ABSTRACT
Information on the status of long-chain polyunsaturated fatty acids (LCPUFAs) in pregnancy and breast milk in very high fish-eating populations is limited. The aim of this study was to examine dietary intake and changes in fatty acid status in a population of pregnant women in the Republic of Seychelles. Serum docosahexaenoic acid (DHA) decreased significantly between 28-week gestation and delivery (n=196). DHA status did not correlate significantly with length of gestation and was not associated with self-reported fish intake, which was high at 527 g/week. In breast milk, the ratio of DHA to arachidonic acid (AA) was consistent with those observed in other high fish-eating populations. Overall the data suggest that high exposure to LCPUFAs from habitual fish consumption does not prevent the documented decrease in LCPUFA status in pregnancy that occurs as a result of foetal accretion in the third trimester of pregnancy.
Subject(s)
Energy Intake/physiology , Fatty Acids, Unsaturated/metabolism , Fishes , Seafood/analysis , Adult , Animals , Child Development/physiology , Diet , Docosahexaenoic Acids/analysis , Docosahexaenoic Acids/blood , Eicosanoic Acids/analysis , Eicosanoic Acids/blood , Fatty Acids, Unsaturated/analysis , Fatty Acids, Unsaturated/blood , Female , Gestational Age , Humans , Infant, Newborn , Milk, Human/chemistry , Milk, Human/metabolism , Nutritional Physiological Phenomena , Postpartum Period/blood , Postpartum Period/metabolism , Pregnancy , Pregnancy Trimester, Third/blood , Pregnancy Trimester, Third/metabolism , SeychellesABSTRACT
OBJECTIVE: To determine the clinical effect of dietary supplementation with low-dose omega-3-polyunsaturated fatty acids on disease activity and endothelial function in patients with systemic lupus erythematosus. METHODS: A 24-week randomised double-blind placebo-controlled parallel trial of the effect of 3 g of omega-3-polyunsaturated fatty acids on 60 patients with systemic lupus erythematosus was performed. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and British Isles Lupus Assessment Group index of disease activity for systemic lupus erythematosus (BILAG), endothelial function using flow-mediated dilation (FMD) of the brachial artery, oxidative stress using platelet 8-isoprostanes and analysis of platelet membrane fatty acids were taken at baseline, 12 and 24 weeks. RESULTS: In the fish oil group there was a significant improvement at 24 weeks in SLAM-R (from 9.4 (SD 3.0) to 6.3 (2.5), p<0.001); in BILAG (from 13.6 (6.0) to 6.7 (3.8), p<0.001); in FMD (from 3.0% (-0.5 to 8.2) to 8.9% (1.3 to 16.9), p<0.001) and in platelet 8-isoprostanes (from 177 pg/mg protein (23-387) to 90 pg/mg protein (32-182), p = 0.007). CONCLUSIONS: Low-dose dietary supplementation with omega-3 fish oils in systemic lupus erythematosus not only has a therapeutic effect on disease activity but also improves endothelial function and reduces oxidative stress and may therefore confer cardiovascular benefits.
Subject(s)
Endothelium, Vascular/physiopathology , Fatty Acids, Omega-3/administration & dosage , Lupus Erythematosus, Systemic/drug therapy , Adult , Biomarkers/blood , Brachial Artery/diagnostic imaging , Brachial Artery/drug effects , Brachial Artery/physiopathology , Cell Membrane/chemistry , Dietary Supplements , Dinoprost/analogs & derivatives , Dinoprost/blood , Docosahexaenoic Acids/analysis , Double-Blind Method , Eicosapentaenoic Acid , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Fatty Acids, Unsaturated/analysis , Female , Humans , Lupus Erythematosus, Systemic/metabolism , Male , Middle Aged , Nitroglycerin , Regional Blood Flow , Statistics, Nonparametric , Treatment Outcome , Ultrasonography, Doppler, Pulsed , Vasodilation , Vasodilator AgentsABSTRACT
Monte Carlo statistical mechanics simulations have been carried out for 150 organic solutes in water. Physically significant descriptors such as the solvent-accessible surface area, numbers of hydrogen bonds, and indices for cohesive interactions in solids are correlated with pharmacologically important properties including octanol/water partition coefficient (log P) and aqueous solubility (log S). The regression equation for log S only requires five descriptors to provide a correlation coefficient, r2, of 0.9 and rms error of 0.7 for the 150 solutes. The descriptors can form a basis for structural modifications to guide an analogue's properties into desired ranges.
Subject(s)
Pharmaceutical Preparations/chemistry , Monte Carlo Method , SolubilityABSTRACT
Ziprasidone is an antipsychotic agent indicated primarily for the treatment of schizophrenia. An intramuscular dosage form of ziprasidone was developed using beta-cyclodextrin sulfobutyl ether (SBECD) to solubilize the drug by complexation. Inclusion complexation of ziprasidone mesylate (ZM) with SBECD was studied by circular dichroism (CD) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, Monte Carlo simulations, phase-solubility studies, and counterion titration. The results of the studies indicate that ZM, of which the counterion is not fully dissociated from the drug, forms a 1:1 inclusion complex with SBECD with the benzisothiazole group positioned in the cavity. A mathematical model was developed to calculate stability constants of inclusion complexes for the ion pair (Z+M-:SBECD) and the dissociated ionic form (Z+:SBECD) of ZM; the values were 7892 and 957 M(-1), respectively. The model also allowed the dissociation constants of noncomplexed and complexed ZM to be calculated; the value of the former is 8-fold greater than the value of the latter. These results indicate that the inclusion complex formation of the ion pair is favored over that of the dissociated ionic form of ZM, and that the dissociation of ZM is suppressed by inclusion complexation with SBECD.
Subject(s)
Antipsychotic Agents/metabolism , Chemistry, Pharmaceutical/methods , Cyclodextrins/metabolism , Piperazines/metabolism , Thiazoles/metabolism , beta-Cyclodextrins , Chromatography, High Pressure Liquid , Drug Stability , Magnetic Resonance Spectroscopy , Models, Theoretical , Molecular Structure , Monte Carlo MethodABSTRACT
Encephalomyocarditis (EMC) virus RNA, selected by its affinity for oligo(dT)-cellulose, contains poly(A) of size : (i) about 14 nucleotide residues long, based on the percentage of radioactivity in the RNA resistant to digestion by a mixture of pancreatic and T1 RNases; (ii) about 15 residues long, as measured by the ratio of the amount of terminal adenosine to internal adenylic acid in isolated poly(A); and (III) in the range 12 to 45 residues, the majority of tracts being about 16 to 18 residues long, based upon electrophoretic mobility on polyacrylamide gels using poly(A) molecules of known size as mol. wt. markers. The poly(A) appears to be located at the 3'-terminus of the virus genome since the tract, liberated by digestion with a mixture of pancreatic and T1 RNases, was shown by compositional analysis to contain a non-phosphorylated 3'-terminus and only adenine residues. The size heterogeneity in the poly(A) tracts revealed by gel electrophoresis is also consistent with a terminal location. Comparison of our data for EMC virus with published data for other picornaviruses suggests that the sizes of poly(A) tracts in polio- and Mengovirus RNA have been overestimated; poly(A) tracts in cardioviruses appear to be smaller than those in poliovirus; the minimum size of poly(A) required for full infectivity of picornavirus RNA has also been overestimated; a tract of at least 13 adenine residues long is required for full infectivity of EMC virus RNA.
