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[PMID]: 24839995
[Au] Autor:Poet TS; Timchalk C; Hotchkiss JA; Bartels MJ
[Ad] Address:Summit Toxicology , Richland, WA , USA .
[Ti] Title:Chlorpyrifos PBPK/PD model for multiple routes of exposure.
[So] Source:Xenobiotica;44(10):868-81, 2014 Oct.
[Is] ISSN:1366-5928
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Abstract 1. Chlorpyrifos (CPF) is an important pesticide used to control crop insects. Human Exposures to CPF will occur primarily through oral exposure to residues on foods. A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model has been developed that describes the relationship between oral, dermal and inhalation doses of CPF and key events in the pathway for cholinergic effects. The model was built on a prior oral model that addressed age-related changes in metabolism and physiology. This multi-route model was developed in rats and humans to validate all scenarios in a parallelogram design. 2. Critical biological effects from CPF exposure require metabolic activation to CPF oxon, and small amounts of metabolism in tissues will potentially have a great effect on pharmacokinetics and pharmacodynamic outcomes. Metabolism (bioactivation and detoxification) was therefore added in diaphragm, brain, lung and skin compartments. Pharmacokinetic data are available for controlled human exposures via the oral and dermal routes and from oral and inhalation studies in rats. The validated model was then used to determine relative dermal versus inhalation uptake from human volunteers exposed to CPF in an indoor scenario.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.3109/00498254.2014.918295

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[PMID]: 25197721
[Au] Autor:Choi T; Chin S
[Ad] Address:Sungkyul University, Anyang 430-742, Republic of Korea.
[Ti] Title:Novel real-time facial wound recovery synthesis using subsurface scattering.
[So] Source:ScientificWorldJournal;2014:965036, 2014.
[Is] ISSN:1537-744X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:We propose a wound recovery synthesis model that illustrates the appearance of a wound healing on a 3-dimensional (3D) face. The H3 model is used to determine the size of the recovering wound. Furthermore, we present our subsurface scattering model that is designed to take the multilayered skin structure of the wound into consideration to represent its color transformation. We also propose a novel real-time rendering method based on the results of an analysis of the characteristics of translucent materials. Finally, we validate the proposed methods with 3D wound-simulation experiments using shading models.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1155/2014/965036

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[PMID]: 25136095
[Au] Autor:Khmaladze Ia; Kelkka T; Guerard S; Wing K; Pizzolla A; Saxena A; Lundqvist K; Holmdahl M; Nandakumar KS; Holmdahl R
[Ad] Address:Medical Inflammation Research, Department of Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden;...
[Ti] Title:Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice.
[So] Source:Proc Natl Acad Sci U S A;111(35):E3669-78, 2014 Sep 2.
[Is] ISSN:1091-6490
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Psoriasis (Ps) and psoriasis arthritis (PsA) are poorly understood common diseases, induced by unknown environmental factors, affecting skin and articular joints. A single i.p. exposure to mannan from Saccharomyces cerevisiae induced an acute inflammation in inbred mouse strains resembling human Ps and PsA-like disease, whereas multiple injections induced a relapsing disease. Exacerbation of disease severity was observed in mice deficient for generation of reactive oxygen species (ROS). Interestingly, restoration of ROS production, specifically in macrophages, ameliorated both skin and joint disease. Neutralization of IL-17A, mainly produced by γδ T cells, completely blocked disease symptoms. Furthermore, mice depleted of granulocytes were resistant to disease development. In contrast, certain acute inflammatory mediators (C5, Fcγ receptor III, mast cells, and histamine) and adaptive immune players (α T and B cells) were redundant in disease induction. Hence, we propose that mannan-induced activation of macrophages leads to TNF-α secretion and stimulation of local γδ T cells secreting IL-17A. The combined action of activated macrophages and IL-17A produced in situ drives neutrophil infiltration in the epidermis and dermis of the skin, leading to disease manifestations. Thus, our finding suggests a new mechanism triggered by exposure to exogenous microbial components, such as mannan, that can induce and exacerbate Ps and PsA.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1073/pnas.1405798111

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[PMID]: 24861801
[Au] Autor:Aguilera J; de Glvez MV; Snchez-Roldn C; Herrera-Ceballos E
[Ad] Address:Photobiological Dermatology Laboratory, Medical Research Centre, Department of Dermatology and Medicine, Faculty of Medicine, University of Malaga, Malaga, Spain.
[Ti] Title:New advances in protection against solar ultraviolet radiation in textiles for summer clothing.
[So] Source:Photochem Photobiol;90(5):1199-206, 2014 Sep.
[Is] ISSN:1751-1097
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Clothing is considered one of the most important tools for photoprotection against harmful solar ultraviolet radiation (UVR). The standard for sun-protective clothing is based on erythema despite other biological effects of UVR on the skin. We analyzed the potential protection against UVR in fabrics destined for summer clothing based on several action spectra. We examined 50 garments classified by type of fabric composition, structure of the fiber yarn and color. The ultraviolet protection factor was calculated based on fabric ultraviolet transmittance corrected for erythema according to the EU standard E-13758 as well as the UVA transmittance of fabrics. UVR protection was also analyzed in base of different action spectra as for previtamin D3, nonmelanoma skin cancer, photoimmunosuppression and photoaging. Most knitted fabrics used for sports T-shirts offered excellent ratings for ultraviolet protection while normal shirts showed very low ratings, particularly against photoaging. The cover is the most influential variable in fabric photoprotection, having an exponential relationship with the UPF. The relation between cover and UVA protection was linearly negative. Information about ultraviolet protection in textiles used for summer clothing should be included in labeling as some types of fabrics, especially those used for shirts, offer very low UVR protection.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/php.12292

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[PMID]: 24807677
[Au] Autor:Anand S; Rollakanti KR; Horst RL; Hasan T; Maytin EV
[Ad] Address:Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH; Department of Dermatology, Cleveland Clinic, Cleveland, OH.
[Ti] Title:Combination of oral vitamin d3 with photodynamic therapy enhances tumor cell death in a murine model of cutaneous squamous cell carcinoma.
[So] Source:Photochem Photobiol;90(5):1126-35, 2014 Sep.
[Is] ISSN:1751-1097
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Photodynamic therapy (PDT), in which 5-ALA (a precursor for protoporphyrin IX, PpIX) is administered prior to exposure to light, is a nonscarring treatment for skin cancers. However, for deep tumors, ALA-PDT is not always effective due to inadequate production of PpIX. We previously developed and reported a combination approach in which the active form of vitamin D3 (calcitriol) is given systemically prior to PDT to improve PpIX accumulation and to enhance PDT-induced tumor cell death; calcitriol, however, poses a risk of hypercalcemia. Here, we tested a possible strategy to circumvent the problem of hypercalcemia by substituting natural dietary vitamin D3 (cholecalciferol; D3 ) for calcitriol. Oral D3 supplementation (10days of a 10-fold elevated D3 diet) enhanced PpIX levels 3- to 4-fold, and PDT-mediated cell death 20-fold, in subcutaneous A431 tumors. PpIX levels and cell viability in normal tissues were not affected. Hydroxylated metabolic forms of D3 were only modestly elevated in serum, indicating minimal hypercalcemic risk. These results show that brief oral administration of cholecalciferol can serve as a safe neoadjuvant to ALA-PDT. We suggest a clinical study, using oral vitamin D3 prior to PDT, should be considered to evaluate this promising new approach to treating human skin cancer.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/php.12286

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[PMID]: 24773136
[Au] Autor:Kwon TR; Mun SK; Oh CT; Hong H; Choi YS; Kim BJ; Kim BJ
[Ad] Address:Department of Medicine, Graduate School, Chung-Ang University, Seoul, Korea; Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea.
[Ti] Title:Therapeutic Effects of Full Spectrum Light on the Development of Atopic Dermatitis-like Lesions in NC/Nga Mice.
[So] Source:Photochem Photobiol;90(5):1160-9, 2014 Sep.
[Is] ISSN:1751-1097
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Full spectrum light (FSL) includes UVA, visible light and infrared light. Many studies have investigated the application of FSL in severe cases of atopic dermatitis (AD) in humans; however, FSL has not yet been studied in an animal model. The purpose of this study was to evaluate the therapeutic effects of FSL on AD-like skin lesions using NC/Nga mice, with the aim of mitigating itching and attenuating the expression of adhesion molecules. We examined the effects of FSL on mite allergen-treated NC/Nga mice by assessing skin symptom severity, ear thickness, serum IgE levels, and the cytokine expression. We examined the histology of lesions using hematoxylin-eosin, toluidine blue and immunohistochemical staining. Our findings suggest that FSL phototherapy exerts positive therapeutic effects on Dermatophagoides farinae (Df)-induced AD-like skin lesions in NC/Nga mice by reducing IgE levels, thus promoting recovery of the skin barrier. The mechanisms by which FSL phototherapy exerts its effects may also involve the inhibition of scratching behavior, reduction of IL-6 levels and reductions in adhesion molecule expression. The present study indicates that FSL phototherapy inhibits the development of AD in NC/Nga mice by suppressing cytokine, chemokine and adhesion molecule expression, and thus, could potentially be useful in treating AD.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/php.12284

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[PMID]: 24749661
[Au] Autor:Bodekaer Larsen M; Petersen B; Philipsen PA; Young A; Thieden E; Wulf HC
[Ad] Address:Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.
[Ti] Title:Sun exposure and Protection Behavior of Danish Farm Children: Parental Influence on Their Children.
[So] Source:Photochem Photobiol;90(5):1193-8, 2014 Sep.
[Is] ISSN:1751-1097
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Healthy sun habits acquired in childhood could reduce skin cancer incidence. We examined the sun exposure and protection behavior of an expected high-exposure group of children, and the association to their parents. Open, prospective cohort study. One hundred and thirty nine participants (40 families) kept daily sun behavior diaries (sun exposure, sunscreen use, sunburns) over a 4-month summer period (15985 diary days). The Pigment Protection Factor (PPF), an objective measure of sun exposure, was measured at two body sites, before and after summer. All participants presented data from the same 115days. Risk behavior (sun exposure of upper body) took place on 9.5days (boys) and 15.6days (girls). Sunburn and sunscreen use were infrequent. Boys' sun exposure resulted in an increased photo protection over the study period of 1.7SED (upper arm) and 0.8SED (shoulder) to elicit erythema. Corresponding values for girls were as follows: 0.9SED (upper arm) and 0.5SED (shoulder). Boys' sunscreen use correlated to their mothers' (r=0.523, P=0.02). Girls' number of risk days (r=0.552, P=0.005) and sun exposure (upper arm: r=0.621, P<0.001) correlated to their mothers'. The children's sun exposure was substantial. Only mothers influenced children's sun behavior and exposure. This may be of relevance in future sun protection campaigns.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1111/php.12280

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[PMID]: 24942999
[Au] Autor:Sun J; Dou W; Shen H; Hu J
[Ad] Address:Department of Pharmacy, General Hospital of Jinan Military Region, Jinan, PR China.
[Ti] Title:A Comparison of the Effects of Nifedipine, Verapamil, and Low-Molecular-Weight Heparin on SLIGRL-NH2-Induced Calcium Influx through Proteinase-Activated Receptor 2 Activation.
[So] Source:Pharmacology;93(5-6):216-9, 2014.
[Is] ISSN:1423-0313
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:BACKGROUND: Proteinase-activated receptor 2 (PAR2) may be implicated in skin disorders. Intracellular calcium mobilization is a key step in PAR2-induced signaling. AIMS: In this study, we investigated the effects of nifedipine, verapamil, and low-molecular-weight heparin (LMWH) on SLIGRL-NH2-induced PAR2-mediated calcium mobilization within cells. METHODS: The intracellular calcium concentration was measured with fluo-8, a fluorescence indicator for free Ca(2+). RESULTS: Our results showed that SLIGRL-NH2 induced a dose-dependent calcium influx. This calcium influx was completely blocked in HaCaT cells and significantly blocked by LMWH in HEK293/PAR2 cells. However, both nifedipine and verapamil failed to inhibit the SLIGRL-NH2-induced calcium influx in either cell line. CONCLUSION: These results indicate that the PAR2 activation-induced calcium mobilization was mediated by intracellular calcium stores but not by extracellular calcium present in the media. 2014 S. Karger AG, Basel.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1159/000362283

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[PMID]: 24931568
[Au] Autor:Grne E; Ueyler N; Abahji T; Fleckenstein J; Irnich D; Mussack T; Hoffmann U; Sommer C; Lang PM
[Ad] Address:Department of Anaesthesiology, University Hospital of Munich, Munich, Germany....
[Ti] Title:Reduced intraepidermal nerve fiber density in patients with chronic ischemic pain in peripheral arterial disease.
[So] Source:Pain;155(9):1784-92, 2014 Sep.
[Is] ISSN:1872-6623
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Chronic ischemic pain in peripheral arterial disease (PAD) is a leading cause of pain in the lower extremities. A neuropathic component of chronic ischemic pain has been shown independent of coexisting diabetes. We aimed to identify a morphological correlate potentially associated with pain and sensory deficits in PAD. Forty patients with symptomatic PAD (Fontaine stages II-IV), 20 with intermittent claudication (CI), and 20 with critical limb ischemia (CLI) were enrolled; 12 volunteers served as healthy controls. All patients were examined using pain scales and questionnaires. All study participants underwent quantitative sensory testing (QST) at the distal calf and skin punch biopsy at the distal leg for determination of intraepidermal nerve fiber density (IENFD). Additionally, S100beta serum levels were measured as a potential marker for ischemic nerve damage. Neuropathic pain questionnaires revealed slightly higher scores and more pronounced pain-induced disability in CLI patients compared to CI patients. QST showed elevated thermal and mechanical detection pain thresholds as well as dynamic mechanical allodynia, particularly in patients with advanced disease. IENFD was reduced in PAD compared to controls (P<0.05), more pronounced in the CLI subgroup (CLI: 1.30.5fibers/mm, CI: 2.90.5fibers/mm, controls: 5.30.6fibers/mm). In particular, increased mechanical and heat pain thresholds negatively correlated with lower IENFD. Mean S100beta levels were in the normal range but were higher in advanced disease. Patients with chronic ischemic pain had a reduced IENFD associated with impaired sensory functions. These findings support the concept of a neuropathic component in ischemic pain.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review

  10 / 595155 MEDLINE  
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[PMID]: 24820863
[Au] Autor:Devigili G; Eleopra R; Pierro T; Lombardi R; Rinaldo S; Lettieri C; Faber CG; Merkies IS; Waxman SG; Lauria G
[Ad] Address:Neurological Unit, University-Hospital "S. Maria della Misericordia", Udine, Italy....
[Ti] Title:Paroxysmal itch caused by gain-of-function Nav1.7 mutation.
[So] Source:Pain;155(9):1702-7, 2014 Sep.
[Is] ISSN:1872-6623
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Itch is a common experience. It can occur in the course of systemic diseases and can be a manifestation of allergies or a consequence of diseases affecting the somatosensory pathway. We describe a kindred characterized by paroxysmal itch caused by a variant in SCN9A gene encoding for the Nav1.7 sodium channel. Patients underwent clinical and somatosensory profile assessment by quantitative sensory testing, nerve conduction study, autonomic cardiovascular reflex, and sympathetic skin response examination, skin biopsy with quantification of intraepidermal nerve fiber density, and SCN9A mutational analysis. The index patient, her mother, and a sister presented with a stereotypical clinical picture characterized by paroxysmal itch attacks involving the shoulders, upper back, and upper limbs, followed by transient burning pain, and triggered by environmental warmth, hot drinks, and spicy food. Somatosensory profile assessment demonstrated a remarkably identical pattern of increased cold and pain thresholds and paradoxical heat sensation. Autonomic tests were negative, whereas skin biopsy revealed decreased intraepidermal nerve fiber density in 2 of the 3 patients. All affected members harbored the 2215A>G I739V substitution in exon 13 of SCN9A gene. Pregabalin treatment reduced itch intensity and attack frequency in all patients. The co-segregation of the I739V variant in the affected members of the family provides evidence, for the first time, that paroxysmal itch can be related to a mutation in sodium channel gene.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:IM
[St] Status:In-Data-Review


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