177 research outputs found
Effect of Ca2+ on thermotropic properties of saturated phosphatidylcholine liposomes
The effect of various concentrations of calcium ion (Ca2+) on dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC) and mixed DPPC/DSPC (1:1) liposomes was studied by differential scanning calorimetry. Ca2+ concentrations of 10 mM and above split the main transition peak of DPPC into two distinguishable components, and, at 30 mM and above, also resulted in the disappearance of a pre-transition peak. The effect of Ca2+ on DSPC liposomes was even more dramatic in that it induced a more definitive split in the main transition peak and caused the loss of the pretransition peak at only 10 mM concentration. The thermograms of the DPPC/DSPC mixed liposomes were unaltered in the presence of Ca2+, even at a concentration of 50 mM. Whether or not Ca2+ is able to alter thermograms of phosphatidylcholine liposomes appears to be dependent on the degree of molecular order of the bilayer prior to interaction with Ca2+.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24008/1/0000257.pd
In situ jejunal uptake from liposomal systems
The in situ uptake from the rat jejunum of liposomes prepared from various saturated phosphatidylcholines in the presence or absence of cholesterol was determined. Liposomes prepared from distearoylphosphatidylcholine, with or without cholesterol, were taken up at the fastest rate (apparent first-order uptake of intact liposomes with a half-life of about 15 min). The lipid components of liposomes could not be found in compartments where liposomes would be expected to accumulate, i.e. liver, spleen, lymph nodes, or thoracic lymphatic duct. Furthermore, inulin, when encapsulated in the liposomes, could not be found in the urine. When either PEG-4000 (a non-absorbable marker) or glucose (an absorbable marker) was entrapped within the liposome, all of the liposomes and markers that were taken up still remained associated with the jejunum and the liposomes remained intact.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24965/1/0000392.pd
Mechanisms of topical delivery of liposomally entrapped drugs
Our research on the mechanism by which liposomally entrapped solutes are transported across the skin was prompted by an investigation reported in the literature which con- cluded with meager supporting evidence that liposomes containing triamcinolone acetonide penetrated the stratum corneum intact and, thereby, increased skin absorption. To elucidate the mechanism we used glucose, hydrocortisone, progesterone and multilamellar DPPC liposomes. Experimental strategies involved: DSC determinations, in vivo permeation of hairless mouse skin by liposomes, by liposome-entrapped solutes (15:1) and by solutes in simple solution; and in vitro release kinetics of liposome-entrapped solutes.The liposomes neither penetrated the skin nor fused with the stratum corneum. Progesterone and hydrocortisone, which were intercalated in the bilayer structure, permeated the skin with ease comparable to free drug. The skin transport of the highly polar glucose entrapped in the aqueous regions of the liposome was markedly slow as compared to the free species. Physical model analysis indicated that the slow release rate of glucose out of the liposome was the rate-determining step as compared to the relatively rapid skin permeation of the free solute. For the hydrophobic progesterone and hydrocortisone, quantitative analyses suggested direct transfer of drug from the liposome to the surface phases of skin and subsequent diffusion through the tissue. Considering this mechanism and owing to increased solubility of lipophilic drugs in liposomes, more total drug may be delivered through the skin by liposomes relative to simple aqueous solution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25506/1/0000047.pd
Chorioamnionitis disrupts erythropoietin and melatonin homeostasis through the placental-fetal-brain axis during critical developmental periods
Introduction: Novel therapeutics are emerging to mitigate damage from perinatal brain injury (PBI). Few newborns with PBI suffer from a singular etiology. Most experience cumulative insults from prenatal inflammation, genetic and epigenetic vulnerability, toxins (opioids, other drug exposures, environmental exposure), hypoxia-ischemia, and postnatal stressors such as sepsis and seizures. Accordingly, tailoring of emerging therapeutic regimens with endogenous repair or neuro-immunomodulatory agents for individuals requires a more precise understanding of ligand, receptor-, and non-receptor-mediated regulation of essential developmental hormones. Given the recent clinical focus on neurorepair for PBI, we hypothesized that there would be injury-induced changes in erythropoietin (EPO), erythropoietin receptor (EPOR), melatonin receptor (MLTR), NAD-dependent deacetylase sirtuin-1 (SIRT1) signaling, and hypoxia inducible factors (HIF1α, HIF2α). Specifically, we predicted that EPO, EPOR, MLTR1, SIRT1, HIF1α and HIF2α alterations after chorioamnionitis (CHORIO) would reflect relative changes observed in human preterm infants. Similarly, we expected unique developmental regulation after injury that would reveal potential clues to mechanisms and timing of inflammatory and oxidative injury after CHORIO that could inform future therapeutic development to treat PBI.Methods: To induce CHORIO, a laparotomy was performed on embryonic day 18 (E18) in rats with transient uterine artery occlusion plus intra-amniotic injection of lipopolysaccharide (LPS). Placentae and fetal brains were collected at 24 h. Brains were also collected on postnatal day 2 (P2), P7, and P21. EPO, EPOR, MLTR1, SIRT1, HIF1α and HIF2α levels were quantified using a clinical electrochemiluminescent biomarker platform, qPCR, and/or RNAscope. MLT levels were quantified with liquid chromatography mass spectrometry.Results: Examination of EPO, EPOR, and MLTR1 at 24 h showed that while placental levels of EPO and MLTR1 mRNA were decreased acutely after CHORIO, cerebral levels of EPO, EPOR and MLTR1 mRNA were increased compared to control. Notably, CHORIO brains at P2 were SIRT1 mRNA deficient with increased HIF1α and HIF2α despite normalized levels of EPO, EPOR and MLTR1, and in the presence of elevated serum EPO levels. Uniquely, brain levels of EPO, EPOR and MLTR1 shifted at P7 and P21, with prominent CHORIO-induced changes in mRNA expression. Reductions at P21 were concomitant with increased serum EPO levels in CHORIO rats compared to controls and variable MLT levels.Discussion: These data reveal that commensurate with robust inflammation through the maternal placental-fetal axis, CHORIO impacts EPO, MLT, SIRT1, and HIF signal transduction defined by dynamic changes in EPO, EPOR, MLTR1, SIRT1, HIF1α and HIF2α mRNA, and EPO protein. Notably, ligand-receptor mismatch, tissue compartment differential regulation, and non-receptor-mediated signaling highlight the importance, complexity and nuance of neural and immune cell development and provide essential clues to mechanisms of injury in PBI. As the placenta, immune cells, and neural cells share many common, developmentally regulated signal transduction pathways, further studies are needed to clarify the perinatal dynamics of EPO and MLT signaling and to capitalize on therapies that target endogenous neurorepair mechanisms
Enhanced production of baryons in high-multiplicity collisions at TeV
The production rate of baryons relative to mesons
in collisions at a center-of-mass energy TeV is measured
by the LHCb experiment. The ratio of to production
cross-sections shows a significant dependence on both the transverse momentum
and the measured charged-particle multiplicity. At low multiplicity, the ratio
measured at LHCb is consistent with the value measured in
collisions, and increases by a factor of with increasing multiplicity.
At relatively low transverse momentum, the ratio of to
cross-sections is higher than what is measured in
collisions, but converges with the ratio as the momentum
increases. These results imply that the evolution of heavy quarks into
final-state hadrons is influenced by the density of the hadronic environment
produced in the collision. Comparisons with a statistical hadronization model
and implications for the mechanisms enforcing quark confinement are discussed.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-027.html (LHCb
public pages
Studies of and production in and Pb collisions
The production of and mesons is studied in proton-proton and
proton-lead collisions collected with the LHCb detector. Proton-proton
collisions are studied at center-of-mass energies of and ,
and proton-lead collisions are studied at a center-of-mass energy per nucleon
of . The studies are performed in center-of-mass rapidity
regions (forward rapidity) and
(backward rapidity) defined relative to the proton beam direction. The
and production cross sections are measured differentially as a function
of transverse momentum for and , respectively. The differential cross sections are used to
calculate nuclear modification factors. The nuclear modification factors for
and mesons agree at both forward and backward rapidity, showing
no significant evidence of mass dependence. The differential cross sections of
mesons are also used to calculate cross section ratios,
which show evidence of a deviation from the world average. These studies offer
new constraints on mass-dependent nuclear effects in heavy-ion collisions, as
well as and meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb
public pages
Observation of Cabibbo-suppressed two-body hadronic decays and precision mass measurement of the baryon
The first observation of the singly Cabibbo-suppressed
and decays
is reported, using proton-proton collision data at a centre-of-mass energy of
, corresponding to an integrated luminosity of , collected with the LHCb detector between 2016 and 2018. The
branching fraction ratios are measured to be
,
. In addition, using the
decay channel, the baryon
mass is measured to be , improving the
precision of the previous world average by a factor of four.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-011.html (LHCb
public pages
Fraction of decays in prompt production measured in pPb collisions at TeV
The fraction of and decays in the prompt
yield, , is measured by
the LHCb detector in pPb collisions at TeV. The study
covers the forward () and backward () rapidity
regions, where is the rapidity in the nucleon-nucleon
center-of-mass system. Forward and backward rapidity samples correspond to
integrated luminosities of 13.6 0.3 nb and 20.8 0.5
nb, respectively. The result is presented as a function of the
transverse momentum in the range 1 GeV/.
The fraction at forward rapidity is compatible with the LHCb
measurement performed in collisions at TeV, whereas the
result at backward rapidity is 2.4 larger than in the forward region
for GeV/. The increase of at low at backward rapidity is compatible with the suppression of the
(2S) contribution to the prompt yield. The lack of in-medium
dissociation of states observed in this study sets an upper limit of
180 MeV on the free energy available in these pPb collisions to dissociate or
inhibit charmonium state formation.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-028.html (LHCb
public pages
A measurement of
Using a dataset corresponding to of integrated
luminosity collected with the LHCb detector between 2011 and 2018 in
proton-proton collisions, the decay-time distributions of the decay modes
and
are studied. The decay-width difference between the light and heavy mass
eigenstates of the meson is measured to be , where the first uncertainty is
statistical and the second systematic.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-025.htm
Observation of strangeness enhancement with charmed mesons in high-multiplicity collisions at TeV
The production of prompt and mesons is measured by the LHCb
experiment in proton-lead () collisions in both the forward
() and backward () rapidity regions at a
nucleon-nucleon center-of-mass energy of TeV.
The nuclear modification factors of both and mesons are
determined as a function of transverse momentum, , and
rapidity. In addition, the to cross-section ratio is measured
as a function of the charged particle multiplicity in the event. An enhanced
to production in high-multiplicity events is observed for the
whole measured range, in particular at low
and backward rapidity, where the significance exceeds six standard deviations.
This constitutes the first observation of strangeness enhancement in charm
quark hadronization in high-multiplicity collisions. The results
are also qualitatively consistent with the presence of quark coalescence as an
additional charm quark hadronization mechanism in high-multiplicity proton-lead
collisions.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-021.html (LHCb
public pages
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