An Exploratory Clinical Study to Monitor Clinical Efficacy of an Occluding Technology Dentifrice in Providing Short Term Relief from Dentinal Hypersensitivity.

OBJECTIVES: To examine dentin hypersensitivity (DH) at multiple time points over a 14-day period in participants who brushed twice daily with a 0.454% SnF2 dentifrice (Test) compared to a 0.76% sodium monofluorophosphate dentifrice with no known anti-sensitivity properties (Control). METHODS: This was a two-week, single-center, randomized, controlled, examiner-blind, two-treatment, parallel-group study in healthy participants with DH. The sensitivity of two selected test teeth and of all sensitive teeth was assessed at baseline and after one, three, seven, 10, and 14 days' treatment in response to evaporative (air) Schiff sensitivity score and visual analogue scale [VAS]) and tactile (tactile threshold) stimuli. DH was also monitored using a shortened version of the Dentin Hypersensitivity Experience Questionnaire (DHEQ) and a single "Tooth Sensitivity Question" (TSQ). RESULTS: Both groups had mean Schiff sensitivity scores that were statistically significantly improved from baseline on all days for the two test teeth and all qualifying teeth (p < 0.0001). There was a statistically significant difference between the dentifrices at Day 1 only, in favor of the Control dentifrice, for the two test teeth (0.28 [95% confidence intervals 0.03,0.53] p = 0.0282) or all qualifying teeth (0.17 [0.02,0.32] p = 0.0273). For tactile threshold, both dentifrices were statistically significantly improved from baseline from Day 3 onwards, with the Test dentifrice showing an improvement at Day 1 (p < 0.05). There were no significant statistical between-treatment differences at any time point. DHEQ questions revealed most participants experienced "sensitivity," "twinging," and "pain," with cold stimuli rated as the highest DH-eliciting. DHEQ Section 1 rating scores improved with the Test dentifrice, but not significantly statistically. DHEQ Section 2 scores statistically significantly improved with both dentifrices (p < 0.0002) with no differences between them. TSQ scores for both groups reduced over the time period. Both dentifrices were generally well-tolerated. CONCLUSIONS: In this study, use of both the Test and Control dentifrices led to DH relief with few statistically significant differences between them. The DHEQ and TSQ showed a reduction of pain during the study period, but there was still a high level of discomfort. Further research on short term relief of DH is required.

A new topical panthenol-containing emollient: Results from two randomized controlled studies assessing its skin moisturization and barrier restoration potential, and the effect on skin microflora.

PURPOSE: Two randomized, intra-individual comparison studies were performed in healthy subjects to evaluate the skin moisturization and barrier restoration potential of a new topical panthenol-containing emollient (NTP-CE) (Study 1), and its effect on skin microflora (Study 2). METHODS: In Study 1 (N = 23), two skin areas, one challenged with 0.5% sodium dodecyl sulfate (SDS) solution and one unchallenged, were treated with NTP-CE for 3 weeks. Transepidermal water loss (TEWL), skin hydration, and intercellular lipid lamellae (ICLL) organization were measured at regular intervals during the study. In Study 2 (N = 20), quantitative bacterial cultures were obtained over 6 h from a skin area undergoing wash stress with 10% SDS with subsequent single application of NTP-CE. RESULTS: In Study 1, mean AUC for TEWL reduction from baseline was more pronounced with NTP-CE compared with control (-168.36 vs. -123.38 g/m2/h, p = 0.023). NTP-CE use was also associated with statistically significant improvements in stratum corneum hydration and an increase in mean ICLL length from baseline (day 22: 120.61 vs. 35.85 nm/1000 nm2, p < 0.001). In Study 2, NTP-CE use had no negative impact on bacterial viability. CONCLUSIONS: NTP-CE use has favorable and lasting effects on barrier function and repair as well as skin hydration without negatively influencing bacterial viability.

Synthesis and analysis of potential α1,3-fucosyltransferase inhibitors.

Fucosyltransferases catalyze the transfer of l-fucose from an activated GDP-ß-l-fucose to various acceptor molecules such as N-acetyllactosamine. Frequently fucosylation is the final step within the glycosylation machinery, and the resulting glycans are involved in various cellular processes such as cell-cell recognition, adhesion and inflammation or tumor metastasis. The selective blocking of these interactions would thus be a potential promising therapeutic strategy. The syntheses and analyses of various potential α1,3-fucosyltransferase inhibitors derived from GDP-ß-l-fucose containing a triazole linker unit is summarized and the observed inhibitory effect was compared with that of small molecules such as GDP or fucose. To examine their specificity and selectivity, all inhibitors were tested with human α1,3-fucosyltransferase IX and Helicobacter pylori α1,3-fucosyltransferase, which is to date the only α1,3-fucosyltransferase with a known high resolution structure. Specific inhibitors which inhibit either H. pylori α1,3-fucosyltransferase or human fucosyltransferase IX with Ki values in the micromolar range were identified. In that regard, acetylated GDP-galactose derivative Ac-3 turned out to inhibit H. pylori α1,3-fucosyltransferase but not human fucosyltransferase IX, whereas GDP-6-amino-ß-l-fucose 17 showed an appreciably better inhibitory effect on fucosyltransferase IX activity than on that of H. pylori fucosyltransferase.

Fluorescently labeled substrates for monitoring α1,3-fucosyltransferase IX activity.

Fucosylation is often the final process in glycan biosynthesis. The resulting glycans are involved in a variety of biological processes, such as cell adhesion, inflammation, or tumor metastasis. Fucosyltransferases catalyze the transfer of fucose residues from the activated donor molecule GDP-ß-L-fucose to various acceptor molecules. However, detailed information about the reaction processes is still lacking for most fucosyltransferases. In this work we have monitored α1,3-fucosyltransferase activity. For both donor and acceptor substrates, the introduction of a fluorescent ATTO dye was the last step in the synthesis. The subsequent conversion of these substrates into fluorescently labeled products by α1,3-fucosyltransferases was examined by high-performance thin-layer chromatography coupled with mass spectrometry as well as dual-color fluorescence cross-correlation spectroscopy, which revealed that both fluorescently labeled donor GDP-ß-L-fucose-ATTO 550 and acceptor N-acetyllactosamine-ATTO 647N were accepted by recombinant human fucosyltransferase IX and Helicobacter pylori α1,3-fucosyltransferase, respectively. Analysis by fluorescence cross-correlation spectroscopy allowed a quick and versatile estimation of the progress of the enzymatic reaction and therefore this method can be used as an alternative method for investigating fucosyltransferase reactions.

A convenient synthesis of nucleoside diphosphate glycopyranoses and other polyphosphorylated bioconjugates.

In this review, we summarize results obtained using a conceptionally new chemical synthesis of NDP-sugars based on cycloSaligenyl (cycloSal) nucleotides as starting material (cycloSal technique). The cycloSal technique not only leads to stereoisomerically defined NDP-sugars in high yield, but the same principle provides very efficient routes towards nucleoside di- and -triphosphates. Moreover, sugar-nucleotides such as CMP-Neu5Ac and dinucleoside polyphosphates are available. Thus, the method offers a nearly universal chemical access towards a large number of highly interesting bioconjugates and biomolecules.

Reliable synthesis of various nucleoside diphosphate glycopyranoses.

A reliable and high yielding synthetic pathway for the synthesis of the biologically highly important class of nucleoside diphosphate sugars (NDP-sugars) was developed by using various cycloSal-nucleotides 1 and 9 as active ester building blocks. The reaction with anomerically pure pyranosyl-1-phosphates 2 led to the target NDP-sugars 20-45 in a nucleophilic displacement reaction, which cleaves the cycloSal moiety in anomerically pure forms. As nucleosides cytidine, uridine, thymidine, adenosine, 2'-deoxy-guanosine and 2',3'-dideoxy-2',3'-didehydrothymidine were used while the phosphates of D-glucose, D-galactose, D-mannose, D-NAc-glucosamine, D-NAc-galactosamine, D-fucose, L-fucose as well as 6-deoxy-D-gulose were introduced.