267 research outputs found
No effect of topical digoxin and furosemide for patients with actinic keratosis
Drug Delivery Technolog
Oral prednisolone suppresses skin inflammation in a healthy volunteer imiquimod challenge model
Imiquimod (IMQ) is a topical agent that induces local inflammation via the Toll-like receptor 7 pathway. Recently, an IMQ-driven skin inflammation model was developed in healthy volunteers for proof-of-pharmacology trials. The aim of this study was to profile the cellular, biochemical, and clinical effects of the marketed anti-inflammatory compound prednisolone in an IMQ model. This randomized, double-blind, placebo-controlled study was conducted in 24 healthy volunteers. Oral prednisolone (0.25 mg/kg/dose) or placebo (1:1) was administered twice daily for 6 consecutive days. Two days after treatment initiation with prednisolone or placebo, 5 mg imiquimod (IMQ) once daily for two following days was applied under occlusion on the tape-stripped skin of the back for 48 h in healthy volunteers. Non-invasive (imaging and biophysical) and invasive (skin punch biopsies and blister induction) assessments were performed, as well as IMQ ex vivo stimulation of whole blood. Prednisolone reduced blood perfusion and skin erythema following 48 h of IMQ application (95% CI [-26.4%, -4.3%], p = 0.0111 and 95% CI [-7.96, -2.13], p = 0.0016). Oral prednisolone suppressed the IMQ-elevated total cell count (95% CI [-79.7%, -16.3%], p = 0.0165), NK and dendritic cells (95% CI [-68.7%, -5.2%], p = 0.0333, 95% CI [-76.9%, -13.9%], p = 0.0184), and classical monocytes (95% CI [-76.7%, -26.6%], p = 0.0043) in blister fluid. Notably, TNF, IL-6, IL-8, and Mx-A responses in blister exudate were also reduced by prednisolone compared to placebo. Oral prednisolone suppresses IMQ-induced skin inflammation, which underlines the value of this cutaneous challenge model in clinical pharmacology studies of novel anti-inflammatory compounds. In these studies, prednisolone can be used as a benchmark.Drug Delivery Technolog
A multimodal, comprehensive characterization of a cutaneous wound model in healthy volunteers
Development of pharmacological interventions for wound treatment is challenging due to both poorly understood wound healing mechanisms and heterogeneous patient populations. A standardized and well-characterized wound healing model in healthy volunteers is needed to aid in-depth pharmacodynamic and efficacy assessments of novel compounds. The current study aims to objectively and comprehensively characterize skin punch biopsy-induced wounds in healthy volunteers with an integrated, multimodal test battery. Eighteen (18) healthy male and female volunteers received three biopsies on the lower back, which were left to heal without intervention. The wound healing process was characterized using a battery of multimodal, non-invasive methods as well as histology and qPCR analysis in re-excised skin punch biopsies. Biophysical and clinical imaging read-outs returned to baseline values in 28 days. Optical coherence tomography detected cutaneous differences throughout the wound healing progression. qPCR analysis showed involvement of proteins, quantified as mRNA fold increase, in one or more healing phases. All modalities used in the study were able to detect differences over time. Using multidimensional data visualization, we were able to create a distinction between wound healing phases. Clinical and histopathological scoring were concordant with non-invasive imaging read-outs. This well-characterized wound healing model in healthy volunteers will be a valuable tool for the standardized testing of novel wound healing treatments.Drug Delivery Technolog
Pharmacodynamic effects of topical Omiganan in patients with mild to moderate atopic dermatitis in a randomized, placebo-controlled, phase II trial
Omiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double-blind, placebo-controlled, phase II trial we explored the efficacy, pharmacodynamics, and safety of topical omiganan once daily in 36 patients with mild to moderate atomic dermatitis. Patients were randomized to apply topical omiganan 1%, omiganan 2.5%, or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements in local objective SCORing Atopic Dematitis index and morning itch were observed in the omiganan 2.5% group compared with the vehicle gel group (-18.5%; 95% confidence interval, -32.9 to -1.0; P = 0.04; and -8.2; 95% confidence interval, -16.3 to -0.2; P = 0.05, respectively). A shift from lesional to nonlesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. Thus, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis, and small but statistically significant improvements in clinical scores were detected. Our findings warrant further exploration in future clinical trials.Drug Delivery Technolog
Plasma Wakefield Acceleration with a Modulated Proton Bunch
The plasma wakefield amplitudes which could be achieved via the modulation of
a long proton bunch are investigated. We find that in the limit of long bunches
compared to the plasma wavelength, the strength of the accelerating fields is
directly proportional to the number of particles in the drive bunch and
inversely proportional to the square of the transverse bunch size. The scaling
laws were tested and verified in detailed simulations using parameters of
existing proton accelerators, and large electric fields were achieved, reaching
1 GV/m for LHC bunches. Energy gains for test electrons beyond 6 TeV were found
in this case.Comment: 9 pages, 7 figure
The energy dependence of angular correlations inferred from mean- fluctuation scale dependence in heavy ion collisions at the SPS and RHIC
We present the first study of the energy dependence of angular
correlations inferred from event-wise mean transverse momentum
fluctuations in heavy ion collisions. We compare our large-acceptance
measurements at CM energies $\sqrt{s_{NN}} =$ 19.6, 62.4, 130 and 200 GeV to
SPS measurements at 12.3 and 17.3 GeV. $p_t$ angular correlation structure
suggests that the principal source of $p_t$ correlations and fluctuations is
minijets (minimum-bias parton fragments). We observe a dramatic increase in
correlations and fluctuations from SPS to RHIC energies, increasing linearly
with $\ln \sqrt{s_{NN}}$ from the onset of observable jet-related
fluctuations near 10 GeV.Comment: 10 pages, 4 figure
Partonic flow and -meson production in Au+Au collisions at = 200 GeV
We present first measurements of the -meson elliptic flow
() and high statistics distributions for different
centralities from = 200 GeV Au+Au collisions at RHIC. In
minimum bias collisions the of the meson is consistent with the
trend observed for mesons. The ratio of the yields of the to those of
the as a function of transverse momentum is consistent with a model
based on the recombination of thermal quarks up to GeV/,
but disagrees at higher momenta. The nuclear modification factor () of
follows the trend observed in the mesons rather than in
baryons, supporting baryon-meson scaling. Since -mesons are
made via coalescence of seemingly thermalized quarks in central Au+Au
collisions, the observations imply hot and dense matter with partonic
collectivity has been formed at RHIC.Comment: 6 pages, 4 figures, submit to PR
Measurement of Transverse Single-Spin Asymmetries for Di-Jet Production in Proton-Proton Collisions at GeV
We report the first measurement of the opening angle distribution between
pairs of jets produced in high-energy collisions of transversely polarized
protons. The measurement probes (Sivers) correlations between the transverse
spin orientation of a proton and the transverse momentum directions of its
partons. With both beams polarized, the wide pseudorapidity () coverage for jets permits separation of Sivers functions for the valence
and sea regions. The resulting asymmetries are all consistent with zero and
considerably smaller than Sivers effects observed in semi-inclusive deep
inelastic scattering (SIDIS). We discuss theoretical attempts to reconcile the
new results with the sizable transverse spin effects seen in SIDIS and forward
hadron production in pp collisions.Comment: 6 pages total, 1 Latex file, 3 PS files with figure
Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at TeV
The elliptic, , triangular, , and quadrangular, , azimuthal
anisotropic flow coefficients are measured for unidentified charged particles,
pions and (anti-)protons in Pb-Pb collisions at TeV
with the ALICE detector at the Large Hadron Collider. Results obtained with the
event plane and four-particle cumulant methods are reported for the
pseudo-rapidity range at different collision centralities and as a
function of transverse momentum, , out to GeV/.
The observed non-zero elliptic and triangular flow depends only weakly on
transverse momentum for GeV/. The small dependence
of the difference between elliptic flow results obtained from the event plane
and four-particle cumulant methods suggests a common origin of flow
fluctuations up to GeV/. The magnitude of the (anti-)proton
elliptic and triangular flow is larger than that of pions out to at least
GeV/ indicating that the particle type dependence persists out
to high .Comment: 16 pages, 5 captioned figures, authors from page 11, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186
Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at = 2.76 TeV
The yield of charged particles associated with high- trigger
particles ( GeV/) is measured with the ALICE detector in
Pb-Pb collisions at = 2.76 TeV relative to proton-proton
collisions at the same energy. The conditional per-trigger yields are extracted
from the narrow jet-like correlation peaks in azimuthal di-hadron correlations.
In the 5% most central collisions, we observe that the yield of associated
charged particles with transverse momenta GeV/ on the
away-side drops to about 60% of that observed in pp collisions, while on the
near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/350
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