin D insufficiency was still evident even in the face of supplement use. Given the potential consequences of hypovitaminosis D on health outcomes, vitamin D supplementation, perhaps at higher doses than currently available, is needed to improve maternal vitamin D nutriture.

Photodissociation of D-3(+) in an intense, femtosecond laser field

H-3(+) is the simplest triatomic molecule and plays an important role in laboratory and astrophysical plasmas. It is very stable both in terms of its electronic and nuclear degrees of freedom but is difficult to study in depth in the laboratory due to its ionic nature. In this communication, experimental results are presented for the strong field dissociation of the isotopic analogue D-3(+), using 30 fs, 800 nm laser pulses with intensities up to 10(16) W cm(-2). By employing a novel experimental set-up, ions were confined in an electrostatic ion trap so that dissociation of the molecule could be studied as it radiatively cools. It was determined that dissociation could only be observed for molecules in ro-vibrational states relatively close to the dissociation limit, while more tightly bound states demonstrated remarkable stability in even the strongest fields.

Non-thiazolidinedione antihyperglycemic agents. 1: Alpha-Heteroatom substituted-beta-phenylpropanoic acids.

A review with 22 refs. The 5-benzylthiazolidine-2,4-dione moiety of insulin sensitizing antidiabetic agents can be replaced by a range of ?-heteroatom functionalized ?-phenylpropanoic acids. ?-Oxy-carboxylic acids show potent antidiabetic activity and one compd., the ?-ethoxyacid (SB 213068), is one of the most potent antihyperglycemic agents yet reported.

Regulation of cyclin D1 by the BRCA1-BARD1 complex

Background BRCA1 and cyclin D₁ are both essential for normal breast development and mutation or aberration of their expression is associated with breast cancer [1,2]. Cyclin D₁ is best known as a G₁ cyclin where it regulates the G₁ to S phase transition by acting as a rate-limiting subunit of CDK4/6 kinase activity. More recently, however, Stacey has demonstrated that cyclin D₁ levels in G₂/M determine whether a cell continues to proliferate or exits the cell cycle [3]. The majority of BRCA1 in the cell is bound to BARD1 through their N-terminal RING domains. Heterodimerization is essential for the stability and correct localization of the complex and confers ubiquitin ligase activity to BRCA1. The importance of the ligase activity of BRCA1 to breast cancer development is inferred from the fact that N-terminal diseaseassociated mutations are proposed to reduce ligase activity [4]. Methods Protein–protein interactions were demonstrated using yeast-two-hybrid and coimmunoprecipitation. Protein levels were altered through overexpression, siRNA and antisense technology. The effect of proteasome inhibitors and cycloheximide treatment was also examined. Results We initially identified cyclin D₁ as a binding partner of BARD1 in a yeast-two-hybrid screen and defined the minimal binding region as the N-terminus of BARD1. This interaction was confirmed in vivo by coimmunoprecipitation. The N-terminus of BARD1 also binds BRCA1 and imparts ubiquitin ligase activity to the complex. Covalent modification of proteins with ubiquitin is a common regulatory mechanism in eukaryotic cells. Traditionally polyubiquitin chains linked through lysine 48 target proteins for degradation by the 26 S proteasome. We have demonstrated that cyclin D₁ protein levels are inversely related to BRCA1 and BARD1 levels in several model systems. Furthermore, regulation of cyclin D1 levels occurs through a post-transcriptional mechanism and requires the ligase activity of BRCA1. Interestingly, this phenomenon is cell-cycle regulated, occurring in G₂/M. Conclusion We propose that cyclin D₁ is a potential substrate for BRCA1 ubiquitination and that this targets cyclin D₁ for proteasomal-mediated degradation. Future work will focus on ascertaining the functional consequence of cyclin D₁ regulation by the BRCA1–BARD1 complex; in particular, the impact of BRCA1, mediated through regulation of cyclin D₁, on the proliferation versus differentiation decision.

MicroRNA-155 Promotes Resolution of Hypoxia-Inducible Factor 1{alpha} Activity

The hypoxia-inducible factor (HIF) is a key regulator of the transcriptional response to hypoxia. While the mechanism underpinning HIF activation is well understood, little is known about its resolution. Both the protein and the mRNA levels of HIF-1a (but not HIF-2a) were decreased in intestinal epithelial cells exposed to prolonged hypoxia. Coincident with this, microRNA (miRNA) array analysis revealed multiple hypoxia-inducible miRNAs. Among these was miRNA-155 (miR-155), which is predicted to target HIF-1a mRNA. We confirmed the hypoxic upregulation of miR-155 in cultured cells and intestinal tissue from mice exposed to hypoxia. Furthermore, a role for HIF-1a in the induction of miR-155 in hypoxia was suggested by the identification of hypoxia response elements in the miR-155 promoter and confirmed experimentally. Application of miR-155 decreased the HIF-1a mRNA, protein, and transcriptional activity in hypoxia, and neutralization of endogenous miR-155 reversed the resolution of HIF-1a stabilization and activity. Based on these data and a mathematical model of HIF-1a suppression by miR-155, we propose that miR-155 induction contributes to an isoform-specific negative-feedback loop for the resolution of HIF-1a activity in cells exposed to prolonged hypoxia, leading to oscillatory behavior of HIF-1a-dependent transcription.

Low vitamin D status adversely affects bone health parameters in adolescents

Background: The effects of subclinical vitamin D deficiency on bone mineral density (BMD) and bone turnover in adolescents, especially in boys, are unclear.

Objective: We aimed to investigate the relations of different stages of vitamin D status and BMD and bone turnover in a representative sample of adolescent boys and girls.

Design: BMD was measured by dual-energy X-ray absorptiometry at the nondominant forearm and dominant heel in a random sample of 12- (n = 260) and 15-y-old (n = 239) boys and 12- (n = 266) and 15-y-old (n = 250) girls. Serum 25-hydroxyvitamin D, parathyroid hormone, osteocalcin, and type I collagen cross-linked C-telopeptide were assessed by using enzyme-linked immunoassays. Relations between vitamin D status and bone health indexes were assessed by using regression modeling.

Results: Using multivariate regression to adjust for potential physical, lifestyle, and dietary confounding factors, we observed that 12-and 15-y-old girls with high vitamin D status (>= 74.1 nmol/L) had significantly greater forearm (but not heel) BMD (beta = 0.018; SE = 0.008; P < 0.05 for each age group) and lower serum parathyroid hormone concentrations and bone turnover markers than did those with low vitamin D status. These associations were evident in subjects sampled throughout the year and in winter only. There was no significant relation between vitamin D status and BMD in boys.

Conclusions: Maintaining serum 25-hydroxyvitamin D concentrations above approximate to 50 nmol/L throughout the year may be a cost-effective means of improving bone health. Increased emphasis on exploring strategies for improving vitamin D status in adolescents is needed.

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 1: Development of a potent and CNS penetrant [3.1.0]-based lead

This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach that provided a robust intellectual property position, in lieu of a traditional, expensive HTS campaign. Members within this new [3.1.0]​-​based series displayed excellent GlyT1 potency, selectivity, free fraction, CNS penetration and efficacy in a preclin. model of schizophrenia (prepulse inhibition)​.