Objective: Study the effects of vitamin D on viral driven innate immune responses, by looking at differences in cytokine production, receptor expression, and endogenous vitamin D levels. Methods: Primary peripheral blood mononuclear cells (PBMC) and epithelial cells (EC) were cultured in the presence of viral ligands and vitamin D. Enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) were used to determine cytokine production and mRNA expression. Results: PBMC stimulated with toll-like receptor 4 ligand (TLR4L), but not viral TLR8L, led to decreased pro- and anti-inflammatory cytokine production in the presence of 1,25(OH)2D3. RIG-like receptor (RLR) activation, on the other hand, in primary EC exhibited decreased pro-inflammatory cytokine production in the presence of vitamin D. Conclusions: Our findings are among the first to show differences between bacterial and viral driven innate immune responses in the presence of vitamin D. As responsiveness in RLR activated primary EC was altered in the presence of vitamin D, our data reveal the importance of studying the immune system as a whole.

Objective: Study the effects of vitamin D on viral driven innate immune responses, by looking at differences in cytokine production, receptor expression, and endogenous vitamin D levels. Methods: Primary peripheral blood mononuclear cells (PBMC) and epithelial cells (EC) were cultured in the presence of viral ligands and vitamin D. Enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) were used to determine cytokine production and mRNA expression. Results: PBMC stimulated with toll-like receptor 4 ligand (TLR4L), but not viral TLR8L, led to decreased pro- and anti-inflammatory cytokine production in the presence of 1,25(OH)2D3. RIG-like receptor (RLR) activation, on the other hand, in primary EC exhibited decreased pro-inflammatory cytokine production in the presence of vitamin D. Conclusions: Our findings are among the first to show differences between bacterial and viral driven innate immune responses in the presence of vitamin D. As responsiveness in RLR activated primary EC was altered in the presence of vitamin D, our data reveal the importance of studying the immune system as a whole.

Syntheses of 2,3-dihydrobenzofurans and 3,4-dihydrobenzopyrans normally involve several stages, therefore efficient syntheses of these compounds are desirable. A number of 3,4-dihydrobenzopyrans derivatives were prepared in one pot syntheses. The reaction is thought to proceed through cation intermediates, involving allylic cations generated by the reaction of allyl alcohols, 1,3-dienes, or diols in the presence of acids such as trifluoroacetic acid (TFA), or in a solution of glacial acetic and a metal catalyst or glacial acetic acid and sulphuric acid, followed by reaction with nucleophiles such as phenols or hydroquinones. This leads to the formation of allyl aryl ethers which rearrange via a [3,3]-sigmatropic reanangement and acid-catalysed intramolecular cyclisation, to give the conesponding 3,4-dihydrobenzopyrans. 5-Formyl-2,3-dihydrobenzofuran and 6-formylamino-3,4-dihydrobenzopyran were synthesized by several routes and the isolated products exhibited cis-trans isomerism. It was found that the introduction of an alkyl substituent at carbon-4 in the model benzopyran locks the 2,3,4-alkyl substituents into axial and equatorial orientations. This may influence the peroxyl-radical scavenging activity of these compounds by altering the extent of orbital overlap between the 2p-type lone pair on the pyran oxygen and the aromatic 1t-electron system. 2,3-Dihydrobenzofurans such as 5-hydroxy-2,3-dihydrobenzofuran have been shown to have better antioxidant activity than alpha-tocopherol due to the influence of the smaller, more strained ring, which allows better overlap of the oxygen lone pair and the 1t-electrons in the aromatic system. 5-Hydroxy-2,3-dihydrobenzofuran was efficiently synthesised in an improvement on the yields previously reported in the literature. A series of substituted 2,3-dihydrobenzofurans were synthesised by the reaction of phenols with allylic alcohols or aldehydes in the presence of trifluoroacetic acid or catalytic amounts of sulphmic acid, which also promoted the acid-catalysed intramolecular cyclisation.

No description available.

The status of vitamin B-6 (B6) nutriture of nine persons (4F;5M) with insulin dependent diabetes mellitus (IDDM), nine persons (5F;4M) with non-insulin dependent diabetes mellitus (NIDDM), and 18 control individuals (9F;9M) was evaluated, using biochemical and dietary indicators of B6 status. The biochemical indices employed were plasma concentration of pyridoxal 5'-phosphate (PLP), urinary 4-pyridoxic acid (4PA) excretion, and urinary kynurenic acid (KA) and xanthurenic, acid (XA) excretion following a tryptophan load test (2 g L-tryptophan oral load). Dietary B6 intake and the ratio of B6 (mg) to dietary protein (g) (B6:protein) were determined. Fasting blood, two consecutive 24 h urine collections and three consecutive daily weighed diet records were obtained on each of two occasions, separated by 30-70 d. Diet records were analyzed for vitamin B-6 and protein intake using nutrient data bases. Samples of 70 foods, for which the data bases lacked B6 values, were obtained and analyzed for total B6 content by a microbiological method. The plasma concentration of PLP was determined by an enzymatic method, and plasma alkaline phosphatase activity by a colorimetric method. Urinary 4PA was separated by HPLC, urinary KA and XA by ion exchange, and each metabolite was determined fluorometrically. The mean daily vitamin B-6 intake of each group exceeded the recommended dietary allowance (RDA). The mean B6:protein ratios ± standard deviations (SD) for the groups of females were 0.0200±0.0027, 0.0304±0.0101, and 0.0254±0.0099 for IDDM, NIDDM and control (C), respectively. The respective B6:protein ratios for the males were 0.0280±0.0040, 0.0242±0.0038 and 0.0241±0.0078. The mean±SD plasma PLP concentrations for females were 22.4±6.8, 21.8±9.6 and 37.4126.8 nmol/L for IDDM, NIDDM and C, respectively. The mean plasma PLP concentrations of the two groups of females with diabetes were at the low end of a range (22.4-25.3 nmol/L) suggested to indicate marginal status, and 56% of the females with diabetes had PLP concentrations below the lower boundary of the marginal range. For the three groups of males the PLP concentrations were in the same rank order as dietary B6 intake; 53.9±18.2, 43.6±7.2 and 37.5±17.7 nmol/L for IDDM, NIDDM and C, respectively. Plasma PLP concentration was strongly and significantly correlated with B6 intake in both diabetes (n=18, r=.744, p<.001) and C (n=18, r=.695, p<.001) groups, but was also negatively associated with plasma AP activity only for the diabetes group (n=18, r=- .454, a=.058). The mean plasma AP activity of females with NIDDM was significantly higher than that of the female C group (p<.01). Greater than normal AP hydrolysis of PLP is thought to have contributed to the low plasma PLP concentrations observed in the females with NIDDM. Levels of urinary 4PA excretion by females were 8.76±2.10, 7.61±12.57 and 8.15±14.43 μmol/d for IDDM, NIDDM and C, respectively, or 87, 63 and 72% of B6 intake. For males the urinary 4PA levels were 12.76±14.53, 10.32±11.77 and 9.81+3.34 μmol/d, respectively, or 76, 68 and 78% of B6 intake. All subjects excreted 4-PA in amounts indicative of adequate B6 status. All means for tryptophan metabolites were within ranges seen for normal subjects, both pre and post-tryptophan load. None of the subjects with diabetes and only one female C subject excreted more than 65 μmol XA in 24 h after the tryptophan load (upper boundary of normal response to 2 g tryptophan load). Mean post-load excretion of XA and KA of diabetes groups was numerically lower than that of same sex controls in all comparisons, although in only one instance was the difference significant (NIDDM females post-load KA, p<.05). The results of the tryptophan load test suggest adequate B6 function in the kynurenine pathway those with diabetes and controls. Individuals with diabetes were found to consume adequate or above amounts of B6 by the standard of the RDA. Low plasma PLP levels were observed in females with IDDM who had the lowest B6 intake, and in females with NIDDM who had the highest plasma AP activity. The present research indicates that low PLP may be present in diabetes, as observed by other investigators, despite seemingly adequate B6 nutriture. However, normal to above normal amounts of urinary 4-PA excretion indicated adequate body stores of B6, and normal response to the tryptophan load test suggested adequate function of B6 in the liver of persons with diabetes. Plasma PLP concentration alone may not be an adequate B6 status indicator in persons with diabetes. Based upon the levels of multiple indicators, the vitamin B-6 status of those persons with diabetes studied was judged to be adequate. / Graduation date: 1991

Graduation date: 1930

Graduation date: 1936

Graduation date: 1945

Graduation date: 1938

Graduation date: 1985