There is significant debate regarding high-density lipoprotein cholesterol (HDL-C) and high-fiber, low-fat diets. The present study was designed to examine the effects of lifestyle modification on the inflammatory/anti-inflammatory properties of HDL in obese men (n = 22) with metabolic syndrome factors. Subjects were placed on a high-fiber, low-fat diet in a 3-wk residential program where food was provided ad libitum and daily aerobic exercise was performed. Fasting blood was drawn pre- and postintervention for serum lipids, lipid hydroperoxides, and the ability of subject HDL to alter low-density lipoprotein (LDL)-induced monocyte chemotactic activity (MCA) in a human artery wall coculture. Induction of MCA by control LDL in the absence of HDL was normalized to 1.0. Values >1.0 after HDL addition indicated proinflammatory HDL; values <1.0 indicated anti-inflammatory HDL. In addition, proteins involved in regulating HDL function, apolipoprotein A-I (apoA-I), paraoxonase 1 and 3, and platelet-activating factor acetylhydrolase were measured. After 3 wk, decreases in total-cholesterol, LDL-cholesterol, HDL-C, triglycerides, total cholesterol-to-HDL cholesterol ratio, and lipid hydroperoxides (all P < 0.05) were noted. The HDL inflammatory index decreased (P < 0.05) from pro- (1.14 +/- 0.11) to anti-inflammatory (0.94 +/- 0.09). ApoA-I level and paraoxonase activity did not change; however, platelet-activating factor acetylhydrolase activity increased (P < 0.05). Despite a quantitative reduction in HDL-C, HDL converted from pro- to anti-inflammatory. These data indicate that intensive lifestyle modification improves the function of HDL even in the face of reduced levels, suggesting increased turnover of proinflammatory HDL.

Introduction: Previous studies have given conflicting results as to whether or not folate metabolism is altered in Down syndrome. Folate is necessary to facilitate metabolism of one-carbon units. Folate accepts one-carbon units from one-carbon unit donors, including formiminoglutamate (FIGLU). Folate deficiency leads to accumulation of FIGLU and impairment of one-carbon unit metabolism. FIGLU is a functional measure of folate deficiency. Materials and Methods: Archived anonymized amniotic fluid specimens were obtained from normal pregnancies and those with Down syndrome. Gas liquid chromatography/mass spectrometry was used to quantitate FIGLU, which is elevated in folate deficiency. A tetra-deuterated FIGLU was used as a standard, and single-ion monitoring was performed. Nonparametric statistical analysis was performed with the Mann-Whitney U test. Results: FIGLU was significantly lower in pregnancies with Down syndrome. The median FIGLU level was 0.9 µmol/l in amniotic fluid from fetuses with Down syndrome. The median FIGLU level was 1.3 in amniotic fluid from control fetuses. This difference was statistically significant (p = 0.009). No statistically significant differences were found with histidine or glutamate. Discussion: There was no evidence of folate deficiency. FIGLU was decreased, not increased. Decreased FIGLU might result from accelerated activity of one or more genes on chromosome 21, by a gene dosage effect. Genes which might explain the reduced FIGLU include one which degrades FIGLU (glutamate formiminotransferase-cyclodeaminase), one which participates in purine synthesis, and one which degrades homocysteine (cystathionine-β-synthase).

Introduction: Organic acids were examined from normal and Down syndrome pregnancies to identify possible differences between the amniotic fluid from fetuses with Down Syndrome compared with that of normal fetuses. Materials and Methods: Amniotic fluids were obtained from prior amniocenteses. Forty-one normal and 22 Down syndrome specimens were assayed using gas chromatography/mass spectrometry. Results and Discussion: 5-Hydroxycaproate, methylsuccinate, α-ketoglutarate, and adipate were significantly elevated in Down syndrome, suggesting riboflavin deficiency. Phenylpyruvate was also significantly elevated in fetuses with Down syndrome. Phenylpyruvate inhibits the metabolism of tetrahydrobiopterin, which is necessary for neurotransmitter metabolism. Elevated phenylpyruvate is consistent with previous research, suggesting a disturbance of tetrahydrobiopterin metabolism in Down syndrome. Conclusion: Organic acid markers for B₂ deficiency are elevated in the amniotic fluid of fetuses with Down syndrome. Elevation of phenylpyruvate may impair neurotransmitter metabolism. Organic acid markers for B₁₂ levels are not different between the Down syndrome and normal group.

Introduction: Some studies of children with Down syndrome have found mild abnormalities in the metabolism of pyridoxine (vitamin B₆); therefore the present question is whether such abnormalities might also be present in the amniotic fluid of fetuses with Down syndrome. Materials and Methods: Archived specimens of amniotic fluid were obtained from chromosomally normal and from fetuses with Down syndrome. Gas chromatography/mass spectrometry quantitized B-related metabolites, including oxalate, xanthurenate, kynurenine and 4-pyridoxic acid. Results: Oxalate, a marker of pyridoxine deficiency, was elevated in the amniotic fluid of fetuses with Down syndrome. This result was statistically significant. The other marker results were not statistically significant. Conclusion: A marker of pyridoxine deficiency, oxalate is elevated in the amniotic fluid of fetuses with Down syndrome. These results in amniotic fluid are consistent with previous studies done in the urine of young children.

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