No description available.

No description available.

No description available.

No description available.

The roles of vitamin C and the effects of supplementation have been under investigation for many years. The purpose of this study was to use high performance liquid chromatography to assess the presence of vitamin C in human sweat, to evaluate sweat as a possible excretory route for vitamin C and to note any effects of vitamin C supplementation. Vitamin C in sweat was determined in samples from 10 active men and women prior to supplementation and weekly for 4 consecutive weeks as the vitamin C supplements were with a reverse-phase liquid chromatograph (Model ALC-202) equipped with a solvent delivery system (Model 6000, Waters Association).The presence of vitamin C in sweat samples was indicated by comparing peaks to those seen with vitamin C observed in sweat samples. Vitamin C was observed in sweat at the end of the first week of supplementation. The pres C.However, 4 and 5 when standards. During the first week of the study, when subjects' diets were not supplemented, vitamin C was not observed in sweat samples. Vitamin C was observed in sweat at the end of the first week o supplementation. The presence of vitamin C in sweat diminished during weeks 4 and 5 when intakes were supplemented with 750 mg and 1000 mg, respectively. It appeared that supplementation affected the presence of vitamin C in human sweat until plasma or tissues were saturated, at which point absorption may have decreased and other means of excretion may have been enhanced.

Call number: LD2668 .T4 1950 M334 / Master of Science

Thesis (Ph.D.)--University of the Witwatersrand, Faculty of Science, 2013.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, in fulfillment of the requirements for the degree of Doctor of Philosophy, April 2013. / Density functional theory (DFT) and time dependent-DFT (TD-DFT) was applied to investigate the geometric and electronic properties of cobalamin (Cbl) models. Model compounds of the type, [B–(Co(III)(L)4–X)–Y]n+ were used, where B and Y were comprised of the alpha (α) and β axial ligands, (L)4 represented the equatorial ligand(s) and X was either hydrogen or a substituent of electron donating or withdrawing character, quantified by the Hammett constant (σp), at C10 of the corrin. All calculations were conducted in the gas phase or implicit solvent medium at the BP86/6-31+G(d,p) level of theory. High-resolution crystal structures of B12, extracted from the Cambridge Crystal Structural Database (CCSD), were used as the source of initial coordinates. DFT was used to explore the trans influence of the lower (α) axial ligand, the cis influence of various equatorial ligands and the cis influence of a substituted corrin ring at the C10 position on the Gibbs free energy (ΔG) and bond dissociation energies (BDEs) of the Co(III)–Cβ bond. Other geometric parameters such as ring distortion, axial bond lengths, equatorial bond lengths and partial charges on the Co metal centre, donor atom of the upper and lower axial ligands as well as the N-donor atoms of the macrocyclic ring are documented and discussed. The use of a broad range of alpha (α) ligands in the cobalamin models from charged and neutral N-donor ligands (NH3, NH2–, NH2–, NH2F, NHF–, NF2–, NH2CH3, NHCH3, NH(CH3)2, N(CH3)3), to naturally occurring amino acids or realistic models of their metal-coordinating side chains (methanethiol, dimethylsulfide, cysteine, methanethiolate, glycine, p-aminopyridine, imidazole, histidine, acetate, 2-propanol, serine and tyrosine), provided significant information on the trans influence of these ligands on the BDE of the Co(III)–C bond (upper axial ligand). The ligands NH3, NH2–, NH2–, NH2F, NHF–, NF2–, NH2CH3, NHCH3, were used to explore electronic effects while NH3, NH2CH3, NH(CH3)2, and N(CH3)3 were used to investigate steric effects. The naturally occurring amino acids or their models focused primarily on exploring why nature chooses an N-donor ligand such as histidine or imidazole instead of an S-donor or O-donor ligand that is also readily available from protein side chains. As the basicity of the α ligand increased in the series NH2F < NH3 < CH3NH2 < (CH3)2NH < (CH3)3N < NHF– < NHCH3– < NH2– < NF2– < NH2–(as assessed by the proton affinities) a normal trans influence was observed between the axial ligands. While the Co(III)–C bond was observed to increase in length, the Co(III)–Nα bond length decreased. The weakening of the Co(III)–C bond was paralleled by the decrease in the Co(III)–C BDE. On the other hand, as the steric bulk of the α ligand (NH3, NH2CH3, NH(CH3)2, and N(CH3)3) increased (assessed by the molar volume and Tolman cone angle), an inverse trans influence (in other words, simultaneous lengthening or shortening) between the upper and lower axial bonds was observed. The Co(III)–C bond showed a marginal increase in length while the Co(III)–Nα bond length steadily increased as the molar volume of the α ligand increased. Interestingly, the large difference in the Co–Nα bond length from the 5-coordinate to the 6-coordinate complex (later referred to as ΔCo–Nα(5c-6c)), paralleled the decrease of the Co(III)–C BDEs. It also became evident from calculations with the amino acids posing as α ligands that the nature of the α ligand (assessed by the absolute chemical hardness (η) of the ligand, with the greater the η value the harder the ligand) plays a major role in the labilisation of the organometallic bond. As the η of the α ligand increased, the Co(III)–C BDE increased. The trans influence of the α ligands resulted in the strengthening (hard ligand) and weakening (soft ligand) of the Co(III)–C bond, as was affirmed by the electron density at the bond critical point (bcp) of the Co(III)–C bond. The N-donor ligands (described as having an intermediate character as the η- values were between the hard and soft ligands) were found to be catalytically suitable (31.89 – 32.45 kcal mol -1), rather than the soft and hard donor ligands. The trans influence of the latter two ligands on the upper axial bond revealed a weakly and strongly bound alkyl group to the Co metal centre, giving Co(III)–C BDEs values of 29.39–32.27 kcal mol-1and 32.54–34.96 kcal mol-1, respectively. In addition to the corrin macrocycle, other equatorial ligands like cobaloxime, corrole, porphyrin, methylcobalt(III) pentaamine, [14-ane]N4, [15-ane]N4 and [16-ane]N4 were used in calculations to explore the cis influence on the labilisation of the Co(III)–C bond. These ligands included saturated and unsaturated cyclic rings. The results showed that the flexibility of the ring increased as the size of the equatorial ligand increased and thus affected the displacement of the Co(III) metal centre from the defined mean plane. This subsequently affected the strength of the organometallic bond, which paralleled the BDEs. The hydrogen atom at C10 of the corrin ring was substituted by electron donating (CH3, OH and NH2) or –withdrawing groups (NO, NO2, CN, COOH and Br) and the cis influence of these groups on the organometallic bond was investigated. A normal trans influence between the axial ligands was observed. As the electron density from the substitutents increased towards the ring, the Co(III)–C bond strengthened and the Co(III)–Nα bond weakened. The increased electron density from the C10 substituents influenced the contraction of the Co–Nα bond length. The greater difference in contraction of the Co–Nα bond length from the 5-coordinate to the 6-coordinate complex (ΔCo–Nα(5c-6c)) resulted in lower Co(III)–C BDEs. The TD-DFT method was used to generate both the absorption and circular dichroism (CD) spectra where the vertical electronic excited states of Co(III) cobalamin species that differ with respect to their upper axial ligand, including FCbl, ClCbl, BrCbl,SeCNCbl and CH3Cbl were calculated. The cis influence for each of the species was analysed within the framework of TD-DFT to assign the major spectral features, in other words, the α/β, D/E and γ bands in the predicted UV-visible spectra. These studies reveal that the “typical” and “atypical” absorption exhibit a high degree of σ-donation from the β-ligand to the Co(III) metal centre and the subsequent destabilisation of the corresponding d-orbitals of Co. Furthermore, as the donor ability of the β ligand increased, the contributions from the antibonding d z2 orbital to the HOMO increased, leading to a strong Co(III)–Nα σ-antibonding interaction, which is consistent with the observed lengthening of the same bond from FCbl, ClCbl, BrCbl, SeCNCbl to CH3Cbl.

Shiu Kwok Keung. / Bibliography: leaf 75 / Thesis (M.Ph.)--Chinese University of Hong Kong, 1984

Introduction: Vitamin D is a micronutrient that possesses immunomodulatory actions. Higher vitamin D status has been associated with decreased incidence of acute respiratory infections (ARI) in a number of observational studies. However, mechanistic in vitro work investigating effects of vitamin D on the immune response to ARIs is lacking, especially for rhinovirus, which is the most common respiratory pathogen. Results of clinical trials of vitamin D supplementation in the prevention of ARIs have also been conflicting, in that some demonstrate a protective effect of this intervention against ARI, while others do not. Methods: An immunological assay of ex vivo stimulation with TLR ligands and pathogens in blood samples from participants with asthma, COPD or neither condition in three randomised controlled trials of vitamin D supplementation for the prevention of ARI and exacerbations was developed. This assay was used in conjunction with cellular profiling of clinical trial blood and sputum samples, and a rhinovirus-infected human alveolar cell line (A549 cells) to determine the effects of vitamin D in the protection against acute respiratory infections. Results: The main finding of cell culture experiments was that A549 cells pre-treated with physiological concentrations of 25-hydroxyvitamin D (25[OH]D, the major circulating vitamin D metabolite) had increased resistance to rhinovirus infection, which was associated with attenuation of rhinovirus-induced intercellular adhesion molecule-1 (ICAM-1) and platelet-activating factor receptor (PafR) expression. Immunological analysis of clinical trial samples did not demonstrate any consistent effect of bolus-dose vitamin D supplementation on circulating or pathogen-stimulated inflammatory profiles, or on inflammatory indices in induced sputum. Conclusions: Co-incubation with 25(OH)D was associated with transient protection against rhinovirus infection in a respiratory epithelial cell line in vitro, but these findings did not translate to any changes in cellular profile or inflammatory mediator release in clinical trials samples following in vivo vitamin D supplementation.