Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone.

BACKGROUND: The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. METHODS: A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles. RESULTS: Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences. CONCLUSION: NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.

Phosphopeptide/phosphoprotein mapping by electron capture dissociation mass spectrometry.

Of methods for dissociation of multiply charged peptide and protein ions, electron capture dissociation (ECD) has the advantages of cleaving between a high proportion of amino acids, without loss of such posttranslational modifications as glycosylation and carboxylation. Here this capability is successfully extended to phosphorylation, for which collisionally activated dissociation (CAD) can cause extensive loss of H3PO4 and HPO3. As shown here, these losses are minimal in ECD spectra, an advantage for measuring the degree of phosphorylation. For phosphorylated peptides, ECD and CAD spectra give complementary backbone cleavages for identifying modification sites. For a 24-kDa heterogeneous phosphoprotein, bovine beta-casein, activated ion ECD cleaved 87 of 208 backbone bonds that identified a phosphorylation site at Ser-15, and localized three more among Ser-17,-18, -19, and -22 and Thr-24, and the last among four other sites. This is the first direct site-specific characterization of this key post-translational modification on a protein without its prior degradation, such as proteolysis.

De novo sequencing of proteolytic peptides by a combination of C-terminal derivatization and nano-electrospray/collision-induced dissociation mass spectrometry.

A series of synthetic peptides (3-15 residues), C-terminally derivatized with 4-aminonaphthalenesulfonic acid (ansa), have been analyzed on a hybrid magnetic sector-orthogonal acceleration time-of-flight tandem mass spectrometer, fitted with a nano-electrospray (nano-ES) interface. Deprotonated molecules generated by negative-ion ES were subjected to collision-induced dissociation (CID) using either methane or xenon as the collision gas, at a collision energy of 400 eV (laboratory frame of reference). As a consequence of charge localization on the sulfonate group, only C-terminal fragment ions were formed, presumably by charge-remote fragmentation mechanisms. Interpretable CID spectra were obtained from fmol amounts of the small peptides (up to 6 residues), whereas low pmol amounts were required for the larger peptides. CID spectra were also recorded of derivatized, previously noncharacterised peptides obtained by proteolysis of cytosolic hamster liver aldehyde dehydrogenase. Interpretation of these CID spectra was based on rules established for the fragmentation of the synthetic peptides. This study shows that derivatization with ansa may be useful in the de novo sequencing of peptides.

Increased asymmetries in 2-deoxyglucose uptake in the brain of freely moving congenitally acallosal mice.

To investigate the role of the corpus callosum in the expression of functional brain asymmetries, we compared left and right uptake of [14C]2-deoxyglucose in 43 brain regions measured in 10 C57B1/6 mice with a normal corpus callosum and in 12 congenitally acallosal mice, after 45 min of free activity in a novel, large open-field arena. The metabolic patterns across the brain appeared to be similar in the two groups of mice, as well as the average direction of asymmetry in tracer incorporation, which was higher at right in most of the brain regions for both acallosals and controls. However, the direction of the metabolic asymmetries of any given region was not consistent across individual animals. The largest asymmetries were found in the central auditory nuclei in both groups of mice, with extreme values in some acallosals. Significantly larger asymmetries were found in acallosal mice for the brain and the cortex as a whole, as well as for the lateral geniculate and pretectal nuclei, the olfactory tubercles, and retrosplenial, infrarhinal and perirhinal cortices. The metabolic asymmetries of the thalamic sensory nuclei were correlated with the asymmetries of the corresponding sensory cortical fields in the acallosal, but not in control mice. On the other hand, asymmetries of the cortical regions were largely intercorrelated in control mice, resulting in a general activation of one hemisphere over the other, while in acallosals they were more independent, resulting in a "patchy" pattern of cortical asymmetries. These results suggest that callosal agenesis, combined with the occurrence of ipsilateral Probst bundles, leads to a loss of co-ordination in the activation of different sensory and motor areas. The impaired co-ordination might then be distributed through cortico-subcortical loops, resulting in larger asymmetries throughout the brain. Thus, a normal corpus callosum appears to balance and synchronize metabolic brain activity, perhaps by smoothing the effects of asymmetrically activated ascending systems.

Charge-remote fragmentation of peptides derivatized with 4-aminonaphthalenesulphonic acid.

A series of small peptides has been studied by negative-ion fast-atom bombardment mass spectrometry with collision-induced dissociation. It has been found that by derivatizing peptides with 4-aminonaphthalenesulphonic acid in a peptide linkage at the C-terminus, negative-ion formation can be enhanced and fragmentation in collision-induced dissociation reactions controlled. The peptide-naphthalenesulphonates show charge-remote fragmentations and the resultant spectra give sequence information.

Analysis of conformationally restricted models for the (1----6)-branch of asparagine-linked oligosaccharides by n.m.r.-spectroscopy and HSEA calculation.

The conformational preferences of the trisaccharide, beta-D-GlcpNAc-(1----2)-alpha-D-Manp-(1----6)-beta-D-GlcpOR (1) have been investigated by n.m.r.-spectroscopy and HSEA calculation. The fixed omega-angle bicyclic analogs 2 and 3, models for the gt and gg rotamers, respectively, of 1, were furthermore examined with the same techniques in an attempt to deduce which of the conformations accessible to 1 was recognized and glycosylated by the enzyme GlcNAc-transferase-V, which acts on a component of the (1----6)-arm of glycoproteins. Only the gg bicyclic 3 was found to be reactive with the enzyme and this study concludes, based on conformational analysis, that 1 as well as the natural Asn-linked oligosaccharide are recognized by GlcNAc-transferase-V in only one of the two local minimum energy conformations energetically accessible to these molecules in their gg rotamer.

Synthesis of p-trifluoroacetamidophenyl beta-D-glucopyranoside 4-(D-ribit-5-yl phosphate) corresponding to the Haemophilus influenzae type A capsular antigen.

The synthesis is described of the title glycoside which corresponds to the Haemophilus influenzae type a capsular antigen. The hydrogenphosphonate method was used with 3,3'-(chlorophosphonylidene)bis(2-oxo-1,3-oxazolidene) as the condensing agent.

Synthesis of phospholipids and nucleoside-phospholipid conjugates via hydrogenphosphonate intermediates.

Chemical synthesis of nucleoside-phospholipid conjugates based on hydrogenphosphonate chemistry has been achieved via coupling of 1,2-dipalmitoylglycero-3-H-phosphonate with suitable protected nucleosides or via coupling of nucleoside H-phosphonates with 1,2-dipalmitoylglycerol. It was also found that 1,2-dipalmitoylglycero-3-H-phosphonate, which is a stable compound, can serve as a convenient intermediate in the synthesis of various phospholipids.