Alternative Reagents for Chemical Noise Reduction in Liquid Chromatography-Mass Spectrometry Using Selective Ion-Molecule Reactions

Reduction of ionic chemical background noise based on selective gas-phase reactions with chosen neutral reagents has been proven to be a very promising approach in liquid chromatography-mass spectrometry (LC-MS). In this study further investigations on alternative reagents including the disulfides (dimethyl disulfide, diethyl disulfide, methyl propyl disulfide), dimethyl trisulfide, ethylene oxide, and butadiene monoxide, for example, have been carried Out. Tandem mass spectrometric Studies of ion/molecule reactions indicate that-besides dimethyl disulfide-ethylene oxide and butadiene monoxide also exhibit very efficient reactions with background ions. Furthermore, it is confirmed that the reactions are very selective according to the test with some analyte ions. In contrast to its rapid reactions with background ions, ethylene oxide does not react, or reacts much less, with these analytes. Therefore, it can be used as an alternative reagent for noise reduction. Although reactions of the other tested neutral reagents with background ions are evaluated, they are generally not suitable as reagents for this purpose because of lack of reactivity or dramatic ion losses during reactions. (J Am Soc Mass Spectrom 2009, 20, 105-111) (C) 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometr

DAG-species in rat liver and serum.

<p>DAG-species in <b>A</b> rat liver and <b>B</b> rat serum. Values given are means±s.d. of the sums of the different chain lengths (C32 – C38) on the left and degree of desaturation (sat – hexa) on the right. Serum data is shown for day 14 and day 20; the control group is shown as black bar, the fructose-fed group is shown as red bar and the FF treated group is shown as a blue bar; significant changes are indicated using *: P<0.05; **: P<0.01; ***: P<0,001.</p

Alternate display format of TAG/DAG-species and FA-species.

<p><b>A</b> fructose-feeding vs control in rat liver; <b>B</b> FF treatment vs Fructose-feeding in rat liver; <b>C</b> fructose-feeding vs control in rat serum; <b>D</b> FF treatment vs Fructose-feeding in rat serum; An algorithm was developed to generate the alternate display form of DAG/TAG-species. In the diagrams the species shown in red have increased levels between the two respective groups, while a blue color indicates a decreased level of the respective species between the two groups. A black coloring indicates no change of the species between the two groups. All species have been colored if the difference of levels between the two groups were >5% of the total amount of the higher level, regardless of the significance of the change. For clarity, only the sections of the diagram containing the combinations of DAG C36 With FA C18 to yield TAG C54 are shown. If there is a fatty acid-DAG combination present with the same direction of change as the corresponding TAG-species, then this combination seems at least to contribute to the composition of the TAG-species. Significant changes are indicated using *: P<0.05; **: P<0.01; ***: P<0,001.</p

TAG-species in rat liver.

<p>Values given are means±s.d. of the sums of the different chain lengths (C46–C60) on the left and degree of desaturation (sat – deca) on the right. Serum data is shown for day 14 and day 20; the control group is shown as black bar, the fructose-fed group is shown as red bar and the FF treated group is shown as a blue bar; significant changes are indicated using *: P<0.05; **: P<0.01; ***: P<0,001.</p

Tissue weights and overall TAG- and DAG-levels.

<p><b>A</b> Organ weight of the animals after the end of treatment; <b>B</b> TAG-levels in rat liver, jejunum and serum and DAG-levels in rat liver and rat jejunum; <b>C</b> Sums of TAG- and DAG-species in rat serum. Tissue samples were taken during study 1, serum samples were taken during study 2; the control group is shown as black bar, the fructose-fed group is shown as red bar and the FF treated group is shown as a blue bar; values given are means±s.d.; significant changes are indicated using *: P<0.05; **: P<0.01; ***: P<0,001.</p

VLDL-secretion after FF treatment.

<p>The control group is shown in black, the fructose-fed group is shown in red and the FF treated group is shown in blue; values given are means±s.d.; significant changes are indicated using *: P<0.05; **: P<0.01; ***: P<0,001.</p

NEFA-species in rat liver and rat serum.

<p><b>A</b> NEFA-species in rat liver homocysteine in rat serum; <b>B</b> NEFA-species in rat serum. The control group is shown as black bar, the fructose-fed group is shown as red bar and the FF treated group is shown as a blue bar; values given are means±s.d.; significant changes are indicated using *: P<0.05; **: P<0.01; ***: P<0,001.</p

Clinical chemistry data, organ weight, food and water consumption.

<p>Values determined in study 1. Values given are mean values of the 6 animals/group with standard deviation included. Significant changes are indicated using *: P<0.05; **: P<0.01; ***: P<0,001. ASAT: aspartate aminotransferase, ALAT: alanine aminotransferase, AP: alkaline phosphatase (AP).</p><p>Clinical chemistry data, organ weight, food and water consumption.</p

Deciphering lipid structures based on platform-independent decision rules

10.1038/NMETH.4470NATURE METHODS14121171-117

The DALI vitamin D randomized controlled trial for gestational diabetes mellitus prevention: No major benefit shown besides vitamin D sufficiency

BACKGROUND & AIMS: As vitamin D deficiency is associated with an increased risk of gestational diabetes mellitus (GDM), we aimed to test vitamin D supplementation as a strategy to reduce GDM risk (evaluated after fasting plasma glucose (FPG), insulin resistance and weight gain) in pregnant overweight/obese women. METHODS: The DALI vitamin D multicenter study enrolled women with prepregnancy body mass index (BMI) ≥ 29 kg/m2, ≤19 + 6 weeks of gestation and without GDM. Participants were randomized to receive 1600 IU/day vitamin D3 or placebo (each with or without lifestyle intervention) on top of (multi)vitamins supplements. Women were assessed for vitamin D status (sufficiency defined as serum 25-hydroxyvitamin D (25(OH)D) ≥ 50 nmol/l), FPG, insulin resistance and weight at baseline, 24-28 and 35-37 weeks. Linear or logistic regression analyses were performed to assess intervention effects. RESULTS: Average baseline serum 25(OH)D was ≥50 nmol/l across all study sites. In the vitamin D intervention arm (n = 79), 97% of participants achieved target serum vitamin 25(OH)D (≥50 nmol/l) at 24-28 weeks and 98% at 35-37 weeks vs 74% and 78% respectively in the placebo arm (n = 75, p < 0.001). A small but significantly lower FPG (-0.14 mmol/l; CI95 -0.28, -0.00) was observed at 35-37 weeks with the vitamin D intervention without any additional difference in metabolic status, perinatal outcomes or adverse event rates. CONCLUSION: In the DALI vitamin D trial, supplementation with 1600 IU vitamin D3/day achieved vitamin D sufficiency in virtually all pregnant women and a small effect in FPG at 35-37 weeks. The potential of vitamin D supplementation for GDM prevention in vitamin D sufficient populations appears to be limited. TRIAL REGISTRATION NUMBER: ISRCTN70595832.status: publishe