129 research outputs found
Human skin penetration of a copper tripeptide in vitro as a function of skin layer
Objective and designSkin retention and penetration by copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate was evaluated in vitro in order to assess its potential for its transdermal delivery as an anti-inflammatory agent.Materials and methodsFlow-through diffusion cells with 1 cm(2) exposure area were used under infinite dose conditions. 0.68% aq. copper tripeptide as permeant was applied on isolated stratum corneum, heat-separated epidermis and dermatomed skin and receptor fluid collected over 48 h in 4 h intervals using inductively coupled plasma mass spectrometry to analyze for copper in tissues and receptor fluid.ResultsThe permeability coefficient of the compound through dermatomed skin was 2.43 ± 0.51 × 10(-4) cm/h; 136.2 ± 17.5 μg/cm(2) copper permeated 1 cm(2) of that tissue over 48 h, while 97 ± 6.6 μg/cm(2) were retained as depot.ConclusionsCopper as tripeptide was delivered in potentially therapeutically effective amounts for inflammatory disease
Human skin penetration of a copper tripeptide in vitro as a function of skin layer
We study a set of 28 GRB light-curves detected between 15 December
2002 and 9 June 2003 by the anti-coincidence shield of the
spectrometer (SPI) of INTEGRAL. During this period it has detected
50 bursts, that have been confirmed by other instruments, with a
time resolution of 50 ms. First, we derive the basic
characteristics of the bursts: various duration measures, the
count peak flux and the count fluence. Second, a sub-sample of 11 bursts with 12 individual, well-separated pulses is studied. We
fit the pulse shape with a model by Kocevski et al. (2003)
and find that the pulses are quite self-similar in shape. There is
also a weak tendency for the pulses with steep power-law decays to
be more asymmetric. Third, the variability of the complex
light-curves is studied by analyzing their power-density-spectra
(PDS) and their RMS variability.
The averaged PDS, of the whole sample, is a power-law with index
of and a break between 1–2 Hz. Fourth, we also
discuss the background and noise levels. We found that the
background noise has a Gaussian distribution and its power is
independent of frequency, i.e., it is white noise. However, it
does not follow a Poisson statistic since on average the variance
is ~1.6 larger than the mean. We discuss our results in
context of the current theoretical picture in which GRBs are
created in an anisotropic, highly relativistic outflow from
collapsing massive stars. Finally, we note that the exact
behaviour of the instrument is not yet known and therefore the
above results should be treated as preliminary.
Acetate Causes Alcohol Hangover Headache in Rats
Background: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache. Methods: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats. Results: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate increased nociceptive behaviors suggesting that acetate, not acetaldehyde, accumulation results in hangover-like hypersensitivity in our model. Since adenosine accumulation is a result of acetate formation, we administered an adenosine antagonist that blocked hypersensitivity. Discussion: Our study shows that acetate contributes to hangover headache. These findings provide insight into the mechanism of hangover headache and the mechanism of headache induction
Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures
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Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models
INTERNAL AND EXTERNAL ENVIRONMENTAL REGULATION OF OPSIN EXPRESSION IN AFRICAN CICHLIDS
Evolutionary biology has long sought to understand the evolution of adaptive phenotypes. While purely genetic factors are often emphasized, environmental influences also significantly contribute to phenotypic variation. In this dissertation, we investigate the environmental regulation of visual sensitivity in cichlids. Cichlid fishes exhibit a diversity of color vision facilitated by differential expression of opsin proteins, including light-induced phenotypic plasticity which was known to occur during development. To determine whether cichlids retain plasticity into adulthood, adult fish were moved between different light environments. Adult fish not only exhibited plasticity of opsin expression, but it was rapid, reversible, and shifted in a direction that would maximize light input to the retina. In order to observe the effect of diurnal variation of light on opsin cycles, we collected retinae from a continuous 25 hour time-series. This enabled us to develop guidelines for qRT-PCR normalization and determined that opsins were most highly expressed in the late afternoon. Opsins also cycled together, suggesting some common diurnally-sensitive regulatory mechanism. Given that there are species differences in plasticity, we sought to determine genetic loci that were affected by light. To determine how quantitative trait loci (QTL) changed between light environments, we raised all generations of a previously studied hybrid cross in a new light environment. One QTL was significant in both environments, indicating it is universally important for opsin expression. However, another QTL was only significant in one light environment, indicating it may be environmentally-sensitive. We propose a possible candidate gene for this locus. Plasticity is prevalent during development, with thyroid hormone (TH) being a common cue for developmental changes. Previous studies have found TH causes opsin expression shifts from short- to long-wavelength sensitivity as organisms age. To see its effect on species of cichlids with different developmental opsin progressions, we treated fish with TH. Interestingly, TH shifted fish to longer-wavelength sensitivities regardless of species. We also uncovered a possible interaction between TH and light-induced plasticity. Characterization of environmental influences on vision will continue to enhance our understanding of the evolution of visual diversity in these incredible fishes
A flow cytometric analysis of macrophage–nanoparticle interactions in vitro: induction of altered Toll-like receptor expression
Joyce M Njoroge, Jeffrey J Yourick, Mary Ann PrincipatoDivision of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708, USA Background: Nanoparticles exhibit unique physiochemical characteristics that provide the basis for their utilization. The diversity of potential and actual applications compels a thorough understanding regarding the consequences of their containment within the cellular environment.Purpose: This paper presents a flow cytometric examination of the biologic effects associated with the internalization of citrate-buffered silver (Ag) nanoparticles (NP) by the murine macrophage cell line, RAW264.7.Materials and methods: Cells were cultured with varying concentrations of citrate-buffered Ag nanoparticle and analyzed for changes in cellular volume, fluorescence emissions, and surface receptor expression.Results: Notable changes in side scatter (SSC) signal occurred following the phagocytosis of citrate-buffered Ag NP representative of the 10 nm, 50 nm, and 100 nm particle size by cultured RAW 264.7 cells. A characteristic associated with the internalization of all the citrated Ag NP sizes tested, was the detection of emitted infra-red and near-infrared wavelength emissions. This characteristic consistently permitted the detection of 10 nm, 50 nm, and 100 nm Ag NP particles internalized within the RAW cells by flow cytometry. A functional distinction between monocyte subsets within the RAW 264.7 cell line was noted as Ag NP are taken up by the F4/80+ subset of cells within the culture. Further, the internalization of Ag NP by the cells resulted in an increased cell surface expression of the Toll-like Receptor (TLR) 3, but not TLR4.Conclusion: Taken together, these results implicate the more mature macrophage in the ingestion of Ag NP; and an influence upon at least one of the Toll receptors present in macrophages following exposure to Ag NP. Further, our flow cytometric approach presents a potentially viable detection method for the identification of occult Ag NP material using an indicator cell line. Keywords: silver nanoparticle, flow cytometry, innate immunity, macrophage, Toll-like recepto
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