93 research outputs found
Activity of different desoximetasone preparations compared to other topical corticosteroids in the vasoconstriction assay
Introduction: We report on a double-blind, vehicle-controlled, single-center confirmatory study with random assignment. The purpose of the study was to investigate the topical bioavailability of different topical corticosteroid formulations in healthy human beings focussing on desoximetasone (DM). Materials and Methods: Two DM 0.25% formulations {[}ointment (DM-o) and fatty ointment (DM-fo, water-free); class III corticosteroids], the corresponding active ingredient-free vehicles and three comparators of different strength {[}clobetasol propionate 0.05% (CP 0.05%), fatty ointment, class IV; hydrocortisone (HC) 1%, fatty ointment, class I, and betamethasone (BM) 0.05%, fatty ointment, class III] were tested using the vasoconstriction assay. The degree of vasoconstriction (blanching) in the treatment field was compared to the one found in untreated control fields using chromametric measurements and clinical assessment. Results/Conclusion: DM-o 0.25%, DM-fo 0.25% and BM 0.05% showed similar vasoconstrictive potential, i.e., clear blanching. In fact, both DM preparations were proven to be non-inferior to BM 0.05%, while CP 0.05% was found a little less active. HC 1.0% and the DM vehicles showed no clear-cut vasoconstrictive effect. No adverse events related to the study medications were observed. Good topical bioavailability of both DM formulations was detected by chromametric measurement and clinical assessment. Copyright (C) 2008 S. Karger AG, Basel
Urinary peptide panel for prognostic assessment of bladder cancer relapse
Non-invasive tools stratifying bladder cancer (BC) patients according to the risk of relapse are urgently
needed to guide clinical intervention. As a follow-up to the previously published study on CE-MSbased urinary biomarkers for BC detection and recurrence monitoring, we expanded the investigation
towards BC patients with longitudinal data. Profling datasets of BC patients with follow-up information
regarding the relapse status were investigated. The peptidomics dataset (n=98) was split into training
and test set. Cox regression was utilized for feature selection in the training set. Investigation of the
entire training set at the single peptide level revealed 36 peptides being strong independent prognostic
markers of disease relapse. Those features were further integrated into a Random Forest-based model
evaluating the risk of relapse for BC patients. Performance of the model was assessed in the test cohort,
showing high signifcance in BC relapse prognosis [HR=5.76, p-value=0.0001, c-index=0.64]. Urinary
peptide profles integrated into a prognostic model allow for quantitative risk assessment of BC relapse
highlighting the need for its incorporation in prospective studies to establish its value in the clinical
management of BC
Molecular Evolution of the Infrared Sensory Gene TRPA1 in Snakes and Implications for Functional Studies
TRPA1 is a calcium ion channel protein recently identified as the infrared receptor in pit organ-containing snakes. Therefore, understanding the molecular evolution of TRPA1 may help to illuminate the origin of “heat vision” in snakes and reveal the molecular mechanism of infrared sensitivity for TRPA1. To this end, we sequenced the infrared sensory gene TRPA1 in 24 snake species, representing nine snake families and multiple non-snake outgroups. We found that TRPA1 is under strong positive selection in the pit-bearing snakes studied, but not in other non-pit snakes and non-snake vertebrates. As a comparison, TRPV1, a gene closely related to TRPA1, was found to be under strong purifying selection in all the species studied, with no difference in the strength of selection between pit-bearing snakes and non-pit snakes. This finding demonstrates that the adaptive evolution of TRPA1 specifically occurred within the pit-bearing snakes and may be related to the functional modification for detecting infrared radiation. In addition, by comparing the TRPA1 protein sequences, we identified 11 amino acid sites that were diverged in pit-bearing snakes but conserved in non-pit snakes and other vertebrates, 21 sites that were diverged only within pit-vipers but conserved in the remaining snakes. These specific amino acid substitutions may be potentially functional important for infrared sensing
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