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Sample records for barrier homeostasis dermal

  1. Epidermal Vascular Endothelial Growth Factor Production Is Required for Permeability Barrier Homeostasis, Dermal Angiogenesis, and the Development of Epidermal Hyperplasia

    Science.gov (United States)

    Elias, Peter M.; Arbiser, Jack; Brown, Barbara E.; Rossiter, Heidemarie; Man, Mao-Qiang; Cerimele, Francesca; Crumrine, Debra; Gunathilake, Roshan; Choi, Eung Ho; Uchida, Yoshikazu; Tschachler, Erwin; Feingold, Kenneth R.

    2008-01-01

    Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf−/− mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis. PMID:18688025

  2. Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: implications for the pathogenesis of psoriasis.

    Science.gov (United States)

    Elias, Peter M; Arbiser, Jack; Brown, Barbara E; Rossiter, Heidemarie; Man, Mao-Qiang; Cerimele, Francesca; Crumrine, Debra; Gunathilake, Roshan; Choi, Eung Ho; Uchida, Yoshikazu; Tschachler, Erwin; Feingold, Kenneth R

    2008-09-01

    Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf(-/-) mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis.

  3. Stratum corneum barrier integrity controls skin homeostasis.

    Science.gov (United States)

    Smith, W

    1999-04-01

    The stratum corneum water barrier controls structural and functional properties of both the epidermis and the dermis. Treatments which chronically disrupt the stratum corneum water barrier can induce changes similar to those seen with 'anti-aging' treatments such as (-Hydroxy acids (AHAs) and Retin Atrade mark. Barrier disruption via daily tape stripping increases epidermal and dermal thickness, superficial and integral skin firmness, and improves skin surface texture. Modest or transitory disruption did not produce such effects. Similar results were observed with topical application of AHAs, retinoids or mild irritants after about 4-6 weeks provided such treatments resulted in prolonged elevation in TEWL (trans-epidermal water loss). Treatments that did not chronically elevate TEWL could also produce positive cosmetic effects, but such effects were in general restricted to the skin surface or epidermis. Irritation, which was observed with some treatments, was not solely responsible for the positive effects observed.

  4. Intestinal barrier homeostasis in inflammatory bowel disease.

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    Goll, Rasmus; van Beelen Granlund, Atle

    2015-01-01

    The single-cell thick intestinal epithelial cell (IEC) lining with its protective layer of mucus is the primary barrier protecting the organism from the harsh environment of the intestinal lumen. Today it is clear that the balancing act necessary to maintain intestinal homeostasis is dependent on the coordinated action of all cell types of the IEC, and that there are no passive bystanders to gut immunity solely acting as absorptive or regenerative cells: Mucin and antimicrobial peptides on the epithelial surface are continually being replenished by goblet and Paneth's cells. Luminal antigens are being sensed by pattern recognition receptors on the enterocytes. The enteroendocrine cells sense the environment and coordinate the intestinal function by releasing neuropeptides acting both on IEC and inflammatory cells. All this while cells are continuously and rapidly being regenerated from a limited number of stem cells close to the intestinal crypt base. This review seeks to describe the cell types and structures of the intestinal epithelial barrier supporting intestinal homeostasis, and how disturbance in these systems might relate to inflammatory bowel disease.

  5. Improved epidermal barrier formation in human skin models by chitosan modulated dermal matrices

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    Mieremet, Arnout; Rietveld, Marion; Absalah, Samira; van Smeden, Jeroen

    2017-01-01

    Full thickness human skin models (FTMs) contain an epidermal and a dermal equivalent. The latter is composed of a collagen dermal matrix which harbours fibroblasts. Current epidermal barrier properties of FTMs do not fully resemble that of native human skin (NHS), which makes these human skin models less suitable for barrier related studies. To further enhance the resemblance of NHS for epidermal morphogenesis and barrier formation, we modulated the collagen dermal matrix with the biocompatible polymer chitosan. Herein, we report that these collagen-chitosan FTMs (CC-FTMs) possess a well-organized epidermis and maintain both the early and late differentiation programs as in FTMs. Distinctively, the epidermal cell activation is reduced in CC-FTMs to levels observed in NHS. Dermal-epidermal interactions are functional in both FTM types, based on the formation of the basement membrane. Evaluation of the barrier structure by the organization of the extracellular lipid matrix of the stratum corneum revealed an elongated repeat distance of the long periodicity phase. The ceramide composition exhibited a higher resemblance of the NHS, based on the carbon chain-length distribution and subclass profile. The inside-out barrier functionality indicated by the transepidermal water loss is significantly improved in the CC-FTMs. The expression of epidermal barrier lipid processing enzymes is marginally affected, although more restricted to a single granular layer. The novel CC-FTM resembles the NHS more closely, which makes them a promising tool for epidermal barrier related studies. PMID:28333992

  6. Homeostasis

    Directory of Open Access Journals (Sweden)

    Anna Negroni

    2015-01-01

    Full Text Available Intestinal epithelial cells (IECs form a physiochemical barrier that separates the intestinal lumen from the host’s internal milieu and is critical for electrolyte passage, nutrient absorption, and interaction with commensal microbiota. Moreover, IECs are strongly involved in the intestinal mucosal inflammatory response as well as in mucosal innate and adaptive immune responses. Cell death in the intestinal barrier is finely controlled, since alterations may lead to severe disorders, including inflammatory diseases. The emerging picture indicates that intestinal epithelial cell death is strictly related to the maintenance of tissue homeostasis. This review is focused on previous reports on different forms of cell death in intestinal epithelium.

  7. Dual-dermal-barrier fashion flaps for the treatment of sacral pressure sores.

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    Hsiao, Yen-Chang; Chuang, Shiow-Shuh

    2015-02-01

    The sacral region is one of the most vulnerable sites for the development of pressure sores. Even when surgical reconstruction is performed, there is a high chance of recurrence. Therefore, the concept of dual-dermal-barrier fashion flaps for sacral pressure sore reconstruction was proposed. From September 2007 to June 2010, nine patients with grade IV sacral pressures were enrolled. Four patients received bilateral myocutaneous V-Y flaps, four patients received bilateral fasciocutaneous V-Y flaps, and one patient received bilateral rotation-advanced flaps for sacral pressure reconstruction. The flaps were designed based on the perforators of the superior gluteal artery in one patient's reconstructive procedure. All flaps' designs were based on dual-dermal-barrier fashion. The mean follow-up time was 16 months (range = 12-25). No recurrence was noted. Only one patient had a complication of mild dehiscence at the middle suture line, occurring 2 weeks after the reconstructive surgery. The dual-dermal fashion flaps are easily duplicated and versatile. The study has shown minimal morbidity and a reasonable outcome.

  8. The effects of heat on skin barrier function and in vivo dermal absorption.

    Science.gov (United States)

    Oliveira, Gabriela; Leverett, Jesse C; Emamzadeh, Mandana; Lane, Majella E

    2014-04-10

    Enhanced delivery of ingredients across the stratum corneum (SC) is of great interest for improving the efficacy of topically applied formulations. Various methods for improving dermal penetration have been reported including galvanic devices and micro-needles. From a safety perspective it is important that such approaches do not compromise SC barrier function. This study investigates the influence of topically applied heat in vivo on the dermal uptake and penetration of a model active, allantoin from gel and lotion formulations. A custom designed device was used to deliver 42°C for 30s daily to human subjects after application of two formulations containing allantoin. The results were compared with sites treated with formulations containing no active and no heat, and a control site. In addition to penetration of allantoin, the integrity of the SC was monitored using trans-epidermal water loss (TEWL) measurements. The results showed that just 30s of 42°C topically applied heat was enough to cause significantly more penetration of allantoin from the lotion formulation compared with no application of heat. TEWL data indicated that the integrity of the skin was not compromised by the treatment. However, the application of heat did not promote enhanced penetration of the active from the gel formulation. Vehicle composition is therefore an important factor when considering thermal enhancement strategies for targeting actives to the skin.

  9. Homeostasis of the gut barrier and potential biomarkers

    NARCIS (Netherlands)

    Wells, Jerry M.; Brummer, Robert J.; Derrien, Muriel; MacDonald, Thomas T.; Troost, Freddy; Cani, Patrice D.; Theodorou, Vassilia; Dekker, Jan; Méheust, Agnes; Vos, De Willem M.; Mercenier, Annick; Nauta, Arjen; Garcia-Rodenas, Clara L.

    2017-01-01

    The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier f

  10. Use of lanthanum to detect changes in the permeability barrier of rat skin after dermal exposure to organic chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Mattie, D.R.; McDougal, J.N.; Chase, M.R.; Hixson, C.J.

    1987-01-01

    Occupational dermal exposures to organic solvents are of importance due to local effects in the skin and systematic toxicity if penetration occurs through the skin. Repeated or prolonged contact with organic solvents have been shown to penetrate the skin; little information is available however, concerning effects on the barrier properties of skin after dermal exposure to solvents. This investigation examines the ultrastructural changes in rat skin after exposure of 3 organic chemicals and to correlate changes with the location of an electron-dense tracer, lanthanum, which is normally excluded by the permeability barrier in the stratum corneum. Male rats were exposed for 24 h to sterile saline, trichloroethylene (TCE), perchloroethylene (PERC), or toluene using dermal-exposure cells developed in this laboratory. Rat skin exposed to saline for 24 h appeared normal. Rat skin exposed to neat TCE, PERC or toluene for 24 h caused acute, coagulative necrosis of the epidermis and upper 1/2 to 1/3 of the dermis.

  11. Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis

    NARCIS (Netherlands)

    Chen, Kang; Chen, Hao; Faas, Marijke M; de Haan, Bart J; Li, Jiahong; Xiao, Ping; Zhang, Hao; Diana, Julien; de Vos, Paul; Sun, Jia

    2017-01-01

    Scope: Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on

  12. Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis

    NARCIS (Netherlands)

    Chen, Kang; Chen, Hao; Faas, Marijke M; de Haan, Bart J; Li, Jiahong; Xiao, Ping; Zhang, Hao; Diana, Julien; de Vos, Paul; Sun, Jia

    Scope: Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on

  13. Acute treatment with kerosene damages the dermal barrier and alters the distribution of topically applied benzo(a)pyrene in mice.

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    LaDow, Kathy; Schumann, Brenda L; Luse, Nicole; Warshawsky, Dave; Pickens, William L; Hoath, Steven B; Talaska, Glenn

    2011-12-01

    The dermal route is important in many occupational exposures. Some materials may reduce the barrier function of the skin to enhance absorption and effect on internal organs. We have reported previously that kerosene cleaning following treatment with used engine oil increased DNA adduct levels in the lungs of mice compared with animals treated with used oil alone. To investigate what other physiological parameters might be affected by kerosene, we conducted in vitro and in vivo measurements of skin barrier function. We also topically applied (3)H-BAP(100 nM in 25 μL acetone) and washed half the mice with 25 μL kerosene 1 hr after carcinogen application. Groups of four mice were euthanized from 1 to 72 hr after treatment. Skin, lungs, and livers were harvested from each animal and stored separately. Kerosene application reduced the barrier function of the skin in vitro beyond the effect of the acetone vehicle and the vehicle plus BAP. In vivo studies indicated that kerosene treatment reduced the barrier function at 4 and 8 hr post application and that the barrier function recovered at 24 hr after a single treatment. The fraction of the radiolabel remaining in the skin of animals treated with (3)H-BAP and washed with kerosene was significantly less than those not washed, beginning at 24 hr (pKerosene treatment compromises dermal barrier function and the ability of the skin to retain water, enhances carcinogen absorption, and alters organ distribution. This appears to contribute to the increase in BAP DNA adducts we reported earlier.

  14. Superficial dermal fibroblasts enhance basement membrane and epidermal barrier formation in tissue-engineered skin: implications for treatment of skin basement membrane disorders.

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    Varkey, Mathew; Ding, Jie; Tredget, Edward E

    2014-02-01

    Basement membrane is a highly specialized structure that binds the dermis and the epidermis of the skin, and is mainly composed of laminins, nidogen, collagen types IV and VII, and the proteoglycans, collagen type XVIII and perlecan, all of which play critical roles in the function and resilience of skin. Both dermal fibroblasts and epidermal keratinocytes contribute to the development of the basement membrane, and in turn the basement membrane and underlying dermis influence the development and function of the epidermal barrier. Disruption of the basement membrane results in skin fragility, extensive painful blistering, and severe recurring wounds as seen in skin basement membrane disorders such as epidermolysis bullosa, a family of life-threatening congenital skin disorders. Currently, there are no successful strategies for treatment of these disorders; we propose the use of tissue-engineered skin as a promising approach for effective wound coverage and to enhance healing. Fibroblasts and keratinocytes isolated from superficial and deep dermis and epidermis, respectively, of tissue from abdominoplasty patients were independently cocultured on collagen-glycosaminoglycan matrices, and the resulting tissue-engineered skin was assessed for functional differences based on the underlying specific dermal fibroblast subpopulation. Tissue-engineered skin with superficial fibroblasts and keratinocytes formed a continuous epidermis with increased epidermal barrier function and expressed higher levels of epidermal proteins, keratin-5, and E-cadherin, compared to that with deep fibroblasts and keratinocytes, which had an intermittent epidermis. Further, tissue-engineered skin with superficial fibroblasts and keratinocytes formed better basement membrane, and produced more laminin-5, nidogen, collagen type VII, compared to that with deep fibroblasts and keratinocytes. Overall, our results demonstrate that tissue-engineered skin with superficial fibroblasts and keratinocytes

  15. Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

    Energy Technology Data Exchange (ETDEWEB)

    J Torin Huzil; S Sivaloganathan; M Kohandel; M Foldvari

    2011-12-31

    The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein and nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.

  16. Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway.

    Directory of Open Access Journals (Sweden)

    Shuichi Segawa

    Full Text Available Probiotics exhibit beneficial effects on human health, particularly in the maintenance of intestinal homeostasis in a complex manner notwithstanding the diversity of an intestinal flora between individuals. Thus, it is highly probable that some common molecules secreted by probiotic and/or commensal bacteria contribute to the maintenance of intestinal homeostasis and protect the intestinal epithelium from injurious stimuli. To address this question, we aimed to isolate the cytoprotective compound from a lactobacillus strain, Lactobacillus brevis SBC8803 which possess the ability to induce cytoprotective heat shock proteins in mouse small intestine. L. brevis was incubated in MRS broth and the supernatant was passed through with a 0.2-µm filter. Caco2/bbe cells were treated with the culture supernatant, and HSP27 expression was evaluated by Western blotting. HSP27-inducible components were separated by ammonium sulfate precipitation, DEAE anion exchange chromatography, gel filtration, and HPLC. Finally, we identified that the HSP27-inducible fraction was polyphosphate (poly P, a simple repeated structure of phosphates, which is a common product of lactobacilli and other bacteria associated with intestinal microflora without any definitive physiological functions. Then, poly P was synthesized by poly P-synthesizing enzyme polyphosphate kinase. The synthesized poly P significantly induced HSP27 from Caco2/BBE cells. In addition, Poly P suppressed the oxidant-induced intestinal permeability in the mouse small intestine and pharmacological inhibitors of p38 MAPK and integrins counteract its protective effect. Daily intrarectal administration of poly P (10 µg improved the inflammation grade and survival rate in 4% sodium dextran sulfate-administered mice. This study, for the first time, demonstrated that poly P is the molecule responsible for maintaining intestinal barrier actions which are mediated through the intestinal integrin β1-p38 MAPK.

  17. Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers

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    Jessica L Williams

    2014-05-01

    Full Text Available In the adult central nervous system (CNS, chemokines and their receptors are involved in developmental, physiological and pathological processes. Although most lines of investigation focus on their ability to induce the migration of cells, recent studies indicate that chemokines also promote cellular interactions and activate signaling pathways that maintain CNS homeostatic functions. Many homeostatic chemokines are expressed on the vasculature of the blood brain barrier including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell expression of these chemokines is known to regulate the entry of leukocytes into the CNS during immunosurveillance, new data indicate that CXCL12 is also involved in diverse cellular activities including adult neurogenesis and neuronal survival, having an opposing role to the homeostatic chemokine, CXCL14, which appears to regulate synaptic inputs to neural precursors. Neuronal expression of CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12 is unique in that it may regulate its own expression levels via binding to its scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of these and other homeostatic chemokines expressed within the CNS, including the possible implications of their dysfunction as a cause of neurologic disease.

  18. Effects of a disrupted blood-brain barrier on cholesterol homeostasis in the brain.

    Science.gov (United States)

    Saeed, Ahmed A; Genové, Guillem; Li, Tian; Lütjohann, Dieter; Olin, Maria; Mast, Natalia; Pikuleva, Irina A; Crick, Peter; Wang, Yuqin; Griffiths, William; Betsholtz, Christer; Björkhem, Ingemar

    2014-08-22

    The presence of the blood-brain barrier (BBB) is critical for cholesterol metabolism in the brain, preventing uptake of lipoprotein-bound cholesterol from the circulation. The metabolic consequences of a leaking BBB for cholesterol metabolism have not been studied previously. Here we used a pericyte-deficient mouse model, Pdgfb(ret/ret), shown to have increased permeability of the BBB to a range of low-molecular mass and high-molecular mass tracers. There was a significant accumulation of plant sterols in the brains of the Pdgfb(ret/ret) mice. By dietary treatment with 0.3% deuterium-labeled cholesterol, we could demonstrate a significant flux of cholesterol from the circulation into the brains of the mutant mice roughly corresponding to about half of the measured turnover of cholesterol in the brain. We expected the cholesterol flux into the brain to cause a down-regulation of cholesterol synthesis. Instead, cholesterol synthesis was increased by about 60%. The levels of 24(S)-hydroxycholesterol (24S-OHC) were significantly reduced in the brains of the pericyte-deficient mice but increased in the circulation. After treatment with 1% cholesterol in diet, the difference in cholesterol synthesis between mutants and controls disappeared. The findings are consistent with increased leakage of 24S-OHC from the brain into the circulation in the pericyte-deficient mice. This oxysterol is an efficient suppressor of cholesterol synthesis, and the results are consistent with a regulatory role of 24S-OHC in the brain. To our knowledge, this is the first demonstration that a defective BBB may lead to increased flux of a lipophilic compound out from the brain. The relevance of the findings for the human situation is discussed.

  19. Dermal administration of manganese porphyrin by iontophoresis.

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    Ito, Fuminori; Imamura, Shinya; Asayama, Shoichiro; Kanamura, Kiyoshi; Kawakami, Hiroyoshi

    2014-08-01

    The present study describes a technique for dermal administration of cationic manganese porphyrin (Mn-porphyrin), an antioxidant with superoxide dismutase (SOD) activity, in hairless mouse. In general, the stratum corneum on the surface of the skin represents a barrier to passive diffusion of therapeutic agents by standard dermal administration. The present study investigated whether, dermal administration of Mn-porphyrin solution using iontophoresis, the electrical dermal administration technique, could overcome this barrier. We visually confirmed that Mn-porphyrin had penetrated to the reverse side of the hairless mouse skin after iontophoresis for a short period. With prolonged iontophoresis, the ratio of detectable Mn-porphyrin solution on the reverse side of the hairless mouse skin increased. In the future, this technique could provide an innovative approach for delivery of this antioxidant in intractable disease.

  20. Superficial Dermal Fibroblasts Enhance Basement Membrane and Epidermal Barrier Formation in Tissue-Engineered Skin: Implications for Treatment of Skin Basement Membrane Disorders

    OpenAIRE

    2013-01-01

    Basement membrane is a highly specialized structure that binds the dermis and the epidermis of the skin, and is mainly composed of laminins, nidogen, collagen types IV and VII, and the proteoglycans, collagen type XVIII and perlecan, all of which play critical roles in the function and resilience of skin. Both dermal fibroblasts and epidermal keratinocytes contribute to the development of the basement membrane, and in turn the basement membrane and underlying dermis influence the development ...

  1. TGF-beta is required for vascular barrier function, endothelial survival and homeostasis of the adult microvasculature.

    Directory of Open Access Journals (Sweden)

    Tony E Walshe

    Full Text Available Pericyte-endothelial cell (EC interactions are critical to both vascular development and vessel stability. We have previously shown that TGF-beta signaling between EC and mural cells participates in vessel stabilization in vitro. We therefore investigated the role of TGF-beta signaling in maintaining microvessel structure and function in the adult mouse retinal microvasculature. TGF-beta signaling was inhibited by systemic expression of soluble endoglin (sEng and inhibition was demonstrated by reduced phospho-smad2 in the adult retina. Blockade of TGF-beta signaling led to increased vascular and neural cell apoptosis in the retina, which was associated with decreased retinal function, as measured by electroretinogram (ERG. Perfusion of the inner retinal vasculature was impaired and was accompanied by defective autoregulation and loss of capillary integrity. Fundus angiography and Evans blue permeability assay revealed a breakdown of the blood-retinal-barrier that was characterized by decreased association between the tight junction proteins zo-1 and occludin. Inhibition of TGF-beta signaling in cocultures of EC and 10T1/2 cells corroborated the in vivo findings, with impaired EC barrier function, dissociation of EC from 10T1/2 cells, and endothelial cell death, supporting the role of EC-mesenchymal interactions in TGF-beta signaling. These results implicate constitutive TGF-beta signaling in maintaining the integrity and function of the adult microvasculature and shed light on the potential role of TGF-beta signaling in vasoproliferative and vascular degenerative retinal diseases.

  2. Complications of Dermal Filling

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    Sajad Ahmad Salati

    2011-11-01

    Full Text Available Dermal fillers have globally become sought after drugs due to the desire of aging population to regain the youthful looks without any surgical operations. But like other procedures, dermal filling can become complicated. Besides the profitability have introduced the factor of malpractice which can bring in misery rather than beauty and youthful body contours. This article briefly reviews the common adverse effects of dermal fillers.

  3. pH homeostasis during coral calcification in a free ocean CO2 enrichment (FOCE) experiment, Heron Island reef flat, Great Barrier Reef.

    Science.gov (United States)

    Georgiou, Lucy; Falter, James; Trotter, Julie; Kline, David I; Holcomb, Michael; Dove, Sophie G; Hoegh-Guldberg, Ove; McCulloch, Malcolm

    2015-10-27

    Geochemical analyses (δ(11)B and Sr/Ca) are reported for the coral Porites cylindrica grown within a free ocean carbon enrichment (FOCE) experiment, conducted on the Heron Island reef flat (Great Barrier Reef) for a 6-mo period from June to early December 2010. The FOCE experiment was designed to simulate the effects of CO2-driven acidification predicted to occur by the end of this century (scenario RCP4.5) while simultaneously maintaining the exposure of corals to natural variations in their environment under in situ conditions. Analyses of skeletal growth (measured from extension rates and skeletal density) showed no systematic differences between low-pH FOCE treatments (ΔpH = ∼-0.05 to -0.25 units below ambient) and present day controls (ΔpH = 0) for calcification rates or the pH of the calcifying fluid (pHcf); the latter was derived from boron isotopic compositions (δ(11)B) of the coral skeleton. Furthermore, individual nubbins exhibited near constant δ(11)B compositions along their primary apical growth axes (±0.02 pHcf units) regardless of the season or treatment. Thus, under the highly dynamic conditions of the Heron Island reef flat, P. cylindrica up-regulated the pH of its calcifying fluid (pHcf ∼8.4-8.6), with each nubbin having near-constant pHcf values independent of the large natural seasonal fluctuations of the reef flat waters (pH ∼7.7 to ∼8.3) or the superimposed FOCE treatments. This newly discovered phenomenon of pH homeostasis during calcification indicates that coral living in highly dynamic environments exert strong physiological controls on the carbonate chemistry of their calcifying fluid, implying a high degree of resilience to ocean acidification within the investigated ranges.

  4. Dermal toxicity elicited by phthalates: evaluation of skin absorption, immunohistology, and functional proteomics.

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    Pan, Tai-Long; Wang, Pei-Wen; Aljuffali, Ibrahim A; Hung, Yi-Yun; Lin, Chwan-Fwu; Fang, Jia-You

    2014-03-01

    The toxicity of phthalates is an important concern in the fields of environmental health and toxicology. Dermal exposure via skin care products, soil, and dust is a main route for phthalate delivery. We had explored the effect of topically-applied phthalates on skin absorption and toxicity. Immunohistology, functional proteomics, and Western blotting were employed as methodologies for validating phthalate toxicity. Among 5 phthalates tested, di(2-ethylhexyl)phthalate (DEHP) showed the highest skin reservoir. Only diethyl phthalate (DEP) and dibutyl phthalate (DBP) could penetrate across skin. Strat-M(®) membrane could be used as permeation barrier for predicting phthalate penetration through skin. The accumulation of DEHP in hair follicles was ∼15nmol/cm(2), which was significantly greater than DBP and DEP. DBP induced apoptosis of keratinocytes and fibroblasts via caspase-3 activation. This result was confirmed by downregulation of 14-3-3 and immunohistology of TUNEL. On the other hand, the HSP60 overexpression and immunostaining of COX-2 suggested inflammatory response induced by DEP and DEHP. The proteomic profiling verified the role of calcium homeostasis on skin inflammation. Some proteins investigated in this study can be sensitive biomarkers for dermal toxicity of phthalates. These included HSPs, 14-3-3, and cytokeratin. This work provided novel platforms for examining phthalate toxicity on skin.

  5. Genetics Home Reference: focal dermal hypoplasia

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    ... Home Health Conditions focal dermal hypoplasia focal dermal hypoplasia Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Focal dermal hypoplasia is a genetic disorder that primarily affects the ...

  6. Review of dermal effects and uptake of petroleum hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Kezic, S.; Kruse, J. [Coronel Institute of Occupational Health, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Jakasa, I. [University of Zagreb, Zagreb (Croatia)

    2010-12-15

    This report serves as an update to and an extension of a previous CONCAWE report on dermal absorption of petroleum hydrocarbons (Petroleum hydrocarbons: their absorption through and effects on the skin, CONCAWE Report 84/54, 1984). To contribute to health risk assessments associated with dermal exposure, this report evaluates experimental data to determine the extent to which petroleum hydrocarbons pass through the skin. These data strongly suggest that dermal exposure to petroleum hydrocarbons, even following long-term exposures such as in occupational settings, will not cause systemic toxicity under normal working conditions and assuming an intact skin barrier. Skin contact with some petroleum products may cause skin irritation, leading to dermatitis, particularly after repeated or prolonged exposure. In addition to these irritating effects, the skin barrier function may be affected following repeated contact with petroleum hydrocarbons, making the skin potentially more susceptible to other irritants, sensitizing agents, and bacteria. In addition, the impaired skin barrier may lead to increased dermal penetration of hydrocarbons and other substances. To avoid this there is a need to minimise skin contact.

  7. Dermal route in systemic exposure

    NARCIS (Netherlands)

    Benford, D.J.; Cocker, J.; Sartorelli, P.; Schneider, T.; Hemmen, J. van; Firth, J.G.

    1999-01-01

    To evaluate risk from dermal exposure, the amount of material on the skin must first be measured. The potential for dermal uptake must then be assessed for the potential health effects from systemic exposure. No standard methods exist for studying these processes, and published data are not comparab

  8. Guided bone regeneration with acellular dermal matrix as a barrier for bone defects%脱细胞真皮基质膜引导骨缺损成骨变化

    Institute of Scientific and Technical Information of China (English)

    贾仁杰; 任玉卿; 徐昊; 王维英; 弋中萍; 赵保东

    2016-01-01

    BACKGROUND:Acel ular dermal matrix has good biocompatibility and absorbability and exhibits superiority in the guided bone regeneration. OBJECTIVE:To compare the histological changes and osteogenic effects in bone defects after guided bone regeneration with acel ular dermal matrix and Bio-Gide membrane. METHODS:Mandibular second, third and fourth premolars and the first molars bilateral y were extracted from 12 beagle dogs. Three months later, four three-wal bone defect models in the mandible of each dog were made, and randomized into acel ular dermal matrix plus bone graft group (acel ular dermal matrix group), Bio-Gide plus bone graft group (Bio-Gide group), bone graft group, and blank control group (no treatment). In the former two groups, acel ular dermal matrix and Bio-Gide were used to cover the bone grafts, respectively. RESULTS AND CONCLUSION:After surgery, al the beagle dogs recovered wel . Al the groups except the control group showed dramatical improvement in histological changes and percentage of new bone area, and this improvement was more significant in the Bio-Gide and acel ular dermal matrix groups. Moreover, there was no significant difference between the Bio-Gide and acel ular dermal matrix groups. Therefore, the acel ular dermal matrix can be a candidate for bone repair instead of Bio-Gide membrane in the clinical practice.%背景:脱细胞真皮基质膜具有良好的生物相容性、可吸收性、引导骨再生性能。目的:比较脱细胞真皮基质膜和Bio-Gide膜引导骨缺损成骨的组织学变化及引导骨再生的效果的差异。  方法:12只比格犬拔除双侧下颌骨第二、三、四前磨牙及第一磨牙3个月后,在每只犬的下颌骨各建立4处标准的三壁骨缺损模型,随机分为脱细胞真皮基质膜联合骨修复材料组、Bio-Gide膜联合骨修复材料组、骨修复材料组、空白对照组。除空白对照组不做任何处理外,将骨修复材料充实于其余3组骨

  9. Generalized mid dermal elastolysis

    Directory of Open Access Journals (Sweden)

    Maria João Cruz

    2011-12-01

    Full Text Available Mid-dermal elastolysis (MDE is a rare skin disorder clinically characterized by the appearance of diffuse fine wrinkling, most often of the trunk and arms. This entity is distinguished from other elastolytic disorders by its characteristic selective loss of elastic fibers of the mid dermis. The aetiopathogenesis of the disease is still unclear as well as the effective treatment. Half of the cases described in the literature are associated with ultraviolet radiation exposure. Other reported triggering conditions such as urticaria, eczema and granuloma annulare suggests different eliciting inflammatory pathways. The authors describe the case of a 38-year-old woman who developed an urticarial eruption during months which progressed to generalized and severe fine wrinkling.

  10. Brain interstitial fluid glutamine homeostasis is controlled by blood-brain barrier SLC7A5/LAT1 amino acid transporter.

    Science.gov (United States)

    Dolgodilina, Elena; Imobersteg, Stefan; Laczko, Endre; Welt, Tobias; Verrey, Francois; Makrides, Victoria

    2016-11-01

    L-glutamine (Gln) is the most abundant amino acid in plasma and cerebrospinal fluid and a precursor for the main central nervous system excitatory (L-glutamate) and inhibitory (γ-aminobutyric acid (GABA)) neurotransmitters. Concentrations of Gln and 13 other brain interstitial fluid amino acids were measured in awake, freely moving mice by hippocampal microdialysis using an extrapolation to zero flow rate method. Interstitial fluid levels for all amino acids including Gln were ∼5-10 times lower than in cerebrospinal fluid. Although the large increase in plasma Gln by intraperitoneal (IP) injection of (15)N2-labeled Gln (hGln) did not increase total interstitial fluid Gln, low levels of hGln were detected in microdialysis samples. Competitive inhibition of system A (SLC38A1&2; SNAT1&2) or system L (SLC7A5&8; LAT1&2) transporters in brain by perfusion with α-(methylamino)-isobutyric acid (MeAIB) or 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) respectively, was tested. The data showed a significantly greater increase in interstitial fluid Gln upon BCH than MeAIB treatment. Furthermore, brain BCH perfusion also strongly increased the influx of hGln into interstitial fluid following IP injection consistent with transstimulation of LAT1-mediated transendothelial transport. Taken together, the data support the independent homeostatic regulation of amino acids in interstitial fluid vs. cerebrospinal fluid and the role of the blood-brain barrier expressed SLC7A5/LAT1 as a key interstitial fluid gatekeeper.

  11. Lipid nanoparticles for dermal drug delivery.

    Science.gov (United States)

    Kakadia, Pratibha G; Conway, Barbara R

    2015-01-01

    Lipid based drug delivery systems have been widely studied and reported over the past decade and offer a useful alternative to other colloidal drug delivery systems. Skin is a popular route of drug delivery for locally and systemically acting drugs and nanoparticles are reported as a potential formulation strategy for dermal delivery. Although the skin acts as a natural physical barrier against penetration of foreign materials, including particulates, opportunities exist for the delivery of therapeutic nanoparticles, especially in diseased and damaged skin and via appendageal routes such as the openings of hair follicles. The extent and ability of nanoparticles to penetrate into the underlying viable tissue is still the subject of debate although recent studies have identified the follicular route as the most likely route of entry; this influences the potential applications of these dosage forms as a drug delivery strategy. This paper reviews present state of art of lipid-based nanocarriers focussing on solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions, their production methods, potential advantages and applications in dermal drug delivery.

  12. Does microbiota composition affect thyroid homeostasis?

    Science.gov (United States)

    Virili, Camilla; Centanni, Marco

    2015-08-01

    The intestinal microbiota is essential for the host to ensure digestive and immunologic homeostasis. When microbiota homeostasis is impaired and dysbiosis occurs, the malfunction of epithelial barrier leads to intestinal and systemic disorders, chiefly immunologic and metabolic. The role of the intestinal tract is crucial in the metabolism of nutrients, drugs, and hormones, including exogenous and endogenous iodothyronines as well as micronutrients involved in thyroid homeostasis. However, the link between thyroid homeostasis and microbiota composition is not yet completely ascertained. A pathogenetic link with dysbiosis has been described in different autoimmune disorders but not yet fully elucidated in autoimmune thyroid disease which represents the most frequent of them. Anyway, it has been suggested that intestinal dysbiosis may trigger autoimmune thyroiditis. Furthermore, hypo- and hyper-thyroidism, often of autoimmune origin, were respectively associated to small intestinal bacterial overgrowth and to changes in microbiota composition. Whether some steps of this thyroid network may be affected by intestinal microbiota composition is briefly discussed below.

  13. Dermal uptake of petroleum substances.

    Science.gov (United States)

    Jakasa, Ivone; Kezic, Sanja; Boogaard, Peter J

    2015-06-01

    Petroleum products are complex substances comprising varying amounts of linear and branched alkanes, alkenes, cycloalkanes, and aromatics which may penetrate the skin at different rates. For proper interpretation of toxic hazard data, understanding their percutaneous absorption is of paramount importance. The extent and significance of dermal absorption of eight petroleum substances, representing different classes of hydrocarbons, was evaluated. Literature data on the steady-state flux and permeability coefficient of these substances were evaluated and compared to those predicted by mathematical models. Reported results spanned over 5-6 orders of magnitude and were largely dependent on experimental conditions in particular on the type of the vehicle used. In general, aromatic hydrocarbons showed higher dermal absorption than more lipophilic aliphatics with similar molecular weight. The results showed high variation and were largely influenced by experimental conditions emphasizing the need of performing the experiments under "in use" scenario. The predictive models overestimated experimental absorption. The overall conclusion is that, based on the observed percutaneous penetration data, dermal exposure to petroleum hydrocarbons, even of aromatics with highest dermal absorption is limited and highly unlikely to be associated with health risks under real use scenarios. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Enhanced dermal delivery of acyclovir using solid lipid nanoparticles.

    Science.gov (United States)

    Jain, Sanyog; Mistry, Meghal A; Swarnakar, Nitin K

    2011-10-01

    The present investigation was enthused by the possibility to develop solid lipid nanoparticles (SLNs) of hydrophilic drug acyclovir (ACV) and evaluate their potential as the carrier for dermal delivery. ACV-loaded SLNs (ACV-SLNs) were prepared by the optimized double emulsion process using Compritol 888 ATO as solid lipid. The prepared SLNs were smooth and spherical in shape with average diameter, polydispersity index, and entrapment efficiency of 262 ± 13 nm, 0.280 ± 0.01, and 40.08 ± 4.39% at 10% (w/w) theoretical drug loading with respect to Compritol 888 ATO content. Differential scanning calorimetry and powder X-ray diffraction pattern revealed that ACV was present in the amorphous state inside the SLNs. In vitro skin permeation studies on human cadaver and Sprague-Dawley rat skin revealed 17.65 and 15.17 times higher accumulation of ACV-SLNs in the dermal tissues in comparison to commercially available ACV cream after 24 h. Mechanism of topical permeation and dermal distribution was studied qualitatively using confocal laser scanning microscopy. While free dye (calcein) failed to penetrate skin barrier, the same encapsulated in SLNs penetrated deeply into the dermal tissue suggesting that pilosebaceous route was followed by SLNs for skin penetration. Histological examination and transdermal epidermal water loss measurement suggested that no major morphological changes occurred on rat skin surface due to the application of SLNs. Overall, it was concluded that ACV-loaded SLNs might be beneficial in improving dermal delivery of antiviral agent(s) for the treatment of topical herpes simplex infection.

  15. Brain iron homeostasis.

    Science.gov (United States)

    Moos, Torben

    2002-11-01

    Iron is essential for virtually all types of cells and organisms. The significance of the iron for brain function is reflected by the presence of receptors for transferrin on brain capillary endothelial cells. The transport of iron into the brain from the circulation is regulated so that the extraction of iron by brain capillary endothelial cells is low in iron-replete conditions and the reverse when the iron need of the brain is high as in conditions with iron deficiency and during development of the brain. Whereas there is good agreement that iron is taken up by means of receptor-mediated uptake of iron-transferrin at the brain barriers, there are contradictory views on how iron is transported further on from the brain barriers and into the brain extracellular space. The prevailing hypothesis for transport of iron across the BBB suggests a mechanism that involves detachment of iron from transferrin within barrier cells followed by recycling of apo-transferrin to blood plasma and release of iron as non-transferrin-bound iron into the brain interstitium from where the iron is taken up by neurons and glial cells. Another hypothesis claims that iron-transferrin is transported into the brain by means of transcytosis through the BBB. This thesis deals with the topic "brain iron homeostasis" defined as the attempts to maintain constant concentrations of iron in the brain internal environment via regulation of iron transport through brain barriers, cellular iron uptake by neurons and glia, and export of iron from brain to blood. The first part deals with transport of iron-transferrin complexes from blood to brain either by transport across the brain barriers or by uptake and retrograde axonal transport in motor neurons projecting beyond the blood-brain barrier. The transport of iron and transport into the brain was examined using radiolabeled iron-transferrin. Intravenous injection of [59Fe-125]transferrin led to an almost two-fold higher accumulation of 59Fe than of

  16. ABCB5 Identifies Immunoregulatory Dermal Cells

    Directory of Open Access Journals (Sweden)

    Tobias Schatton

    2015-09-01

    Full Text Available Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5 identifies dermal immunoregulatory cells (DIRCs capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1. Purified Abcb5+ DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5+ DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.

  17. ABCB5 identifies immunoregulatory dermal cells

    Science.gov (United States)

    Schatton, Tobias; Yang, Jun; Kleffel, Sonja; Uehara, Mayuko; Barthel, Steven R.; Schlapbach, Christoph; Zhan, Qian; Dudeney, Stephen; Mueller, Hansgeorg; Lee, Nayoung; de Vries, Juliane C.; Meier, Barbara; Vander Beken, Seppe; Kluth, Mark A.; Ganss, Christoph; Sharpe, Arlene H.; Waaga-Gasser, Ana Maria; Sayegh, Mohamed H.; Abdi, Reza; Scharffetter-Kochanek, Karin; Murphy, George F.; Kupper, Thomas S.; Frank, Natasha Y.; Frank, Markus H.

    2015-01-01

    Summary Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly-defined immunomodulatory cell populations poses a barrier to this field. Here we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5+ DIRCs suppressed T-cell proliferation, evaded immune rejection, homed to recipient immune tissues and induced Tregs in vivo. In fully MHC-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T-cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5+ DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy. PMID:26321644

  18. Dermal absorption of chlorpyrifos in human volunteers

    NARCIS (Netherlands)

    Meuling, W.J.; Ravensberg, L.C.; Roza, L.; Hemmen, J.J. van

    2005-01-01

    Objective: The methods and results are described of a study on the dermal absorption of chlorpyrifos (CPF) in humans established via urinary excretion of the metabolite 3,5,6-trichloro-2-pyridinol (TCP). Methods: Two dermal, single, doses of CPF were applied in two study groups (A and B) each

  19. Biomechanical properties of four dermal substitutes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guo-an; NING Fang-gang; ZHAO Nan-ming

    2007-01-01

    @@ Many kinds of cell-free dermal substitutes have been developed during the past several years, however,their biomechanical properties, including hysteresis,stress relaxation, creep, and non-linear stress-strain, are still unknown. In this study, we tested these biomechanical characteristics of four dermal substitutes,and compared them with those of fresh human skin (FHS).

  20. From dermal exposure to internal dose

    NARCIS (Netherlands)

    Sandt, J.J.M. van de; Dellarco, M.; Hemmen, J.J. van

    2007-01-01

    Exposure scenarios form an essential basis for chemical risk assessment reports under the new EU chemicals regulation REACH (Registration, Evaluation, Authorisation and restriction of Chemicals). In case the dermal route of exposure is predominant, information on both exposure and dermal bioavailabi

  1. Phosphate homeostasis and disorders.

    Science.gov (United States)

    Manghat, P; Sodi, R; Swaminathan, R

    2014-11-01

    Recent studies of inherited disorders of phosphate metabolism have shed new light on the understanding of phosphate metabolism. Phosphate has important functions in the body and several mechanisms have evolved to regulate phosphate balance including vitamin D, parathyroid hormone and phosphatonins such as fibroblast growth factor-23 (FGF23). Disorders of phosphate homeostasis leading to hypo- and hyperphosphataemia are common and have clinical and biochemical consequences. Notably, recent studies have linked hyperphosphataemia with an increased risk of cardiovascular disease. This review outlines the recent advances in the understanding of phosphate homeostasis and describes the causes, investigation and management of hypo- and hyperphosphataemia.

  2. Can probiotics modulate human disease by impacting intestinal barrier function?

    NARCIS (Netherlands)

    Bron, Peter A.; Kleerebezem, Michiel; Brummer, Robert Jan; Cani, Patrice D.; Mercenier, Annick; MacDonald, Thomas T.; Garcia-Ródenas, Clara L.; Wells, Jerry M.

    2017-01-01

    Intestinal barrier integrity is a prerequisite for homeostasis of mucosal function, which is balanced to maximise absorptive capacity, while maintaining efficient defensive reactions against chemical and microbial challenges. Evidence is mounting that disruption of epithelial barrier integrity is

  3. Dermal benefits of topical D-ribose

    Directory of Open Access Journals (Sweden)

    Linda M Shecterle

    2009-09-01

    Full Text Available Linda M Shecterle, John A St. CyrJacqmar, Inc., Minneapolis, MN, USAAbstract: Our aging skin undergoes changes with reductions in collagenous and elastic fibers, fibroblasts, mast cells, and macrophages with free radical production, which can result in reduced skin tone and wrinkle formation. Fibroblasts are important for dermal integrity and function with a decrease in function producing less skin tone, thinning, and wrinkle formation. Dermal levels of adenosine triphosphate (ATP decline with aging, potentially altering dermal function. Supplemental D-ribose, a natural occurring carbohydrate, enhances ATP regeneration. D-ribosebased studies demonstrated benefits in both cell culture fibroblastic activities and a subsequent clinical study in women with decreased skin tone with wrinkles. Supplemental D-ribose may offer this needed cellular benefit.Keywords: dermal, fibroblast, ATP, aging, wrinkles

  4. Antioxidant Nanoplatforms for Dermal Delivery: Melatonin.

    Science.gov (United States)

    Milán, Aroha Belen Sánchez; Campmany, Ana C Calpena; Naveros, Beatriz Clares

    2017-02-22

    Melatonin (MLT) is emerging as a promising therapeutic agent, mainly due to its role as antioxidant. Substantial evidences show that melatonin is potentially effective on a variety of diseases as cancer, inflammation and neurodegenerative diseases. The excellent antioxidant capacity with pharmacokinetics characteristics and the emerging search for new pharmaceutical nanotechnology based systems, make it particularly attractive to elaborate nanoplatforms based on MLT for biomedical or cosmetic dermal applications. Different nanosystems for dermal delivery have been investigated. These nanosystems are expected to play a significant role in the protection of therapeutic functions of MLT, enhanced transdermal permeability and dermal delivery profiles. These nanocarriers not only transport MLT, but also increase the solubility, bioavailability, half-life and antioxidant activity. In the current review, we will focus on nanocarrier production strategies, dermal MLT application and delivery advances in vivo and in vitro. Equally, future perspectives of this assisted MLT delivery will be also discussed.

  5. Nanofeatured silk fibroin membranes for dermal wound healing applications.

    Science.gov (United States)

    Karahaliloğlu, Zeynep; Ercan, Batur; Denkbaş, Emir B; Webster, Thomas J

    2015-01-01

    As an effort to create the next generation of improved skin graft materials, in this study, we modified the surfaces of a previously investigated material, silk fibroin, using a NaOH alkaline treatment to obtain a biologically inspired nanofeatured surface morphology. Such surfaces were characterized for roughness, energy, and chemistry. In addition, keratinocyte (skin-forming cells) adhesion and proliferation on such nanofeatured silk fibroin wound dressings were studied in an initial attempt to determine the promotion of an epidermal cover on the wound bed to form a new epidermal barrier. Dermal fibroblast adhesion and proliferation were also studied to assess the ability of nanostructured silk fibroin to replace damaged dermal tissue in chronic wounds (i.e., for diabetic foot ulcers). Results demonstrated for the first time that keratinocyte and fibroblast cell density was greater on nanofeatured silk fibroin membranes compared with non-treated silk fibroin surfaces. The enhancement in cellular functions was correlated with an increase in silk surface nanotopography, wettability and change in chemistry after NaOH treatment. Due to the present promising results, the newly developed nanofeatured silk fibroin membranes are exciting alternative skin graft materials which should be further studied for various skin patch and wound dressing applications.

  6. Evaluation of the biocompatibility and cell segregation performance of acellular dermal matrix as barrier membrane on guided tissue regeneration in vitro%脱细胞真皮基质作为屏障膜的细胞相容性及细胞封闭性的体外研究

    Institute of Scientific and Technical Information of China (English)

    陈武; 王韦玮; 时新站; 陈宁

    2013-01-01

    目的:研究脱细胞真皮基质(acellular dermal matrix,ADM)对人牙周膜细胞增殖及上皮细胞的封闭性能的影响,评估其作为引导组织再生屏障膜的可行性.方法:取因正畸需要拔除的新鲜第一前磨牙,刮取根中1/3牙周膜组织,组织块法进行人牙周膜细胞(human periodontal ligament cells,HPDLCs)的原代培养.将ADM膜、膨体聚四氟乙烯(expanded polytetrafluoroethylene,e-PTFE)膜预处理后与HPDLCs共培养,MTT法检测1、3、5、7d的细胞增殖活性.将Tca8113细胞接种于膜材料一侧表面,培养5、10d后,采用DAPI细胞核染色,在荧光显微镜下观察细胞在膜材料两面的分布情况,接种细胞面记为ADM组与e-PTFE组,另一面记为ADM’组与e-PTFE’组.数据采用SPSS 13.0软件包进行t检验.结果:3、5、7d时,ADM组和空白对照组的OD值显著高于e-PTFE组(P<0.05),ADM组与空白对照组的OD值差异无显著性(P>0.05).ADM组与ADM’组、e-PTFE组与e-PTFE’组在5、10d时细胞计数均有显著差异(P<0.05);ADM’组与e-PTFE’组在5、10 d时细胞计数无显著差异(P>0.05).结论:ADM膜比e-PTFE更有利于HPDLCs的增殖,且两者对上皮细胞的封闭作用相似.与e-PTFE相比,ADM更适合用于引导牙周组织再生术.%PURPOSE:To investigate the proliferation of human periodontal ligament cell on acellular dermal matrix (ADM) and the epithelial cell segregation performance of ADM and evaluate the feasibility of ADM as barrier membrane of guided tissue regeneration.METHODS:Human periodontal ligament cells (HPDLCs) of the 3rd to 5th passage were seeded onto 96-well plates(with ADM and e-PTFE inside) with 2000 cells per well.The cells were cultured in Dulbecco's modified eagle medium (DMEM).The MTT colorimetric assay method was performed at day 1,3,5 and 7 after incubation.The optical density (OD) of each well was measured spectrophotometrically at 490 nm to monitor effects on cell proliferation.The data was analyzed using

  7. TSLP and Immune Homeostasis

    Directory of Open Access Journals (Sweden)

    Shino Hanabuchi

    2012-01-01

    Full Text Available In an immune system, dendritic cells (DCs are professional antigen-presenting cells (APCs as well as powerful sensors of danger signals. When DCs receive signals from infection and tissue stress, they immediately activate and instruct the initiation of appropriate immune responses to T cells. However, it has remained unclear how the tissue microenvironment in a steady state shapes the function of DCs. Recent many works on thymic stromal lymphopoietin (TSLP, an epithelial cell-derived cytokine that has the strong ability to activate DCs, provide evidence that TSLP mediates crosstalk between epithelial cells and DCs, involving in DC-mediated immune homeostasis. Here, we review recent progress made on how TSLP expressed within the thymus and peripheral lymphoid and non-lymphoid tissues regulates DC-mediated T-cell development in the thymus and T-cell homeostasis in the periphery.

  8. Alcohol disrupts sleep homeostasis.

    Science.gov (United States)

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  9. Bioactives from probiotics for dermal health: functions and benefits.

    Science.gov (United States)

    Lew, L-C; Liong, M-T

    2013-05-01

    Probiotics have been extensively reviewed for decades, emphasizing on improving general gut health. Recently, more studies showed that probiotics may exert other health-promoting effects beyond gut well-being, attributed to the rise of the gut-brain axis correlations. Some of these new benefits include skin health such as improving atopic eczema, atopic dermatitis, healing of burn and scars, skin-rejuvenating properties and improving skin innate immunity. Increasing evidence has also showed that bacterial compounds such as cell wall fragments, their metabolites and dead bacteria can elicit certain immune responses on the skin and improve skin barrier functions. This review aimed to underline the mechanisms or the exact compounds underlying the benefits of bacterial extract on the skin based on evidences from in vivo and in vitro studies. This review could be of help in screening of probiotic strains with potential dermal enhancing properties for topical applications.

  10. Defense against dermal exposures is only skin deep

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Nielsen, Flemming; Sørensen, Jens Ahm

    2007-01-01

    The OECD guideline for studies on percutaneous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical...... or mechanical damage, due to different medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline procedures to study the in vitro percutaneous penetration through human skin of a number of model...... substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present...

  11. Site-specific rectocele repair with dermal graft augmentation: comparison of porcine dermal xenograft (Pelvicol) and human dermal allograft.

    Science.gov (United States)

    Biehl, Roger C; Moore, Robert D; Miklos, John R; Kohli, Neeraj; Anand, Indu S; Mattox, T Fleming

    2008-01-01

    This study is a retrospective chart review comparing 195 women who underwent rectocele repair with either a porcine dermal xenograft or human allogenic cadaveric dermal graft augmentation over a two year period. A site-specific defect repair was completed prior to augmentation with the graft. Examinations were performed preoperatively and postoperatively using the pelvic organ prolapse quantification system. Questionnaires were used to assess constipation and dyspareunia. De novo dyspareunia and cure rates for constipation and dyspareunia were not statistically different between the two groups. Site-specific fascial rectocele repairs with xenograft or allograft augmentation were found to have similar complication rates as well as objective and subjective cure rates.

  12. Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators.

    Directory of Open Access Journals (Sweden)

    Pornthep Sirimahachaiyakul

    Full Text Available Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses.Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium.Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium.Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring.

  13. Homeostasis in anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Per eSodersten

    2014-08-01

    Full Text Available Brainstem and hypothalamic orexigenic/anorexigenic networks are thought to maintain body weight homeostasis in response to hormonal and metabolic feedback from peripheral sites. This approach has not been successful in managing over- and underweight patients. It is suggested that concept of homeostasis has been misinterpreted; rather than exerting control, the brain permits eating in proportion to the amount of physical activity necessary to obtain food. In support, animal experiments have shown that while a hypothalamic orexigen excites eating when food is abundant, it inhibits eating and stimulates foraging when food is in short supply. As the physical price of food approaches zero, eating and body weight increase without constraints. Conversely, in anorexia nervosa body weight is homeostatically regulated, the high level of physical activity in anorexia is displaced hoarding for food that keeps body weight constantly low. A treatment based on this point of view, providing patients with computerized mealtime support to re-establish normal eating behavior, has brought 75% of patients with eating disorders into remission, reduced the rate of relapse to 10%, and eliminated mortality.

  14. Acid-Base Homeostasis.

    Science.gov (United States)

    Hamm, L Lee; Nakhoul, Nazih; Hering-Smith, Kathleen S

    2015-12-07

    Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3(-) and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3(-) is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

  15. Ageing and water homeostasis

    Science.gov (United States)

    Robertson, David; Jordan, Jens; Jacob, Giris; Ketch, Terry; Shannon, John R.; Biaggioni, Italo

    2002-01-01

    This review outlines current knowledge concerning fluid intake and volume homeostasis in ageing. The physiology of vasopressin is summarized. Studies have been carried out to determine orthostatic changes in plasma volume and to assess the effect of water ingestion in normal subjects, elderly subjects, and patients with dysautonomias. About 14% of plasma volume shifts out of the vasculature within 30 minutes of upright posture. Oral ingestion of water raises blood pressure in individuals with impaired autonomic reflexes and is an important source of noise in blood pressure trials in the elderly. On the average, oral ingestion of 16 ounces (473ml) of water raises blood pressure 11 mmHg in elderly normal subjects. In patients with autonomic impairment, such as multiple system atrophy, strikingly exaggerated pressor effects of water have been seen with blood pressure elevations greater than 75 mmHg not at all uncommon. Ingestion of water is a major determinant of blood pressure in the elderly population. Volume homeostasis is importantly affected by posture and large changes in plasma volume may occur within 30 minutes when upright posture is assumed.

  16. New in vitro dermal absorption database and the prediction of dermal absorption under finite conditions for risk assessment purposes

    NARCIS (Netherlands)

    Buist, H.E.; Burgsteden, J.A. van; Freidig, A.P.; Maas, W.J.M.; Sandt, J.J.M. van de

    2010-01-01

    Most QSARs for dermal absorption predict the permeability coefficient, Kp, of a molecule, which is valid for infinite dose conditions. In practice, dermal exposure mostly occurs under finite dose conditions. Therefore, a simple model to predict finite dose dermal absorption from infinite

  17. Assessment of dermal exposure to chemicals

    NARCIS (Netherlands)

    Hemmen, J.J. van; Brouwer, D.H.

    1995-01-01

    The methods for the dermal exposure assessment vary in their complexity and are in some sense complementary to each other. The most easy-to-use methods involve a pseudo-skin-approach, such as gloves and removal by washing. In some cases generic modelling appears to be possible. The experimental

  18. Focal dermal hypoplasia: A rare case report

    Directory of Open Access Journals (Sweden)

    Sahana M Srinivas

    2015-01-01

    Full Text Available Focal dermal hypoplasia (Goltz syndrome is a rare genetic multisystem disorder primarily involving the skin, skeletal system, eyes, and face. We report the case of an eight-month-old female child who presented with multiple hypopigmented atrophic macules along the lines of blaschko, skeletal anomalies, umbilical hernia, developmental delay, hypoplastic nails, syndactyly, and lobster claw deformity characteristic of Goltz syndrome.

  19. Assessment of dermal exposure to chemicals

    NARCIS (Netherlands)

    Hemmen, J.J. van; Brouwer, D.H.

    1995-01-01

    The methods for the dermal exposure assessment vary in their complexity and are in some sense complementary to each other. The most easy-to-use methods involve a pseudo-skin-approach, such as gloves and removal by washing. In some cases generic modelling appears to be possible. The experimental meth

  20. Acellular Dermal Matrix in Postmastectomy Breast Reconstruction

    NARCIS (Netherlands)

    A.M.S. Ibrahim (Ahmed)

    2014-01-01

    markdownabstract__Abstract__ Over the last decade the use of acellular dermal matrix (ADM) in reconstructive breast surgery has been transformative. Some authors have gone as far as to suggest that it is the single most important advancement in prosthetic breast reconstruction. ADMs are able

  1. Pain emotion and homeostasis.

    Science.gov (United States)

    Panerai, Alberto E

    2011-05-01

    Pain has always been considered as part of a defensive strategy, whose specific role is to signal an immediate, active danger. This definition partially fits acute pain, but certainly not chronic pain, that is maintained also in the absence of an active noxa or danger and that nowadays is considered a disease by itself. Moreover, acute pain is not only an automatic alerting system, but its severity and characteristics can change depending on the surrounding environment. The affective, emotional components of pain have been and are the object of extensive attention and research by psychologists, philosophers, physiologists and also pharmacologists. Pain itself can be considered to share the same genesis as emotions and as a specific emotion in contributing to the maintenance of the homeostasis of each unique subject. Interestingly, this role of pain reaches its maximal development in the human; some even argue that it is specific for the human primate.

  2. Regulation of cholesterol homeostasis.

    Science.gov (United States)

    van der Wulp, Mariëtte Y M; Verkade, Henkjan J; Groen, Albert K

    2013-04-10

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-coding RNA's. The last two decades insight into underlying mechanisms has increased vastly but there are still a lot of unknowns, particularly regarding intracellular cholesterol transport. After decades of concentration on the liver, in recent years the intestine has come into focus as an important control point in cholesterol homeostasis. This review will discuss current knowledge of cholesterol physiology, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and new (possible) therapeutic options for hypercholesterolemia.

  3. Attenuation fluctuations and local dermal reflectivity are indicators of immune cell infiltrate and epidermal hyperplasia in skin inflammation

    Science.gov (United States)

    Phillips, Kevin G.; Wang, Yun; Choudhury, Niloy; Levitz, David; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven

    2012-02-01

    Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses responsible for skin homeostasis. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of psoriasis remains under investigated. To elucidate the spatial-temporal morphological evolution of psoriasis we undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to non-invasively document dermal alterations due to immune cell infiltration and epidermal hyperplasia in an Imiquimod (IMQ) induced model of psoriasis-like inflammation in DBA2/C57Bl6 hybrid mice. Quantitative appraisal of dermal architectural changes was achieved through a three parameter fit of OCT axial scans in the dermis of the form A(z) = ρ exp(-mu;z +ɛ(z)). Ensemble averaging of the fit parameters over 2000 axial scans per mouse in each treatment arm revealed that the local dermal reflectivity ρ, decreased significantly in response to 6 day IMQ treatment (p = 0.0001), as did the standard deviation of the attenuation fluctuation std(ɛ(z)), (p = 0.04), in comparison to cream controls and day 1 treatments. No significant changes were observed in the average dermal attenuation rate, μ. Our results suggest these label-free OCT-based metrics can be deployed to investigate new therapeutic targets in animal models as well as aid in clinical staging of psoriasis in conjunction with the psoriasis area and severity index.

  4. A Physiologist's View of Homeostasis

    Science.gov (United States)

    Modell, Harold; Cliff, William; Michael, Joel; McFarland, Jenny; Wenderoth, Mary Pat; Wright, Ann

    2015-01-01

    Homeostasis is a core concept necessary for understanding the many regulatory mechanisms in physiology. Claude Bernard originally proposed the concept of the constancy of the "milieu interieur," but his discussion was rather abstract. Walter Cannon introduced the term "homeostasis" and expanded Bernard's notion of…

  5. of Energy Homeostasis

    Directory of Open Access Journals (Sweden)

    Xian Liu

    2015-01-01

    Full Text Available Sex differences exist in the complex regulation of energy homeostasis that utilizes central and peripheral systems. It is widely accepted that sex steroids, especially estrogens, are important physiological and pathological components in this sex-specific regulation. Estrogens exert their biological functions via estrogen receptors (ERs. ERα, a classic nuclear receptor, contributes to metabolic regulation and sexual behavior more than other ER subtypes. Physiological and molecular studies have identified multiple ERα-rich nuclei in the hypothalamus of the central nervous system (CNS as sites of actions that mediate effects of estrogens. Much of our understanding of ERα regulation has been obtained using transgenic models such as ERα global or nuclei-specific knockout mice. A fundamental question concerning how ERα is regulated in wild-type animals, including humans, in response to alterations in steroid hormone levels, due to experimental manipulation (i.e., castration and hormone replacement or physiological stages (i.e., puberty, pregnancy, and menopause, lacks consistent answers. This review discusses how different sex hormones affect ERα expression in the hypothalamus. This information will contribute to the knowledge of estrogen action in the CNS, further our understanding of discrepancies in correlation of altered sex hormone levels with metabolic disturbances when comparing both sexes, and improve health issues in postmenopausal women.

  6. Dermal fillers for tissue augmentation: an overview

    Directory of Open Access Journals (Sweden)

    Zeplin, Philip H.

    2014-06-01

    Full Text Available [english] Treatments with dermal fillers for tissue augmentation constitute the majority of all non-surgical procedures in plastic surgery. Newly developed products get launched and the market grows continuously, but the “ideal” substance has yet not been found. The substances used these days are high molecular compounds. They have substantial differences in their physicochemical properties and are suspended in complex matrices. This overview describes the latest history of dermal fillers and the commonly used substances of different origin and formalizes the need for the development of systematic procedures of standardized pre-clinical tests with subsequent certification as well as the establishment of interdisciplinary clinical guidelines to ensure custumer’s safety.

  7. Chemical sterilization of allograft dermal tissues.

    Science.gov (United States)

    Phipps, Abigail; Vaynshteyn, Edward; Kowalski, John B; Ngo, Manh-Dan; Merritt, Karen; Osborne, Joel; Chnari, Evangelia

    2017-08-10

    Common terminal sterilization methods are known to alter the natural structure and properties of soft tissues. One approach to providing safe grafts with preserved biological properties is the combination of a validated chemical sterilization process followed by an aseptic packaging process. This combination of processes is an accepted method for production of sterile healthcare products as described in ANSI/AAMI ST67:2011. This article describes the validation of the peracetic acid and ethanol-based (PAAE) chemical sterilization process for allograft dermal tissues at the Musculoskeletal Transplant Foundation (MTF, Edison, NJ). The sterilization capability of the PAAE solution used during routine production of aseptically processed dermal tissue forms was determined based on requirements of relevant ISO standards, ISO 14161:2009 and ISO 14937:2009. The resistance of spores of Bacillus subtilis, Clostridium sporogenes, Mycobacterium terrae, Pseudomonas aeruginosa, Enterococcus faecium, and Staphylococcus aureus to the chemical sterilization process employed by MTF was determined. Using a worst-case scenario testing strategy, the D value was calculated for the most resistant microorganism, Bacillus. The 12D time parameter determined the minimum time required to achieve a SAL of 10(-6). Microbiological performance qualification demonstrated a complete kill of 10(6) spores at just a quarter of the full cycle time. The validation demonstrated that the PAAE sterilization process is robust, achieves sterilization of allograft dermal tissue to a SAL 10(-6), and that in combination with aseptic processing secures the microbiological safety of allograft dermal tissue while avoiding structural and biochemical tissue damage previously observed with other sterilization methods such as ionizing irradiation.

  8. Dermal mass aspirate from a Persian cat.

    Science.gov (United States)

    Zimmerman, Kurt; Feldman, Bernard; Robertson, John; Herring, Erin S; Manning, Thomas

    2003-01-01

    A 1-year-old spayed female Persian cat with alopecia and weight loss had numerous variably ulcerated dermal nodules. Cytologic examination of an aspirate of one of the nodules revealed pyogranulomatous inflammation along with septate hyphae and basophilic round bodies, 0.5-1.0 microm in diameter, surrounded by a thin clear halo (arthrospores). The cytologic diagnosis was dermatophytic pseudomycetoma. Histologically, there were dermal granulomas containing poorly staining, septate hyphae with bulbous spores embedded within abundant amorphous eosinophilic material (Splendore-Hoeppli reaction), and the histologic diagnosis was pseudomycetoma-associated chronic multifocal severe granulomatous dermatitis with lymphocytic perifolliculitis and furunculosis. Microsporum canis was cultured from the lesion. Pseudomycetomas are distinguished from fungal mycetomas, or eumycotic mycetomas, by the findings of multiple lesions, lack of a history of skin trauma, an association with dermatophytes, most commonly Microsporum canis, and, histologically, lack of true cement material and a more abundant Splendore-Hoeppli reaction in pseudomycetomas. Additionally, pseudomycetomas differ from dermatophytosis, in which lesions are restricted to epidermal structures. Persian cats have a high incidence of pseudomycetoma formation, suggesting a heritable predisposition. The prognosis is fair with systemic antifungal therapy. When examining cytologic specimens from Persian cats with single or multiple dermal nodules, especially if pyogranulomatous inflammation is present, a diagnosis of pseudomycetoma should be suspected and is warranted if arthrospores and refractile septate hyphae are present.

  9. Posterior repair with perforated porcine dermal graft

    Directory of Open Access Journals (Sweden)

    G. Bernard Taylor

    2008-02-01

    Full Text Available OBJECTIVE: To compare postoperative vaginal incision separation and healing in patients undergoing posterior repair with perforated porcine dermal grafts with those that received grafts without perforations. Secondarily, the tensile properties of the perforated and non-perforated grafts were measured and compared. MATERIALS AND METHODS: This was a non-randomized retrospective cohort analysis of women with stage II or greater rectoceles who underwent posterior repair with perforated and non-perforated porcine dermal grafts (PelvicolTM CR Bard Covington, GA USA. The incidence of postoperative vaginal incision separation (dehiscence was compared. A secondary analysis to assess graft tensile strength, suture pull out strength, and flexibility after perforation was performed using standard test method TM 0133 and ASTM bending and resistance protocols. RESULTS: Seventeen percent of patients (21/127 who received grafts without perforations developed vaginal incision dehiscence compared to 7% (5/71 of patients who received perforated grafts (p = 0.078. Four patients with vaginal incision dehiscence with non-perforated grafts required surgical revision to facilitate healing. Neither tensile strength or suture pull out strength were significantly different between perforated and non-perforated grafts (p = 0.81, p = 0.29, respectively. There was no difference in the flexibility of the two grafts (p = 0.20. CONCLUSION: Perforated porcine dermal grafts retain their tensile properties and are associated with fewer vaginal incision dehiscences.

  10. Evaluation of electric arc furnace-processed steel slag for dermal corrosion, irritation, and sensitization from dermal contact.

    Science.gov (United States)

    Suh, Mina; Troese, Matthew J; Hall, Debra A; Yasso, Blair; Yzenas, John J; Proctor, Debora M

    2014-12-01

    Electric arc furnace (EAF) steel slag is alkaline (pH of ~11-12) and contains metals, most notably chromium and nickel, and thus has potential to cause dermal irritation and sensitization at sufficient dose. Dermal contact with EAF slag occurs in many occupational and environmental settings because it is used widely in construction and other industrial sectors for various applications including asphaltic paving, road bases, construction fill, and as feed for cement kilns construction. However, no published study has characterized the potential for dermal effects associated with EAF slag. To assess dermal irritation, corrosion and sensitizing potential of EAF slag, in vitro and in vivo dermal toxicity assays were conducted based on the Organisation for Economic Co-operation and Development (OECD) guidelines. In vitro dermal corrosion and irritation testing (OECD 431 and 439) of EAF slag was conducted using the reconstructed human epidermal (RHE) tissue model. In vivo dermal toxicity and delayed contact sensitization testing (OECD 404 and 406) were conducted in rabbits and guinea pigs, respectively. EAF slag was not corrosive and not irritating in any tests. The results of the delayed contact dermal sensitization test indicate that EAF slag is not a dermal sensitizer. These findings are supported by the observation that metals in EAF slag occur as oxides of low solubility with leachates that are well below toxicity characteristic leaching procedure (TCLP) limits. Based on these results and in accordance to the OECD guidelines, EAF slag is not considered a dermal sensitizer, corrosive or irritant.

  11. Why Homeodynamics, Not Homeostasis?

    Directory of Open Access Journals (Sweden)

    David Lloyd

    2001-01-01

    Full Text Available Ideas of homeostasis derive from the concept of the organism as an open system. These ideas can be traced back to Heraclitus. Hopkins, Bernard, Hill, Cannon, Weiner and von Bertalanffy developed further the mechanistic basis of turnover of biological components, and Schoenheimer and Rittenberg were pioneers of experimental approaches to the problems of measuring pool sizes and dynamic fluxes. From the second half of the twentieth century, a biophysical theory mainly founded on self-organisation and Dynamic Systems Theory allowed us to approach the quantitative and qualitative analysis of the organised complexity that characterises living systems. This combination of theoretical framework and more refined experimental techniques revealed that feedback control of steady states is a mode of operation that, although providing stability, is only one of many modes and may be the exception rather than the rule. The concept of homeodynamics that we introduce here offers a radically new and all-embracing concept that departs from the classical homeostatic idea that emphasises the stability of the internal milieu toward perturbation. Indeed, biological systems are homeody- namic because of their ability to dynamically self-organise at bifurcation points of their behaviour where they lose stability. Consequently, they exhibit diverse behaviour; in addition to monotonic stationary states, living systems display complex behaviour with all its emergent characteristics, i.e., bistable switches, thresholds, waves, gradients, mutual entrainment, and periodic as well as chaotic behaviour, as evidenced in cellular phenomena such as dynamic (supramolecular organisation and flux coordination. These processes may proceed on different spatial scales, as well as across time scales, from the very rapid processes within and between molecules in membranes to the slow time scales of evolutionary change. It is dynamic organisation under homeodynamic conditions that make

  12. Cholesterol metabolism and homeostasis in the brain.

    Science.gov (United States)

    Zhang, Juan; Liu, Qiang

    2015-04-01

    Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier. The content of cholesterol in brain must be accurately maintained in order to keep brain function well. Defects in brain cholesterol metabolism has been shown to be implicated in neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), and some cognitive deficits typical of the old age. The brain contains large amount of cholesterol, but the cholesterol metabolism and its complex homeostasis regulation are currently poorly understood. This review will seek to integrate current knowledge about the brain cholesterol metabolism with molecular mechanisms.

  13. Mechanics of epithelial tissue homeostasis and morphogenesis.

    Science.gov (United States)

    Guillot, Charlène; Lecuit, Thomas

    2013-06-07

    Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.

  14. Apoptosis, Necrosis, and Necroptosis in the Gut and Intestinal Homeostasis.

    Science.gov (United States)

    Negroni, Anna; Cucchiara, Salvatore; Stronati, Laura

    2015-01-01

    Intestinal epithelial cells (IECs) form a physiochemical barrier that separates the intestinal lumen from the host's internal milieu and is critical for electrolyte passage, nutrient absorption, and interaction with commensal microbiota. Moreover, IECs are strongly involved in the intestinal mucosal inflammatory response as well as in mucosal innate and adaptive immune responses. Cell death in the intestinal barrier is finely controlled, since alterations may lead to severe disorders, including inflammatory diseases. The emerging picture indicates that intestinal epithelial cell death is strictly related to the maintenance of tissue homeostasis. This review is focused on previous reports on different forms of cell death in intestinal epithelium.

  15. Desmosome assembly, homeostasis, and desmosomal disease

    Directory of Open Access Journals (Sweden)

    Cirillo N

    2016-02-01

    Full Text Available Nicola Cirillo1,2 1Melbourne Dental School and Oral Health CRC, The University of Melbourne, Melbourne, VIC, Australia; 2Research Unit, Centre for Innovation, Research, Education, and Health (IRIS, Caposele, Italy Abstract: Cell–cell adhesion is involved in all aspects of tissue behavior in multicellular organisms, from tissue morphogenesis (regulation of cell shape, apoptosis, cell movement, and development of complex structures to aging and disease. A major player in the dynamic regulation of intercellular contacts is the desmosome. Knowledge of the desmosome has evolved over 150 years from the notion of a static, punctuate, adhesive barrier structure to one of the finely tuned multifunctional complexes involved in the regulation of numerous and diverse aspects of keratinocyte physiology and disease. In this context, nondesmosomal regulatory molecules have been acquiring increasing importance in the study of desmosome homeostasis and have become part of the extended desmosomal interactome named "desmo-adhesome". Among these associated molecules, kinases are the prominent regulators of both desmosome remodeling and acquisition of hyperadhesion, two novel concepts in cell–cell adhesion. Spatiotemporal changes in the expression and regulation of desmosomal proteins also underlie a number of genetic, infectious, autoimmune, and malignant conditions. In addition to offering a systems-level view of the molecular composition of desmosomes, we also discuss the mechanisms that regulate, and disrupt, desmosome homeostasis. Keywords: cell adhesion, desmo-adhesome, pemphigus, cancer

  16. Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Malpass, Gloria E., E-mail: gloria.malpass@gmail.com [Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157 (United States); Arimilli, Subhashini, E-mail: sarimill@wakehealth.edu [Department of Microbiology and Immunology, Wake Forest University Health Sciences, Winston-Salem, NC 27157 (United States); Prasad, G.L., E-mail: prasadg@rjrt.com [R and D Department, R.J. Reynolds Tobacco Company, Winston-Salem, NC 27102 (United States); Howlett, Allyn C., E-mail: ahowlett@wakehealth.edu [Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157 (United States)

    2014-09-01

    Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1 h or 5 h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1 h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1 h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5 h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1 h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5 h), which was increased by nicotine but suppressed by other components of STE. Within 2 h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research. - Highlights: • Tobacco product preparations (TPPs) alter gene expression in dermal fibroblasts. • Some immediate early genes critical to the inflammatory process are affected. • Different TPPs produce differential responses in certain pro-inflammatory genes.

  17. File list: Unc.Epd.50.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Epd.50.AllAg.Dermal_fibroblasts mm9 Unclassified Epidermis Dermal fibroblasts h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Epd.50.AllAg.Dermal_fibroblasts.bed ...

  18. File list: Unc.Epd.20.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Epd.20.AllAg.Dermal_fibroblasts mm9 Unclassified Epidermis Dermal fibroblasts h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Epd.20.AllAg.Dermal_fibroblasts.bed ...

  19. Evaluation of lymphangiogenesis in acellular dermal matrix

    Directory of Open Access Journals (Sweden)

    Mario Cherubino

    2014-01-01

    Full Text Available Introduction: Much attention has been directed towards understanding the phenomena of angiogenesis and lymphangiogenesis in wound healing. Thanks to the manifold dermal substitute available nowadays, wound treatment has improved greatly. Many studies have been published about angiogenesis and cell invasion in INTEGRA® . On the other hand, the development of the lymphatic network in acellular dermal matrix (ADM is a more obscure matter. In this article, we aim to characterize the different phases of host cell invasion in ADM. Special attention was given to lymphangiogenic aspects. Materials and Methods: Among 57 rats selected to analyse the role of ADM in lymphangiogenesis, we created four groups. We performed an excision procedure on both thighs of these rats: On the left one we did not perform any action except repairing the borders of the wound; while on the right one we used INTEGRA® implant. The excision biopsy was performed at four different times: First group after 7 days, second after 14 days, third after 21 days and fourth after 28 days. For our microscopic evaluation, we used the classical staining technique of haematoxylin and eosin and a semi-quantitative method in order to evaluate cellularity counts. To assess angiogenesis and lymphangiogenesis development we employed PROX-1 Ab and CD31/PECAM for immunohistochemical analysis. Results: We found remarkable wound contraction in defects that healed by secondary intention while minor wound contraction was observed in defects treated with ADM. At day 7, optical microscopy revealed a more plentiful cellularity in the granulation tissue compared with the dermal regeneration matrix. The immunohistochemical process highlighted vascular and lymphatic cells in both groups. After 14 days a high grade of fibrosis was noticeable in the non-treated group. At day 21, both lymphatic and vascular endothelial cells were better developed in the group with a dermal matrix application. At day 28

  20. Histological changes of acellular dermal matrix used as guided tissue regeneration barrier membrane in vivo%脱细胞真皮基质作为引导组织再生屏障膜在体内的组织学变化研究

    Institute of Scientific and Technical Information of China (English)

    王乾锋; 刘宏伟; 郑秋林

    2010-01-01

    目的 观察脱细胞真皮基质(acellular dermal matrix,ADM)作为引导组织再生(guided tissue regeneration,GTR)屏障膜时的体内组织学变化,探索其作为GTR屏障膜的可行性.方法 在兔下颌前磨牙颊侧根面形成一开窗型牙周缺损模型,将ADM作为GTR屏障膜覆盖和固定于缺损区表面,观察术后4周和8周时ADM的降解、血管化、炎性反应等组织学变化情况.结果 术后4周时,ADM无明显降解,基本保持其原来完整结构;8周时,ADM出现轻中度降解,但结缔组织尚未突破整层ADM.结论 ADM可以作为GTR的屏障膜.

  1. Calcium Homeostasis in ageing neurons

    Directory of Open Access Journals (Sweden)

    Vassiliki eNikoletopoulou

    2012-10-01

    Full Text Available The nervous system becomes increasingly vulnerable to insults and prone to dysfunction during ageing. Age-related decline of neuronal function is manifested by the late onset of many neurodegenerative disorders, as well as by reduced signalling and processing capacity of individual neuron populations. Recent findings indicate that impairment of Ca2+ homeostasis underlies the increased susceptibility of neurons to damage, associated with the ageing process. However, the impact of ageing on Ca2+ homeostasis in neurons remains largely unknown. Here, we survey the molecular mechanisms that mediate neuronal Ca2+ homeostasis and discuss the impact of ageing on their efficacy. To address the question of how ageing impinges on Ca2+ homeostasis, we consider potential nodes through which mechanisms regulating Ca2+ levels interface with molecular pathways known to influence the process of ageing and senescent decline. Delineation of this crosstalk would facilitate the development of interventions aiming to fortify neurons against age-associated functional deterioration and death by augmenting Ca2+ homeostasis.

  2. Dermal pharmacokinetics of microemulsion formulations determined by in vivo microdialysis

    DEFF Research Database (Denmark)

    Kreilgaard, Mads

    2001-01-01

    To investigate the potential of improving dermal drug delivery of hydrophilic and lipophilic substances by formulation in microemulsion vehicles and to establish a reliable pharmacokinetic model to analyze cutaneous microdialysis data.......To investigate the potential of improving dermal drug delivery of hydrophilic and lipophilic substances by formulation in microemulsion vehicles and to establish a reliable pharmacokinetic model to analyze cutaneous microdialysis data....

  3. Spectrum of PORCN mutations in Focal Dermal Hypoplasia

    Science.gov (United States)

    Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome (OMIM 305600), is a genetic disorder that affects multiple organ systems early in development. Features of FDH include skin abnormalities, (hypoplasia, atrophy, linear pigmentation, and herniation of fat through dermal defects); papillomas...

  4. Novel PORCN mutations in focal dermal hypoplasia.

    Science.gov (United States)

    Froyen, G; Govaerts, K; Van Esch, H; Verbeeck, J; Tuomi, M-L; Heikkilä, H; Torniainen, S; Devriendt, K; Fryns, J-P; Marynen, P; Järvelä, I; Ala-Mello, S

    2009-12-01

    Focal dermal hypoplasia (FDH), Goltz or Goltz-Gorlin syndrome, is an X-linked dominant multisystem disorder characterized primarily by involvement of the skin, skeletal system and eyes. We screened for mutations in the PORCN gene in eight patients of Belgian and Finnish origin with firm clinical suspicion of FDH. First, we performed quantitative PCR (qPCR) analysis to define the copy number at this locus. Next, we sequenced the coding regions and flanking intronic sequences of the PORCN gene. Three de novo mutations were identified in our patients with FDH: a 150-kb deletion removing six genes including PORCN, as defined by qPCR and X-array-CGH, and two heterozygous missense mutations; c.992T>G (p.L331R) in exon 11 and c.1094G>A (p.R365Q) in exon 13 of the gene. Both point mutations changed highly conserved amino acids and were not found in 300 control X chromosomes. The three patients in whom mutations were identified all present with characteristic dermal findings together with limb manifestations, which were not seen in our mutation-negative patients. The clinical characteristics of our patients with PORCN mutations were compared with the previously reported mutation-positive cases. In this report, we summarize the literature on PORCN mutations and associated phenotypes.

  5. [Cerebellar abscesses secondary to infection of an occipital dermal sinus].

    Science.gov (United States)

    García Galera, A; Martínez León, M I; Pérez da Rosa, S; Ros López, B

    2013-09-01

    A dermal sinus is a congenital defect arising from a closure failure of the neural tube that results in different degrees of communication between the skin and the central nervous system. A dermal sinus can occur anywhere from the root of the nose to the conus medullaris, and the occipital location is the second most common. Dermal sinuses are often found in association with dermoid or epidermoid cysts and less frequently with teratomas. Patients with an occipital dermoid cyst associated with a dermal sinus can develop meningitis and/or abscesses as the first clinical manifestation of the disease due to the dermoid cyst itself becoming abscessed or to the formation of secondary abscesses; few cases of the formation of secondary abscesses have been reported. We present a case of a dermoid cyst associated with an infected dermal sinus and posterior development of cerebellar abscesses and hydrocephalus.

  6. Late-onset Ito's nevus: an uncommon acquired dermal melanocytosis.

    Science.gov (United States)

    Mataix, Javier; López, Norberto; Haro, Rosario; González, Elena; Angulo, Jorge; Requena, Luis

    2007-08-01

    Dermal melanocytoses comprise a variety of congenital and acquired conditions characterized by a sparse population of intradermal dendritic, variably pigmented, spindle-shaped melanocytes. While Mongolian spot, Ota's and Ito's nevi are usually present at birth or appear around puberty; acquired dermal melanocytoses that appear in adult life are extremely rare. They include the facial lesions of acquired bilateral nevus of Ota-like macules, also named Hori's nevus, and the acquired unilateral nevus of Ota, also known as Sun's nevus. Uncommon extrafacial examples of acquired dermal melanocytoses include lesions involving upper extremities, wrist, back, lower extremities and dorsal aspects of the hands and feet. They are more prevalent among Asian women. In general, dermal melanocytoses are rare lesions in Caucasian patients and acquired variants are exceedingly uncommon. We report a rare example of acquired Ito's nevus that appeared in a Caucasian elderly woman and review the literature about acquired dermal melanocytoses.

  7. Homeostasis of T Cell Diversity

    Institute of Scientific and Technical Information of China (English)

    Vinay S. Mahajan; Ilya B. Leskov; Jianzhu Chen

    2005-01-01

    T cell homeostasis commonly refers to the maintenance of relatively stable T cell numbers in the peripheral lymphoid organs. Among the large numbers of T cells in the periphery, T cells exhibit structural diversity, I.e., the expression of a diverse repertoire of T cell receptors (TCRs), and functional diversity, I.e., the presence of T cells at na(I)ve, effector, and memory developmental stages. Although the homeostasis of T cell numbers has been extensively studied, investigation of the mechanisms underlying the maintenance of structural and functional diversity of T cells is still at an early stage. The fundamental feature throughout T cell development is the interaction between the TCR and either self or foreign peptides in association with MHC molecules. In this review, we present evidence showing that homeostasis of T cell number and diversity is mediated through competition for limiting resources.The number of T cells is maintained through competition for limiting cytokines, whereas the diversity of T cells is maintained by competition for self-peptide-MHC complexes. In other words, diversity of the self-peptide repertoire limits the structural (TCR) diversity of a T cell population. We speculate that cognate low affinity self-peptides,acting as weak agonists and antagonists, regulate the homeostasis of T cell diversity whereas non-cognate or null peptides which are extremely abundant for any given TCR, may contribute to the homeostasis of T cell number by providing survival signals. Moreover, self-peptides and cytokines may form specialized niches for the regulation of T cell homeostasis.

  8. Homeostasis of T Cell Diversity

    Institute of Scientific and Technical Information of China (English)

    VinayS.Mahajan; IlyaB.Leskov; JianzhuChen

    2005-01-01

    T cell homeostasis commonly refers to the maintenance of relatively stable T cell numbers in the peripheral lymphoid organs. Among the large numbers of T cells in the periphery, T cells exhibit structural diversity, i.e., the expression of a diverse repertoire of T cell receptors (TCRs), and functional diversity, i.e., the presence of T cells at naive, effector, and memory developmental stages. Although the homeostasis of T cell numbers has been extensively studied, investigation of the mechanisms underlying the maintenance of structural and functional diversity of T cells is still at an early stage. The fundamental feature throughout T cell development is the interaction between the TCR and either self or foreign peptides in association with MHC molecules. In this review, we present evidence showing that homeostasis of T cell number and diversity is mediated through competition for limiting resources. The number of T cells is maintained through competition for limiting cytokines, whereas the diversity of T cells is maintained by competition for self-peptide-MHC complexes. In other words, diversity of the self-peptide repertoire limits the structural (TCR) diversity of a T cell population. We speculate that cognate low affinity self-peptides, acting as weak agonists and antagonists, regulate the homeostasis of T cell diversity whereas non-cognate or null peptides which are extremely abundant for any given TCR, may contribute to the homeostasis of T cell number by providing survival signals. Moreover, self-peptides and cytokines may form specialized niches for the regulation of T cell homeostasis. Cellular & Molecular Immunology. 2005;2(1): 1-10.

  9. Hypocellular Plaque-Like CD34-Positive Dermal Fibroma (Medallion-Like Dermal Dendrocyte Hamartoma) Presenting as a Skin-Colored Dermal Nodule.

    Science.gov (United States)

    Mutgi, Krishna A J; Chitgopeker, Pooja; Ciliberto, Heather; Stone, Mary S

    2016-01-01

    Plaque-like CD34-positive dermal fibromas, also known as medallion-like dermal dendrocyte hamartomas (MDDHs), are a recently recognized group of congenital and acquired spindle cell neoplasms that may appear histologically similar to dermatofibrosarcoma protuberans. Recognizing the clinical heterogeneity of this neoplasm and the subtle pathologic differences are crucial to making the correct diagnosis and avoiding the aggressive surgical intervention required to treat a dermatofibrosarcoma protuberans. We present the case of a 9-year-old girl with an acquired variant of a plaque-like CD34-positive dermal fibroma without clinical epidermal change. Our case expands the clinical spectrum to include an acquired variant of a plaque-like CD34-positive dermal fibroma without clinical epidermal change. Examination of more cases is needed to determine whether all clinical variants are truly subtypes of the same neoplasm or represent distinct CD34-positive spindle cell proliferations.

  10. Disorders of erythrocyte volume homeostasis.

    Science.gov (United States)

    Glogowska, E; Gallagher, P G

    2015-05-01

    Inherited disorders of erythrocyte volume homeostasis are a heterogeneous group of rare disorders with phenotypes ranging from dehydrated to overhydrated erythrocytes. Clinical, laboratory, physiologic, and genetic heterogeneities characterize this group of disorders. A series of recent reports have provided novel insights into our understanding of the genetic bases underlying some of these disorders of red cell volume regulation. This report reviews this progress in understanding determinants that influence erythrocyte hydration and how they have yielded a better understanding of the pathways that influence cellular water and solute homeostasis.

  11. Long-term homeostasis and wound healing in an in vitro epithelial stem cell niche model

    Science.gov (United States)

    Miyashita, Hideyuki; Niwano, Hiroko; Yoshida, Satoru; Hatou, Shin; Inagaki, Emi; Tsubota, Kazuo; Shimmura, Shigeto

    2017-01-01

    Cultures of epithelial cells are limited by the proliferative capacity of primary cells and cell senescence. Herein we show that primary human epithelial cell sheets cultured without dermal equivalents maintained homeostasis in vitro for at least 1 year. Transparency of these sheets enabled live observation of pigmented melanocytes and Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) labeled epithelial cells during wound healing. Cell turn over and KRT15 expression pattern stabilized within 3 months, when KRT15 bright clusters often associated with niche-like melanocytes became apparent. EdU labels were retained in a subset of epithelial cells and melanocytes after 6 months chasing, suggesting their slow cell cycling property. FUCCI-labeling demonstrated robust cell migration and proliferation following wounding. Transparency and long-term (1 year) homeostasis of this model will be a powerful tool for the study of wound healing and cell linage tracing. PMID:28233843

  12. Development of a permeation panel to test dermal protective clothing against sprayed coatings.

    Science.gov (United States)

    Ceballos, Diana M; Yost, Michael G; Whittaker, Stephen G; Reeb-Whitaker, Carolyn; Camp, Janice; Dills, Russell

    2011-03-01

    performance against polymerizing materials. Thin (0.10-0.13 mm) latex gloves were determined to be ineffective barriers to the isocyanates commonly found in clear coats. Because this type of glove is used frequently in auto body shops, the potential for isocyanate exposure is of concern. Permeation tests with other dermal protective clothing materials and other clear coat formulations are needed to make recommendations about alternative materials.

  13. Dermal graft correction of extraordinary chordee.

    Science.gov (United States)

    Kogan, S J; Reda, E F; Smey, P L; Levitt, S B

    1983-11-01

    Severe degrees of primary chordee and persistent or recurrent chordee following previous surgical attempts at correction present a challenging problem. Inadequate resection of involved tissues, which may involve all layers of the penile investiture, or recurrent scarring of the ventral skin, Buck's fascia and tunica albuginea is usually the cause. Reoperation to achieve penile straightening often is unsuccessful unless all chordee-bearing tissue is resected extensively. Excision of large segments of tunica albuginea or wide separation of the margins creates a defect that tends to heal by dense scarring unless the defect is bridged by a graft. Various autogenous materials have been used, including blood vessel, fascia, free fat graft, dermis and tunica albuginea, as well as prosthestic materials, such as polytetrafluoroethylene, with varying results. A series of patients with extensive chordee is presented in whom tunical resection was necessary to achieve penile straightening. The results of free dermal graft replacement of the tunica are reported.

  14. Prenatal Diagnosis of Congenital Dermal Sinus

    Directory of Open Access Journals (Sweden)

    Sharif Sakr

    2015-04-01

    Full Text Available Background - Congenital dermal sinus (CDS is an uncommon form of spinal dysraphism. Although postdelivery identification in the neonate is aided by several associated physical examination findings, establishing this diagnosis prenatally has proven to be elusive. Case Report - We present a case of CDS where the prenatal findings at 20 weeks gestation led to the diagnosis, which was confirmed postnatally. The associated protrusion of fibrotic membranes through the sinus tract helped in the identification of this lesion prenatally, but created confusion with a more common type of lesion, an open neural tube defect. This is the first case report in the literature describing prenatal diagnosis of fetal CDS. Conclusion - Prenatal diagnosis with postnatal confirmation of CDS leads to early intervention, better long-term outcomes, and lesser complications.

  15. Dermal and Ophthalmic Findings in Pseudohypoaldosteronism

    Science.gov (United States)

    Korkut, Sabriye; Gökalp, Emir; Özdemir, Ahmet; Kurtoğlu, Selim; Demirtaş, Şafak; Gül, Ülkü; Baştuğ, Osman

    2015-01-01

    Pseudohypoaldosteronism (PHA) is defined as a state of resistance to aldosterone, a hormone crucial for electrolyte equilibrium. The genetically transmitted type of PHA is primary hypoaldosteronism. Secondary hypoaldosteronism develops as a result of hydronephrosis or hydroureter. PHA patients suffer from severe hyponatremia and a severe clinical condition due to severe loss of salt can be encountered in the neonatal period. Dermal findings in the form of miliaria rubra can also develop in these patients. With the loss of salt, abnormal accumulation of sebum in the eye due to a defect in the sodium channels can also occur. In this paper, a case of PHA in a newborn showing typical dermatological and ophthalmological findings is presented. PMID:26316441

  16. [Generalized granuloma annulare or diffuse dermal histiocytosis?].

    Science.gov (United States)

    Kretzschmar, L; Biel, K; Luger, T A; Goerdt, S

    1995-08-01

    Generalized granuloma annulare is a rare variant of granuloma annulare affecting the trunk and extremities with a multitude of lesions. In contrast to localized granuloma annulare, generalized granuloma annulare occurs in older patients, shows a stronger association with diabetes, and is characteristically chronic. Like our 55-year-old patient, most patients present with papules and annular plaques; less often, macular or non-annular lesions may be encountered. Histology often fails to show necrobiotic or necrotic connective tissue changes demarcated by a palisading granuloma. Instead, there are diffuse dermal, band-like or nodular aggregations of histiocytes intermingled with some multinucleated giant cells and a predominantly lymphocytic infiltrate in the periphery. Because of its special characteristics, it has been suggested that generalized granuloma annulare might constitute a separate disease entity and that it should be classed among the primary cutaneous histiocytoses as a diffuse dermal histiocytosis. Using immunohistochemistry to determine the macrophage phenotype of the lesional histiocytes, we have shown that generalized granuloma annulare is not a cutaneous histiocytosis. Neither MS-1 high-molecular-weight protein, a new specific marker for cutaneous non-Langerhans cell histiocytoses, nor CD1a, the well-known marker for Langerhans cells and Langerhans cell histiocytoses, is expressed by the lesional histiocytes of our patient. In contrast, the antigen expression pattern was diagnostic for non-infectious granulomas and was highly similar to that in localized granuloma annulare. In contrast to the successful treatment of localized granuloma annulare reported with intralesional interferon beta-1, systemic treatment with interferon alpha-2b (9 x 10(6) units three times a week) was ineffective.

  17. Acellular Dermal Matrix as GTR Barrier Membrane on Periodontal Regeneration in the Treatment of Class Ⅱ Furcation Defects%脱细胞真皮基质作为GTR屏障膜治疗Ⅱ度根分叉缺损的实验研究

    Institute of Scientific and Technical Information of China (English)

    王乾锋; 刘宏伟

    2013-01-01

    目的:观察脱细胞真皮基质(acellular dermal matrix,ADM) 作为引导组织再生(guided tissue regeneration,GTR)屏障膜在治疗Ⅱ度根分叉缺损时的牙周组织再生情况.方法:在犬的两侧下颌第三、四前磨牙制造Ⅱ度根分叉缺损模型,将ADM作为GTR屏障膜覆盖在根分叉缺损区表面,于术后8周观察和测量根分叉处牙周组织的再生情况,并与空白对照组作比较.结果:术后8周,ADM组和空白对照组的临床附着丧失(clinical attachment loss,CAL)平均分别为1.90 mm 和2.85 mm,差异有统计学意义(P<0.05);ADM 组的新骨面积、新骨高度、新生牙骨质高度分别为8.23 mm2、4.52 mm、4.72 mm,明显大于对照组的1.75 mm2、0.91 mm、0.94 mm,而上皮和结缔组织面积则小于对照组,分别为0.02、0.54 mm2 和0.10、5.56 mm2,差异均有统计学意义(P<0.05).结论:ADM 作为GTR屏障膜治疗下颌Ⅱ度根分叉缺损,能比空白对照组获得更多的临床附着和再生牙周组织.

  18. Dermal grafts for correction of severe chordee associated with hypospadias.

    Science.gov (United States)

    Horton, C E; Gearhart, J P; Jeffs, R D

    1993-08-01

    We report on 24 patients with hypospadias and severe chordee that could not be straightened with conventional techniques. We used small dermal grafts to augment the ventral tunica albuginea, which resulted in a completely straight, normal appearing erection in all patients. Subsequent urethroplasty was not complicated by the presence of the dermal graft. This procedure is technically straightforward and consistently results in a completely straight penis. Although required only rarely in hypospadias surgery, we recommend the dermal graft technique of tunica albuginea augmentation for cases of refractory chordee.

  19. Dermal reflectivity determined by optical coherence tomography is an indicator of epidermal hyperplasia and dermal edema within inflamed skin

    Science.gov (United States)

    Phillips, Kevin G.; Wang, Yun; Levitz, David; Choudhury, Niloy; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven L.

    2011-04-01

    Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of inflammation in psoriasis remain unclear. We undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to noninvasively document cutaneous alterations in mouse skin treated topically with Imiquimod (IMQ), an established model of a psoriasis-like disease. Quantitative appraisal of dermal architectural changes was achieved through a two parameter fit of OCT axial scans in the dermis of the form A(x, y, z) = ρ(x, y)exp [ - μ(x, y)z]. Ensemble averaging over 2000 axial scans per mouse in each treatment arm revealed no significant changes in the average dermal attenuation rate, , however the average local dermal reflectivity , decreased significantly following 1, 3, and 6 days of IMQ treatment (p collagen fiber bundle enlargement, occur prior to epidermal thickness changes due to hyperplasia and dermal thickness changes due to edema. Dermal reflectivity positively correlated with epidermal hyperplasia (repi2 = 0.78) and dermal edema (rderm2 = 0.86). Our results suggest that dermal reflectivity as measured by OCT can be utilized to quantify a psoriasis-like disease in mice, and thus has the potential to aid in the quantitative assessment of psoriasis in humans.

  20. Disorders of Erythrocyte Volume Homeostasis

    OpenAIRE

    Glogowska, Edyta; Gallagher, Patrick G.

    2015-01-01

    Inherited disorders of erythrocyte volume homeostasis are a heterogeneous group of rare disorders with phenotypes ranging from dehydrated to overhydrated erythrocytes. Clinical, laboratory, physiologic, and genetic heterogeneity characterize this group of disorders. A series of recent reports have provided novel insights into our understanding of the genetic bases underlying some of these disorders of red cell volume regulation. This report reviews this progress in understanding determinants ...

  1. Focal dermal hypoplasia: Unusual presentation in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Awadh Alamri

    2016-01-01

    Full Text Available Focal dermal hypoplasia (Goltz syndrome is a rare genetic multisystem characterized by multiple abnormalities of ectodermal and mesodermal origin. It is found predominantly in females. We report a case of a two month-old baby girl who had dermal hypoplasia, atrophic skin lesions with telangiectasia in a linear pattern, fat herniations, papillomas and cleft of the upper lip, ectrodactyly, claw hands, microphthalmia and unusual association of gastrointestinal omphalocele.

  2. Acquired ichthyosis and impaired dermal lipogenesis in Hodgkin's disease.

    Science.gov (United States)

    Cooper, M F; Wilson, P D; Hartop, P J; Shuster, S

    1980-06-01

    Epidermal lipid biosynthesis was normal in patients with mild ichthyosis due to Hodgkin's disease, but greatly reduced in one patient with severe ichthyosis. Dermal (sebaceous) lipid synthesis was decreased in all patients with Hodgkin's disease, whether or not they had ichthyosis, and was greatly reduced in the patient with severe ichthyosis. Neither the mechanism nor the possible relationship between the dermal and epidermal changes is understood.

  3. Evaluation of dermal fillers with noncontact optical coherence elastography

    Science.gov (United States)

    Singh, Manmohan; Wang, Shang; Yee, Richard W.; Han, Zhaolong; Aglyamov, Salavat R.; Larin, Kirill V.

    2017-02-01

    Over 2 million dermal filler procedures are performed each year in the USA alone, and this figure is only expected to increase as the aging population continues to grow. Dermal filler treatments can last from a few months to years depending on the type of filler and its placement. Although adverse reactions are rare, they can be quite severe due to ischemic events and filler migration. Previously, techniques such as ultrasound or magnetic resonance imaging have been used to evaluate the filler injections. However, these techniques are not practical for real-time filler injection guidance due to limitations such as the physical presence of the transducer. In this work, we propose the use of optical coherence tomography (OCT) for image-guided dermal filler injections due to the high spatial and temporal resolution of OCT. In addition, we utilize a noncontact optical coherence elastography (OCE) technique, to evaluate the efficacy of the dermal filler injection. A grid of air-pulse OCE measurements was taken, and the dynamic response of the skin to the air-pulse was translated to the Young's modulus and shear viscosity. Our results show that OCT was able to visualize the dermal filler injection process, and that OCE was able to localize the dermal filler injection sites. Combined with functional techniques such as optical microangiography, and recent advanced in OCT hardware, OCT may be able to provide real-time injection guidance in 3D by visualizing blood vessels to prevent ischemic events.

  4. Microneedle technologies for (trans)dermal drug and vaccine delivery.

    Science.gov (United States)

    van der Maaden, Koen; Jiskoot, Wim; Bouwstra, Joke

    2012-07-20

    Microneedles have been used for the dermal and transdermal delivery of a broad range of drugs, such as small molecular weight drugs, oligonucleotides, DNA, peptides, proteins and inactivated viruses. However, until now there are no microneedle-based (trans)dermal drug delivery systems on the market. In the past decade various types of microneedles have been developed by a number of production processes. Numerous geometries of microneedles have been designed from various materials. These microneedles have been used for different approaches of microneedle-based (trans)dermal drug delivery. Following a brief introduction about dermal and transdermal drug delivery, this review describes different production methods for solid and hollow microneedles as well as conditions that influence skin penetration. Besides, the four microneedle-based (trans)dermal drug delivery approaches are discussed: "poke and flow", "poke and patch", "poke and release", and "coat and poke". A separate section of this review is devoted to the use of microneedles for the delivery of therapeutic proteins and vaccines. Finally, we give our view on research and development that is needed to render microneedle-based (trans)dermal drug delivery technologies clinically useful in the near future.

  5. Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients.

    Science.gov (United States)

    Api, Anne Marie; Basketter, David A; Cadby, Peter A; Cano, Marie-France; Ellis, Graham; Gerberick, G Frank; Griem, Peter; McNamee, Pauline M; Ryan, Cindy A; Safford, Robert

    2008-10-01

    Based on chemical, cellular, and molecular understanding of dermal sensitization, an exposure-based quantitative risk assessment (QRA) can be conducted to determine safe use levels of fragrance ingredients in different consumer product types. The key steps are: (1) determination of benchmarks (no expected sensitization induction level (NESIL)); (2) application of sensitization assessment factors (SAF); and (3) consumer exposure (CEL) calculation through product use. Using these parameters, an acceptable exposure level (AEL) can be calculated and compared with the CEL. The ratio of AEL to CEL must be favorable to support safe use of the potential skin sensitizer. This ratio must be calculated for the fragrance ingredient in each product type. Based on the Research Institute for Fragrance Materials, Inc. (RIFM) Expert Panel's recommendation, RIFM and the International Fragrance Association (IFRA) have adopted the dermal sensitization QRA approach described in this review for fragrance ingredients identified as potential dermal sensitizers. This now forms the fragrance industry's core strategy for primary prevention of dermal sensitization to these materials in consumer products. This methodology is used to determine global fragrance industry product management practices (IFRA Standards) for fragrance ingredients that are potential dermal sensitizers. This paper describes the principles of the recommended approach, provides detailed review of all the information used in the dermal sensitization QRA approach for fragrance ingredients and presents key conclusions for its use now and refinement in the future.

  6. Long-Term Followup of Dermal Substitution with Acellular Dermal Implant in Burns and Postburn Scar Corrections

    OpenAIRE

    Juhasz, I.; Kiss, B.; Lukacs, L.; Erdei, I.; Peter, Z.; Remenyik, E.

    2010-01-01

    Full-thickness burn and other types of deep skin loss will result in scar formation. For at least partial replacement of the lost dermal layer, there are several options to use biotechnologically derived extracellular matrix components or tissue scaffolds of cadaver skin origin. In a survey, we have collected data on 18 pts who have previously received acellular dermal implant Alloderm. The age of these patients at the injury varied between 16 months and 84 years. The average area of the impl...

  7. Advances in research on labyrinth membranous barriers

    Institute of Scientific and Technical Information of China (English)

    Wenfang Sun; Wuqing Wang

    2015-01-01

    Integrity of the membranous labyrinth barrier system is of critical importance, which promotes inner ear homeostasis and maintains its features. The membranous labyrinth barrier system is divided into several subsets of barriers which, although independent from each other, are interrelated. The same substance may demonstrate different permeability characteristics through different barriers and under different conditions, while different substances can have different permeability features even in the same barrier under the same condition. All parts of the mem-branous labyrinth barrier structure, including their morphology, enzymes and channel proteins, and theirs permeability characteristics under various physiological and pathological conditions are reviewed in this paper. Infections, noise exposure, ototoxicity may all increase perme-ability of the barriers and lead to disturbances in inner ear homeostasis. Copyright © 2015 The Authors. Production & hosting by Elsevier (Singapore) Pte Ltd On behalf of PLA General Hospital Department of Otolaryngology Head and Neck Surgery. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  8. Fine needle aspiration cytology of dermal cylindroma

    Directory of Open Access Journals (Sweden)

    Parikshaa Gupta

    2014-01-01

    Full Text Available In this paper, we have described fine needle aspiration cytology (FNAC of a rare case of dermal cylindroma. A 40-year-old female presented with a lateral mid-cervical swelling fixed to the skin. FNAC smears showed multiple clusters of small, round to oval cells with hyperchromatic nuclei, inconspicuous nucleoli and scant cytoplasm. In addition, the background showed deposits of basement membrane type material. This was dark magenta colored pinkish globular material. The globules were occasionally surrounded by the basal type of cells. Occasional cells with elongated nuclei were also noted. Cytological diagnosis of skin adnexal tumor possibly cylindroma was offered. Subsequent histopathology of the swelling showed sheets and clusters of cells in a jigsaw puzzle-like fashion. Deposition of abundant basement membrane-like material was noted in between the tumor cells. A diagnosis of cylindorma was offered. FNAC along with the subcutaneous location of the tumor and absence of primary salivary gland tumor may help to diagnose such rare case.

  9. Dermal factors influencing measurement of skin autofluorescence.

    Science.gov (United States)

    Noordzij, Margaretha J; Lefrandt, Joop D; Graaff, Reindert; Smit, Andries J

    2011-02-01

    Skin autofluorescence (SAF) is a noninvasive marker of accumulation of advanced glycation end products. It predicts cardiovascular complications and mortality in diabetes and renal failure. We assessed the influence of potential common confounders in SAF measurement, by determining the effects of endogenous and exogenous local dermal changes by body creams, hyperemia, vasoconstriction, and hydration. SAF was measured before and after local administration of body lotion, day cream, sunscreen, or self-browning cream and after attempts to remove these effects with alcohol swabs and washing. SAF was measured before and during three hyperemia maneuvers: vasoconstriction and on a dry and wet skin. The body lotion increased SAF by 18%. Day cream, sunscreen, and self-browning cream gave an increase of >100%. Except for body lotion, subsequent cleaning with alcohol swabs and washing with soap did not return SAF to baseline values. The effect of self-browning cream persisted for 2 weeks and that of sunscreen for 4 days. Hyperemia caused by a hot bath, capsicum cream, or postocclusive reactive hyperemia gave a decrease in SAF of, respectively, 18%, 22%, and 2.3%. Vasoconstriction caused by immersing the arm in cold water gave a 10% increase. Hydration state did not influence SAF. Measurement of SAF is strongly affected by several skin creams. This effect was often not fully corrected by alcohol swabs and washing with soap and may persist for many days. Marked hyperemia and vasoconstriction also influence SAF. We advise avoiding these potential error sources.

  10. Emotional intelligence and electro-dermal activity.

    Science.gov (United States)

    Zysberg, Leehu

    2012-09-01

    Emotional intelligence (EI) is a promising concept in our understanding of emotional regulation, related behaviors and pathologies. However, research linking EI to underlying physiological and biological structure and responses is meager. This study explored potential associations of EI with electro-dermal activity (EDA) responses to emotionally arousing visual stimuli. It was hypothesized that higher levels of EI will associate with more efficient emotional regulation as reflected by EDA. Eighty-four healthy participants were exposed to stimuli consisting of a series of 12 images designed to evoke positive or negative emotional responses, presented in a counterbalanced order. A self-report questionnaire and a computer based test of EI were administered along with a demographic questionnaire. EDA measures were taken during the exposure to the above stimuli using BIOPACK MP150. EI test scores (Beta = .35, .32; p self-report measure of EI and other demographics (e.g., gender. ethnicity) did not show any associations with the outcome measures. The results support the relevance of the concept to our understanding of emotional responses and regulation. The findings are briefly discussed within the context of underlying mechanisms of EI as well as measure validity and relevance.

  11. Zinc homeostasis and neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Bernadeta eSzewczyk

    2013-07-01

    Full Text Available Zinc is an essential trace element, whose importance to the function of the central nervous system (CNS is increasingly being appreciated. Alterations in zinc dyshomeostasis has been suggested as a key factor in the development of several neuropsychiatric disorders. In the CNS, zinc occurs in two forms: the first being tightly bound to proteins and, secondly, the free, cytoplasmic or extracellular form found in presynaptic vesicles. Under normal conditions, zinc released from the synaptic vesicles modulates both ionotropic and metabotropic post-synaptic receptors. While under clinical conditions such as traumatic brain injury, stroke or epilepsy, the excess influx of zinc into neurons has been found to result in neurotoxicity and damage to postsynaptic neurons. On the other hand, a growing body of evidence suggests that a deficiency, rather than an excess, of zinc leads to an increased risk for the development of neurological disorders. Indeed, zinc deficiency has been shown to affect neurogenesis and increase neuronal apoptosis, which can lead to learning and memory deficits. Altered zinc homeostasis is also suggested as a risk factor for depression, Alzheimer’s disease, aging and other neurodegenerative disorders. Under normal CNS physiology, homeostatic controls are put in place to avoid the accumulation of excess zinc or its deficiency. This cellular zinc homeostasis results from the actions of a coordinated regulation effected by different proteins involved in the uptake, excretion and intracellular storage/trafficking of zinc. These proteins include membranous transporters (ZnT and Zip and metallothioneins (MT which control intracellular zinc levels. Interestingly, alterations in ZnT and MT have been recently reported in both aging and Alzheimer’s disease. This paper provides an overview of both clinical and experimental evidence that implicates a dysfunction in zinc homeostasis in the pathophysiology of depression, Alzheimer

  12. Asphalt fume dermal carcinogenicity potential: I. dermal carcinogenicity evaluation of asphalt (bitumen) fume condensates.

    Science.gov (United States)

    Clark, Charles R; Burnett, Donald M; Parker, Craig M; Arp, Earl W; Swanson, Mark S; Minsavage, Gary D; Kriech, Anthony J; Osborn, Linda V; Freeman, James J; Barter, Robert A; Newton, Paul E; Beazley, Shelley L; Stewart, Christopher W

    2011-10-01

    Asphalt (bitumen) fume condensates collected from the headspace above paving and Type III built up roofing asphalt (BURA) tanks were evaluated in two-year dermal carcinogenicity assays in male C3H/HeNCrl mice. A third sample was generated from the BURA using a NIOSH laboratory generation method. Similar to earlier NIOSH studies, the BURA fume condensates were applied dermally in mineral oil twice per week; the paving sample was applied 7 days/week for a total weekly dose of 50 mg/wk in both studies. A single benign papilloma was observed in a group of 80 mice exposed to paving fume condensate at the end of the two-year study and only mild skin irritation was observed. The lab generated BURA fume condensate resulted in statistically significant (P<0.0001) increases in squamous cell carcinomas (35 animals or 55% of animals at risk). The field-matched BURA condensate showed a weaker but significant (P=0.0063) increase (8 carcinomas or 13% of animals) and a longer average latency (90 weeks vs. 76 for the lab fume). Significant irritation was observed in both BURA condensates. It is concluded that the paving fume condensate was not carcinogenic under the test conditions and that the field-matched BURA fume condensate produced a weak tumor response compared to the lab generated sample.

  13. Human Dermal Stem/Progenitor Cell-Derived Conditioned Medium Improves Senescent Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Ji-Yong Jung

    2015-08-01

    Full Text Available Adult skin stem cells are recognized as potential therapeutics to rejuvenate aged skin. We previously demonstrated that human dermal stem/progenitor cells (hDSPCs with multipotent capacity could be enriched from human dermal fibroblasts using collagen type IV. However, the effects of hDSPCs on cellular senescence remain to be elucidated. In the present study, we investigated whether conditioned medium (CM collected from hDSPC cultures (hDSPC-CM exhibits beneficial effects on senescent fibroblasts. We found that hDSPC-CM promoted proliferation and decreased the expression level of senescence-associated β-galactosidase in senescent fibroblasts. In addition, p53 phosphorylation and p21 expression were significantly reduced in senescent fibroblasts treated with hDSPC-CM. hDSPC-CM restored the expression levels of collagen type I, collagen type III, and tissue inhibitor of metalloproteinase, and antagonized the increase of matrix metalloproteinase 1 expression. Finally, we demonstrated that hDSPC-CM significantly reduced reactive oxygen species levels by specifically up-regulating the expression level of superoxide dismutase 2. Taken together, these data suggest that hDSPC-CM can be applied as a potential therapeutic agent for improving human aged skin.

  14. Activation of epithelial STAT3 regulates intestinal homeostasis.

    Science.gov (United States)

    Neufert, Clemens; Pickert, Geethanjali; Zheng, Yan; Wittkopf, Nadine; Warntjen, Moritz; Nikolaev, Alexei; Ouyang, Wenjun; Neurath, Markus F; Becker, Christoph

    2010-02-15

    The intestinal epithelium that lines the mucosal surface along the GI-tract is a key player for the intestinal homeostasis of the healthy individual. In case of a mucosal damage or a barrier defect as seen in patients with inflammatory bowel disease, the balance is disturbed, and translocation of intestinal microbes to the submucosa is facilitated. We recently demonstrated a pivotal role of STAT3 activation in intestinal epithelial cells (IEC) for the restoration of the balance at the mucosal surface of the gut in an experimental colitis model. STAT3 was rapidly induced in intestinal epithelial cells upon challenge of mice in both experimental colitis and intestinal wound healing models. STAT3 activation was found to be dispensable in the steady-state conditions but was important for efficient regeneration of the epithelium in response to injury. Here, we extend our previous findings by showing epithelial STAT3 activation in human patients suffering from IBD and provide additional insights how the activation of epithelial STAT3 by IL-22 regulates intestinal homeostasis and mucosal wound healing. We also demonstrate that antibody-mediated neutralization of IL-22 has little impact on the development of experimental colitis in mice, but significantly delays recovery from colitis. Thus, our data suggest that targeting the STAT3 signaling pathway in IEC is a promising therapeutic approach in situations when the intestinal homeostasis is disturbed, e.g., as seen in Crohn's disease or Ulcerative colitis.

  15. A physiologist's view of homeostasis.

    Science.gov (United States)

    Modell, Harold; Cliff, William; Michael, Joel; McFarland, Jenny; Wenderoth, Mary Pat; Wright, Ann

    2015-12-01

    Homeostasis is a core concept necessary for understanding the many regulatory mechanisms in physiology. Claude Bernard originally proposed the concept of the constancy of the "milieu interieur," but his discussion was rather abstract. Walter Cannon introduced the term "homeostasis" and expanded Bernard's notion of "constancy" of the internal environment in an explicit and concrete way. In the 1960s, homeostatic regulatory mechanisms in physiology began to be described as discrete processes following the application of engineering control system analysis to physiological systems. Unfortunately, many undergraduate texts continue to highlight abstract aspects of the concept rather than emphasizing a general model that can be specifically and comprehensively applied to all homeostatic mechanisms. As a result, students and instructors alike often fail to develop a clear, concise model with which to think about such systems. In this article, we present a standard model for homeostatic mechanisms to be used at the undergraduate level. We discuss common sources of confusion ("sticky points") that arise from inconsistencies in vocabulary and illustrations found in popular undergraduate texts. Finally, we propose a simplified model and vocabulary set for helping undergraduate students build effective mental models of homeostatic regulation in physiological systems.

  16. Alteration of Skin Properties with Autologous Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Rajesh L. Thangapazham

    2014-05-01

    Full Text Available Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices.

  17. Copper Homeostasis in Mycobacterium tuberculosis

    Science.gov (United States)

    Shi, Xiaoshan; Darwin, K. Heran

    2015-01-01

    Copper (Cu) is a trace element essential for the growth and development of almost all organisms, including bacteria. However, Cu overload in most systems is toxic. Studies show Cu accumulates in macrophage phagosomes infected with bacteria, suggesting Cu provides an innate immune mechanism to combat invading pathogens. To counteract the host-supplied Cu, increasing evidence suggests that bacteria have evolved Cu resistance mechanisms to facilitate their pathogenesis. In particular, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has evolved multiple pathways to respond to Cu. Here, we summarize what is currently known about Cu homeostasis in Mtb and discuss potential sources of Cu encountered by this and other pathogens in a mammalian host. PMID:25614981

  18. Pesticides re-entry dermal exposure of workers in greenhouses.

    Science.gov (United States)

    Caffarelli, V; Conte, E; Correnti, A; Gatti, R; Musmeci, F; Morali, G; Spagnoli, G; Tranfo, G; Triolo, L; Vita, M; Zappa, G

    2004-01-01

    This research has the aim to evaluate the risk of pesticide dermal exposure for workers in greenhouses. We considered the following crops: tomato, cucumber and strawberry, largely spread in Bracciano lake district. The pesticides monitored were: tetradifon on strawberry: metalaxyl, azoxystrobin and fenarimol on cucumber; acrinathrin, azoxystrobin and chlorpyrifos ethyl on tomato. The dermal exposure was evaluated by Dislodgeable Foliar Residue (DFR) measurements employing transfer coefficients got from literature. For risk evaluation, we have compared the dermal exposures with Acceptable Operator Exposure Levels (AOEL). The re-entry time were obtained intercepting the dose decay curves with AOEL values. The re-entry times result higher than two days in the cases of chlorpyrifos on tomato (re-entry time: 3 days), azoxystrobin on tomato (4 days), and tetradifon on strawberry (8 days). The need of measuring specific transfer coefficients is pointed out.

  19. Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sterry, W.; Pullmann, H.; Steigleder, G.K.

    1981-01-01

    To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of /sup 3/H-thymidine-labeled infiltrating cells (/sup 3/H-index). A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the /sup 3/H-index is moderately elevated in stage I and high in stage III. The /sup 3/H-index is within normal range in dermal infiltrate of Sezary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis. In parapsoriasis en plaques two groups can be distinguished: in the small plaque variant (chronic superficial dermatitis) the /sup 3/H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity. Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.

  20. Blaschko Linear Enamel Defects - A Marker for Focal Dermal Hypoplasia: Case Report of Focal Dermal Hypoplasia

    Directory of Open Access Journals (Sweden)

    Stefan Gysin

    2015-05-01

    Full Text Available Focal dermal hypoplasia (FDH is a rare genetic skin disorder. The inheritance of FDH or Goltz-Gorlin syndrome is X-linked dominant and the disease is associated with a PORCN gene mutation. This gene plays a key role in the Wnt pathway, which has an impact on embryonic development. Every tissue derived from meso- and ectoderm can be affected. Patients suffer from cutaneous, ocular, osseous, oral and dental defects. The skin and dental alterations manifest along the Blaschko lines. We present a woman (born in 1962 suffering from FDH with congenital skin changes and Blaschko linear enamel defects. Typical symptoms (e.g. fat herniations, scoliosis, syndactyly, microphthalmia, caries and alopecia plus vertical grooving of all teeth gave a first indication. Molecular genetic testing confirmed the definitive diagnosis of FDH. We hypothesize that, in the context of typical skin changes, visible Blaschko lines on the teeth in the form of vertical grooves are almost pathognomonic for FDH.

  1. Dermal Exposure during Filling, Loading and Brushing with Products Containing 2-(2-Butoxyethoxy)ethanol

    NARCIS (Netherlands)

    Gijsbers, J.H.J.; Tielemans, E.; Brouwer, D.H.; Hemmen, J.J. van

    2004-01-01

    Introduction: Limited quantitative information is available on dermal exposure to chemicals during various industrial activities. Therefore, within the scope of the EU-funded RISKOFDERM project, potential dermal exposure was measured during three different tasks: filling, loading and brushing. DEGBE

  2. Successful breast reconstruction using acellular dermal matrix can be recommended in healthy non-smoking patients

    DEFF Research Database (Denmark)

    Gunnarsson, Gudjon Leifur; Børsen-Koch, Mikkel; Arffmann, Susanne

    2013-01-01

    We present Scandinavia's first series of immediate alloplastic breast reconstructions with an acellular dermal matrix.......We present Scandinavia's first series of immediate alloplastic breast reconstructions with an acellular dermal matrix....

  3. [Exploratory study on the micro-remodeling of dermal tissue].

    Science.gov (United States)

    Jiang, Yu-zhi; Ding, Gui-fu; Lu, Shu-liang

    2009-10-01

    To explore the effect of three-dimensional structure of dermal matrix on biological behavior of fibroblasts (Fb) in the microcosmic perspective. The three-dimensional structure of dermal tissue was analyzed by plane geometric and trigonometric function. Microdots structure array with cell adhesion effect was designed by computer-assisted design software according to the adhesive and non-adhesive components of dermal tissue. Four sizes (8 microm x 3 microm, space 6 microm; 16 microm x 3 microm, space 6 microm; 16 microm x 5 microm, space 8 microm; 20 microm x 3 microm, space 2 microm) of micropier grid used for cell culture (MPGCC) with cell-adhesive microdots, built up with micro-pattern printing and molecule self-assembly method were used to culture dermal Fb. Fb cultured with cell culture matrix without micropier grid was set up as control. The expression of skeleton protein (alpha-SMA) of Fb, cell viability and cell secretion were detected with immunohistochemistry, fluorescent immunohistochemistry, MTT test and the hydroxyproline content assay. The three-dimensional structure of dermal tissue could be simulated by MPGCC as shown in arithmetic analysis. Compared with those of control group [(12 +/- 3)% and (0.53 +/- 0.03) microg/mg, (0.35 +/- 0.04)], the expression of alpha-SMA [(49 +/- 3)%, (61 +/- 3)%, (47 +/- 4)%, (51 +/- 3)%] and the content of hydroxyproline [(0.95 +/- 0.04), (0.87 +/- 0.03), (0.81 +/- 0.03), (0.77 +/- 0.03) microg/mg] were increased significantly (P cell viability of Fb (0.12 +/- 0.03, 0.13 +/- 0.04, 0.14 +/- 0.03, 0.19 +/- 0.03) cultured in MPGCC was decreased significantly (P cell viability and the content of hydroxyproline of Fb cultured in four sizes of MPGCC were also significantly changed as compared with one another (P < 0.05). MPGCC may be the basic functional unit of dermal template, or unit of dermal template to call. Different three-dimensional circumstances for dermal tissue can result in different template effect and wound

  4. Probiotics and Dermal Applications%益生菌皮肤应用

    Institute of Scientific and Technical Information of China (English)

    陈伟; 孟庆娜

    2014-01-01

    Probiotics can contribute to modulate cutaneous microflora,lipid barrier,and skin immune system,leading to the preservation of the skin homeostasis.This review outlines skin microflora and their applications.%研究显示,某些益生菌能够调整表皮微生物群,类脂屏障和皮肤的免疫系统,进而维持皮肤稳态。本文介绍了皮肤的微生态系统及益生菌应用。

  5. File list: InP.Epd.10.AllAg.Dermal_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Epd.10.AllAg.Dermal_fibroblast hg19 Input control Epidermis Dermal fibroblast S...,SRX447386,SRX666594,SRX447389,SRX200051,SRX864096,SRX200053 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Epd.10.AllAg.Dermal_fibroblast.bed ...

  6. File list: NoD.Epd.05.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Epd.05.AllAg.Dermal_fibroblasts mm9 No description Epidermis Dermal fibroblasts... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Epd.05.AllAg.Dermal_fibroblasts.bed ...

  7. File list: ALL.Epd.20.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Epd.20.AllAg.Dermal_fibroblasts mm9 All antigens Epidermis Dermal fibroblasts S...26,SRX310225,SRX310224,SRX388187 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Epd.20.AllAg.Dermal_fibroblasts.bed ...

  8. File list: InP.Epd.50.AllAg.Dermal_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Epd.50.AllAg.Dermal_fibroblast hg19 Input control Epidermis Dermal fibroblast S...,SRX200045,SRX864096,SRX200053,SRX200051,SRX447389,SRX447386 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Epd.50.AllAg.Dermal_fibroblast.bed ...

  9. File list: Oth.Epd.20.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Epd.20.AllAg.Dermal_fibroblasts mm9 TFs and others Epidermis Dermal fibroblasts... SRX247302,SRX382120,SRX247301,SRX247303,SRX382119,SRX310229,SRX310227,SRX310225 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Epd.20.AllAg.Dermal_fibroblasts.bed ...

  10. Validation of the dermal exposure model in ECETOC TRA.

    Science.gov (United States)

    Marquart, Hans; Franken, Remy; Goede, Henk; Fransman, Wouter; Schinkel, Jody

    2017-08-01

    The ECETOC TRA model (presently version 3.1) is often used to estimate worker inhalation and dermal exposure in regulatory risk assessment. The dermal model in ECETOC TRA has not yet been validated by comparison with independent measured exposure levels. This was the goal of the present study. Measured exposure levels and relevant contextual information were gathered via literature search, websites of relevant occupational health institutes and direct requests for data to industry. Exposure data were clustered in so-called exposure cases, which are sets of data from one data source that are expected to have the same values for input parameters in the ECETOC TRA dermal exposure model. For each exposure case, the 75th percentile of measured values was calculated, because the model intends to estimate these values. The input values for the parameters in ECETOC TRA were assigned by an expert elicitation and consensus building process, based on descriptions of relevant contextual information.From more than 35 data sources, 106 useful exposure cases were derived, that were used for direct comparison with the model estimates. The exposure cases covered a large part of the ECETOC TRA dermal exposure model. The model explained 37% of the variance in the 75th percentiles of measured values. In around 80% of the exposure cases, the model estimate was higher than the 75th percentile of measured values. In the remaining exposure cases, the model estimate may not be sufficiently conservative.The model was shown to have a clear bias towards (severe) overestimation of dermal exposure at low measured exposure values, while all cases of apparent underestimation by the ECETOC TRA dermal exposure model occurred at high measured exposure values. This can be partly explained by a built-in bias in the effect of concentration of substance in product used, duration of exposure and the use of protective gloves in the model. The effect of protective gloves was calculated to be on average a

  11. Dermal Lipogenesis Inhibits Adiponectin Production in Human Dermal Fibroblasts while Exogenous Adiponectin Administration Prevents against UVA-Induced Dermal Matrix Degradation in Human Skin.

    Science.gov (United States)

    Fang, Chien-Liang; Huang, Ling-Hung; Tsai, Hung-Yueh; Chang, Hsin-I

    2016-07-14

    Adiponectin is one of the most abundant adipokines from the subcutaneous fat, and regulates multiple activities through endocrine, paracrine, or autocrine mechanisms. However, its expression in adipogenic induced fibroblasts, and the potential role in photoaging has not been determined. Here, human dermal fibroblasts, Hs68, were presented as a cell model of dermal lipogenesis through stimulation of adipogenic differentiation medium (ADM). Similar to other studies in murine pre-adipocyte models (i.e., 3T3-L1), Hs68 fibroblasts showed a tendency to lipogenesis based on lipid accumulation, triglyceride formation, and the expressions of PPAR-γ, lipoprotein lipase (LPL), and FABP4 mRNA. As expected, ADM-treated fibroblasts displayed a reduction on adiponectin expression. Next, we emphasized the photoprotective effects of adiponectin against UVA-induced damage in Hs68 fibroblasts. UVA radiation can downregulate cell adhesion strength and elastic modulus of Hs68 fibroblasts. Moreover, UVA radiation could induce the mRNA expressions of epidermal growth factor receptor (EGFR), adiponectin receptor 1 (AdipoR1), matrix metalloproteinase-1 (MMP-1), MMP-3, and cyclooxygenase-2 (COX-2), but downregulate the mRNA expressions of type I and type III collagen. On the other hand, post-treatment of adiponectin can partially overcome UVA-induced reduction in the cell adhesion strength of Hs68 fibroblasts through the activation of AdipoR1 and the suppression of EGF-R. In addition, post-treatment of adiponectin indicated the increase of type III collagen and elastin mRNA expression and the decrease of MMP-1 and MMP-3 mRNA expression, but a limited degree of recovery of elastic modulus on UVA-irradiated Hs68 fibroblasts. Overall, these results suggest that dermal lipogenesis may inhibit the expression of adiponectin while exogenous adiponectin administration prevents against UVA-induced dermal matrix degradation in Hs68 fibroblasts.

  12. Genetically engineered mouse models to evaluate the role of Wnt secretion in bone development and homeostasis.

    Science.gov (United States)

    Williams, Bart O

    2016-03-01

    Alterations in components of the Wnt signaling pathway are associated with altered bone development and homeostasis in several human diseases. We created genetically engineered mouse models (GEMMs) that mimic the cellular defect associated with the Porcupine mutations in patients with Goltz Syndrome/Focal Dermal Hypoplasia. These GEMMs were established by utilizing mice containing a conditionally inactivatable allele of Wntless/GPR177 (a gene encoding a protein required for the transport of Porcupine-modified ligand to the plasma membrane for secretion). We crossed this strain to another which drives cre-mediated gene deletion in mature osteoblasts (Osteocalcin-cre) resulted in mice lacking the ability to secrete Wnt ligands in this cell type. These mice displayed severely reduced bone mass and provide a model to understand the effects of disrupting the ability to secrete Wnt ligands on the skeletal system.

  13. Task-based dermal exposure models for regulatory risk assessment

    NARCIS (Netherlands)

    Warren, N.D.; Marquart, H.; Christopher, Y.; Laitinen, J.; Hemmen, J.J. van

    2006-01-01

    The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of ne

  14. Crosslinking of dermal sheep collagen using hexamethylene diisocyanate

    NARCIS (Netherlands)

    Olde Damink, L.H.H.; Dijkstra, P.J.; Luyn, van M.J.A.; Wachem, van P.B.; Nieuwenhuis, P.; Feijen, J.

    1995-01-01

    The use of hexamethylene diisocyanate (HMDIC) as a crosslinking agent for dermal sheep collagen (DSC) was studied. Because HMDIC is only slightly water soluble, a surfactant was used to obtain a clear and micellar crosslinking solution and to promote the penetration of HMDIC in the DSC matrix. Using

  15. Differential Apoptosis in Mucosal and Dermal Wound Healing

    Science.gov (United States)

    Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

    2014-01-01

    Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; pwound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

  16. Dermal Uptake of Organic Vapors Commonly Found in Indoor Air

    DEFF Research Database (Denmark)

    Weschler, Charles J.; Nazaroff, William W

    2014-01-01

    . In this group are common parabens, lower molecular weight phthalates, o-phenylphenol, Texanol, ethylene glycol, and α-terpineol. For other compounds, estimated dermal uptakes are small compared to inhalation. Examples include aliphatic hydrocarbons, single ring aromatics, terpenes, chlorinated solvents...

  17. CROSS-LINKING OF DERMAL SHEEP COLLAGEN USING HEXAMETHYLENE DIISOCYANATE

    NARCIS (Netherlands)

    DAMINK, LHHO; DIJKSTRA, PJ; VANLUYN, MJA; VANWACHEM, PB; NIEUWENHUIS, P; FEIJEN, J

    1995-01-01

    The use of hexamethylene diisocyanate (HMDIC) as a crosslinking agent for dermal sheep collagen (DSC) was studied. Because HMDIC is on ly slightly water soluble, a surfactant was used to obtain a clear and micellar crosslinking solution and to promote the penetration of HMDIC in the DSC matrix. Usin

  18. The Effect of Gynostemma pentaphyllum Extract on Mouse Dermal Fibroblasts.

    Science.gov (United States)

    Lobo, Sara Nadia; Qi, Yu Qing; Liu, Quan Zhong

    2014-01-01

    Background. The objective of this paper is to demonstrate the effect of Gynostemma pentaphyllum extract on mouse dermal fibroblasts. Recent studies have shown that this plant may possess great antioxidant properties, which can be very beneficial in combating oxidative stress. Methods. Gynostemma pentaphyllum extract was prepared and mouse dermal fibroblasts were obtained and cultured as per our laboratory protocols. Twelve samples of cells were cultured under the same conditions and both negative and positive controls were established. Induction of oxidative stress was carried out using ultraviolet C (UVC) light. Viable cell count was carried out, using microscopy. The analysis of the overall results was processed using SPSS version 16.0. Results. Statistical analysis showed strong positive correlation between the concentration of Gynostemma pentaphyllum and the mean duration of cell viability (rs = 1), with a high level of statistical significance (P Gynostemma pentaphyllum extract prolongs viability of mouse dermal fibroblasts damaged by UVC light-induced oxidative stress. The results show the potential benefits of this extract on dermal cell aging.

  19. PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES

    Science.gov (United States)

    PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATESM.J.K. Selgrade, E.H. Boykin, N.H. Coates, D.L. Doerfler, S.H. GavettExperimental Toxicology Div., National Health and Environmental Research Laboratory, Office of Research and Developmen...

  20. Cerebellair abces door een occipitale dermale sinus bij een zuigeling

    NARCIS (Netherlands)

    Groen, R J; van Ouwerkerk, W J

    1994-01-01

    A 7.5-month-old girl was admitted with the clinical signs and symptoms of raised intracranial pressure. This was caused by an obstructive hydrocephalus, due to cerebellar abscesses induced by an infected contiguous complete occipital dermal sinus. Staphylococcus aureus was cultured. The patient was

  1. Task-based dermal exposure models for regulatory risk assessment

    NARCIS (Netherlands)

    Warren, N.D.; Marquart, H.; Christopher, Y.; Laitinen, J.; Hemmen, J.J. van

    2006-01-01

    The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of

  2. In vivo dermal absorption of pyrethroid pesticides in the rat.

    Science.gov (United States)

    The potential for exposure to pyrethroid pesticides has risen recently because of their increased use. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin and permethrin in the rat. Hair on the dorsal side of anesthetized adult m...

  3. Novel System for Testing Dermal and Epidermal Toxicity in Vitro

    Science.gov (United States)

    1990-02-15

    months of this contract, we have been successful at establishing primary culture from 20 neonatal foreskin samples (from routine circumcisions ) and 6...objectives: 1. Established an inventory of neonatal and adult keratinocytes and fibroblasts. Modified the procedure for establishing and passing these...thymidine incorporation into adherent cell populations. Substrates utilized included neonatal fibroblast dermal equivalents (from foreskin) and adult

  4. 40 CFR 799.9120 - TSCA acute dermal toxicity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA acute dermal toxicity. 799.9120 Section 799.9120 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES...) Preparations. Healthy young adult animals are acclimatized to the laboratory conditions for at least 5...

  5. Defense against dermal exposures is only skin deep

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Nielsen, Flemming; Sørensen, Jens Ahm

    2007-01-01

    substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present...

  6. Taurine Homeostasis and Volume Control.

    Science.gov (United States)

    Pasantes-Morales, Herminia

    2017-01-01

    Taurine content is high (mM) in mammalian brain. By its major role as an osmolyte, taurine contributes to the cell volume control, which is particularly critical in the brain. Taurine participates in osmotic adjustments required to maintain the organization and size of intracellular compartments. It counteracts volume fluctuations in unbalanced transmembrane fluxes of ions and neurotransmitters, preserving the functional synaptic contacts. Taurine has a key role in the long-term adaptation to chronic hyponatremia as well as in other pathologies leading to brain edema. Together with other osmolytes, taurine corrects cell shrinkage, preventing mysfunction of organelles and apoptosis. Swelling corrective taurine efflux occurs through a leak pathway, likely formed by LCRR8 protein isoforms. Shrinkage-activated influx comes largely by the increased activity of the Na(+)/Cl(-)-dependent transporter. The brain taurine pool results from the equilibrium between (i) dietary intake and active transport into the cell, (ii) synthesis in the brain itself or import of that synthesized elsewhere, and (iii) leak and posterior excretion. The interplay between these elements preserves brain taurine homeostasis in physiological conditions and permits the proper adjustments upon deviations of normal in the internal/external environment.

  7. Redox Homeostasis in Pancreatic Cells

    Directory of Open Access Journals (Sweden)

    Petr Ježek

    2012-01-01

    Full Text Available We reviewed mechanisms that determine reactive oxygen species (redox homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreatic β cells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion in β cell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreatic β cells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreatic β cells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreatic β cells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release.

  8. Inhalation and dermal exposure among asphalt paving workers.

    Science.gov (United States)

    McClean, M D; Rinehart, R D; Ngo, L; Eisen, E A; Kelsey, K T; Herrick, R F

    2004-11-01

    The primary objective of this study was to identify determinants of inhalation and dermal exposure to polycyclic aromatic compounds (PACs) among asphalt paving workers. The study population included three groups of highway construction workers: 20 asphalt paving workers, as well as 12 millers and 6 roadside construction workers who did not work with hot-mix asphalt. During multiple consecutive work shifts, personal air samples were collected from each worker's breathing zone using a Teflon filter and cassette holder connected in series with an XAD-2 sorbent tube, while dermal patch samples were collected from the underside of each worker's wrist. All exposure samples were analyzed for PACs, pyrene and benzo[a]pyrene. Inhalation and dermal PAC exposures were highest among asphalt paving workers. Among paving workers, inhalation and dermal PAC exposures varied significantly by task, crew, recycled asphalt product (RAP) and work rate (inhalation only). Asphalt mix containing high RAP was associated with a 5-fold increase in inhalation PAC exposures and a 2-fold increase in dermal PAC exposure, compared with low RAP mix. The inhalation PAC exposures were consistent with the workers' proximity to the primary source of asphalt fume (paver operators > screedmen > rakers > roller operators), such that the adjusted mean exposures among paver operators (5.0 microg/m3, low RAP; 24 microg/m3, high RAP) were 12 times higher than among roller operators (0.4 microg/m3, low RAP; 2.0 microg/m3, high RAP). The dermal PAC exposures were consistent with the degree to which the workers have actual contact with asphalt-contaminated surfaces (rakers > screedmen > paver operators > roller operators), such that the adjusted mean exposures among rakers (175 ng/cm2, low RAP; 417 ng/cm2, high RAP) were approximately 6 times higher than among roller operators (27 ng/cm2, low RAP; 65 ng/cm2, high RAP). Paving task, RAP content and crew were also found to be significant determinants of

  9. JAM-related proteins in mucosal homeostasis and inflammation.

    Science.gov (United States)

    Luissint, Anny-Claude; Nusrat, Asma; Parkos, Charles A

    2014-03-01

    Mucosal surfaces are lined by epithelial cells that form a physical barrier protecting the body against external noxious substances and pathogens. At a molecular level, the mucosal barrier is regulated by tight junctions (TJs) that seal the paracellular space between adjacent epithelial cells. Transmembrane proteins within TJs include junctional adhesion molecules (JAMs) that belong to the cortical thymocyte marker for Xenopus family of proteins. JAM family encompasses three classical members (JAM-A, JAM-B, and JAM-C) and related molecules including JAM4, JAM-like protein, Coxsackie and adenovirus receptor (CAR), CAR-like membrane protein and endothelial cell-selective adhesion molecule. JAMs have multiple functions that include regulation of endothelial and epithelial paracellular permeability, leukocyte recruitment during inflammation, angiogenesis, cell migration, and proliferation. In this review, we summarize the current knowledge regarding the roles of the JAM family members in the regulation of mucosal homeostasis and leukocyte trafficking with a particular emphasis on barrier function and its perturbation during pathological inflammation.

  10. Multi-layered environmental regulation on the homeostasis of stem cells: The saga of hair growth and alopecia

    Science.gov (United States)

    Chen, Chih-Chiang; Chuong, Cheng Ming

    2013-01-01

    Stem cells are fascinating because of their potential in regenerative medicine. Stem cell homeostasis has been thought to be mainly regulated by signals from their adjacent micro-environment named the “stem cell niche”. However, recent studies reveal that there can be multiple layers of environmental controls. Here we review these environmental controls using the paradigm of hair stem cells, because to observe and analyze the growth of hair is easier due to their characteristic cyclic regeneration pattern. The length of hair fibers is regulated by the duration of the growth period. In the hair follicles, hair stem cells located in the follicle bulge interact with signals from the dermal papilla. Outside of the follicle, activation of hair stem cells has been shown to be modulated by molecules released from the intra-dermal adipose tissue as well as body hormone status, immune function, neural activities, and aging. The general physiological status of an individual is further influenced by circadian rhythms and changing seasons. The interactive networks of these environmental factors provide new understanding on how stem cell homeostasis is regulated, inspiring new insights for regenerative medicine. Therapies do not necessarily have to be achieved by using stem cells themselves which may constitute a higher risk but by modulating stem cell activity through targeting one or multiple layers of their micro- and macro-environments. PMID:22391240

  11. Multi-layered environmental regulation on the homeostasis of stem cells: the saga of hair growth and alopecia.

    Science.gov (United States)

    Chen, Chih-Chiang; Chuong, Cheng Ming

    2012-04-01

    Stem cells are fascinating because of their potential in regenerative medicine. Stem cell homeostasis has been thought to be mainly regulated by signals from their adjacent micro-environment named the "stem cell niche". However, recent studies reveal that there can be multiple layers of environmental controls. Here we review these environmental controls using the paradigm of hair stem cells, because to observe and analyze the growth of hair is easier due to their characteristic cyclic regeneration pattern. The length of hair fibers is regulated by the duration of the growth period. In the hair follicles, hair stem cells located in the follicle bulge interact with signals from the dermal papilla. Outside of the follicle, activation of hair stem cells has been shown to be modulated by molecules released from the intra-dermal adipose tissue as well as body hormone status, immune function, neural activities, and aging. The general physiological status of an individual is further influenced by circadian rhythms and changing seasons. The interactive networks of these environmental factors provide new understanding on how stem cell homeostasis is regulated, inspiring new insights for regenerative medicine. Therapies do not necessarily have to be achieved by using stem cells themselves which may constitute a higher risk but by modulating stem cell activity through targeting one or multiple layers of their micro- and macro-environments.

  12. Dermal exposure and urinary 1-hydroxypyrene among asphalt roofing workers.

    Science.gov (United States)

    McClean, M D; Rinehart, R D; Sapkota, A; Cavallari, J M; Herrick, R F

    2007-01-01

    The primary objective of this study was to identify significant determinants of dermal exposure to polycyclic aromatic compounds (PACs) among asphalt roofing workers and use urinary 1-hydroxyprene (1-OHP) measurements to evaluate the effect of dermal exposure on total absorbed dose. The study population included 26 asphalt roofing workers who performed three primary tasks: tearing off old roofs (tear-off), putting down new roofs (put-down), and operating the kettle at ground level (kettle). During multiple consecutive work shifts (90 workerdays), dermal patch samples were collected from the underside of each worker's wrists and were analyzed for PACs, pyrene, and benzo(a)pyrene (BAP). During the same work week, urine samples were collected at pre-shift, post-shift, and bedtime each day and were analyzed for 1-OHP (205 urine samples). Linear mixed effects models were used to evaluate the dermal measurements for the purpose of identifying important determinants of exposure, and to evaluate urinary 1-OHP measurements for the purpose of identifying important determinants of total absorbed dose. Dermal exposures to PAC, pyrene, and BAP were found to vary significantly by roofing task (tear-off > put-down > kettle) and by the presence of an old coal tar pitch roof (pitch > no pitch). For each of the three analytes, the adjusted mean dermal exposures associated with tear-off (812 ng PAC/cm2, 14.9 ng pyrene/cm2, 4.5 ng BAP/cm2) were approximately four times higher than exposures associated with operating the kettle (181 ng PAC/cm2, 4.1 ng pyrene/cm2, 1.1 ng BAP/cm2). Exposure to coal tar pitch was associated with a 6-fold increase in PAC exposure (p = 0.0005), an 8-fold increase in pyrene exposure (p pitch roof was removed, accounting for a 3.7-fold difference at pre-shift (p = 0.01), a 5.0-fold difference at post-shift (p = 0.004), and a 7.2-fold difference at bedtime (p = 0.002). The pyrene measurements obtained during the work shift were found to be strongly correlated

  13. Applications of acellular dermal matrix in revision breast reconstruction surgery.

    Science.gov (United States)

    Spear, Scott L; Sher, Sarah R; Al-Attar, Ali; Pittman, Troy

    2014-01-01

    Acellular dermal matrix has been used for over a decade in primary breast reconstruction. Few articles have specifically examined its use in revision breast reconstruction for fold malposition, capsular contracture, rippling, and symmastia. One hundred thirty-five revision breast reconstructive procedures using acellular dermal matrix (AlloDerm) in 118 patients (154 breasts) over a 5-year period were reviewed. Most procedures were revisions or part of the second stage of previous mastectomy reconstructions; three were revisions after reconstruction of congenital chest wall deformities. Fifty-seven revisions (37 percent) were for inferior fold malposition, followed by 40 (25.9 percent) for inferior pole support, 42 (27.2 percent) for capsular contracture, 10 (6.4 percent) for rippling, and five (3.2 percent) for symmastia. The overall complication rate was 5 percent. Revisions with acellular dermal matrix were successful in 147 of 154 breasts (95.5 percent). The most common complication was capsular contracture, occurring in five breasts (3.2 percent). There was one infection (0.6 percent), failure to lower the inframammary fold in one breast (0.6 percent), and one persistence of rippling (0.6 percent). The mean follow-up was 207 days. Acellular dermal matrix has proven to be a reliable tool for managing some of the most common and challenging problems in implant-based breast reconstruction. Although there are few published data on the success of more conventional solutions to fold malposition, lower pole support, and capsular contracture, the addition of acellular dermal matrix to buttress these repairs has been shown to provide a high likelihood of success with a low risk of complications.

  14. Calcium homeostasis in barley aleurone

    Energy Technology Data Exchange (ETDEWEB)

    Jones, R.L.

    1990-02-21

    Under the auspices of the Department of Energy we investigated calcium homeostasis in aleurone cells of barley. This investigation was initiated to explore the role played by extracellular Ca{sup 2+} in gibberellic acid (GA)-induced synthesis and secretion of hydrolases in the aleurone layer. We have focused our attention on four topics that relate to the role of Ca{sup 2+} in regulating the synthesis of {alpha}-amylase. First, we determined the stoichiometry of Ca{sup 2+} binding to the two principal classes of barley {alpha}-amylase and examined some of the biochemical and physical properties of the native and Ca{sup 2+}-depleted forms of the enzyme. Second, since {alpha}-amylase is a Ca{sup 2+} containing metalloenzyme that binds one atom of Ca{sup 2+} per molecule, we developed methods to determine the concentration of Ca{sup 2+} in the cytosol of the aleurone cell. We developed a technique for introducing Ca{sup 2+}-sensitive dyes into aleurone protoplasts that allows the measurement of Ca{sup 2+} in both cytosol and endoplasmic reticulum (ER). Third, because the results of our Ca{sup 2+} measurements showed higher levels of Ca{sup 2+} in the ER than in the cytosol, we examined Ca{sup 2+} transport into the ER of control and GA-treated aleurone tissue. And fourth, we applied the technique of patch-clamping to the barley aleurone protoplast to examine ion transport at the plasma membrane. Our results with the patch-clamp technique established the presence of K{sup +} channels in the plasma membrane of the aleurone protoplast, and they showed that this cell is ideally suited for the application of this methodology for studying ion transport. 34 refs.

  15. Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

    Energy Technology Data Exchange (ETDEWEB)

    Tashiro, Kanae [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Shishido, Mayumi [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Fujimoto, Keiko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan); Hirota, Yuko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Yo, Kazuyuki; Gomi, Takamasa [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Tanaka, Yoshitaka, E-mail: tanakay@bioc.phar.kyushu-u.ac.jp [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan)

    2014-01-03

    Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.

  16. Brain Barrier Breakdown as a Cause and Consequence of Neuroinflammation in Sepsis.

    Science.gov (United States)

    Danielski, Lucineia Gainski; Giustina, Amanda Della; Badawy, Marwa; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

    2017-01-14

    The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) are important for the maintenance of brain homeostasis. During sepsis, peripheral production of proinflammatory cytokines and reactive oxygen species are responsible for structural alterations in those brain barriers. Thus, an increasing permeability of these barriers can lead to the activation of glial cells such as microglia and the production of cytotoxic mediators which in turn act on the brain barriers, damaging them further. Thereby, in this review, we try to highlight how the brain barrier's permeability is not only a cause but a consequence of brain injury in sepsis.

  17. Intestinal antimicrobial peptides during homeostasis, infection and disease

    Directory of Open Access Journals (Sweden)

    Luciana R Muniz

    2012-10-01

    Full Text Available Antimicrobial peptides (AMPs, including defensins and cathelicidins, constitute an arsenal of innate regulators of paramount importance in the gut. The intestinal epithelium is exposed to myriad of enteric pathogens and these endogenous peptides are essential to fend off microbes and protect against infections. It is becoming increasingly evident that AMPs shape the composition of the commensal microbiota and help maintain intestinal homeostasis. They contribute to innate immunity, hence playing important functions in health and disease. AMP expression is tightly controlled by the engagement of pattern recognition receptors (PRRs and their impairment is linked to abnormal host responses to infection and inflammatory bowel diseases (IBD. In this review, we provide an overview of the mucosal immune barriers and the intricate crosstalk between the host and the microbiota during homeostasis. We focus on the AMPs and pay particular attention to how PRRs promote their secretion in the intestine. Furthermore, we discuss their production and main functions in three different scenarios, at steady state, throughout infection with enteric pathogens and IBD.

  18. Air pollution particles and iron homeostasis

    Science.gov (United States)

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, fun...

  19. Air pollution particles and iron homeostasis

    Science.gov (United States)

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, fun...

  20. Iron Homeostasis and Nutritional Iron Deficiency123

    OpenAIRE

    2011-01-01

    Nonheme food ferritin (FTN) iron minerals, nonheme iron complexes, and heme iron contribute to the balance between food iron absorption and body iron homeostasis. Iron absorption depends on membrane transporter proteins DMT1, PCP/HCP1, ferroportin (FPN), TRF2, and matriptase 2. Mutations in DMT1 and matriptase-2 cause iron deficiency; mutations in FPN, HFE, and TRF2 cause iron excess. Intracellular iron homeostasis depends on coordinated regulation of iron trafficking and storage proteins enc...

  1. Efek Pemberian Suntikan Subkutan Vitamin C Terhadap Luka Insisi Dermal

    Directory of Open Access Journals (Sweden)

    Surya Darma

    2013-09-01

    Full Text Available Abstrak Vitamin C berfungsi sebagai kofaktor enzyme prolil dan lysil hydroxilase. Enzym tersebut berfungsi dalam proses hidroksilasi yang membentuk ikatan hidroksiprolin dan hidroksilisin pada fibroblast dalam membentuk kolagen. Selain itu Vitaimin C juga berfungsi meregulasi dan menstabilkan trankripsi gen mRNA prokolagen pada proses pembentukan kolagen di dermis. Berdasarkan hal tersebut diatas, peneliti tertarik untuk membuktikan apakah pemberian vitamin C subkutan disekitar luka insisi dermal berefek pada pembentukan kolagen yang lebih padat dalam proses penyembuhan luka. Metode: Penelitian eksperimental ini menggunakan tikus Wistar sebanyak 32 ekor, yang dibagi menjadi 2 kelompok yaitu 16 ekor sebagai kontrol dan 16 ekor lagi sebagai perlakuan. Pada kedua kelompok dilakukan insisi di punggung sepanjang 2 cm. Kelompok perlakuan diberi suntikan vitamin C subkutan disekitar luka insisi dermal sebanyak 9 mg (0,09ml, sedangkan kelompokkontrol tidak diberikan.Pada hari kelima dilakukan pengambilan jaringan luka pada kedua sampel untuk pemeriksaan kepadatan kolagen secara mikroskopik. Hasil:Kepadatan kolagen pada hari kelimamenunjukkan perbedaan yang bermakna dari efek penyuntikan vitamin C subkutan terhadap kepadatan kolagen (χ2 = 5,833; P<0,05. Kesimpulan: Penyuntikan vitamin C subkutan disekitar luka insisi dermal efektif dalam meeningkatan kepadatan kolagen. Kata kunci: suntikan vitamin C subkutan, kepadatan kolagen. Abstract Vitamin C functions as enzyme co-factor for prolyl and hidroxylase lysil. The enzyme functions in hydroxylase process that builds hydroxyproline and hydroxylysine bondsin fibroblast in the synthesis of collagen. Besides that, vitamin C also functions in regulating and stabilizing procollagen mRNA gen transcription in dermal collagen synthesis. Based on the facts above, researchers are interested to prove whether subcutaneous injection of vitamin C around dermal insisional wound would result in more compact collagen

  2. Efek Pemberian Suntikan Subkutan Vitamin C Terhadap Luka Insisi Dermal

    Directory of Open Access Journals (Sweden)

    Surya Darma

    2014-09-01

    Full Text Available Abstrak Vitamin C berfungsi sebagai kofaktor enzyme prolil dan lysil hydroxilase. Enzym tersebut berfungsi dalam proses hidroksilasi yang membentuk ikatan hidroksiprolin dan hidroksilisin pada fibroblast dalam membentuk kolagen. Selain itu Vitaimin C juga berfungsi meregulasi dan menstabilkan trankripsi gen mRNA prokolagen pada proses pembentukan kolagen di dermis. Berdasarkan hal tersebut diatas, peneliti tertarik untuk membuktikan apakah pemberian vitamin C subkutan disekitar luka insisi dermal berefek pada pembentukan kolagen yang lebih padat dalam proses penyembuhan luka. Metode: Penelitian eksperimental ini menggunakan tikus Wistar sebanyak 32 ekor, yang dibagi menjadi 2 kelompok yaitu 16 ekor sebagai kontrol dan 16 ekor lagi sebagai perlakuan. Pada kedua kelompok dilakukan insisi di punggung sepanjang 2 cm. Kelompok perlakuan diberi suntikan vitamin C subkutan disekitar luka insisi dermal sebanyak 9 mg (0,09ml, sedangkan kelompokkontrol tidak diberikan.Pada hari kelima dilakukan pengambilan jaringan luka pada kedua sampel untuk pemeriksaan kepadatan kolagen secara mikroskopik. Hasil:Kepadatan kolagen pada hari kelimamenunjukkan perbedaan yang bermakna dari efek penyuntikan vitamin C subkutan terhadap kepadatan kolagen (χ2 = 5,833; P<0,05. Kesimpulan: Penyuntikan vitamin C subkutan disekitar luka insisi dermal efektif dalam meeningkatan kepadatan kolagen. Kata kunci: suntikan vitamin C subkutan, kepadatan kolagen.Abstract Vitamin C functions as enzyme co-factor for prolyl and hidroxylase lysil. The enzyme functions in hydroxylase process that builds hydroxyproline and hydroxylysine bondsin fibroblast in the synthesis of collagen. Besides that, vitamin C also functions in regulating and stabilizing procollagen mRNA gen transcription in dermal collagen synthesis. Based on the facts above, researchers are interested to prove whether subcutaneous injection of vitamin C around dermal insisional wound would result in more compact collagen

  3. Enhancing dermal and bone regeneration in calvarial defect surgery

    Directory of Open Access Journals (Sweden)

    Bruno Zanotti

    2014-01-01

    Full Text Available Introduction: To optimize the functional and esthetic result of cranioplasty, it is necessary to choose appropriate materials and take steps to preserve and support tissue vitality. As far as materials are concerned, custom-made porous hydroxyapatite implants are biomimetic, and therefore, provide good biological interaction and biointegration. However, before it is fully integrated, this material has relatively low mechanical resistance. Therefore, to reduce the risk of postoperative implant fracture, it would be desirable to accelerate regeneration of the tissues around and within the graft. Objectives: The objective was to determine whether integrating growth-factor-rich platelet gel or supportive dermal matrix into hydroxyapatite implant cranioplasty can accelerate bone remodeling and promote soft tissue regeneration, respectively. Materials and Methods: The investigation was performed on cranioplasty patients fitted with hydroxyapatite cranial implants between 2004 and 2010. In 7 patients, platelet gel was applied to the bone/prosthesis interface during surgery, and in a further 5 patients, characterized by thin, hypotrophic skin coverage of the cranial lacuna, a sheet of dermal matrix was applied between the prosthesis and the overlying soft tissue. In several of the former groups, platelet gel mixed with hydroxyapatite granules was used to fill small gaps between the skull and the implant. To confirm osteointegration, cranial computed tomography (CT scans were taken at 3-6 month intervals for 1-year, and magnetic resonance imaging (MRI was used to confirm dermal integrity. Results: Clinical examination performed a few weeks after surgery revealed good dermal regeneration, with thicker, healthier skin, apparently with a better blood supply, which was confirmed by MRI at 3-6 months. Furthermore, at 3-6 months, CT showed good biomimetism of the porous hydroxyapatite scaffold. Locations at which platelet gel and hydroxyapatite granules were

  4. Enhancing dermal and bone regeneration in calvarial defect surgery.

    Science.gov (United States)

    Zanotti, Bruno; Zingaretti, Nicola; Almesberger, Daria; Verlicchi, Angela; Stefini, Roberto; Ragonese, Mauro; Guarneri, Gianni Franco; Parodi, Pier Camillo

    2014-01-01

    To optimize the functional and esthetic result of cranioplasty, it is necessary to choose appropriate materials and take steps to preserve and support tissue vitality. As far as materials are concerned, custom-made porous hydroxyapatite implants are biomimetic, and therefore, provide good biological interaction and biointegration. However, before it is fully integrated, this material has relatively low mechanical resistance. Therefore, to reduce the risk of postoperative implant fracture, it would be desirable to accelerate regeneration of the tissues around and within the graft. The objective was to determine whether integrating growth-factor-rich platelet gel or supportive dermal matrix into hydroxyapatite implant cranioplasty can accelerate bone remodeling and promote soft tissue regeneration, respectively. The investigation was performed on cranioplasty patients fitted with hydroxyapatite cranial implants between 2004 and 2010. In 7 patients, platelet gel was applied to the bone/prosthesis interface during surgery, and in a further 5 patients, characterized by thin, hypotrophic skin coverage of the cranial lacuna, a sheet of dermal matrix was applied between the prosthesis and the overlying soft tissue. In several of the former groups, platelet gel mixed with hydroxyapatite granules was used to fill small gaps between the skull and the implant. To confirm osteointegration, cranial computed tomography (CT) scans were taken at 3-6 month intervals for 1-year, and magnetic resonance imaging (MRI) was used to confirm dermal integrity. Clinical examination performed a few weeks after surgery revealed good dermal regeneration, with thicker, healthier skin, apparently with a better blood supply, which was confirmed by MRI at 3-6 months. Furthermore, at 3-6 months, CT showed good biomimetism of the porous hydroxyapatite scaffold. Locations at which platelet gel and hydroxyapatite granules were used to fill gaps between the implant and skull appeared to show more rapid

  5. Inhalational and dermal exposures during spray application of biocides.

    Science.gov (United States)

    Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

    2005-01-01

    Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a

  6. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeate

  7. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeate

  8. Dermal fat graft from simultaneous abdominoplasty as an adjunct to revision aesthetic and reconstructive breast surgery: A poor man's acellular dermal matrix?

    Directory of Open Access Journals (Sweden)

    F. Xie

    2014-01-01

    CONCLUSION: We herein report the use of free dermal fat graft in revision aesthetic and reconstructive surgery in a manner akin to recent acellular dermal matrix use. The comparable enhanced aesthetic outcomes, minimal complication rate and substantial cost savings merit dissemination to a global audience and encourage surgeons to consider this economic alternative.

  9. Neutrophil Functions in Periodontal Homeostasis

    Directory of Open Access Journals (Sweden)

    Ricarda Cortés-Vieyra

    2016-01-01

    Full Text Available Oral tissues are constantly exposed to damage from the mechanical effort of eating and to microorganisms, mostly bacteria. In healthy gingiva tissue remodeling and a balance between bacteria and innate immune cells are maintained. However, excess of bacteria biofilm (plaque creates an inflammation state that recruits more immune cells, mainly neutrophils to the gingiva. Neutrophils create a barrier for bacteria to reach inside tissues. When neutrophils are insufficient, bacteria thrive causing more inflammation that has been associated with systemic effects on other conditions such as atherosclerosis, diabetes, and cancer. But paradoxically when neutrophils persist, they can also promote a chronic inflammatory state that leads to periodontitis, a condition that leads to damage of the bone-supporting tissues. In periodontitis, bone loss is a serious complication. How a neutrophil balance is needed for maintaining healthy oral tissues is the focus of this review. We present recent evidence on how alterations in neutrophil number and function can lead to inflammatory bone loss, and how some oral bacteria signal neutrophils to block their antimicrobial functions and promote an inflammatory state. Also, based on this new information, novel therapeutic approaches are discussed.

  10. Dermal versus total uptake of benzene from mineral spirits solvent during parts washing.

    Science.gov (United States)

    Bogen, Kenneth T; Sheehan, Patrick J

    2014-07-01

    Quantitative approaches to assessing exposure to, and associated risk from, benzene in mineral spirits solvent (MSS), used widely in parts washing and degreasing operations, have focused primarily on the respiratory pathway. The dermal contribution to total benzene uptake from such operations remains uncertain because measuring in vivo experimental dermal uptake of this volatile human carcinogen is difficult. Unprotected dermal uptake involves simultaneous sustained immersion events and transient splash/wipe events, each yielding residues subject to evaporation as well as dermal uptake. A two-process dermal exposure framework to assess dermal uptake to normal and damaged skin was applied to estimate potential daily dermal benzene dose (Dskin ) to workers who used historical or current formulations of recycled MSS in manual parts washers. Measures of evaporation and absorption of MSS dermally applied to human subjects were modeled to estimate in vivo dermal uptake of benzene in MSS. Uncertainty and interindividual variability in Dskin was characterized by Monte Carlo simulation, conditioned on uncertainty and/or variability estimated for each model input. Dermal exposures are estimated to average 33% of total (inhalation + dermal) benzene parts washing dose, with approximately equal predicted portions of dermal dose due to splash/wipe and to continuous contact with MSS. The estimated median (95th percentile) dermal and total daily benzene doses from parts washing are: 0.0069 (0.024) and 0.025 (0.18) mg/day using current, and 0.027 (0.085) and 0.098 (0.69) mg/day using historical, MSS solvents, respectively. © 2014 Society for Risk Analysis.

  11. Mathematical analysis of dermal absorption rate of heavy metals.

    Science.gov (United States)

    Batkin, Izmail; Bolic, Miodrag

    2015-08-01

    Presently 90 - 95% of children in the US wear disposable diapers before completing their toilet training at average age of 30 months. The diaper absorbs urine and liquid component from feces contaminated with excreted toxicants. In this initial study, we posit that the long contact between the diaper and the skin leads to increased dermal reabsorption of excreted body toxicants, mainly heavy metals, which are statistically associated with autism and neurodevelopmental disorder. We developed a mathematical model to analyse the increase of the level of toxicants due to dermal reabsorption after excretion. This simple kinetic model gives us the average reabsorbtion factor in the range of 1.6 to 5. The limitation of this work is that only mathematical model has been considered and it has not been verified experimentally.

  12. A metabolically active dermal replacement (Dermagraft) for vestibuloplasty.

    Science.gov (United States)

    Raguse, J D; Gath, H J

    2005-05-01

    This article describes the use of tissue-engineered dermal replacement in the vestibular extension instead of palatal donor tissue or (split-thickness) skin graft. In three patients the living human-derived fibroblast skin substitute (Dermagraft) was implanted on the wound surface after mucogingival junction and supraperiosteal dissection. Following application of Dermagraft, epithelial closure starting from the resection margins of the defect was observed, obviating further surgical treatment. Vestibular depth was increased and no scarring or frena occurred. Tissue-engineered dermal replacement consisting of living human fibroblasts appears to be a useful substitute for autogenous grafts in pre-prosthetic surgery, offering the advantages of unlimited availability, good colour match and no donor site morbidity.

  13. Focal dermal hypoplasia: ultrastructural abnormalities of the connective tissue.

    Science.gov (United States)

    del Carmen Boente, María; Asial, Raúl A; Winik, Beatriz C

    2007-02-01

    We followed over 10 years three girls with focal dermal hypoplasia syndrome. The histopathological changes demonstrated at the optical level an hypoplastic dermis with thin and scarce collagen bundles and a marked diminution of elastic fibers. Mature adipose tissue was found scattered within the papillary and reticular dermis. No alterations in the basal membrane were observed by immunocytochemical or ultrastructural techniques. Ultrastructurally, in the skin-affected areas, loosely arranged collagen bundles composed of few fibrils were seen scattered in the extracellular matrix. Scarce elastic fibers of normal morphology were also observed. Fibroblasts were smaller, oval-shaped, and diminished in number with a poorly developed cytoplasm. In these fibroblasts, the most conspicuous feature was a remarkable and irregular thickening of the nuclear fibrous lamina. Taking into account that a common link between all laminopaties may be a failure of stem cells to regenerate mesenchymal tissue, this failure would induce the dermal hypoplasia observed in our patients presenting Goltz syndrome.

  14. Clinical, pathological, and etiologic aspects of acquired dermal melanocytosis.

    Science.gov (United States)

    Mizoguchi, M; Murakami, F; Ito, M; Asano, M; Baba, T; Kawa, Y; Kubota, Y

    1997-06-01

    To study the pathogenesis of acquired dermal melanocytosis (ADM), we reviewed the clinical, immunohistochemical, and ultrastructural features of 34 cases (female, 33, and male, 1) of ADM. The patients' ages at onset ranged from 8 to 51 years and averaged 26.8 +/- 12.7 years. There was a positive family history. Gray-brown macules were mostly recognized on the face. Not only active dermal melanocytes but also non-pigmented c-KIT- and TRP-2-positive immature melanocytes were detected in the dermis. Taken together those clinical and histological findings, activation of pre-existing immature melanocytes by sunlight, estrogen, and/or progesterone, and some other factors, may be the most likely mode of the development of ADM. Moreover, using cultured murine neural crest cells as a model of c-KIT-positive immature melanocytes, we confirmed that endothelin-1, which is produced and secreted by keratinocytes after UV-irradiation, affects melanocytes and accelerated melanogenesis.

  15. Mycobacterium chelonae Facial Infections Following Injection of Dermal Filler

    OpenAIRE

    Rodriguez, Jan M.; Xie, Yingda L.; Winthrop, Kevin L; Schafer, Sean; Sehdev, Paul; Solomon, Joel; Jensen, Bette; Toney, Nadege C.; Lewis, Paul F.

    2013-01-01

    A cluster of 3 facial Mycobacterium chelonae infections occurred after cosmetic dermal filler injections at a plastic surgery clinic. Pulsed-field gel electrophoresis showed that M chelonae isolated from the clinic tap water were identical to the patient wound isolates. Review of injection procedures identified application of nonsterile ice to the skin prior to injection as a possible source of M chelonae. Surveys of regional laboratories and a national plastic surgery listserv identified no ...

  16. Dermal tolerance of Sterillium, a propanol-based hand rub.

    Science.gov (United States)

    Kampf, G; Muscatiello, M

    2003-12-01

    Alcohol-based hand rubs have been used for hygienic hand disinfection in hospitals for decades. In order to achieve good compliance with hand hygiene practices in the healthcare setting, dermal tolerance of a hand rub product is crucial. Sterillium, which is used in many European countries for hygienic hand disinfection, is based on iso-propanol, n-propanol and mecetronium etilsulphate. The potential for dermal irritation and sensitization of commercially available propanol-based hand rubs containing emollients has not been studied systematically. We therefore studied the dermal tolerance of Sterillium in a repetitive occlusive patch test on 55 subjects. Sterillium was applied to one site on the back under an occlusive patch during an induction phase (total of nine applications over a three-week period) and two weeks later to a virgin site on the back during a challenge phase (one application). Twenty-four hours after removal of the patches (induction phase and challenge phase), and in addition, after 48 and 72 h (challenge phase), the sites were graded for skin reactions using a standardized scoring scale. In the induction phase, two of the 55 subjects had a barely perceptible minimal erythema at one of nine time points. The remaining 53 subjects had no skin reaction at any time. In the challenge phase, all 55 subjects had no skin reaction at all. The absence of significant reactions with respect to severity and frequency demonstrates the favourable dermal tolerance of the hand rub product. The lack of irritation or sensitization potential could enhance compliance with hand hygiene among healthcare workers.

  17. Generation of human induced pluripotent stem cells from dermal fibroblasts

    OpenAIRE

    2008-01-01

    The generation of patient-specific pluripotent stem cells has the potential to accelerate the implementation of stem cells for clinical treatment of degenerative diseases. Technologies including somatic cell nuclear transfer and cell fusion might generate such cells but are hindered by issues that might prevent them from being used clinically. Here, we describe methods to use dermal fibroblasts easily obtained from an individual human to generate human induced pluripotent stem (iPS) cells by ...

  18. Dermal type I collagen assessment by digital image analysis*

    OpenAIRE

    Brianezi, Gabrielli; Grandi, Fabrizio; Bagatin, Ediléia; Enokihara, Mílvia Maria S. S.; Miot, Hélio Amante [UNESP

    2015-01-01

    Type I collagen is the main dermal component, and its evaluation is relevant to quantitative studies in dermatopathology. However, visual gradation (0 to 4+) has low precision and high subjectivity levels. This study aimed to develop and validate a digital morphometric analysis technique to estimate type I collagen levels in the papillary dermis. Four evaluators visually quantified (0 to 4+) the density of type I collagen in 63 images of forearm skin biopsies marked by immunohistochemistry an...

  19. Immune Suppression by Dermal Application of JP-8 Jet Fuel

    Science.gov (United States)

    2008-10-13

    transmitting the immunosuppressive signal from the skin to the immune system ( Limon -Flores, et al., Mast Cells mediate the Immune suppression Induced by...human and murine data. Nat Rev Immunol 7, 93-104. Byrne, S. N., Limon -Flores, A. Y. and Ullrich, S. E. (2008). Mast cell migration from the skin to...Ramos, G., Limon -Flores, A. Y. and Ullrich, S. E. (2007). Dermal exposure to jet fuel suppresses delayed-type hypersensitivity: a critical role

  20. Toxicity of dermally applied alpha-cypermethrin in rats.

    Science.gov (United States)

    Luty, S; Latuszyńska, J; Halliop, J; Tochman, A; Obuchowska, D; Przylepa, E; Korczak, E

    1998-01-01

    The aim of the study was to assess the immunotoxic effect of dermally applied alpha-cypermethrin in rats based on phagocytic and bactericidal activity of neutrophils of peripheral blood, and the general toxic effect based on histological and ultrastructural examination of internal organs. The preparation was dermally applied in doses of 50 mg/kg and 250 mg/kg. It was administered to the tail skin of female Wistar rats, 4 hours daily for 28 days. After the experiment, the animals were anaesthetized and heart blood was taken in order to evaluate the activity of granulocyte system. The following organs were taken for histological examinations: brain, lung, heart, liver, spleen, kidneys, thymus and lymphatic nodes. Lung, liver, kidney and heart were used for ultrastructural studies. The results of the study showed that bactericidal and phagocytic activity of neutrophils was stimulated after administration of 50 mg/kg alpha-cypermethrin. Dermal application of the preparation resulted in slight histological changes in liver, kidney, lung and brain. Pathological changes in heart were observed only on the level of ultrastructure.

  1. Dopamine regulates angiogenesis in normal dermal wound tissues.

    Directory of Open Access Journals (Sweden)

    Saurav Shome

    Full Text Available Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D(2 DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D(2 DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D(2 DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D(2 DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities.

  2. Dermal insecticide residues from birds inhabiting an orchard

    Science.gov (United States)

    Vyas, N.B.; Spann, J.W.; Hulse, C.S.; Gentry, S.; Borges, S.L.

    2007-01-01

    The US Environmental Protection Agency conducts risk assessments of insecticide applications to wild birds using a model that is limited to the dietary route of exposure. However, free-flying birds are also exposed to insecticides via the inhalation and dermal routes. We measured azinphos-methyl residues on the skin plus feathers and the feet of brown-headed cowbirds (Molothrus ater) in order to quantify dermal exposure to songbirds that entered and inhabited an apple (Malus x domestica) orchard following an insecticide application. Exposure to azinphos-methyl was measured by sampling birds from an aviary that was built around an apple tree. Birds sampled at 36 h and 7-day post-application were placed in the aviary within 1 h after the application whereas birds exposed for 3 days were released into the aviary 4-day post-application. Residues on vegetation and soil were also measured. Azinphos-methyl residues were detected from the skin plus feathers and the feet from all exposure periods. Our results underscore the importance of incorporating dermal exposure into avian pesticide risk assessments.

  3. Citral: identifying a threshold for induction of dermal sensitization.

    Science.gov (United States)

    Lalko, Jon; Api, Anne Marie

    2008-10-01

    Citral [CAS# 5392-40-5; EINECS# 226-394-6; RIFM # 116; cis- and trans-3,7-dimethyl-2,6-Octadienal] is an important fragrance ingredient appreciated for its powerful lemon-aroma. It is widely used in fragrance formulations and incorporated into numerous consumer products. A comprehensive review of the dermal sensitization data available for citral was undertaken with the goal of identifying a threshold for the induction of dermal sensitization. In 2007, a complete literature search was conducted. On-line databases that were surveyed included Chemical Abstract Services and the National Library of Medicine. In addition, the toxicologic database of the Research Institute for Fragrance materials, Inc. (RIFM) was searched, which includes numerous unpublished reports. Based on a weight of evidence approach, the data from this survey demonstrate that the human NOEL (No Observed Effect Level) for induction of dermal sensitization to citral is 1400 microg/cm(2). The identification of this induction threshold will allow for risk assessments to focus on primary prevention of contact allergy to citral based on a new Quantitative Risk Assessment (QRA) paradigm. This subsequent assessment will form the basis of a risk management approach; specifically a new IFRA (International Fragrance Association) standard on the use of citral in consumer products.

  4. Human acellular dermal wound matrix: evidence and experience.

    Science.gov (United States)

    Kirsner, Robert S; Bohn, Greg; Driver, Vickie R; Mills, Joseph L; Nanney, Lillian B; Williams, Marie L; Wu, Stephanie C

    2015-12-01

    A chronic wound fails to complete an orderly and timely reparative process and places patients at increased risk for wound complications that negatively impact quality of life and require greater health care expenditure. The role of extracellular matrix (ECM) is critical in normal and chronic wound repair. Not only is ECM the largest component of the dermal skin layer, but also ECM proteins provide structure and cell signalling that are necessary for successful tissue repair. Chronic wounds are characterised by their inflammatory and proteolytic environment, which degrades the ECM. Human acellular dermal matrices, which provide an ECM scaffold, therefore, are being used to treat chronic wounds. The ideal human acellular dermal wound matrix (HADWM) would support regenerative healing, providing a structure that could be repopulated by the body's cells. Experienced wound care investigators and clinicians discussed the function of ECM, the evidence related to a specific HADWM (Graftjacket(®) regenerative tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San Antonio, TX), and their clinical experience with this scaffold. This article distills these discussions into an evidence-based and practical overview for treating chronic lower extremity wounds with this HADWM. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  5. Amorphous cyclosporin A nanoparticles for enhanced dermal bioavailability.

    Science.gov (United States)

    Romero, Gregori B; Arntjen, Anja; Keck, Cornelia M; Müller, Rainer H

    2016-02-10

    Cylosporin A (CyA) was formulated as amorphous nanoparticle suspension to increase dermal penetration, e.g. applicable in psoriasis. The suspension consisted of 5% CyA in water, stabilized with vitamin E polyethylene glycol succinate (TPGS, Kolliphor TPGS) and was produced by bead milling. The diameter of the bulk population was about 350 nm, laser diffraction diameter 99% was 690 nm. The suspension was physically stable over one year of storage at room temperature, and most important the amorphous state also remained stable. Despite the high dispersitivity and related large surface area in contact with water, the drug content reduced only by 5% over 1 year of storage. i.e. the formulation is feasible as commercial product with expiry date. The CyA nanoparticles and μm-sized CyA particles were incorporated into hydroxypropylcellulose (HPC) gels and the penetration studied into fresh pig ear skin applying the tape stripping method. At tape number 30, the penetrated cumulative amount of CyA from nanoparticles was 6.3 fold higher compared to the μm-sized raw drug powder (450.1 μg/cm(2) vs. 71.3 μg/cm(2)). A theoretical mechanism is presented to explain the observed superiority in penetration. Based on amorphous CyA nanoparticles, dermal formulations for improved dermal CyA delivery seem to be feasible. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Galvanic microparticles increase migration of human dermal fibroblasts in a wound-healing model via reactive oxygen species pathway.

    Science.gov (United States)

    Tandon, Nina; Cimetta, Elisa; Villasante, Aranzazu; Kupferstein, Nicolette; Southall, Michael D; Fassih, Ali; Xie, Junxia; Sun, Ying; Vunjak-Novakovic, Gordana

    2014-01-01

    Electrical signals have been implied in many biological mechanisms, including wound healing, which has been associated with transient electrical currents not present in intact skin. One method to generate electrical signals similar to those naturally occurring in wounds is by supplementation of galvanic particles dispersed in a cream or gel. We constructed a three-layered model of skin consisting of human dermal fibroblasts in hydrogel (mimic of dermis), a hydrogel barrier layer (mimic of epidermis) and galvanic microparticles in hydrogel (mimic of a cream containing galvanic particles applied to skin). Using this model, we investigated the effects of the properties and amounts of Cu/Zn galvanic particles on adult human dermal fibroblasts in terms of the speed of wound closing and gene expression. The collected data suggest that the effects on wound closing are due to the ROS-mediated enhancement of fibroblast migration, which is in turn mediated by the BMP/SMAD signaling pathway. These results imply that topical low-grade electric currents via microparticles could enhance wound healing.

  7. Dermal uptake and percutaneous penetration of ten flame retardants in a human skin ex vivo model.

    Science.gov (United States)

    Frederiksen, Marie; Vorkamp, Katrin; Jensen, Niels Martin; Sørensen, Jens Ahm; Knudsen, Lisbeth E; Sørensen, Lars S; Webster, Thomas F; Nielsen, Jesper B

    2016-11-01

    The dermal uptake and percutaneous penetration of ten organic flame retardants was measured using an ex vivo human skin model. The studied compounds were DBDPE, BTBPE, TBP-DBPE, EH-TBB, BEH-TEBP, α, β and γ-HBCDD as well as syn- and anti-DDC-CO. Little or none of the applied flame retardants was recovered in either type of the receptor fluids used (physiological and worst-case). However, significant fractions were recovered in the skin depot, particularly in the upper skin layers. The primary effect of the worst-case receptor fluid was deeper penetration into the skin. The recovered mass was used to calculate lower- and upper-bound permeability coefficients kp. Despite large structural variation between the studied compounds, a clear, significant decreasing trend of kp was observed with increasing log Kow. The results indicate that the dermis may provide a significant barrier for these highly lipophilic compounds. However, based on our results, dermal uptake should be considered in exposure assessments, though it may proceed in a time-lagged manner compared to less hydrophobic compounds.

  8. Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

    Science.gov (United States)

    Özcan, İpek; Azizoğlu, Erkan; Şenyiğit, Taner; Özyazıcı, Mine; Özer, Özgen

    2013-01-01

    The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders. PMID:23390364

  9. Galvanic microparticles increase migration of human dermal fibroblasts in a wound-healing model via reactive oxygen species pathway

    Science.gov (United States)

    Tandon, Nina; Cimetta, Elisa; Villasante, Aranzazu; Kupferstein, Nicolette; Southall, Michael D.; Fassih, Ali; Xie, Junxia; Sun, Ying; Vunjak-Novakovic, Gordana

    2015-01-01

    Electrical signals have been implied in many biological mechanisms, including wound healing, which has been associated with transient electrical currents not present in intact skin. One method to generate electrical signals similar to those naturally occurring in wounds is by supplementation of galvanic particles dispersed in a cream or gel. We constructed a three-layered model of skin consisting of human dermal fibroblasts in hydrogel (mimic of dermis), a hydrogel barrier layer (mimic of epidermis) and galvanic microparticles in hydrogel (mimic of a cream containing galvanic particles applied to skin). Using this model, we investigated the effects of the properties and amounts of Cu/Zn galvanic particles on adult human dermal fibroblasts in terms of the speed of wound closing and gene expression. The collected data suggest that the effects on wound closing are due to the ROS-mediated enhancement of fibroblast migration, which is in turn mediated by the BMP/SMAD signaling pathway. These results imply that topical low-grade electric currents via microparticles could enhance wound healing. PMID:24113575

  10. Embryonic dermal condensation and adult dermal papilla induce hair follicles in adult glabrous epidermis through different mechanisms

    OpenAIRE

    2006-01-01

    Hair induction in the adult glabrous epidermis by the embryonic dermis was compared with that by the adult dermis. Recombinant skin, composed of the adult sole epidermis and the embryonic dermis containing dermal condensations (DC), was transplanted onto the back of nude mice. The epidermis of transplants formed hairs. Histology on the induction process demonstrated the formation of placode-like tissues, indicating that the transplant produces hair follicles through a mechanism similar to tha...

  11. Acute and subchronic dermal toxicity of nanosilver in guinea pig

    Directory of Open Access Journals (Sweden)

    Arbabi Bidgoli S

    2011-04-01

    Full Text Available M Korani1, SM Rezayat1,2,4, K Gilani3, S Arbabi Bidgoli4, S Adeli11Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences; 2Department of Nanotechnology, Faculty of Advanced Sciences and Technology in Medicine, Tehran University of Medical Sciences; 3Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences; 4Department of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS, Tehran, IranAbstract: Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 µg/mL in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 µg/mL in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater

  12. Significant chemical burns associated with dermal exposure to laundry pod detergent.

    Science.gov (United States)

    Russell, Jason L; Wiles, Devin A; Kenney, Brian; Spiller, Henry A

    2014-09-01

    Concentrated laundry pods have been reported to cause significant clinical effects including oropharyngeal burns and respiratory distress requiring intubation. Dermal burns have been reported, but no incidents of serious isolated dermal injury have been published. We report a case of significant, isolated dermal injury as a result of dermal exposure to a concentrated laundry detergent pod. Total body surface area partial thickness burns in this case were estimated at approximately 2 % with an additional 4-5 % of total body surface area (TBSA) displaying superficial burns/chemical dermatitis. Health-care providers should be aware of this complication and should perform thorough dermal decontamination in the event of an exposure. Parents should be educated regarding the dangers associated with dermal exposure to laundry pod compounds and the need to secure these items away from children as well as proper decontamination techniques should an exposure occur.

  13. Long-Term Followup of Dermal Substitution with Acellular Dermal Implant in Burns and Postburn Scar Corrections

    Directory of Open Access Journals (Sweden)

    I. Juhasz

    2010-01-01

    Full Text Available Full-thickness burn and other types of deep skin loss will result in scar formation. For at least partial replacement of the lost dermal layer, there are several options to use biotechnologically derived extracellular matrix components or tissue scaffolds of cadaver skin origin. In a survey, we have collected data on 18 pts who have previously received acellular dermal implant Alloderm. The age of these patients at the injury varied between 16 months and 84 years. The average area of the implants was 185 cm2. Among those, 15 implant sites of 14 patients were assessed at an average of 50 months after surgery. The scar function was assessed by using the modified Vancouver Scar Scale. We have found that the overall scar quality and function was significantly better over the implanted areas than over the surrounding skin. Also these areas received a better score for scar height and pliability. Our findings suggest that acellular dermal implants are especially useful tools in the treatment of full-thickness burns as well as postburn scar contractures.

  14. A TRILAYER DERMAL EQUIVALENT CONTAINING SILVER NANOPARTICLES WITH ENHANCED ANTIBACTERIAL PROPERTY

    Institute of Scientific and Technical Information of China (English)

    马列; 高长有

    2009-01-01

    A dermal equivalent having a trilayered structure was designed by combining a silver nanoparticles incorporated chitosan film with a bilayer collagen-chitosan/silicon membrane dermal equivalent(BDE).The silver nanoparticles prepared at different conditions were characterized by UV-Vis and transmission electron microscopy(TEM).The macroscopic sharp and the microstructure of the trilayer dermal equivalent(TDE) were also studied.Then,the in vitro antibacterial property of TDE was evaluated by the antibacter...

  15. Iron homeostasis: new players, newer insights.

    Science.gov (United States)

    Edison, Eunice S; Bajel, Ashish; Chandy, Mammen

    2008-12-01

    Although iron is a relatively abundant element in the universe, it is estimated that more than 2 billion people worldwide suffer from iron deficiency anemia. Iron deficiency results in impaired production of iron-containing proteins, the most prominent of which is hemoglobin. Cellular iron deficiency inhibits cell growth and subsequently leads to cell death. Hemochromatosis, an inherited disorder results in disproportionate absorption of iron and the extra iron builds up in tissues resulting in organ damage. As both iron deficiency and iron overload have adverse effects, cellular and systemic iron homeostasis is critically important. Recent advances in the field of iron metabolism have led to newer understanding of the pathways involved in iron homeostasis and the diseases which arise from alteration in the regulators. Although insight into this complex regulation of the proteins involved in iron homeostasis has been obtained mainly through animal studies, it is most likely that this knowledge can be directly extrapolated to humans.

  16. Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function

    OpenAIRE

    Boer, Magdalena; Duchnik, Ewa; Maleszka, Romuald; Marchlewicz, Mariola

    2016-01-01

    The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part – stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transep...

  17. Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis.

    Science.gov (United States)

    Driskell, Ryan R; Giangreco, Adam; Jensen, Kim B; Mulder, Klaas W; Watt, Fiona M

    2009-08-01

    The dermal papilla comprises the specialised mesenchymal cells at the base of the hair follicle. Communication between dermal papilla cells and the overlying epithelium is essential for differentiation of the hair follicle lineages. We report that Sox2 is expressed in all dermal papillae at E16.5, but from E18.5 onwards expression is confined to a subset of dermal papillae. In postnatal skin, Sox2 is only expressed in the dermal papillae of guard/awl/auchene follicles, whereas CD133 is expressed both in guard/awl/auchene and in zigzag dermal papillae. Using transgenic mice that express GFP under the control of the Sox2 promoter, we isolated Sox2(+) (GFP(+)) CD133(+) cells and compared them with Sox2(-) (GFP(-)) CD133(+) dermal papilla cells. In addition to the 'core' dermal papilla gene signature, each subpopulation expressed distinct sets of genes. GFP(+) CD133(+) cells had upregulated Wnt, FGF and BMP pathways and expressed neural crest markers. In GFP(-) CD133(+) cells, the hedgehog, IGF, Notch and integrin pathways were prominent. In skin reconstitution assays, hair follicles failed to form when dermis was depleted of both GFP(+) CD133(+) and GFP(-) CD133(+) cells. In the absence of GFP(+) CD133(+) cells, awl/auchene hairs failed to form and only zigzag hairs were found. We have thus demonstrated a previously unrecognised heterogeneity in dermal papilla cells and shown that Sox2-positive cells specify particular hair follicle types.

  18. Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route.

    Science.gov (United States)

    Lauterbach, Andreas; Müller-Goymann, Christel C

    2015-11-01

    Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations.

  19. Liposomal formulation for dermal and transdermal drug delivery: past, present and future.

    Science.gov (United States)

    Nounou, Mohamed I; El-Khordagui, Labiba K; Khalafallah, Nawal A; Khalil, Said A

    2008-01-01

    Although the formulation of effective topical drug delivery system is one of the most sophisticated pharmaceutical preparations, it has attracted researchers due to many medical advantages associated with it. Topical drug delivery systems can act superficially on skin surface, locally in dermal layer of the skin or transdermally to provide successful delivery of drug molecules to the systemic circulation avoiding the traditional problems and limitations of conventional routes of drug delivery. Many novel formulations have been utilized topically to enhance either permeability or drug targeting to a specific layer of the skin such as Liposomes, ethosomes, transfersomes, niosomes and catezomes. The main problem with all of these formulations is that there is no distinct barrier between the targeting and localization action to a certain layer of the skin and the transdermal action to the circulation of these preparations. Any minimal change in the formulation could transform it from a local targeting preparation to a systemic one. This article deals with the innovations pertaining to the use of various types of liposomal preparations and liposomal like preparations for topical drug delivery and the patents associated with it.

  20. Dermal echogenicity: a biological indicator of individual cumulative UVR exposure?

    Science.gov (United States)

    Sandby-Møller, Jane; Thieden, Elisabeth; Philipsen, Peter Alshede; Schmidt, Grethe; Wulf, Hans Christian

    2004-04-01

    Dermal alterations due to chronic UVR exposure may influence dermal ultrasound echogenicity, and a subepidermal low-echogenic band has been proposed as a marker of photoaging. The aim of this study was to determine whether dermal echogenicity could be used as a biological UVR dosimeter. We included 201 subjects (138 healthy volunteers, 31 patients with basal cell carcinoma, and 32 patients with cutaneous malignant melanoma). The number of low-echogenic pixels in the upper dermis relative to the lower dermis (LEP(u/l)) was determined in sun-exposed and sun-protected skin. Individual UVR exposure data were collected retrospectively and prospectively using a questionnaire and electronic personal UVR dosimeters. Age, but not sex, skin type, constitutive pigmentation or smoking, correlated significantly with LEP(u/l) at all body sites. Different measures of individual UVR exposure were significantly positively correlated with LEP(u/l) (together r(2)=0.39, dorsal forearm), but separately the correlations were poor ( r(2)=0.04-0.19). LEP(u/l) was higher in the dorsal forearm in a group with high UVR exposure compared to a low-exposure group ( P=0.007). Skin cancer patients in general had a lower LEP(u/l) than healthy subjects. The results indicate that the age-related increase in LEP(u/l) might be attributed mainly to UVR exposure, and that the methods used to obtain the UVR exposure data might not be sufficiently sensitive or specific. Genetic factors might also influence LEP(u/l). We consider LEP(u/l) to be a sensitive and specific marker for UVR exposure at the dorsal aspect of the forearm in healthy subjects.

  1. Abdominal wall repair with human acellular dermal autograft

    Directory of Open Access Journals (Sweden)

    Roel E. Genders

    2011-12-01

    Full Text Available Repair of abdominal wall defects in the presence of contamination or infection is a significant problem. The loss of tissue warrants enforcement of the abdominal wall, preferably by autologous material. However, autologous repair often requires extensive surgery. This paper presents a review of available literature of placement of an acellular human dermis to repair an abdominal fascia defect, in contaminated as well as in non-contaminated surgical fields. It is illustrated with a case report that describes the successful reconstruction of an infected abdominal wall defect with a human acellular dermis allograft. A systematic literature review was undertaken with searches performed in the Pubmed and Cochrane databases for the period up till March 2009, using the search terms Alloderm [Substance Name], Hernia [Mesh] and the key words acellular dermis, acellular dermal matrix, human acellular dermal allograft and abdominal wall defect. To assess methodological quality, each article was subjected to a modification of the methodological index for non-randomized studies (MINORS according to Slim et al. Two items from the original index were not included because none of the studies selected had an unbiased assessment of the study end points and in none of the studies was a prospective calculation of the study size performed. Seventeen studies were included in the review. Data were extracted regarding study design, number of patients, surgical technique, followup period, contaminated or non-contaminated area of the fascia defect, mortality and morbidity (hemorrhage, seroma, wound dehiscence, infection of the operative procedure, the longterm results (removal of the graft, reherniation and bulging and level of evidencey. A total of 169 short-term complications and 151 longterm complications occurred after 643 surgical procedures reconstructing both contaminated and clean abdominal wall defects by implantation of an HADA. Human acellular dermal allograft

  2. Molecular monitoring of equine joint homeostasis

    NARCIS (Netherlands)

    de Grauw, J.C.

    2010-01-01

    Chronic joint disorders are a major cause of impaired mobility and loss of quality of life in both humans and horses. Regardless of the primary insult, any joint disorder is characterized by an upset in normal joint homeostasis, the balance between tissue anabolism and catabolism that is normally ma

  3. Achieving global perfect homeostasis through transporter regulation

    Science.gov (United States)

    Springer, Michael

    2017-01-01

    Nutrient homeostasis—the maintenance of relatively constant internal nutrient concentrations in fluctuating external environments—is essential to the survival of most organisms. Transcriptional regulation of plasma membrane transporters by internal nutrient concentrations is typically assumed to be the main mechanism by which homeostasis is achieved. While this mechanism is homeostatic we show that it does not achieve global perfect homeostasis—a condition where internal nutrient concentrations are completely independent of external nutrient concentrations for all external nutrient concentrations. We show that the criterion for global perfect homeostasis is that transporter levels must be inversely proportional to net nutrient flux into the cell and that downregulation of active transporters (activity-dependent regulation) is a simple and biologically plausible mechanism that meets this criterion. Activity-dependent transporter regulation creates a trade-off between robustness and efficiency, i.e., the system's ability to withstand perturbation in external nutrients and the transporter production rate needed to maintain homeostasis. Additionally, we show that a system that utilizes both activity-dependent transporter downregulation and regulation of transporter synthesis by internal nutrient levels can create a system that mitigates the shortcomings of each of the individual mechanisms. This analysis highlights the utility of activity-dependent regulation in achieving homeostasis and calls for a re-examination of the mechanisms of regulation of other homeostatic systems. PMID:28414718

  4. Calcium homeostasis in fly photoreceptor cells

    NARCIS (Netherlands)

    Oberwinkler, J

    2002-01-01

    In fly photoreceptor cells, two processes dominate the Ca2+ homeostasis: light-induced Ca2+ influx through members of the TRP family of ion channels, and Ca2+ extrusion by Na+/Ca2+ exchange.Ca2+ release from intracellular stores is quantitatively insignificant. Both, the light-activated channels and

  5. Molecular monitoring of equine joint homeostasis

    NARCIS (Netherlands)

    de Grauw, J.C.

    2010-01-01

    Chronic joint disorders are a major cause of impaired mobility and loss of quality of life in both humans and horses. Regardless of the primary insult, any joint disorder is characterized by an upset in normal joint homeostasis, the balance between tissue anabolism and catabolism that is normally ma

  6. Soft tissue augmentation - Use of hyaluronic acid as dermal filler

    Directory of Open Access Journals (Sweden)

    Vedamurthy Maya

    2004-01-01

    Full Text Available Soft tissue augmentation has revolutionized the treatment of the aging face. It is a technique in which a substance is injected under the skin. The concept of utilizing materials for soft tissue augmentation actually began around 1950 with the use of fluid silicone. Today we have a large armamentarium of implant materials to delay the tell tale signs of aging. Filling has replaced conventional surgery in facial rejuvenation. In this article, the emphasis will be on hyaluronic acid as this substance is easily available in India and ranks among the most widely used dermal fillers.

  7. Dermal exposure from transfer of lubricants and fuels by consumers.

    Science.gov (United States)

    Galea, Karen S; Davis, Alice; Todd, Davis; MacCalman, Laura; McGonagle, Carolyn; Cherrie, John W

    2014-11-01

    Consumer uses of fuels and lubricants in Europe are subject to the Registration, Evaluation, Authorization and restriction of CHemicals (REACH) legislation. Ten volunteers completed a series of exposure situations to simulate filling a vehicle fuel tank with diesel (ES1 Diesel), adding lubricant to a car engine (two situations, one filling point easier to reach (ES2 Easy) than the other (ES3 Hard)) and lubricating a bicycle chain (ES4 Bike). Dermal exposure to the hands and forearms was assessed using a wipe sampling method. A high proportion of samples was less than the limit of detection (ES1=38%, ES3=60%, ES2 and 4, both 78%). In ES1 Diesel, dermal exposure to the hands and forearms ranged from <0.25 μg/cm(2) to 96.21 μg/cm(2). Significantly higher dermal exposure was observed when a lower level of care was taken to complete the task. In ES2 Easy and ES3 Hard, the hand and forearm results ranged from <0.1 μg/cm(2) to 3.33 μg/cm(2) and from <0.1 μg/cm(2) to 3.54 μg/cm(2), respectively. In ES4 Bike, the hand and forearm exposures ranged from <0.35 μg/cm(2) to 5.25 μg/cm(2). Not all volunteers fully complied with the ES4 instructions, thus highlighting that this situation may have more variability in consumer behaviour. The ratio of the amount measured on the hands and forearms to the amount of product handled for ES1 Diesel, ES2 Easy and ES3 Hard was less than 0.0001%, for ES4 Bike it was 0.04%. Mixed effect models showed that the between and within volunteer variations are small for all except ES1 Diesel, where the within volunteer variation was relatively large (likely due to the few high measurements). This study reports dermal exposure measurement data, which will be of value when updating REACH and other exposure assessments for these, and similar, petroleum products.

  8. Dermal tunneling: a proposed treatment for depressed scars*

    Science.gov (United States)

    Lima, Emerson Vasconcelos de Andrade

    2016-01-01

    Depressed facial scars are still a challenge in medical literature, despite the wide range of proposed treatments. Subcision is a technique that is frequently performed to improve this type of lesions. This article proposes a new method to release depressed scars, reported and named by the author as dermal tunneling. This study presents a simple and didactic manner to perform this method. The results in 17 patients with facial scars were considered promising. Thus, the technique was deemed to be safe and reproducible. PMID:27828658

  9. Effect of microemulsions on cell viability of human dermal fibroblasts

    Science.gov (United States)

    Li, Juyi; Mironava, Tatsiana; Simon, Marcia; Rafailovich, Miriam; Garti, Nissim

    Microemulsions are optically clear, thermostable and isotropic mixture consisting of water, oil and surfactants. Their advantages of ease preparation, spontaneous formation, long-term stability and enhanced solubility of bioactive materials make them great potentials as vehicles in food and pharmaceutical applications. In this study, comparative in vitro cytotoxicity tests were performed to select a best formulation of microemulsion with the least toxicity for human dermal fibroblasts. Three different kinds of oils and six different kinds of surfactants were used to form microemulsions by different ratios. The effect of oil type and surfactant type as well as their proportions on cell proliferation and viability were tested.

  10. Genotoxic exposure and biological effects in the rubber manufacturing industry. Relevance of the dermal route

    NARCIS (Netherlands)

    Vermeulen, R.

    2001-01-01

    This thesis describes an industry wide survey on genotoxic exposure and biological effects in the rubber manifacturing industry. Chapters are devoted to long-term trends in inhalable and dermal contamination levels, identification of dermal exposure pathways and the assessment of mutagenic

  11. Shh maintains dermal papilla identity and hair morphogenesis via a Noggin-Shh regulatory loop.

    Science.gov (United States)

    Woo, Wei-Meng; Zhen, Hanson H; Oro, Anthony E

    2012-06-01

    During hair follicle morphogenesis, dermal papillae (DPs) function as mesenchymal signaling centers that cross-talk with overlying epithelium to regulate morphogenesis. While the DP regulates hair follicle formation, relatively little is known about the molecular basis of DP formation. The morphogen Sonic hedgehog (Shh) is known for regulating hair follicle epithelial growth, with excessive signaling resulting in basal cell carcinomas. Here, we investigate how dermal-specific Shh signaling contributes to DP formation and hair growth. Using a Cre-lox genetic model and RNAi in hair follicle reconstitution assays, we demonstrate that dermal Smoothened (Smo) loss of function results in the loss of the DP precursor, the dermal condensate, and a stage 2 hair follicle arrest phenotype reminiscent of Shh(-/-) skin. Surprisingly, dermal Smo does not regulate cell survival or epithelial proliferation. Rather, molecular screening and immunostaining studies reveal that dermal Shh signaling controls the expression of a subset of DP-specific signature genes. Using a hairpin/cDNA lentiviral system, we show that overexpression of the Shh-dependent gene Noggin, but not Sox2 or Sox18, can partially rescue the dermal Smo knockdown hair follicle phenotype by increasing the expression of epithelial Shh. Our findings suggest that dermal Shh signaling regulates specific DP signatures to maintain DP maturation while maintaining a reciprocal Shh-Noggin signaling loop to drive hair follicle morphogenesis.

  12. High matrix metalloproteinase levels are associated with dermal graft failure in diabetic foot ulcers.

    Science.gov (United States)

    Izzo, Valentina; Meloni, Marco; Vainieri, Erika; Giurato, Laura; Ruotolo, Valeria; Uccioli, Luigi

    2014-09-01

    The aim of our study is to analyze factors, including matrix metalloproteinase (MMP) levels, that could influence the integration of dermal grafts in diabetic foot ulcers. From September 2012 to September 2013, 35 diabetic patients with IIA lesion (Texas Wound Classification) and an extensive foot tissue loss were considered suitable for dermal graft. Before the enrollment we ensured the best local conditions: adequate blood supply, control of infection, and offloading. The MMP level of each lesion was evaluated blindly before the application of dermal substitutes. At 1-month follow-up, we analyzed the correlation between clinical patient characteristics, local wound features including MMP levels, dermal substitute applied, and the outcome expressed in terms of dermal graft integration. We observed dermal graft integration in 28/35 patients (80% of our population). In multivariate analysis high MMP level was the only negative predictor for dermal graft integration (P < .0007). In addition, we divided the patients into 2 groups according to MMP levels: group 1 with low protease activity (24 patients) and group 2 with elevated protease activity (11 patients). The integration of the dermal graft was 100% in group 1 (n = 24 patients) and 36.4% in group 2 (n = 4patients), P < .0001. According to our data, the evaluation of MMP levels may be useful to choose the right strategy to get the best results in terms of clinical success and cost saving. However, further studies are necessary to confirm these findings.

  13. A new model for preclinical testing of dermal substitutes for human skin reconstruction.

    Science.gov (United States)

    Hartmann-Fritsch, Fabienne; Biedermann, Thomas; Braziulis, Erik; Meuli, Martin; Reichmann, Ernst

    2013-05-01

    Currently, acellular dermal substitutes used for skin reconstruction are usually covered with split-thickness skin grafts. The goal of this study was to develop an animal model in which such dermal substitutes can be tested under standardized conditions using a bioengineered dermo-epidermal skin graft for coverage. Bioengineered grafts consisting of collagen type I hydrogels with incorporated human fibroblasts and human keratinocytes seeded on these gels were produced. Two different dermal substitutes, namely Matriderm(®), and an acellular collagen type I hydrogel, were applied onto full-thickness skin wounds created on the back of immuno-incompetent rats. As control, no dermal substitute was used. As coverage for the dermal substitutes either the bioengineered grafts were used, or, as controls, human split-thickness skin or neonatal rat epidermis were used. Grafts were excised 21 days post-transplantation. Histology and immunofluorescence was performed to investigate survival, epidermis formation, and vascularization of the grafts. The bioengineered grafts survived on all tested dermal substitutes. Epidermis formation and vascularization were comparable to the controls. We could successfully use human bioengineered grafts to test different dermal substitutes. This novel model can be used to investigate newly designed dermal substitutes in detail and in a standardized way.

  14. Dermal exposure assessment to benzene and toluene using charcoal cloth pads

    NARCIS (Netherlands)

    Wendel de Joode, B. van; Tielemans, E.; Vermeulen, R.; Wegh, H.; Kromhout, H.

    2005-01-01

    Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and

  15. Patterns of Dermal Exposure to Hazardous Substances in European Union Workplaces

    NARCIS (Netherlands)

    Rajan-Sithamparanadarajah, R.; Roff, M.; Delgado, P.; Eriksson, K.; Fransman, W.; Gijsbers, J.H.J.; Hughson, G.; Mäkinen, M.; Hemmen, J.J. van

    2004-01-01

    Workplace dermal exposure assessment is a complex task that aims to understand the dynamic interaction between the skin and the hazardous substances present in the surrounding environment. A European project known as RISKOFDERM gathered dermal exposure data in 85 workplaces (industrial and other typ

  16. Harmonization of future needs for dermal exposure assessment and modeling : a workshop report

    NARCIS (Netherlands)

    Marquart, H.; Maidment, S.; Mcclaflin, J.L.; Fehrenbacher, M.C.

    2001-01-01

    Dermal exposure assessment and modeling is still in early phases of development. This article presents the results of a workshop organized to harmonize the future needs in this field. Methods for dermal exposure assessment either assess the mass of contaminant that is transferred to the skin, or the

  17. Classification of Dermal Exposure Modifiers and Assignment of Values for a Risk Assessment Toolkit

    NARCIS (Netherlands)

    Goede, H.A.; Tijssen, S.C.H.A.; Schipper, H.J.; Warren, N.; Oppl, R.; Kalberlah, F.; Hemmen, J.J. van

    2003-01-01

    This paper describes how default dermal exposure values can be adjusted with modifier values for specific work situations. The work presented here is supplementary to a toolkit developed for the EU RISKOFDERM project. This toolkit is intended for the assessment and management of dermal risks in smal

  18. Patterns of Dermal Exposure to Hazardous Substances in European Union Workplaces

    NARCIS (Netherlands)

    Rajan-Sithamparanadarajah, R.; Roff, M.; Delgado, P.; Eriksson, K.; Fransman, W.; Gijsbers, J.H.J.; Hughson, G.; Mäkinen, M.; Hemmen, J.J. van

    2004-01-01

    Workplace dermal exposure assessment is a complex task that aims to understand the dynamic interaction between the skin and the hazardous substances present in the surrounding environment. A European project known as RISKOFDERM gathered dermal exposure data in 85 workplaces (industrial and other

  19. Variability of Task-based Dermal Exposure Measurements from a Variety of Workplaces

    NARCIS (Netherlands)

    Kromhout, H.; Fransman, W.; Vermeulen, R.; Roff, M.; Hemmen, J.J. van

    2004-01-01

    Introduction: The RISKOFDERM project collected task-based estimates of potential dermal exposure from a wide range of industries and services from around Europe. A formal statistical analysis was carried out to explore the main components of variability in dermal exposure levels. The central

  20. A dermal model for spray painters, part I : subjective exposure modelling of spray paint deposition

    NARCIS (Netherlands)

    Brouwer, D.H.; Semple, S.; Marquart, J.; Cherrie, J.W.

    2001-01-01

    The discriminative power of existing dermal exposure models is limited. Most models only allow occupational hygienists to rank workers between and within workplaces according to broad bands of dermal exposure. No allowance is made for the work practices of different individuals. In this study a

  1. Variability of Task-based Dermal Exposure Measurements from a Variety of Workplaces

    NARCIS (Netherlands)

    Kromhout, H.; Fransman, W.; Vermeulen, R.; Roff, M.; Hemmen, J.J. van

    2004-01-01

    Introduction: The RISKOFDERM project collected task-based estimates of potential dermal exposure from a wide range of industries and services from around Europe. A formal statistical analysis was carried out to explore the main components of variability in dermal exposure levels. The central researc

  2. Methods for assessing risks of dermal exposures in the workplace.

    Science.gov (United States)

    McDougal, James N; Boeniger, Mark F

    2002-07-01

    The skin as a route of entry for toxic chemicals has caused increasing concern over the last decade. The assessment of systemic hazards from dermal exposures has evolved over time, often limited by the amount of experimental data available. The result is that there are many methods being used to assess safety of chemicals in the workplace. The process of assessing hazards of skin contact includes estimating the amount of substance that may end up on the skin and estimating the amount that might reach internal organs. Most times, toxicology studies by the dermal route are not available and extrapolations from other exposure routes are necessary. The hazards of particular chemicals can be expressed as "skin notations", actual exposure levels, or safe exposure times. Characterizing the risk of a specific procedure in the workplace involves determining the ratio of exposure standards to an expected exposure. The purpose of this review is to address each of the steps in the process and describe the assumptions that are part of the process. Methods are compared by describing their strengths and weaknesses. Recommendations for research in this area are also included.

  3. Dermal and transdermal delivery of pharmaceutically relevant macromolecules.

    Science.gov (United States)

    Münch, S; Wohlrab, J; Neubert, R H H

    2017-10-01

    The skin offers an attractive way for dermal and transdermal drug delivery that is why the drug still needs certain qualities to transcend the outermost layer of the skin, the stratum corneum. The requirements are: drugs with a maximum molecular weight of 1kDa, high lipophilicity and a certain polarity. This would restrict the use of a transdermal delivery of macromolecules, which would make the drug more effective in therapeutic administration. Various studies have shown that macromolecules without support do not penetrate the human skin. This effect can be achieved using physical and chemical methods, as well as biological peptides. The most popular physical method is the use of microneedles to create micropores in the skin and release the active agent in different sections. But also, other methods have been tested. Microjets, lasers, electroporation, sonophoresis and iontophoresis are also promising methods to successfully deliver dermal and transdermal macromolecules. Additionally, there are different penetration enhancer groups and biological peptides, which are also considered to be interesting approaches of enabling macromolecules to travel along the skin. All these methods will be described and evaluated in this review article. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The dermal carcinogenic potential of unrefined and hydrotreated lubricating oils.

    Science.gov (United States)

    McKee, R H; Daughtrey, W C; Freeman, J J; Federici, T M; Phillips, R D; Plutnick, R T

    1989-08-01

    Unrefined lubricating oils contain relatively high levels of polycyclic aromatic hydrocarbons (PAH) and have been shown to induce tumors in mouse skin. Exxon has developed a new method of refining these materials, a severe hydrotreatment process that is optimized for PAH removal. The specific objectives of the current study were to assess PAH reduction and then to evaluate directly the dermal carcinogenic potential of the materials that spanned the range of products produced by this method. The test samples included unrefined light and heavy vacuum distillates from a naphthenic crude oil, as well as the corresponding severely hydrotreated products. Two sets of samples were prepared to assess the effects of various operating parameters in the reactor. Additionally, positive (benzo[a]pyrene), negative (white mineral oil) and vehicle (toluene) control groups were included to assess the sensitivity and specificity of the bioassay. Each sample was applied in twice-weekly aliquots to the backs of 40 male C3H mice. In the analytical studies, significant reductions in the levels of several specific PAH were demonstrated. In the dermal carcinogenesis studies, the unrefined oils and the positive control induced tumors and also significantly reduced survival. None of the mice treated with severely hydrotreated oils or with the negative or vehicle controls developed skin tumors, and survival of these mice was not significantly different from the control. Thus, the data demonstrated that this new, severe hydrotreatment process was an effective means of converting carcinogenic feedstocks to non-carcinogenic products.

  5. Complications caused by injection of dermal filler in Danish patients

    DEFF Research Database (Denmark)

    Uth, Charlotte Caspara; Elberg, Jens Jørgen; Zachariae, Claus

    2016-01-01

    Background: The usage of dermal fillers has increased significantly in recent years. Soft tissue augmentation with fillers helps to diminish the facial lines and to restore volume and fullness in the face at a relatively low cost. With the increasing number of treatments, the number of complicati......Background: The usage of dermal fillers has increased significantly in recent years. Soft tissue augmentation with fillers helps to diminish the facial lines and to restore volume and fullness in the face at a relatively low cost. With the increasing number of treatments, the number...... of complications is likely to increase as well.  Methods: A total of 37 patients with complications were collected retrospectively during a period of 13 years using original data files. Information on the type, date, number and location of the injections, type and date of complications, treatment, bacteria...... and complications was 2 years (range 1 day–8 years). The most common reported complications were edema (81 %), noduli (67.7 %), infections (54.1 %), discoloration (51.4 %), and granuloma formation (48.6 %). Surgical removal of the filler material was attempted in four patients.  Conclusions: With the increased use...

  6. Distribution of kerosene components in rats following dermal exposure.

    Science.gov (United States)

    Tsujino, Y; Hieda, Y; Kimura, K; Eto, H; Yakabe, T; Takayama, K; Dekio, S

    2002-08-01

    The systemic distribution of kerosene components in blood and tissues was analysed in rats following dermal exposure. Four types of trimethylbenzenes (TMBs) and aliphatic hydrocarbons (AHCs) with carbon numbers 9-16 (C(9)-C(16)) were analysed as major kerosene components by capillary gas chromatography/mass spectrometry (GC/MS). The kerosene components were detected in blood and all tissues after a small piece of cotton soaked with kerosene was applied to the abdominal skin. The amounts of TMBs detected were higher than those of AHCs. Greater increases in TMB levels were found in adipose tissue in an exposure duration-dependent manner. The amounts of TMBs detected were only at trace levels following post-mortem dermal exposure to kerosene. These findings suggest that kerosene components were absorbed percutaneously and distributed to various organs via the blood circulation. Post-mortem or ante-mortem exposure to kerosene could be distinguished when the exposure duration was relatively long. Adipose tissue would seem to be the most useful for estimating the degree of kerosene exposure.

  7. A study of uniaxial tension on the superficial dermal microvasculature.

    Science.gov (United States)

    Barnhill, R L; Bader, D L; Ryan, T J

    1984-05-01

    A spring-loaded apparatus was designed to apply uniaxial tension to forearm skin in 17 human subjects--10 normals, 6 psoriatics, and 1 patient with scleroderma. Simultaneously, the effects of stretching on the upper dermal vasculature were observed stereomicroscopically. Progressive changes (collapse) in the superficial microvasculature--vertical capillary loops and horizontal subpapillary plexus--with increasing tension were photographed. Force and strains were recorded at the points of disappearance of virtually all vessels. An average force of 11.9 newtons (N), accompanied by a mean strain of 10.3%, resulted in occlusion of all vessels. A much higher force (18.5 N) was necessary to occlude blood flow in the 1 patient with scleroderma. In summary, we have described a new technique for the study of mechanical forces on the blood supply of the epidermis. The data have shown that uniaxial tension has important effects on the superficial dermal microvasculature, resulting in impedance and obliteration of blood flow at relatively low magnitudes.

  8. Acellular dermal matrix based nipple reconstruction: A modified technique

    Directory of Open Access Journals (Sweden)

    Raghavan Vidya

    2017-09-01

    Full Text Available Nipple areolar reconstruction (NAR has evolved with the advancement in breast reconstruction and can improve self-esteem and, consequently, patient satisfaction. Although a variety of reconstruction techniques have been described in the literature varying from nipple sharing, local flaps to alloplastic and allograft augmentation, over time, loss of nipple projection remains a major problem. Acellular dermal matrices (ADM have revolutionised breast reconstruction more recently. We discuss the use of ADM to act as a base plate and strut to give support to the base and offer nipple bulk and projection in a primary procedure of NAR with a local clover shaped dermal flap in 5 breasts (4 patients. We used 5-point Likert scales (1 = highly unsatisfied, 5 = highly satisfied to assess patient satisfaction. Median age was 46 years (range: 38–55 years. Nipple projection of 8 mm, 7 mm, and 7 mms were achieved in the unilateral cases and 6 mm in the bilateral case over a median 18 month period. All patients reported at least a 4 on the Likert scale. We had no post-operative complications. It seems that nipple areolar reconstruction [NAR] using ADM can achieve nipple projection which is considered aesthetically pleasing for patients.

  9. Effect of Arctium lappa (burdock) extract on canine dermal fibroblasts.

    Science.gov (United States)

    Pomari, Elena; Stefanon, Bruno; Colitti, Monica

    2013-12-15

    Although the biological activities of Arctium lappa (burdock) have been already investigated in human and other species, data evaluating the molecular mechanisms have not been reported in the dog. In this study we analyzed for the first time the effect of a root extract of burdock on molecular responses in canine dermal fibroblasts with H2O2 stimulation (H group), with burdock treatment (B group) and with H2O2 stimulation and burdock treatment (BH group), using RNAseq technology. Differentially expressed genes (P<0.05) of H, B and BH groups in comparison to the untreated sample (negative control, C group) were identified with MeV software and were functional annotated and monitored for signaling pathways and candidate biomarkers using the Ingenuity Pathways Analysis (IPA). The expression profile of canine dermal fibroblasts treated with burdock extract with or without H2O2 stimulation, showed an up-regulation of mitochondrial superoxide dismutase (SOD2), disheveled 3 (DVL3) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2). The data suggested that burdock has implications in cell adhesion and gene expression with the modulation of Wnt/β catenin signaling and Chondroitin Sulphate Biosynthesis that are particularly important for the wound healing process.

  10. The Use of Dermal Autograft for Fascial Repair of TRAM Flap Donor Sites

    Directory of Open Access Journals (Sweden)

    Ali Arab Kheradmand

    2010-03-01

    Full Text Available Closure of fascia after transverse rectus abdominis musculocutaneous (TRAM flap has usually been performed with direct closure or synthetic material. The dermal autograft was removed from zone IV of flap was an alternative to reinforce fascial closure. The dermal autograft was used in 34 patients after TRAM harvest for breast, head and neck reconstruction and Prolene mesh was used in 42 other patients for closure of fascial defect. All patients were followed by physical examinations. Average follow-up in the dermal autograft group was 27.3 versus 20.7 months in the second group. In the dermal autograft group, one patient complained of bulging of the anterior abdominal wall; one developed a wound infection. In the second group, one patients experienced true hernia. Dermal autografts are a useful alternative to mesh repair of fascial defects after TRAM flap harvest.

  11. Hanford Tank Ventilation System Condensates and Headspace Vapors: An Assessment of Potential Dermal Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Huckaby, James L.; Springer, David L.

    2006-04-24

    This study considers the question of whether potential dermal exposures to Hanford high-level radioactive waste tank headspace vapors and their condensates could result in significant exposure to workers. Three types of potential exposures were evaluated; dermal contact with aqueous condensate, organic condensate, and direct contact with head space vapors. The dermal absorption rates from aqueous and organic condensates were estimated for selected chemicals using a model described by EPA (1992) with a modified correlation for dermal permeability suggested by Wilschut et al. (1995). Dermal absorption rates of vapors were estimated using a model given by AIHA (2000). Results were compared to an ''equivalent inhalation dose'' calculated by multiplying the inhalation occupational exposure limit by a nominal daily inhalation rate. The results should provide guidance for industrial hygienists to prepare specific recommendations based on specific scenarios.

  12. Deriving Default Dermal Exposure Values for Use in a Risk Assessment Toolkit for Small and Medium-sized Enterprises

    NARCIS (Netherlands)

    Warren, N.; Goede, H.A.; Tijssen, S.C.H.A.; Oppl, R.; Schipper, H.J.; Hemmen, J.J. van

    2003-01-01

    This paper describes the derivation of default task-based dermal exposure values for use in a risk assessment toolkit for small and medium-sized enterprises (SMEs). A set of separately determined dermal exposure modifiers have been applied to published studies of dermal exposure to obtain 'normalize

  13. Assessment of dermal exposure to bitumen condensate among road paving and mastic crews with an observational method

    NARCIS (Netherlands)

    Agostini, M.; Fransman, W.; Vocht, F.D.; Joode, B.V.W.D.; Kromhout, H.

    2011-01-01

    Objective: To assess dermal exposure to bitumen condensate among road pavers and indoor mastic workers in multiple crews using a semi-quantitative observational method [DeRmal Exposure Assessment Method (DREAM)].Methods: Two skilled observers assessed dermal exposure to bitumen condensate among 85 a

  14. Evaluation of dermal substitute in a novel co-transplantation model with autologous epidermal sheet.

    Directory of Open Access Journals (Sweden)

    Guofeng Huang

    Full Text Available The development of more and more new dermal substitutes requires a reliable and effective animal model to evaluate their safety and efficacy. In this study we constructed a novel animal model using co-transplantation of autologous epidermal sheets with dermal substitutes to repair full-thickness skin defects. Autologous epidermal sheets were obtained by digesting the basement membrane (BM and dermal components from rat split-thickness skins in Dispase II solution (1.2 u/ml at 4 °C for 8, 10 and 12 h. H&E, immunohistochemical and live/dead staining showed that the epidermal sheet preserved an intact epidermis without any BM or dermal components, and a high percentage of viable cells (92.10 ± 4.19% and P63 positive cells (67.43 ± 4.21% under an optimized condition. Porcine acellular dermal matrixes were co-transplanted with the autologous epidermal sheets to repair full-thickness skin defects in Sprague-Dawley rats. The epidermal sheets survived and completely re-covered the wounds within 3 weeks. Histological staining showed that the newly formed stratified epidermis attached directly onto the dermal matrix. Inflammatory cell infiltration and vascularization of the dermal matrix were not significantly different from those in the subcutaneous implantation model. Collagen IV and laminin distributed continuously at the epidermis and dermal matrix junction 4 weeks after transplantation. Transmission electron microscopy further confirmed the presence of continuous lamina densa and hemidesmosome structures. This novel animal model can be used not only to observe the biocompatibility of dermal substitutes, but also to evaluate their effects on new epidermis and BM formation. Therefore, it is a simple and reliable model for evaluating the safety and efficacy of dermal substitutes.

  15. Thiol/disulfide homeostasis in asphalt workers.

    Science.gov (United States)

    Yilmaz, Ömer Hınç; Bal, Ceylan; Neşelioglu, Salim; Büyükşekerci, Murat; Gündüzöz, Meşide; Eren, Funda; Tutkun, Lutfiye; Yilmaz, Fatma Meric

    2016-09-02

    The aim of this study was to investigate thiol/disulfide homeostasis in asphalt workers who are exposed to polycyclic aromatic hydrocarbons occupationally. The study was carried out in 34 nonsmoker asphalt workers. Additionally, 35 healthy nonsmoker volunteers were recruited as control group. Thiol and disulfide concentrations were determined using the novel automated measurement method. Levels of urinary 1-OH-pyrene were analyzed by liquid chromatography. Disulfide/thiol ratio was significantly higher in exposed group (p = .034). Also, a positive correlation was detected between disulfide/thiol ratio and 1-OH-pyrene values (r = .249, p = .036). Thiol/disulfide homeostasis was found to be disturbed in asphalt workers. The novel test used in this study may be useful for evaluating the oxidative status in polycyclic aromatic hydrocarbon (PAH) exposure.

  16. Transcranial electrical stimulation accelerates human sleep homeostasis.

    Directory of Open Access Journals (Sweden)

    Davide Reato

    Full Text Available The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO in the human electro-encephalogram (EEG. A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.

  17. The liver in regulation of iron homeostasis.

    Science.gov (United States)

    Rishi, Gautam; Subramaniam, V Nathan

    2017-09-01

    The liver is one of the largest and most functionally diverse organs in the human body. In addition to roles in detoxification of xenobiotics, digestion, synthesis of important plasma proteins, gluconeogenesis, lipid metabolism, and storage, the liver also plays a significant role in iron homeostasis. Apart from being the storage site for excess body iron, it also plays a vital role in regulating the amount of iron released into the blood by enterocytes and macrophages. Since iron is essential for many important physiological and molecular processes, it increases the importance of liver in the proper functioning of the body's metabolism. This hepatic iron-regulatory function can be attributed to the expression of many liver-specific or liver-enriched proteins, all of which play an important role in the regulation of iron homeostasis. This review focuses on these proteins and their known roles in the regulation of body iron metabolism. Copyright © 2017 the American Physiological Society.

  18. The Impact of Melatonin on Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Zeynep Arzu Yeğin

    2009-12-01

    Full Text Available Objective: Melatonin is a pineal product mainly charged with the maintenance of antioxidant conditions in human. This study is performed to identify the short-term effect of melatonin on glucose homeostasis in diabetic patients. Materials and Methods: Melatonin and placebo were given perorally to sixty patients. Blood glucose and insulin levels were measured with constant intervals. Results: No significant correlation was found among the levels of glucose, insulin and HOMA-IR index at any time after melatonin/placebo administration.Conclusions: Prospective studies with long-term use of melatonin are needed to define the exact role of melatonin in glucose homeostasis. Turk Jem 2009; 13: 52-5

  19. Molecular regulators of phosphate homeostasis in plants.

    Science.gov (United States)

    Lin, Wei-Yi; Lin, Shu-I; Chiou, Tzyy-Jen

    2009-01-01

    An appropriate cellular phosphate (Pi) concentration is indispensable for essential physiological and biochemical processes. To maintain cellular Pi homeostasis, plants have developed a series of adaptive responses to facilitate external Pi acquisition and to limit Pi consumption and to adjust Pi recycling internally when the Pi supply is inadequate. Over the past decade, significant progress has been made toward understanding such regulation at the molecular level. In this review, the focus is on the molecular regulators that mediate cellular Pi concentrations. The regulators are introduced and organized according to their original identification procedures, by the forward genetic approach of mutant screening or by reverse genetic analysis. These genes are involved in Pi uptake, allocation or remobilization or are upstream regulators, such as transcriptional factors or signalling molecules. In the future, integration of current knowledge and exploration of new technology is expected to offer new insights into molecular mechanisms that maintain Pi homeostasis.

  20. Homeostasis as the Mechanism of Evolution

    Directory of Open Access Journals (Sweden)

    John S. Torday

    2015-09-01

    Full Text Available Homeostasis is conventionally thought of merely as a synchronic (same time servo-mechanism that maintains the status quo for organismal physiology. However, when seen from the perspective of developmental physiology, homeostasis is a robust, dynamic, intergenerational, diachronic (across-time mechanism for the maintenance, perpetuation and modification of physiologic structure and function. The integral relationships generated by cell-cell signaling for the mechanisms of embryogenesis, physiology and repair provide the needed insight to the scale-free universality of the homeostatic principle, offering a novel opportunity for a Systems approach to Biology. Starting with the inception of life itself, with the advent of reproduction during meiosis and mitosis, moving forward both ontogenetically and phylogenetically through the evolutionary steps involved in adaptation to an ever-changing environment, Biology and Evolution Theory need no longer default to teleology.

  1. Iron Homeostasis in Health and Disease

    Directory of Open Access Journals (Sweden)

    Raffaella Gozzelino

    2016-01-01

    Full Text Available Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport and diminished activity of Fe-dependent enzymes, and also iron excess that may catalyze the formation of highly reactive hydroxyl radicals, oxidative stress, and programmed cell death. The advance in understanding the main players and mechanisms involved in iron regulation significantly improved since the discovery of genes responsible for hemochromatosis, the IRE/IRPs machinery, and the hepcidin-ferroportin axis. This review provides an update on the molecular mechanisms regulating cellular and systemic Fe homeostasis and their roles in pathophysiologic conditions that involve alterations of iron metabolism, and provides novel therapeutic strategies to prevent the deleterious effect of its deficiency/overload.

  2. Neutrophils in Homeostasis, Immunity, and Cancer.

    Science.gov (United States)

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Dermal adipocytes and hair cycling: is spatial heterogeneity a characteristic feature of the dermal adipose tissue depot?

    Science.gov (United States)

    Kruglikov, Ilja L; Scherer, Philipp E

    2016-04-01

    Adipocytes are widely distributed in the dermis, in a unique fat depot referred to as dermal white adipose tissue (dWAT). In rodents, dWAT is present as widespread thin layers, whereas in pigs and humans, it is present in clusters referred to as 'dermal cones' around the pilosebaceous units. This distinct layer of fat cells located above the subcutaneous white adipose tissue is important for proper hair follicle (HF) cycling in rodents. Murine HFs produce spatially restricted synchronous patches after their second postnatal cycle which correlates with the spatial heterogeneity of murine dWAT. Similarly, the cycling of HFs in humans may also be related to the spatial distribution of dWAT, making the difference between murine and human HF cycling of more quantitative than of qualitative nature. This should allow the production of small spatially correlated HF patches in human skin, and we propose that this process can be regulated by paracrine signalling involving a number of signalling modules, including the hedgehog pathway. This pathway is an established player in HF cycling, but is also involved in the regulation of adipogenesis and may therefore be a key regulator of the process across species. We also suggest that the spatial heterogeneity of dWAT is connected not only to HF cycling, but may also be related to other physiological and pathological processes in the skin.

  4. THE WORLD VIEW, IDENTITY AND SOCIOCULTUR HOMEOSTASIS

    Directory of Open Access Journals (Sweden)

    Marina Yur’evna Neronova

    2016-02-01

    Full Text Available The paper presents the relationship between the phenomenon of world view and sociocultural identity both individuals and the community as a whole. The research is being carried out in the context of current crisis of world view accepted in so-called art Nouveau era. This paper also presents the identity crisis typical for modern civilized societies. A new notion of sociocultural homeostasis is introduced in connection with analyzable phenomena and their mutual relations.Purpose. Study of the relationship between the phenomenon of the world view and sociocultural identity as a structural and functional mechanism.Methodology. Phenomenological and systematic methods with the elements of historical method were employed. Cultural analysis is based on using both axiological and phenomenological approach, and also the elements of semiotic approach.Results. The dependence of identity on the world view is revealed (or is being revealed?, the phenomenon of sociocultural homeostasis is singled out (or is being singled out in the capacity of the mechanism setting up the correspondence in the contradictory unity between the world view as a subjective image and concrete reality as an objective part of this contradictory. The analysis of sociocultural homeostasis is carried out (or is being carried out and the conclusion is being drown that instability of the latter leads to serious problems in the identification of both individuals and communities as a whole. Besides, (moreover the relationship between the legitimacy level of the world view and stability of sociocultural homeostasis is established. (is being established.Practical implications: the system of education.

  5. Abnormal calcium homeostasis in peripheral neuropathies

    OpenAIRE

    2009-01-01

    Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The cent...

  6. Smart parking barrier

    KAUST Repository

    Alharbi, Abdulrazaq M.

    2016-05-06

    Various methods and systems are provided for smart parking barriers. In one example, among others, a smart parking barrier system includes a movable parking barrier located at one end of a parking space, a barrier drive configured to control positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking space and a second position that allows access to the parking space. The parking controller can initiate movement of the movable parking barrier in response to a positive identification of an individual allowed to use the parking space. The parking controller can identify the individual through, e.g., a RFID tag, a mobile device (e.g., a remote control, smartphone, tablet, etc.), an access card, biometric information, or other appropriate identifier.

  7. Sleep and bodily functions: the physiological interplay between body homeostasis and sleep homeostasis.

    Science.gov (United States)

    Amici, R; Bastianini, S; Berteotti, C; Cerri, M; Del Vecchio, F; Lo Martire, V; Luppi, M; Perez, E; Silvani, A; Zamboni, G; Zoccoli, G

    2014-01-01

    Body homeostasis and sleep homeostasis may both rely on the complex integrative activity carried out by the hypothalamus. Thus, the three main wake-sleep (WS) states (i.e. wakefulness, NREM sleep, and REM sleep) may be better understood if the different cardio-respiratory and metabolic parameters, which are under the integrated control of the autonomic and the endocrine systems, are studied during sleep monitoring. According to this view, many physiological events can be considered as an expression of the activity that physiological regulations should perform in order to cope with the need to fulfill body and sleep homeostasis. This review is aimed at making an assessment of data showing the existence of a physiological interplay between body homeostasis and sleep homeostasis, starting from the spontaneous changes observed in the somatic and autonomic activity during sleep, through evidence showing the deep changes occurring in the central integration of bodily functions during the different WS states, to the changes in the WS states observed when body homeostasis is challenged by the external environment and when the return to normal ambient conditions allows sleep homeo- stasis to run without apparent physiological restrictions. The data summarized in this review suggest that an approach to the dichotomy between NREM and REM sleep based on physiological regulations may offer a framework within which observations that a traditional behavioral approach may overlook can be interpreted. The study of the interplay between body and sleep homeostasis appears, therefore, to be a way to understand the function of complex organisms beyond that of the specific regulations.

  8. Regulation of energy homeostasis via GPR120

    Directory of Open Access Journals (Sweden)

    Atsuhiko eIchimura

    2014-07-01

    Full Text Available Free fatty acids (FFAs are fundamental units of key nutrients. FFAs exert various biological functions, depending on the chain length and degree of desaturation. Recent studies have shown that several FFAs act as ligands of G-protein-coupled receptors (GPCRs, activate intracellular signaling and exert physiological functions via these GPCRs. GPR120 (also known as free fatty acid receptor 4, FFAR4 is activated by unsaturated medium- to long-chain FFAs and has a critical role in various physiological homeostasis mechanisms such as incretin hormone secretion, food preference, anti-inflammation and adipogenesis. Recent studies showed that a lipid sensor GPR120 has a key role in sensing dietary fat in white adipose tissue and regulates the whole body energy homeostasis in both humans and rodents. Genetic study in human identified the loss-of-functional mutation of GPR120 associated with obesity and insulin resistance. In addition, dysfunction of GPR120 has been linked as a novel risk factor for diet-induced obesity. This review aims to provide evidence from the recent development in physiological function of GPR120 and discusses its functional roles in regulation of energy homeostasis and its potential as drug targets.

  9. Bitter taste receptors influence glucose homeostasis.

    Science.gov (United States)

    Dotson, Cedrick D; Zhang, Lan; Xu, Hong; Shin, Yu-Kyong; Vigues, Stephan; Ott, Sandra H; Elson, Amanda E T; Choi, Hyun Jin; Shaw, Hillary; Egan, Josephine M; Mitchell, Braxton D; Li, Xiaodong; Steinle, Nanette I; Munger, Steven D

    2008-01-01

    TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca(2+) and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease.

  10. Endocannabinoids and energy homeostasis: an update.

    Science.gov (United States)

    Cristino, Luigia; Becker, Thorsten; Di Marzo, Vincenzo

    2014-01-01

    The endocannabinoid system (ECS) is a widespread intercellular signaling system that plays a critical role in energy homeostasis, meant as the precise matching of caloric intake with energy expenditure which normally keeps body weight stable over time. Complex interactions between environmental and neurohormonal systems directly contribute to the balance of energy homeostasis. This review highlights established and more recent data on the brain circuits in which the ECS plays an important regulatory role, with focus on the hypothalamus, a region where numerous interacting systems regulating feeding, satiety, stress, and other motivational states coexist. Although not meant as an exhaustive review of the field, this article will discuss how endocannabinoid tone, in addition to reinforcing reward circuitries and modulating food intake and the salience of food, controls lipid and glucose metabolism in several peripheral organs, particularly the liver and adipose tissue. Direct actions in the skeletal muscle and pancreas are also emerging and are briefly discussed. This review provides new perspectives into endocannabinoid control of the neurochemical causes and consequences of energy homeostasis imbalance, a knowledge that might lead to new potential treatments for obesity and related morbidities.

  11. Bitter taste receptors influence glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Cedrick D Dotson

    Full Text Available TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca(2+ and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1, an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease.

  12. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

    Science.gov (United States)

    Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

    2012-01-01

    Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

  13. Androgen receptor accelerates premature senescence of human dermal papilla cells in association with DNA damage.

    Directory of Open Access Journals (Sweden)

    Yi-Chien Yang

    Full Text Available The dermal papilla, located in the hair follicle, expresses androgen receptor and plays an important role in hair growth. Androgen/Androgen receptor actions have been implicated in the pathogenesis of androgenetic alopecia, but the exact mechanism is not well known. Recent studies suggest that balding dermal papilla cells exhibit premature senescence, upregulation of p16(INK4a, and nuclear expression of DNA damage markers. To investigate whether androgen/AR signaling influences the premature senescence of dermal papilla cells, we first compared frontal scalp dermal papilla cells of androgenetic alopecia patients with matched normal controls and observed that premature senescence is more prominent in the dermal papilla cells of androgenetic alopecia patients. Exposure of androgen induced premature senescence in dermal papilla cells from non-balding frontal and transitional zone of balding scalp follicles but not in beard follicles. Overexpression of the AR promoted androgen-induced premature senescence in association with p16(INK4a upregulation, whereas knockdown of the androgen receptor diminished the effects of androgen. An analysis of γ-H2AX expression in response to androgen/androgen receptor signaling suggested that DNA damage contributes to androgen/androgen receptor-accelerated premature senescence. These results define androgen/androgen receptor signaling as an accelerator of premature senescence in dermal papilla cells and suggest that the androgen/androgen receptor-mediated DNA damage-p16(INK4a axis is a potential therapeutic target in the treatment of androgenetic alopecia.

  14. Dermal lesions after post mortem petrol-exposure.

    Science.gov (United States)

    Bux, R; Stengel, P D; Schnabel, A

    2006-11-10

    The effect of post mortem contact of the skin with petrol was investigated in 18 corpses with exposure times between 10 min and 24 h. The earliest onset of skin changes was observed within 2 h of exposure. They consisted of swelling and wrinkling with detachment of the upper layers of the skin (positive Nikolski's sign). Histologically the lesions appeared as non-vital acantholyses located in the prickle-cell layer with formation of intra-epidermal bullae. An influence of age and sex could be excluded, the earlier onset of lesions at 22 degrees C than at 4 degrees C was not statistically significant. These findings prove that post mortem petrol exposure may lead to dermal lesions.

  15. Complex wound management utilizing an artificial dermal matrix.

    Science.gov (United States)

    Muangman, Pornprom; Engrav, Loren H; Heimbach, David M; Harunari, Nobuyuki; Honari, Shari; Gibran, Nicole S; Klein, Matthew B

    2006-08-01

    The benefits of the Integra Dermal Regeneration Template in the management of extensive burn injuries have been well documented. Integra can reduce donor- and graft-site scarring and has been reported to be capable of vascularizing over small areas of exposed bone and tendon. Given these potential advantages, we have used Integra for a variety of other reconstruction applications. We performed a retrospective review of patients with complex wounds treated with Integra at our burn center. Integra was used in the management of a variety of wounds, including necrotizing fasciitis, extremity degloving injury, meningococcemia, Marjolin ulcer, postburn lip reconstruction, and fourth-degree burns with exposed bone or tendon. Engraftment rates of Integra and autograft were 98% +/- 4% and 97% +/- 4%, respectively. All areas of graft loss healed without need for regrafting. The benefits of Integra in the management of acute burn wounds can be extended to other traumatic and complex wounds.

  16. Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

    Science.gov (United States)

    Cohen, Brandon E; Bashey, Sameer; Cole, Christine; Abraham, Jerrold L; Ragsdale, Bruce; Ngo, Binh

    2016-12-01

    Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.

  17. Post-kala-azar dermal leishmaniasis associated with AIDS

    Directory of Open Access Journals (Sweden)

    Bittencourt Achiléa

    2003-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

  18. Post-kala-azar dermal leishmaniasis associated with AIDS

    Directory of Open Access Journals (Sweden)

    Bittencourt Achiléa

    2002-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

  19. Acute concentrated phenol dermal burns: Complications and management

    Directory of Open Access Journals (Sweden)

    Tapan Jayantilal Parikh

    2015-01-01

    Full Text Available Phenol burns can result in multiple organ failure. This is a case report of acute severe phenol dermal burn after accidental splash of 94% phenol on 35-year-old patient′s body who was brought to hospital after 90 min of exposure. Decontamination was done with high-density water and glycerol. Early complications in form of metabolic acidosis and acute renal failure required hemodialysis. Extensive protein denaturation was managed with IV albumin and high protein diet. Patient also developed pleural effusion and acute respiratory distress syndrome, but these were successfully managed by intercostal drain tube insertion and noninvasive ventilation. The patient survived after multiple organ failures and widespread burns despite the fact that it has been observed that outcome of phenol burns with >60 2 inches of skin affected or two or more organs failure involving renal system is nearly fatal.

  20. Sonographic Appearance of Dermal and Subcutaneous Sarcoidosis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ja Yoon; Bae, Young A; Hong, Hyeok Jin; Kwon, Kye Won [Dept. of Radiology, Bundang Jesaeng General Hospital, Seongnam (Korea, Republic of)

    2012-08-15

    Sarcoidosis is a systemic granulomatous disease of unknown origin that mainly involves lung and skin, but rarely involves subcutaneous tissue. While some studies have reported on CT or MR imaging findings of subcutaneous sarcoidosis, there is only one report on sonographic findings of subcutaneous sarcoidosis, recently published in the US. Familiarity with ultrasonographic findings of subcutaneous sarcoidosis might be helpful for the early diagnosis in patient with palpable nodules and image follow-up for subcutaneous sarcoidosis. Here we report on the sonographic appearance of subcutaneous sarcoidosis involving dermal and subcutaneous tissue over axilla and sole, a case diagnosed as sarcoidosis and improved by steroid treatment, along with a review of the relevant literature.

  1. ACUTE DERMAL TOXICITY STUDIES OF TROISTM IN NEWZEALAND WHITE RABBITS

    Directory of Open Access Journals (Sweden)

    Anurag Payasi

    2010-06-01

    Full Text Available The study was performed to assess the acute dermal toxicity of TroisTM in Newzealand white rabbit. Test substance was applied as such to the shaven skin of group of rabbits at the dose of 2000 mg/Kg body weight. Control group of animals were similarly treated but only with base. Following dosing up to 14 days the rabbits were observed for mortality and clinical sign of toxicity. No visible signs of toxicity after treatment were observed on the animals of both control and treated animals up to 14 days. Various haematological and biochemical parameters were evaluated and found to be in the normal limit, which indicates that no sign of toxicity in NewZealand white rabbits after 14 days treatment in respect to control group, proving safety of TroisTM in topical application.

  2. Lycopene from tomatoes: vesicular nanocarrier formulations for dermal delivery.

    Science.gov (United States)

    Ascenso, Andreia; Pinho, Sónia; Eleutério, Carla; Praça, Fabíola Garcia; Bentley, Maria Vitória Lopes Badra; Oliveira, Helena; Santos, Conceição; Silva, Olga; Simões, Sandra

    2013-07-31

    This experimental work aimed to develop a simple, fast, economic, and environmentally friendly process for the extraction of lycopene from tomato and incorporate this lycopene-rich extract into ultradeformable vesicular nanocarriers suitable for topical application. Lycopene extraction was conducted without a cosolvent for 30 min. The extracts were analyzed and incorporated in transfersomes and ethosomes. These formulations were characterized, and the cellular uptake was observed by confocal microscopy. Dermal delivery of lycopene formulations was tested under in vitro and in vivo conditions. Lycopene extraction proved to be quite safe and selective. The vesicular formulation was taken up by the cells, being more concentrated around the nucleus. Epicutaneous application of lycopene formulations decreased the level of anthralin-induced ear swelling by 97 and 87%, in a manner nonstatistically different from the positive control. These results support the idea that the lycopene-rich extract may be a good alternative to the expensive commercial lycopene for incorporation into advanced topical delivery systems.

  3. [Assessment of predictive dermal exposure to chemicals in the work environment].

    Science.gov (United States)

    Jankowska, Agnieszka; Czerczak, Sławomir; Kupczewska-Dobecka, Małgorzata

    2017-06-27

    Assessment of dermal exposure to chemicals in the work environment is problematic, mainly as a result of the lack of measurement data on occupational exposure to chemicals. Due to common prevalence of occupational skin exposure and its health consequences it is necessary to look for efficient solutions allowing for reliable exposure assessment. The aim of the study is to present predictive models used to assess non-measured dermal exposure, as well as to acquaint Polish users with the principles of the selected model functioning. This paper presents examples of models to assist the employer in the the assessment of occupational exposure associated with the skin contact with chemicals, developed in European Union (EU) countries, as well as in countries outside the EU. Based on the literature data dermal exposure models EASE (Estimation and Assessment of Substance Exposure), COSHH Essentials (Control of Substances Hazardous to Health Regulations), DREAM (Dermal Exposure Assessment Method), Stoffenmanager , ECETOC TRA (European Centre for Ecotoxicology and Toxicology of Chemicals Targeted Risk Assessment), MEASE (Metal's EASE), PHED (Pesticide Handlers Exposure Database), DERM (Dermal Exposure Ranking Method) and RISKOFDERM (Risk Assessment of Occupational Dermal Exposure to Chemicals) were briefly described. Moreover the characteristics of RISKOFDERM, guidelines for its use, information on input and output data were further detailed. Problem of full work shift dermal exposure assessment is described. An example of exposure assessment using RISKOFDERM and effectiveness evaluation to date were also presented. When no measurements are available, RISKOFDERM allows dermal exposure assessment and thus can improve the risk assessment quality and effectiveness of dermal risk management. Med Pr 2017;68(4):557-569. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  4. CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Rong-hui, E-mail: fan_ronghuixa@163.com [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Zhu, Xiu-mei; Sun, Yao-wen [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Peng, Hui-zi [Department of Cosmetology Plastic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Wu, Hang-li; Gao, Wen-jie [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China)

    2016-07-08

    Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.

  5. Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function.

    Science.gov (United States)

    Boer, Magdalena; Duchnik, Ewa; Maleszka, Romuald; Marchlewicz, Mariola

    2016-02-01

    The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part - stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transepidermal water loss and sebum excretion. The knowledge of biophysical skin processes may be useful for the implementation of prophylactic actions whose aim is to restore the barrier function.

  6. Structural and biophysical characteristics of human skin in maintaining proper epidermal barrier function

    Directory of Open Access Journals (Sweden)

    Magdalena Boer

    2016-02-01

    Full Text Available The complex structure of human skin and its physicochemical properties turn it into an efficient outermost defence line against exogenous factors, and help maintain homeostasis of the human body. This role is played by the epidermal barrier with its major part – stratum corneum. The condition of the epidermal barrier depends on individual and environmental factors. The most important biophysical parameters characterizing the status of this barrier are the skin pH, epidermal hydration, transepidermal water loss and sebum excretion. The knowledge of biophysical skin processes may be useful for the implementation of prophylactic actions whose aim is to restore the barrier function.

  7. Sirtinol treatment reduces inflammation in human dermal microvascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Angela Orecchia

    Full Text Available Histone deacetylases (HDAC are key enzymes in the epigenetic control of gene expression. Recently, inhibitors of class I and class II HDAC have been successfully employed for the treatment of different inflammatory diseases such as rheumatoid arthritis, colitis, airway inflammation and asthma. So far, little is known so far about a similar therapeutic effect of inhibitors specifically directed against sirtuins, the class III HDAC. In this study, we investigated the expression and localization of endogenous sirtuins in primary human dermal microvascular endothelial cells (HDMEC, a cell type playing a key role in the development and maintenance of skin inflammation. We then examined the biological activity of sirtinol, a specific sirtuin inhibitor, in HDMEC response to pro-inflammatory cytokines. We found that, even though sirtinol treatment alone affected only long-term cell proliferation, it diminishes HDMEC inflammatory responses to tumor necrosis factor (TNFα and interleukin (IL-1β. In fact, sirtinol significantly reduced membrane expression of adhesion molecules in TNFã- or IL-1β-stimulated cells, as well as the amount of CXCL10 and CCL2 released by HDMEC following TNFα treatment. Notably, sirtinol drastically decreased monocyte adhesion on activated HDMEC. Using selective inhibitors for Sirt1 and Sirt2, we showed a predominant involvement of Sirt1 inhibition in the modulation of adhesion molecule expression and monocyte adhesion on activated HDMEC. Finally, we demonstrated the in vivo expression of Sirt1 in the dermal vessels of normal and psoriatic skin. Altogether, these findings indicated that sirtuins may represent a promising therapeutic target for the treatment of inflammatory skin diseases characterized by a prominent microvessel involvement.

  8. In vitro dermal penetration study of carbofuran, carbosulfan, and furathiocarb

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kwang-Hyeon [Department of Pharmacology, Inje University, College of Medicine, 614-735, Busan (Korea); Kim, Jeong-Han [School of Agricultural Biotechnology, Seoul National University, 441-744, Suwon (Korea)

    2003-05-01

    In this study, the dermal penetration rate of carbofuran, carbosulfan, and furathiocarb has been measured with rat abdominal skin using the static diffusion cell. The technical grades of three compounds were applied at different doses on skin surface mounted in static diffusion cell and incubated at 32 C for 48 h with shaking. The same procedures were carried out with furathiocarb EC (emulsifiable concentrate) and WP (wettable powder). At regular intervals, the receptor fluid in cell was sampled and analyzed by HPLC. Only carbofuran was found in carbosulfan- or furathiocarb-treated samples, suggesting they converted into carbofuran while passing through the skin layer. The quantity of insecticide penetrating skin increased with time and applied dose. The skin penetration rate increased with the water solubility of insecticides. The dermal penetration rates of carbofuran, furathiocarb, and carbosulfan were determined as 1.05 {mu}g/cm{sup 2} per h (r{sup 2}=0.991), 0.46 {mu}g/cm{sup 2} per h (r{sup 2}=0.984) and 0.14 {mu}g/cm{sup 2} per h (r{sup 2}=0.967), respectively. There was no significant difference in rate of skin penetration between furathiocarb EC (1.42 {mu}g/cm{sup 2} per h, r{sup 2}=0.988) and WP (1.35 {mu}g/cm{sup 2} per h, r{sup 2}=0.982), while furathiocarb technical grade showed a lower skin penetration rate. In vitro models may be used to predict percutaneous absorption and are useful in selecting safer formulations for field application of pesticide. (orig.)

  9. Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers.

    Science.gov (United States)

    Berthet, Aurélie; Bouchard, Michèle; Vernez, David

    2012-03-01

    To better assess biomonitoring data in workers exposed to captan and folpet, the kinetics of ring metabolites [tetrahydrophthalimide (THPI), phthalimide (PI) and phthalic acid] were determined in urine and plasma of dermally exposed volunteers. A 10  mg kg(-1) dose of each fungicide was applied on 80  cm(2) of the forearm and left without occlusion or washing for 24  h. Blood samples were withdrawn at fixed time periods over the 72  h following application and complete urine voids were collected over 96  h post-dosing, for metabolite analysis. In the hours following treatment, a progressive increase in plasma levels of THPI and PI was observed, with peak levels being reached at 24  h for THPI and 10  h for PI. The ensuing elimination phase appeared monophasic with a mean elimination half-life (t(½) ) of 24.7 and 29.7 h for THPI and PI, respectively. In urine, time courses PI and phthalic acid excretion rate rapidly evolved in parallel, and a mean elimination t(½) of 28.8 and 29.6  h, respectively, was calculated from these curves. THPI was eliminated slightly faster, with a mean t(½) of 18.7  h. Over the 96  h period post-application, metabolites were almost completely excreted, and on average 0.02% of captan dose was recovered in urine as THPI while 1.8% of the folpet dose was excreted as phthalic acid and 0.002% as PI, suggesting a low dermal absorption fraction for both fungicides. This study showed the potential use of THPI, PI and phthalic acid as key biomarkers of exposure to captan and folpet.

  10. Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

    Directory of Open Access Journals (Sweden)

    Özcan İ

    2013-01-01

    Full Text Available İpek Özcan, Erkan Azizoğlu, Taner Şenyiğit, Mine Özyazıcı, Özgen ÖzerEge University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Bornova, Izmir, TurkeyAbstract: The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%, were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01% was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.Keywords: skin permeation, anti-inflammatory activity, skin blanching, TEWL

  11. Measurements of dermal uptake of nicotine directly from air and clothing

    DEFF Research Database (Denmark)

    Bekö, Gabriel; Morrison, Glenn C.; Weschler, Charles J.

    2016-01-01

    Dermal uptake directly from air is a significant contributor to total exposure for certain organic compounds, and has been recently experimentally verified for two phthalates. The objective of the current study was to investigate whether airborne nicotine can be dermally absorbed. Two bare...... a shirt previously exposed to tobacco smoke. Urine samples were subsequently analyzed for nicotine and two of its metabolites. The results demonstrate that nicotine can be dermally absorbed directly from air at rates comparable to passive smoking. Wearing clean clothes significantly decreases uptake...

  12. Histologic fate of dermal grafts following implantation for temporomandibular joint meniscal perforation: a preliminary study.

    Science.gov (United States)

    Stewart, H M; Hann, J R; DeTomasi, D C; Neville, B W; DeChamplain, R W

    1986-11-01

    A study was carried out to evaluate the histologic changes of meniscus perforation repair associated with dermal grafts to the temporomandibular joint of cynomolgus monkeys (Macaca fascicularis) following surgical perforation of the meniscus. Dermal grafts were studied histologically at 3-week, 6-week, 3-month, and 6-month intervals. Results showed early attachment of the dermal graft to the meniscus, followed by gradual incorporation of the graft into the meniscus and subsequent return of the meniscal-graft complex to a normal meniscal architecture.

  13. Blood-neural barrier: its diversity and coordinated cell-to-cell communication.

    Science.gov (United States)

    Choi, Yoon Kyung; Kim, Kyu-Won

    2008-05-31

    The cerebral microvessels possess barrier characteristics which are tightly sealed excluding many toxic substances and protecting neural tissues. The specialized blood-neural barriers as well as the cerebral microvascular barrier are recognized in the retina, inner ear, spinal cord, and cerebrospinal fluid. Microvascular endothelial cells in the brain closely interact with other components such as astrocytes, pericytes, perivascular microglia and neurons to form functional 'neurovascular unit'. Communication between endothelial cells and other surrounding cells enhances the barrier functions, consequently resulting in maintenance and elaboration of proper brain homeostasis. Furthermore, the disruption of the neurovascular unit is closely involved in cerebrovascular disorders. In this review, we focus on the location and function of these various blood-neural barriers, and the importance of the cell-to-cell communication for development and maintenance of the barrier integrity at the neurovascular unit. We also demonstrate the close relation between the alteration of the blood-neural barriers and cerebrovascular disorders.

  14. Ultraviolet irradiation induces CYR61/CCN1, a mediator of collagen homeostasis, through activation of transcription factor AP-1 in human skin fibroblasts.

    Science.gov (United States)

    Quan, Taihao; Qin, Zhaoping; Xu, Yiru; He, Tianyuan; Kang, Sewon; Voorhees, John J; Fisher, Gary J

    2010-06-01

    UV irradiation from the sun elevates the production of collagen-degrading matrix metalloproteinases (MMPs) and reduces the production of new collagen. This imbalance of collagen homeostasis impairs the structure and function of the dermal collagenous extracellular matrix (ECM), thereby promoting premature skin aging (photoaging). We report here that aberrant dermal collagen homeostasis in UV-irradiated human skin is mediated in part by a CCN-family member, cysteine-rich protein-61 (CYR61/CCN1). CYR61 is significantly elevated in acutely UV-irradiated human skin in vivo, and UV-irradiated human skin fibroblasts. Knockdown of CYR61 significantly attenuates UV irradiation-induced inhibition of type-I procollagen and upregulation of MMP-1. Determination of CYR61 mRNA and protein indicates that the primary mechanism of CYR61 induction by UV irradiation is transcriptional. Analysis of CYR61 proximal promoter showed that a sequence conforming to the consensus binding site for transcription factor activator protein-1 (AP-1) is required for promoter activity. UV irradiation increased the binding of AP-1-family members c-Jun and c-Fos to this AP-1 site. Furthermore, functional blockade of c-Jun or knockdown of c-Jun significantly reduced the UV irradiation-induced activation of CYR61 promoter and CYR61 gene expression. These data show that CYR61 is transcriptionally regulated by UV irradiation through transcription factor AP-1, and mediates altered collagen homeostasis that occurs in response to UV irradiation in human skin fibroblasts.

  15. Nitric oxide and plant iron homeostasis.

    Science.gov (United States)

    Buet, Agustina; Simontacchi, Marcela

    2015-03-01

    Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes.

  16. The commensal microbiota drives immune homeostasis

    Directory of Open Access Journals (Sweden)

    Marie-Claire eArrieta

    2012-03-01

    Full Text Available For millions of years, microbes have coexisted with eukaryotic cells at the mucosal surfaces of vertebrates in a complex, yet usually harmonious symbiosis. An ever-expanding number of reports describe how eliminating or shifting the intestinal microbiota has profound effects on the development and functionality of the mucosal and systemic immune systems. Here, we examine some of the mechanisms by which bacterial signals affect immune homeostasis. Focusing on the strategies that microbes use to keep our immune system healthy, as opposed to trying to correct the immune imbalances caused by dysbiosis, may prove to be a more astute and efficient way of treating immune-mediated disease.

  17. Epididymis cholesterol homeostasis and sperm fertilizing ability

    Institute of Scientific and Technical Information of China (English)

    Fabrice Saez; Aurélia Ouvrier; Jo(e)l R Drevet

    2011-01-01

    Cholesterol, being the starting point of steroid hormone synthesis, is a long known modulator of both female and male reproductive physiology especially at the level of the gonads and the impact cholesterol has on gametogenesis. Less is known about the effects cholesterol homeostasis may have on postgonadic reproductive functions. Lately, several data have been reported showing how imbalanced cholesterol levels may particularly affect the post-testicular events of sperm maturation that lead to fully fertile male gametes. This review will focus on that aspect and essentially centers on how cholesterol is important for the physiology of the mammalian epididymis and spermatozoa.

  18. Potassium homeostasis in chronic kidney disease.

    Science.gov (United States)

    Palmer, Biff F

    2016-04-01

    Adaptive increases in renal and gastrointestinal excretion of K+ help to prevent hyperkalemia in patients with CKD as long as the GFR remains > 15-20 mL/min. Once the GFR falls below these values, the impact of factors known to adversely affect K+ homeostasis is significantly magnified. Impaired renal K+ excretion can be the result of conditions that severely limit distal Na+ delivery, decreased mineralocorticoid levels or activity, or a distal tubular defect (Table 2). In clinical practice, hyperkalemia is usually the result of a combination of factors superimposed on renal dysfunction.

  19. Nickel metallomics: general themes guiding nickel homeostasis.

    Science.gov (United States)

    Sydor, Andrew M; Zamble, Deborah B

    2013-01-01

    The nickel metallome describes the distribution and speciation of nickel within the cells of organisms that utilize this element. This distribution is a consequence of nickel homeostasis, which includes import, storage, and export of nickel, incorporation into metalloenzymes, and the modulation of these and associated cellular systems through nickel-regulated transcription. In this chapter, we review the current knowledge of the most common nickel proteins in prokaryotic organisms with a focus on their coordination environments. Several underlying themes emerge upon review of these nickel systems, which illustrate the common principles applied by nature to shape the nickel metallome of the cell.

  20. TALE homeodomain proteins regulate site-specific terminal differentiation, LCE genes and epidermal barrier.

    Science.gov (United States)

    Jackson, Ben; Brown, Stuart J; Avilion, Ariel A; O'Shaughnessy, Ryan F L; Sully, Katherine; Akinduro, Olufolake; Murphy, Mark; Cleary, Michael L; Byrne, Carolyn

    2011-05-15

    The epidermal barrier varies over the body surface to accommodate regional environmental stresses. Regional skin barrier variation is produced by site-dependent epidermal differentiation from common keratinocyte precursors and often manifests as site-specific skin disease or irritation. There is strong evidence for body-site-dependent dermal programming of epidermal differentiation in which the epidermis responds by altering expression of key barrier proteins, but the underlying mechanisms have not been defined. The LCE multigene cluster encodes barrier proteins that are differentially expressed over the body surface, and perturbation of LCE cluster expression is linked to the common regional skin disease psoriasis. LCE subclusters comprise genes expressed variably in either external barrier-forming epithelia (e.g. skin) or in internal epithelia with less stringent barriers (e.g. tongue). We demonstrate here that a complex of TALE homeobox transcription factors PBX1, PBX2 and Pknox (homologues of Drosophila Extradenticle and Homothorax) preferentially regulate external rather than internal LCE gene expression, competitively binding with SP1 and SP3. Perturbation of TALE protein expression in stratified squamous epithelia in mice produces external but not internal barrier abnormalities. We conclude that epidermal barrier genes, such as the LCE multigene cluster, are regulated by TALE homeodomain transcription factors to produce regional epidermal barriers.

  1. Safety-barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2007-01-01

    are discussed. A simple method for quantification of safety-barrier diagrams is proposed, including situations where safety barriers depend on shared common elements. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk......Safety-barrier diagrams and the related so-called "bow-tie" diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation with other methods such as fault trees and Bayesian networks...... analysis with operational safety management....

  2. Extremal surface barriers

    Energy Technology Data Exchange (ETDEWEB)

    Engelhardt, Netta; Wall, Aron C. [Department of Physics, University of California,Santa Barbara, CA 93106 (United States)

    2014-03-13

    We present a generic condition for Lorentzian manifolds to have a barrier that limits the reach of boundary-anchored extremal surfaces of arbitrary dimension. We show that any surface with nonpositive extrinsic curvature is a barrier, in the sense that extremal surfaces cannot be continuously deformed past it. Furthermore, the outermost barrier surface has nonnegative extrinsic curvature. Under certain conditions, we show that the existence of trapped surfaces implies a barrier, and conversely. In the context of AdS/CFT, these barriers imply that it is impossible to reconstruct the entire bulk using extremal surfaces. We comment on the implications for the firewall controversy.

  3. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  4. Targeted deletion of Crif1 in mouse epidermis impairs skin homeostasis and hair morphogenesis

    Science.gov (United States)

    Shin, Jung-Min; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Kim, Ji-Young; Im, Myung; Lee, Young; Seo, Young-Joon; Shong, Minho; Lee, Jeung-Hoon; Kim, Chang Deok

    2017-01-01

    The epidermis, which consists mainly of keratinocytes, acts as a physical barrier to infections by regulating keratinocyte proliferation and differentiation. Hair follicles undergo continuous cycling to produce new one. Therefore, optimum supply of energy from the mitochondria is essential for maintaining skin homeostasis and hair growth. CRIF1 is a mitochondrial protein that regulates mitoribosome-mediated synthesis and insertion of mitochondrial oxidative phosphorylation polypeptides into the mitochondrial membrane in mammals. Recent studies reveal that conditional knockout (cKO) of Crif1 in specific tissues of mice induced mitochondrial dysfunction. To determine whether the mitochondrial function of keratinocytes affects skin homeostasis and hair morphogenesis, we generated epidermis-specific Crif1 cKO mice. Deletion of Crif1 in epidermis resulted in impaired mitochondrial function and Crif1 cKO mice died within a week. Keratinocyte proliferation and differentiation were markedly inhibited in Crif1 cKO mice. Furthermore, hair follicle morphogenesis of Crif1 cKO mice was disrupted by down-regulation of Wnt/β-catenin signaling. These results demonstrate that mitochondrial function in keratinocytes is essential for maintaining epidermal homeostasis and hair follicle morphogenesis. PMID:28317864

  5. A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ian Smyth

    2008-09-01

    Full Text Available Harlequin Ichthyosis (HI is a severe and often lethal hyperkeratotic skin disease caused by mutations in the ABCA12 transport protein. In keratinocytes, ABCA12 is thought to regulate the transfer of lipids into small intracellular trafficking vesicles known as lamellar bodies. However, the nature and scope of this regulation remains unclear. As part of an original recessive mouse ENU mutagenesis screen, we have identified and characterised an animal model of HI and showed that it displays many of the hallmarks of the disease including hyperkeratosis, loss of barrier function, and defects in lipid homeostasis. We have used this model to follow disease progression in utero and present evidence that loss of Abca12 function leads to premature differentiation of basal keratinocytes. A comprehensive analysis of lipid levels in mutant epidermis demonstrated profound defects in lipid homeostasis, illustrating for the first time the extent to which Abca12 plays a pivotal role in maintaining lipid balance in the skin. To further investigate the scope of Abca12's activity, we have utilised cells from the mutant mouse to ascribe direct transport functions to the protein and, in doing so, we demonstrate activities independent of its role in lamellar body function. These cells have severely impaired lipid efflux leading to intracellular accumulation of neutral lipids. Furthermore, we identify Abca12 as a mediator of Abca1-regulated cellular cholesterol efflux, a finding that may have significant implications for other diseases of lipid metabolism and homeostasis, including atherosclerosis.

  6. TISSUE INTERACTIONS WITH DERMAL SHEEP COLLAGEN IMPLANTS - A TRANSMISSION ELECTRON-MICROSCOPIC EVALUATION

    NARCIS (Netherlands)

    VANWACHEM, PB; VANLUYN, MJA; DAMINK, LO; FEIJEN, J; NIEUWENHUIS, P

    1991-01-01

    Tissue interactions with discs of dermal sheep collagen (DSC), subcutaneously implanted in rats, were evaluated using transmission electron microscopy. DSC cross-linked with hexamethylenediisocyanate (HDSC) had already been tested previously. In the present study, we compared tissue interactions of

  7. The Effectiveness of Porcine Dermal Collagen (Permacol®) on Wound Healing in the Rat Model

    National Research Council Canada - National Science Library

    Kalin, Murat; Kuru, Serdar; Kismet, Kemal; Barlas, Aziz Mutlu; Akgun, Yusuf Akif; Astarci, Hesna Muzeyyen; Ustun, Huseyin; Ertas, Ertugrul

    2015-01-01

    Porcine acellular dermal collagen (PDC), which is a biological material derived from processing porcine dermis, has already been used for urologic, gynecologic, plastic, and general surgery procedures up to now...

  8. Influence of ethylene oxide gas treatment on the in vitro degradation behaviour of dermal sheep collagen

    NARCIS (Netherlands)

    Olde damink, L.H.H.; Olde Damink, L.H.H.; Dijkstra, Pieter J.; van Luyn, M.J.A.; van Wachem, P.B.; Nieuwenhuis, P.; Feijen, Jan

    1995-01-01

    The influence of ethylene oxide gas treatment on the in vitro degradation behavior of noncrosslinked, glutaraldehyde crosslinked or hexamethylene diisocyanate crosslinked dermal sheep collagen (DSC) using bacterial collagenase is described. The results obtained were compared with the degradation

  9. In vitro dermal absorption of decabromodiphenyl ethane in rat and human skin

    Data.gov (United States)

    U.S. Environmental Protection Agency — In vitro dermal absorption of decabromodiphenyl ethane in rat and human skin. This dataset is associated with the following publication: Knudsen, G., J.M. Sanders,...

  10. In vitro bioaccessibility of copper azole following simulated dermal transfer from pressure-treated wood

    Data.gov (United States)

    U.S. Environmental Protection Agency — In vitro bioaccessibility of copper azole following simulated dermal transfer from pressure-treated wood. This dataset is associated with the following publication:...

  11. Tissue immunostaining for factor XIIIa in dermal dendrocytes of pityriasis alba skin lesions

    National Research Council Canada - National Science Library

    Carneiro, Francisca Regina Oliveira; Amaral, Gabriela Borborema do; Mendes, Maiana Darwich; Quaresma, Juarez Antônio Simões

    2014-01-01

    .... However, its etiology remains uncertain. OBJECTIVE: The objective of the present study was to evaluate the immunoexpression of factor XIIIa in dermal dendrocytes of skin lesions of pityriasis alba. METHOD...

  12. Osteopathia striata: a characteristic X-ray finding in focal dermal hypoplasia (Goltz-Gorlin syndrome)

    Energy Technology Data Exchange (ETDEWEB)

    Barthels, W.; Boepple, D.; Petzel, H.

    1982-12-01

    Two cases of the very rare Goltz-Gorlin syndrome are presented. The relationship of osteopathia striata and focal dermal hypoplasia is discussed, and it is concluded that the osteopathia striata represents the characteristic picture of this ectopic mesodermal abnormality.

  13. Influence of ethylene oxide gas treatment on the in vitro degradation behavior of dermal sheep collagen

    NARCIS (Netherlands)

    Olde Damink, L.H.H.; Dijkstra, P.J.; Luyn, van M.J.A.; Wachem, van P.B.; Nieuwenhuis, P.; Feijen, J.

    1995-01-01

    The influence of ethylene oxide gas treatment on the in vitro degradation behavior of noncrosslinked, glutaraldehyde crosslinked or hexamethylene diisocyanate crosslinked dermal sheep collagen (DSC) using bacterial collagenase is described. The results obtained were compared with the degradation beh

  14. Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans

    DEFF Research Database (Denmark)

    Grimbaldeston, Michele A; Skov, Lone; Finlay-Jones, John J;

    2002-01-01

    Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic factor associated with the development of basal cell carcinoma (BCC). The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise......, display variations in dermal mast cell prevalence. In a study of Danish and South Australian BCC patients and control subjects, one 4-mm punch biopsy of non-sun-exposed buttock skin was sampled from each participant. This skin site was investigated to avoid any changes in mast cell prevalence caused...... dermal area (expressed as mast cells per square millimeter). This technique enabled us to detect heterogeneity of dermal mast cell prevalence in buttock skin between individuals and provided evidence of an association between high dermal mast cell prevalence and BCC development in two diverse populations...

  15. Functional trade-off between strength and thermal capacity of dermal armor: Insights from girdled lizards.

    Science.gov (United States)

    Broeckhoven, Chris; du Plessis, Anton; Hui, Cang

    2017-10-01

    The presence of dermal armor is often unambiguously considered the result of an evolutionary predator-prey arms-race. Recent studies focusing predominantly on osteoderms - mineralized elements embedded in the dermis layer of various extant and extinct vertebrates - have instead proposed that dermal armor might exhibit additional functionalities besides protection. Multiple divergent functionalities could impose conflicting demands on a phenotype, yet, functional trade-offs in dermal armor have rarely been investigated. Here, we use high-resolution micro-computed tomography and voxel-based simulations to test for a trade-off between the strength and thermal capacity of osteoderms using two armored cordylid lizards as model organisms. We demonstrate that high vascularization, associated with improved thermal capacity might limit the strength of osteoderms. These results call for a holistic, cautionary future approach to studies investigating dermal armor, especially those aiming to inspire artificial protective materials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER DERMAL AND INTRATRACHAEL (IT) EXPOSURES

    Science.gov (United States)

    ABSTRACT for 2001 DMS213TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY INMICE AFTER DERMAL AND INTRATRACHEAL (IT) EXPOSURES. E Boykin, M Ward, MJ Selgrade, and D Sailstad. NHEERL, ORD, US EPA, RTP, NC, USA.TMA causes respiratory hypersensitivity (RH) responses. W...

  17. A Fibrocontractive Mechanochemical Model of Dermal Wound Closure Incorporating Realistic Growth Factor Kinetics

    KAUST Repository

    Murphy, Kelly E.

    2012-01-13

    Fibroblasts and their activated phenotype, myofibroblasts, are the primary cell types involved in the contraction associated with dermal wound healing. Recent experimental evidence indicates that the transformation from fibroblasts to myofibroblasts involves two distinct processes: The cells are stimulated to change phenotype by the combined actions of transforming growth factor β (TGFβ) and mechanical tension. This observation indicates a need for a detailed exploration of the effect of the strong interactions between the mechanical changes and growth factors in dermal wound healing. We review the experimental findings in detail and develop a model of dermal wound healing that incorporates these phenomena. Our model includes the interactions between TGFβ and collagenase, providing a more biologically realistic form for the growth factor kinetics than those included in previous mechanochemical descriptions. A comparison is made between the model predictions and experimental data on human dermal wound healing and all the essential features are well matched. © 2012 Society for Mathematical Biology.

  18. Consciousness, endogenous generation of goals and homeostasis

    Science.gov (United States)

    Tsitolovsky, Lev E.

    2015-08-01

    Behaviour can be both unpredictable and goal directed, as animals act in correspondence with their motivation. Motivation arises when neurons in specific brain areas leave the state of homeostatic equilibrium and are injured. The basic goal of organisms and living cells is to maintain their life and their functional state is optimal if it does not lead to physiological damage. This can somehow be sensed by neurons and the occurrence of damage elicits homeostatic protection to recover excitability and the ability to produces spikes. It can be argued that the neuron's activity is guided on the scale of "damage-protection" and it behaves as an object possessing minimum awareness. The approach of death increases cellular efforts to operate. Thus, homeostasis may evidently produce both maintenance of life and will. The question is - how does homeostasis reach the optimum? We have no possibility of determining how the cell evaluates its own states, e.g. as "too little free energy" or in terms of "threat" to life. In any case, the approach of death increases cellular efforts to operate. For the outside observer, this is reminiscent of intentional action and a manifestation of will.

  19. Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis

    Directory of Open Access Journals (Sweden)

    Arya Bagus Boedi Iswanto

    2017-04-01

    Full Text Available Abstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD, which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs is highly controlled by plasmodesmata callose (PDC, which is synthesized by callose synthases (CalS and degraded by β-1,3-glucanases (BGs. In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft–processed PDC.

  20. Control of bacterial iron homeostasis by manganese

    Science.gov (United States)

    Puri, Sumant; Hohle, Thomas H.; O'Brian, Mark R.

    2010-01-01

    Perception and response to nutritional iron availability by bacteria are essential to control cellular iron homeostasis. The Irr protein from Bradyrhizobium japonicum senses iron through the status of heme biosynthesis to globally regulate iron-dependent gene expression. Heme binds directly to Irr to trigger its degradation. Here, we show that severe manganese limitation created by growth of a Mn2+ transport mutant in manganese-limited media resulted in a cellular iron deficiency. In wild-type cells, Irr levels were attenuated under manganese limitation, resulting in reduced promoter occupancy of target genes and altered iron-dependent gene expression. Irr levels were high regardless of manganese availability in a heme-deficient mutant, indicating that manganese normally affects heme-dependent degradation of Irr. Manganese altered the secondary structure of Irr in vitro and inhibited binding of heme to the protein. We propose that manganese limitation destabilizes Irr under low-iron conditions by lowering the threshold of heme that can trigger Irr degradation. The findings implicate a mechanism for the control of iron homeostasis by manganese in a bacterium. PMID:20498065

  1. Lipoproteins, cholesterol homeostasis and cardiac health

    Directory of Open Access Journals (Sweden)

    Tyler F. Daniels, Karen M. Killinger, Jennifer J. Michal, Raymond W. Wright Jr., Zhihua Jiang

    2009-01-01

    Full Text Available Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

  2. Maternal dietary restriction alters offspring's sleep homeostasis.

    Directory of Open Access Journals (Sweden)

    Noriyuki Shimizu

    Full Text Available Nutritional state in the gestation period influences fetal growth and development. We hypothesized that undernutrition during gestation would affect offspring sleep architecture and/or homeostasis. Pregnant female mice were assigned to either control (fed ad libitum; AD or 50% dietary restriction (DR groups from gestation day 12 to parturition. After parturition, dams were fed AD chow. After weaning, the pups were also fed AD into adulthood. At adulthood (aged 8-9 weeks, we carried out sleep recordings. Although offspring mice displayed a significantly reduced body weight at birth, their weights recovered three days after birth. Enhancement of electroencephalogram (EEG slow wave activity (SWA during non-rapid eye movement (NREM sleep was observed in the DR mice over a 24-hour period without changing the diurnal pattern or amounts of wake, NREM, or rapid eye movement (REM sleep. In addition, DR mice also displayed an enhancement of EEG-SWA rebound after a 6-hour sleep deprivation and a higher threshold for waking in the face of external stimuli. DR adult offspring mice exhibited small but significant increases in the expression of hypothalamic peroxisome proliferator-activated receptor α (Pparα and brain-specific carnitine palmitoyltransferase 1 (Cpt1c mRNA, two genes involved in lipid metabolism. Undernutrition during pregnancy may influence sleep homeostasis, with offspring exhibiting greater sleep pressure.

  3. MAVS maintains mitochondrial homeostasis via autophagy

    Science.gov (United States)

    Sun, Xiaofeng; Sun, Liwei; Zhao, Yuanyuan; Li, Ying; Lin, Wei; Chen, Dahua; Sun, Qinmiao

    2016-01-01

    Mitochondrial antiviral signalling protein (MAVS) acts as a critical adaptor protein to transduce antiviral signalling by physically interacting with activated RIG-I and MDA5 receptors. MAVS executes its functions at the outer membrane of mitochondria to regulate downstream antiviral signalling, indicating that the mitochondria provides a functional platform for innate antiviral signalling transduction. However, little is known about whether and how MAVS-mediated antiviral signalling contributes to mitochondrial homeostasis. Here we show that the activation of MAVS is sufficient to induce autophagic signalling, which may mediate the turnover of the damaged mitochondria. Importantly, we find MAVS directly interacts with LC3 through its LC3-binding motif ‘YxxI’, suggesting that MAVS might act as an autophagy receptor to mediate mitochondrial turnover upon excessive activation of RLR signalling. Furthermore, we provide evidence that both MAVS self-aggregation and its interaction with TRAF2/6 proteins are important for MAVS-mediated mitochondrial turnover. Collectively, our findings suggest that MAVS acts as a potential receptor for mitochondria-associated autophagic signalling to maintain mitochondrial homeostasis. PMID:27551434

  4. Acute calcium homeostasis in MHS swine.

    Science.gov (United States)

    Harrison, G G; Morrell, D F; Brain, V; Jaros, G G

    1987-07-01

    To elucidate a pathogenesis for the reduction in bone calcium content observed in MHS individuals, we studied the acute calcium homeostasis of MHS swine. This was achieved by the serial measurement, with a calcium selective electrode, of calcium transients in Landrace MHS (five) and control Landrace/large white cross MH negative (five) swine following IV bolus injection of calcium gluconate 0.1 mmol X kg-1--a dose which induced an acute 45 per cent increase in plasma ionised calcium. Experimental animals were anaesthetised with ketamine 10 mg X kg-1 IM, thiopentone (intermittent divided doses) 15-25 mg X kg-1 (total) IV and N2O/O2 (FIO2 0.3) by IPPV to maintain a normal blood gas, acid/base state. The plasma ionised calcium decay curve observed in MHS swine did not differ from that of control normal swine. Further it was noted that the induced acute rise in plasma ionised calcium failed to trigger the MH syndrome in any MHS swine. It is concluded that the mechanisms of acute calcium homeostasis in MHS swine are normal. An explanation for the reduction in bone calcium content observed in MHS individuals must be sought, therefore, through study of the slow long-term component of the calcium regulatory process. In addition, the conventional strictures placed on the use, in MHS patients, of calcium gluconate are called in question.

  5. The Regulation of Iron Absorption and Homeostasis

    Science.gov (United States)

    Wallace, Daniel F

    2016-01-01

    Iron is an essential element in biology, required for numerous cellular processes. Either too much or too little iron can be detrimental, and organisms have developed mechanisms for balancing iron within safe limits. In mammals there are no controlled mechanisms for the excretion of excess iron, hence body iron homeostasis is regulated at the sites of absorption, utilisation and recycling. This review will discuss the discoveries that have been made in the past 20 years into advancing our understanding of iron homeostasis and its regulation. The study of iron-associated disorders, such as the iron overload condition hereditary haemochromatosis and various forms of anaemia have been instrumental in increasing our knowledge in this area, as have cellular and animal model studies. The liver has emerged as the major site of systemic iron regulation, being the location where the iron regulatory hormone hepcidin is produced. Hepcidin is a negative regulator of iron absorption and recycling, achieving this by binding to the only known cellular iron exporter ferroportin and causing its internalisation and degradation, thereby reducing iron efflux from target cells and reducing serum iron levels. Much of the research in the iron metabolism field has focussed on the regulation of hepcidin and its interaction with ferroportin. The advances in this area have greatly increased our knowledge of iron metabolism and its regulation and have led to the development of novel diagnostics and therapeutics for iron-associated disorders.

  6. Air pollution particles and iron homeostasis | Science ...

    Science.gov (United States)

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, functional groups at the surface of retained particle complex iron available in the cell. In response to a reduction in concentrations of requisite iron, a functional deficiency can result intracellularly. Superoxide production by the cell exposed to a particle increases ferrireduction which facilitates import of iron with the objective being the reversal of the metal deficiency. Failure to resolve the functional iron deficiency following cell exposure to particles activates kinases and transcription factors resulting in a release of inflammatory mediators and inflammation. Tissue injury is the end product of this disruption in iron homeostasis initiated by the particle exposure. Elevation of available iron to the cell precludes deficiency of the metal and either diminishes or eliminates biological effects.General Significance: Recognition of the pathway for biological effects after particle exposure to involve a functional deficiency of iron suggests novel therapies such as metal supplementation (e.g. inhaled and oral). In addition, the demonstration of a shared mechanism of biological effects allows understanding the common clinical, physiological, and pathological presentation fol

  7. Circadian dysregulation disrupts bile acid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Ma

    Full Text Available BACKGROUND: Bile acids are potentially toxic compounds and their levels of hepatic production, uptake and export are tightly regulated by many inputs, including circadian rhythm. We tested the impact of disrupting the peripheral circadian clock on integral steps of bile acid homeostasis. METHODOLOGY/PRINCIPAL FINDINGS: Both restricted feeding, which phase shifts peripheral clocks, and genetic ablation in Per1(-/-/Per2(-/- (PERDKO mice disrupted normal bile acid control and resulted in hepatic cholestasis. Restricted feeding caused a dramatic, transient elevation in hepatic bile acid levels that was associated with activation of the xenobiotic receptors CAR and PXR and elevated serum aspartate aminotransferase (AST, indicative of liver damage. In the PERDKO mice, serum bile acid levels were elevated and the circadian expression of key bile acid synthesis and transport genes, including Cyp7A1 and NTCP, was lost. This was associated with blunted expression of a primary clock output, the transcription factor DBP, which transactivates the promoters of both genes. CONCLUSIONS/SIGNIFICANCE: We conclude that disruption of the circadian clock results in dysregulation of bile acid homeostasis that mimics cholestatic disease.

  8. Iron homeostasis related genes in rice

    Directory of Open Access Journals (Sweden)

    Gross Jeferson

    2003-01-01

    Full Text Available Iron is essential for plants. However, excess iron is toxic, leading to oxidative stress and decreased productivity. Therefore, plants must use finely tuned mechanisms to keep iron homeostasis in each of their organs, tissues, cells and organelles. A few of the genes involved in iron homeostasis in plants have been identified recently, and we used some of their protein sequences as queries to look for corresponding genes in the rice (Oryza sativa genome. We have assigned possible functions to thirty-nine new rice genes. Together with four previously reported sequences, we analyzed a total of forty-three genes belonging to five known protein families: eighteen YS (Yellow Stripe, two FRO (Fe3+-chelate reductase oxidase, thirteen ZIP (Zinc regulated transporter / Iron regulated transporter Protein, eight NRAMP (Natural Resistance - Associated Macrophage Protein, and two Ferritin proteins. The possible cellular localization and number of potential transmembrane domains were evaluated, and phylogenetic analysis performed for each gene family. Annotation of genomic sequences was performed. The presence and number of homologues in each gene family in rice and Arabidopsis is discussed in light of the established iron acquisition strategies used by each one of these two plants.

  9. Vitamin D, calcium homeostasis and aging

    Science.gov (United States)

    Veldurthy, Vaishali; Wei, Ran; Oz, Leyla; Dhawan, Puneet; Jeon, Yong Heui; Christakos, Sylvia

    2016-01-01

    Osteoporosis is characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. Evidence is accumulating for an important role of calcium deficiency as the process of aging is associated with disturbed calcium balance. Vitamin D is the principal factor that maintains calcium homeostasis. Increasing evidence indicates that the reason for disturbed calcium balance with age is inadequate vitamin D levels in the elderly. In this article, an overview of our current understanding of vitamin D, its metabolism, and mechanisms involved in vitamin D-mediated maintenance of calcium homeostasis is presented. In addition, mechanisms involved in age-related dysregulation of 1,25(OH)2D3 action, recommended daily doses of vitamin D and calcium, and the use of vitamin D analogs for the treatment of osteoporosis (which remains controversial) are reviewed. Elucidation of the molecular pathways of vitamin D action and modifications that occur with aging will be an active area of future research that has the potential to reveal new therapeutic strategies to maintain calcium balance. PMID:27790378

  10. Plant transporters involved in heavy metal homeostasis

    Directory of Open Access Journals (Sweden)

    Dorina Podar

    2010-12-01

    Full Text Available Transition metal ions (predominately manganese, iron, cobalt, nickel, copper and zinc havean array of catalytic and regulatory roles in the growth and development of all living organisms.However, an excess of these metal ions can also be toxic to any life form and therefore every cell andwhole organism needs to maintain the concentration of these essential nutrient metals within a narrowrange: a process known as metal homeostasis. Heavy metal ions are taken up into cells by selectivetransporters and as they cannot be degraded, the “desired” levels of metal ions are achieved by anumber of strategies that involve: chelation, sequestration and export out of the cell. Cation DiffusionFacilitators (CDF is a large family of transporters involved in maintaining the cytosolic metalconcentration. They transport different heavy metal divalent ions, but exhibit main affinity for zinc, ironand manganese. Metal Tolerance Proteins (MTPs are a subfamily of the Cation Diffusion Facilitator (CDFfamily found in plants. There has been much interest in these heavy metal transporters in order toprovide an insight into plant metal homeostasis, which has significant implications in human health andphytoremediation. Although data regarding the CDFs/MTPs mechanism is gathering there is still littleinformation with respect to metal selectivity determinants.

  11. Bovine versus Porcine Acellular Dermal Matrix: A Comparison of Mechanical Properties

    Directory of Open Access Journals (Sweden)

    David M. Adelman, MD, PhD, FACS

    2014-05-01

    Conclusions: Before implantation, BADM is inherently stronger than PADM at equivalent thicknesses and considerably stronger at increased thicknesses. These results corroborate clinical data from a previous study in which PADM was associated with a higher intraoperative device failure rate. Although numerous properties of acellular dermal matrix contribute to clinical outcomes, surgeons should consider initial mechanical strength properties when choosing acellular dermal matrices for load-bearing applications such as hernia repair.

  12. Laser-induced transepidermal elimination of dermal content by fractional photothermolysis.

    Science.gov (United States)

    Hantash, Basil M; Bedi, Vikramaditya P; Sudireddy, Vasanthi; Struck, Steven K; Herron, G Scott; Chan, Kin Foong

    2006-01-01

    The wound healing process in skin is studied in human subjects treated with fractional photothermolysis. In-vivo histological evaluation of vacuoles formed over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm single-mode fiber laser system delivers an array of 60 microm or 140 microm 1e2 incidence microbeam spot size at variable pulse energy and density. Treatments span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar formation within the epidermis. The re-epithelialization process with repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1-day post-treatment. The dermal-epidermal (DE) junction is weakened and separated just above zones of dermal coagulation. Complete loss of dermal cell viability is noted within the confines of the MTZs 1-day post-treatment, as assessed by lactate dehydrogenase. All cells falling outside the irradiation field remain viable. Content within the epidermal vacuoles stain positively with Gomori trichrome, suggesting a dermal origin. However, the positive staining could be due to loss of specificity after thermal alteration. Nevertheless, this dermal extrusion hypothesis is supported by very specific positive staining with an antihuman elastin antibody. Fractional photothermolysis creates microthermal lesions that allow transport and extrusion of dermal content through a compromised DE junction. Some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the epidermis to eventually be exfoliated through the stratum corneum. This is the first report of a nonablative laser-induced transport mechanism by which dermal content can be predictably extruded biologically through the epidermis. Thus, treatment with the 1550-nm fiber laser may provide the first therapeutic option for clinical indications, including pigmentary disorders such as medically

  13. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    OpenAIRE

    Quan, Taihao; Fisher, Gary J.

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin d...

  14. Tissue immunostaining for factor XIIIa in dermal dendrocytes of pityriasis alba skin lesions

    OpenAIRE

    Carneiro, Francisca Regina Oliveira; Amaral,Gabriela Borborema do; Mendes,Maiana Darwich; Quaresma,Juarez Antônio Simões

    2014-01-01

    BACKGROUND: Pityriasis alba affects 1% of the world population and about 9.9% of the children in Brazil. However, its etiology remains uncertain. OBJECTIVE: The objective of the present study was to evaluate the immunoexpression of factor XIIIa in dermal dendrocytes of skin lesions of pityriasis alba. METHOD: Twenty patients with pityriasis alba and 20 patients with atopic dermatitis underwent biopsy. The dermal dendrocytes marked by factor XIIIa were counted by means of immunohistochemic...

  15. Hyaluronic acid dermal fillers: can adjunctive lidocaine improve patient satisfaction without decreasing efficacy or duration?

    OpenAIRE

    Lynnelle Smith; Kimberly Cockerham

    2011-01-01

    Lynnelle Smith1, Kimberly Cockerham21Ophthalmology Department, Loma Linda University, Loma Linda, CA, USA; 2Ophthalmology Department, Stanford University, Palo Alto, CA, USAAbstract: Hyaluronic acid (HA) dermal fillers are the most widely used injectables to augment facial volume without surgery. HA dermal fillers are popular because of their ease of administration, predictable effectiveness, good safety profile, and quick patient recovery. The most common patient complaint is pain. Our goal ...

  16. Characterization and evolution of dermal filaments from patients with Morgellons disease

    OpenAIRE

    Middelveen MJ; Mayne PJ; Kahn DG; Stricker RB

    2013-01-01

    Marianne J Middelveen,1 Peter J Mayne,1 Douglas G Kahn,2 Raphael B Stricker11International Lyme and Associated Diseases Society, Bethesda, MD, USA; 2Department of Pathology, Olive View–UCLA Medical Center, Sylmar, CA, USAAbstract: Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either s...

  17. Intestinal epithelial barrier function and tight junction proteins with heat and exercise

    DEFF Research Database (Denmark)

    Dokladny, Karol; Zuhl, Micah N; Moseley, Pope L

    2016-01-01

    (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional...... interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise....

  18. Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and E.

    Science.gov (United States)

    Spector, Reynold; Johanson, Conrad E

    2007-10-01

    With the application of genetic and molecular biology techniques, there has been substantial progress in understanding how vitamins are transferred across the mammalian blood-brain barrier and choroid plexus into brain and CSF and how vitamin homeostasis in brain is achieved. In most cases (with the exception of the sodium-dependent multivitamin transporter for biotin, pantothenic acid, and lipoic acid), the vitamins are transported by separate carriers through the blood-brain barrier or choroid plexus. Then the vitamins are accumulated by brain cells by separate, specialized systems. This review focuses on six vitamins (B(1), B(3), B(6), pantothenic acid, biotin, and E) and the newer genetic information including relevant 'knockdown' or 'knockout' models in mice and humans. The overall objective is to integrate this newer information with previous physiological and biochemical observations to achieve a better understanding of vitamin transport and homeostasis in brain. This is especially important in view of the newly described non-cofactor vitamin roles in brain (e.g. of B(1), B(3), B(6), and E) and the potential roles of vitamins in the therapy of brain disorders.

  19. Alkaline ceramidase 1 is essential for mammalian skin homeostasis and regulating whole-body energy expenditure.

    Science.gov (United States)

    Liakath-Ali, Kifayathullah; Vancollie, Valerie E; Lelliott, Christopher J; Speak, Anneliese O; Lafont, David; Protheroe, Hayley J; Ingvorsen, Camilla; Galli, Antonella; Green, Angela; Gleeson, Diane; Ryder, Ed; Glover, Leanne; Vizcay-Barrena, Gema; Karp, Natasha A; Arends, Mark J; Brenn, Thomas; Spiegel, Sarah; Adams, David J; Watt, Fiona M; van der Weyden, Louise

    2016-07-01

    The epidermis is the outermost layer of skin that acts as a barrier to protect the body from the external environment and to control water and heat loss. This barrier function is established through the multistage differentiation of keratinocytes and the presence of bioactive sphingolipids such as ceramides, the levels of which are tightly regulated by a balance of ceramide synthase and ceramidase activities. Here we reveal the essential role of alkaline ceramidase 1 (Acer1) in the skin. Acer1-deficient (Acer1(-/-) ) mice showed elevated levels of ceramide in the skin, aberrant hair shaft cuticle formation and cyclic alopecia. We demonstrate that Acer1 is specifically expressed in differentiated interfollicular epidermis, infundibulum and sebaceous glands and consequently Acer1(-/-) mice have significant alterations in infundibulum and sebaceous gland architecture. Acer1(-/-) skin also shows perturbed hair follicle stem cell compartments. These alterations result in Acer1(-/-) mice showing increased transepidermal water loss and a hypermetabolism phenotype with associated reduction of fat content with age. We conclude that Acer1 is indispensable for mammalian skin homeostasis and whole-body energy homeostasis. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  20. The determinants of dermal exposure ranking method (DERM): a pesticide exposure assessment approach for developing countries.

    Science.gov (United States)

    Blanco, Luis E; Aragón, Aurora; Lundberg, Ingvar; Wesseling, Catharina; Nise, Gun

    2008-08-01

    A new method for assessment of dermal exposure to pesticides in subsistence farmers by use of determinants of dermal exposure is described. The method, called the determinants of dermal exposure ranking method (DERM), is a combination of checklists and expert rating assessment. Thus, determinants are listed in a form, which is used to check their presence and to assess them using a simple algorithm based on two factors, the type of transport process (T value) and the area of body surface exposed (A value). In addition, the type of clothing worn during applications is included as a protection factor. We applied the DERM to real pesticide applications, characterizing dermal exposure and comparing DERM estimates with earlier developed semiquantitative visual scores based on fluorescent tracer, the total visual score (TVS) and contaminated body area (CBA). DERM showed a very good level of agreement with both the TVS (r = 0.69; P = 0.000) and the CBA (r = 0.67; P = 0.000). DERM allowed identification of the determinants that had the highest effect on exposure and the farmers with the highest exposure. In conclusion, DERM provided information on the determinants responsible for dermal exposure in a group of subsistence farmers. This can be useful to design monitoring and preventive programs, define priorities for intervention and prioritize and select most adequate measurement strategies. DERM promises to be a low-cost easy-to-use method to assess dermal exposure to pesticides in developing country conditions.

  1. Collagen/chitosan based two-compartment and bi-functional dermal scaffolds for skin regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Feng [Department of Plastic Surgery and Burns, Shenzhen Second People' s Hospital, Shenzhen 518035 (China); Wang, Mingbo [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); She, Zhending [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Shenzhen Lando Biomaterials Co., Ltd., Shenzhen 518057 (China); Fan, Kunwu; Xu, Cheng [Department of Plastic Surgery and Burns, Shenzhen Second People' s Hospital, Shenzhen 518035 (China); Chu, Bin; Chen, Changsheng [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Shi, Shengjun, E-mail: shengjunshi@yahoo.com [The Burns Department of Zhujiang Hospital, Southern Medical University, Guangzhou 510280 (China); Tan, Rongwei, E-mail: tanrw@landobiom.com [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Shenzhen Lando Biomaterials Co., Ltd., Shenzhen 518057 (China)

    2015-07-01

    Inspired from the sophisticated bilayer structures of natural dermis, here, we reported collagen/chitosan based two-compartment and bi-functional dermal scaffolds. Two functions refer to mediating rapid angiogenesis based on recombinant human vascular endothelial growth factor (rhVEGF) and antibacterial from gentamicin, which were encapsulated in PLGA microspheres. The gentamicin and rhVEGF encapsulated PLGA microspheres were further combined with collagen/chitosan mixtures in low (lower layer) and high (upper layer) concentrations, and molded to generate the two-compartment and bi-functional scaffolds. Based on morphology and pore structure analyses, it was found that the scaffold has a distinct double layered porous and connective structure with PLGA microspheres encapsulated. Statistical analysis indicated that the pores in the upper layer and in the lower layer have great variations in diameter, indicative of a two-compartment structure. The release profiles of gentamicin and rhVEGF exceeded 28 and 49 days, respectively. In vitro culture of mouse fibroblasts showed that the scaffold can facilitate cell adhesion and proliferation. Moreover, the scaffold can obviously inhibit proliferation of Staphylococcus aureus and Serratia marcescens, exhibiting its unique antibacterial effect. The two-compartment and bi-functional dermal scaffolds can be a promising candidate for skin regeneration. - Highlights: • The dermal scaffold is inspired from the bilayer structures of natural dermis. • The dermal scaffold has two-compartment structures. • The dermal scaffold containing VEGF and gentamicin encapsulated PLGA microspheres • The dermal scaffold can facilitate cell adhesion and proliferation.

  2. Optical coherence tomography for image-guided dermal filler injection and biomechanical evaluation

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    Singh, Manmohan; Wang, Shang; Yee, Richard W.; Han, Zhaolong; Aglyamov, Salavat R.; Larin, Kirill V.

    2017-02-01

    Dermal fillers are a very popular anti-ag ing treatment with estimated sales in the billions of dollars and millions of procedures performed. As the aging population continues to grow, these figures are only e xpected to increase. Dermal fillers have various compositions depending on their intended applicati on. Reactions to dermal fillers can be severe, such as ischemic events and filler migration to the eyes. Howe ver, these adverse reactions are rare. Nevertheless, the capability to perform imag e-guided filler injections would minimize th e risk of such reacti ons. In addition, the biomechanical properties of various fillers have been evalua ted, but there has been no investigation on the effects of filler on the biomechanical properties of skin. In this work, we utilize optical cohe rence tomography (OCT) for visualizing dermal filler injections with micrometer-scale sp atial resolution. In addition, we utilize noncontact optical coherence elastography (OCE) to quantify the changes in the biomechan ical properties of pig skin after the dermal filler injections. OCT was successfully able to visualize the dermal filler injecti on process, and OCE showed that the viscoelasticity of the pig skin was increased locally at the filler injection sites. OCT may be able to provide real-time image guidance in 3D, and when combined with functional OCT techniques such as optical microangiography, could be used to avoid blood vessels during the injection.

  3. Characterization of dermal plates from armored catfish Pterygoplichthys pardalis reveals sandwich-like nanocomposite structure.

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    Ebenstein, Donna; Calderon, Carlos; Troncoso, Omar P; Torres, Fernando G

    2015-05-01

    Dermal plates from armored catfish are bony structures that cover their body. In this paper we characterized structural, chemical, and nanomechanical properties of the dermal plates from the Amazonian fish Pterygoplichthys pardalis. Analysis of the morphology of the plates using scanning electron microscopy (SEM) revealed that the dermal plates have a sandwich-like structure composed of an inner porous matrix surrounded by two external dense layers. This is different from the plywood-like laminated structure of elasmoid fish scales but similar to the structure of osteoderms found in the dermal armour of some reptiles and mammals. Chemical analysis performed using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results revealed similarities between the composition of P. pardalis plates and the elasmoid fish scales of Arapaima gigas. Reduced moduli of P. pardalis plates measured using nanoindentation were also consistent with reported values for A. gigas scales, but further revealed that the dermal plate is an anisotropic and heterogeneous material, similar to many other fish scales and osteoderms. It is postulated that the sandwich-like structure of the dermal plates provides a lightweight and tough protective layer.

  4. The application of dermal papillary rings in dermatology by in vivo confocal laser scanning microscopy

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    Xiang, W. Z.; Xu, A. E.; Xu, J.; Bi, Z. G.; Shang, Y. B.; Ren, Q. S.

    2010-08-01

    Confocal laser scanning microscopy (CLSM) allows noninvasive visualization of human skin in vivo, without needing to fix or section the tissue. Melanocytes and pigmented keratinocytes at the level of the basal layer form bright dermal papillary rings which are readily amenable to identify in confocal images. Our purpose was to explore the role of dermal papillary rings in assessment of lesion location, the diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. Seventy-one patients were imaged with the VivaScope 1500 reflectance confocal microscope provided by Lucid, Inc. The results indicate that dermal papillary rings can assess the location of lesion; the application of dermal papillary rings can provide diagnostic support and differential diagnosis for vitiligo, nevus depigmentosus, tinea versicolor, halo nevus, common nevi, and assess the therapeutic efficacy of NBUVB phototherapy plus topical 0.1 percent tacrolimus ointment for vitiligo. In conclusion, our findings indicate that the dermal papillary rings play an important role in the assessment the location of lesion, diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. CLSM may be a promising tool for noninvasive examination in dermatology. However, larger studies are needed to expand the application of dermal papillary rings in dermatology.

  5. Exposure to pesticides with dermal toxicity in farmers of Community of Valencia

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    Caterina Brandon Garcia

    2010-12-01

    Full Text Available Introduction: Dermal route has a toxicological importance, as well as substances such as entry, but by frequent local effects. In applications of pesticides by farmers is common and important the dermal exposure to pesticides, so the dermal route in this sector of activity could be of particular relevance. Objective: To determine the hazard of dermal exposure in farmers using pesticides and to propose specific preventive measures. Material and methods: A transversal descriptive study based on a questionnaire designed by the researchers, replying to the 238 attendees at the courses for pesticide handler card basic level Department of Health Xativa-Ontinyent (Valencia in 2009. Pesticides used were collected over the past 12 months and reviewed their R phrases (risk phrases looking for dermal effects. Results: 55 % of pesticides had some phrase R on skin problems. The phrase R38 "Irritating to skin" was found in 16 products, used by 59.05 % of respondents and the R43 "Possibility of sensitization by skin contact" at 7, used by 23.91 %. Conclusions: The skin irritation effect was related to more dermal exposure to these pesticides. It is necessary to emphasize the skin protection in the courses for workers who apply these products. Skin problems should be included damages for workplace exposure to pesticides.

  6. Sexual dimorphisms in the dermal denticles of the lesser-spotted catshark, Scyliorhinus canicula (Linnaeus, 1758.

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    Neil Crooks

    Full Text Available The dermal layers of several elasmobranch species have been shown to be sexually dimorphic. Generally, when this occurs the females have thicker dermal layers compared to those of males. This sexual dimorphism has been suggested to occur as a response to male biting during mating. Although male biting as a copulatory behaviour in Scyliorhinus canicula has been widely speculated to occur, only relatively recently has this behaviour been observed. Male S. canicula use their mouths to bite the female's pectoral and caudal fins as part of their pre-copulatory behaviour and to grasp females during copulation. Previous work has shown that female S. canicula have a thicker epidermis compared to that of males. The structure of the dermal denticles in females may also differ from that of males in order to protect against male biting or to provide a greater degree of friction in order to allow the male more purchase. This study reveals that the length, width and density of the dermal denticles of mature male and female S. canicula are sexually dimorphic across the integument in areas where males have been observed to bite and wrap themselves around females (pectoral fin, area posterior to the pectoral fin, caudal fin, and pelvic girdle. No significant differences in the dermal denticle dimensions were found in other body areas examined (head, dorsal skin and caudal peduncle. Sexually dimorphic dermal denticles in mature S. canicula could be a response to male biting/wrapping as part of the copulatory process.

  7. Human dermal exposure to galaxolide from personal care products.

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    Correia, P; Cruz, A; Santos, L; Alves, A

    2013-06-01

    Musks are synthetic fragrances applied on personal care and household products as fixatives, by retarding the release of other fragrances with higher volatility. Galaxolide is the most used polycyclic musk since the 90th decade, and it has been detected in several environmental and biological matrices, particularly in human tissues and fluids. For exposure assessment purposes, large-monitoring data need to be obtained and rapid but reliable analytical techniques are requested. The main objective of this study is to develop and validate a new and fast analytical methodology to quantify galaxolide in personal care products and to apply this method to real matrices like skin care products (creams and lotions), shower products (soap bar), hair care products (shampoo and hair conditioner) and oral care products (toothpaste), to evaluate the human dermal exposure risk. A dispersive solid-phase extraction is proposed, using QuEChERS methodology, followed by HPLC with fluorescence detection. Some extraction parameters were studied, like the ratio of sample/solvent amounts, the homogenization time, the salt addition effect and the used sorbents. The validation parameters of the developed method were the following: a linearity range of 0.005-1.002 mg kg⁻¹ sample, a limit of detection of 0.001 mg kg⁻¹ sample, repeatability between 0.7% and 11.3% (variation coefficient of six standard injections), an intermediate precision of 2.5% (variation coefficient of six independent analysis of the same sample), mean recoveries ranging from 65% (soap bar) to 95% (body cream) and 3% of global uncertainty in most of the working range. The time of analysis, including the extraction steps, is 60 min, allowing a throughput of 4 samples h⁻¹ . Galaxolide was detected in all of the seven analysed products in concentrations ranging from 0.04 ± 0.01 mg kg⁻¹ sample (toothpaste) to 280.78 ± 8.19 mg kg⁻¹ sample (perfumed body cream), which may correspond to a significant estimated

  8. Glutathione in Cerebral Microvascular Endothelial Biology and Pathobiology: Implications for Brain Homeostasis

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    Wei Li

    2012-01-01

    Full Text Available The integrity of the vascular endothelium of the blood-brain barrier (BBB is central to cerebrovascular homeostasis. Given the function of the BBB as a physical and metabolic barrier that buffers the systemic environment, oxidative damage to the endothelial monolayer will have significant deleterious impact on the metabolic, immunological, and neurological functions of the brain. Glutathione (GSH is a ubiquitous major thiol within mammalian cells that plays important roles in antioxidant defense, oxidation-reduction reactions in metabolic pathways, and redox signaling. The existence of distinct GSH pools within the subcellular organelles supports an elegant mode for independent redox regulation of metabolic processes, including those that control cell fate. GSH-dependent homeostatic control of neurovascular function is relatively unexplored. Significantly, GSH regulation of two aspects of endothelial function is paramount to barrier preservation, namely, GSH protection against oxidative endothelial cell injury and GSH control of postdamage cell proliferation in endothelial repair and/or wound healing. This paper highlights our current insights and hypotheses into the role of GSH in cerebral microvascular biology and pathobiology with special focus on endothelial GSH and vascular integrity, oxidative disruption of endothelial barrier function, GSH regulation of endothelial cell proliferation, and the pathological implications of GSH disruption in oxidative stress-associated neurovascular disorders, such as diabetes and stroke.

  9. Barriers to screening mammography.

    Science.gov (United States)

    Sarma, Elizabeth A

    2015-01-01

    Breast cancer (BRCA) is the second most commonly diagnosed cancer among women in the USA, and mammography is an effective means for the early detection of BRCA. Identifying the barriers to screening mammography can inform research, policy and practice aiming to increase mammography adherence. A literature review was conducted to determine common barriers to screening mammography adherence. PsycINFO and PubMed databases were searched to identify studies published between 2000 and 2012 that examined barriers associated with reduced mammography adherence. Three thematic groups of barriers, based on social ecology, were identified from the literature: healthcare system-level, social and individual-level barriers. Researchers must consider screening behaviour in context and, therefore, should simultaneously consider each level of barriers when attempting to understand screening behaviour and create interventions to increase mammography adherence.

  10. HYALURONIC ACID IN DERMAL REJUVENATION: AN IN VITRO STUDY.

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    Avantaggiato, A; Pascali, M; Lauritano, D; Cura, F; Pezzetti, F; Palmieri, A

    2015-01-01

    The purpose of this paper is to evaluate the role of hyaluronic acid in bio-revitalization by testing several extracellular matrix biological parameters in cultured dermal fibroblasts. To this aim, fibroblastic expressed genes after exposition to three hyaluronic acid medical devices were evaluated. Cells were seeded on a layer of three different medical devices containing 6.2, 10 and 20 mg/ml of hyaluronic acid for 24 h. Real Time Polymerase Chain Reaction was performed to investigate gene expressions. Genes encoding hyaluronic acid synthesis and degradation, Metalloproteinases 2 and 3 and Desmoplakin production as well as GDF6, and IGF1 were activated by hyaluronic acid products. The in vitro study showed similar effects on tested genes despite a different concentration of hyaluronic acid contained in the medical devices and the simultaneous presence of other additives. Based on the reported data, gene activations are an aspect of metabolic modulation of signalling pathways rather than the proportional production of a specific connective tissue molecule. Indeed different hyaluronic acid concentration and the presence of other additives did not change the overall effect on the studied genes. We believe that the optimization of extracellular matrix micro-environment, obtained by enhanced structural support with hyaluronic acid, leads to functional and metabolic improvement.

  11. Inheritance of hereditary equine regional dermal asthenia in Quarter Horses.

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    Tryon, Robert C; White, Stephen D; Famula, Thomas R; Schultheiss, Patricia C; Hamar, Dwayne W; Bannasch, Danika L

    2005-03-01

    To assess heritability and mode of inheritance for hereditary equine regional dermal asthenia (HERDA) in Quarter Horses. 1,295 horses with Quarter Horse bloodlines, including 58 horses affected with HERDA. Horses were classified as affected or unaffected or as undetermined when data were insufficient to assess phenotype. Pedigree data were analyzed to determine the probable mode of inheritance. Heritability was estimated by use of Bayesian statistical methods. Heritability (mean+/-SD) of HERDA was estimated to be 0.38+/-0.13, with both sexes having an equal probability of being affected. Results for evaluation of the pedigrees were consistent with a single Mendelian autosomal recessive mode of inheritance. HERDA in Quarter Horses is an inherited disease, and affected horses are more likely to produce affected offspring. An autosomal recessive mode of inheritance should be considered by people making breeding decisions involving Quarter Horses when a first-degree relative has been confirmed with HERDA or has produced affected offspring. In addition, breeders whose horses have produced affected offspring can reduce the likelihood of producing affected horses in the future by avoiding inbreeding.

  12. Evaluation of dermal symptoms in hypothyroidism and hyperthyroidism.

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    Razi, Ahad; Golforoushan, Farideh; Nejad, Amir Bahrami Shahla Babaee; Goldust, Mohamad

    2013-06-01

    Many symptoms arise in thyroid diseases. The aim of this study was to evaluate the dermal symptoms in hypothyroidism and hyperthyroidism. In this cross sectional study, 120 patients with hyperthyroidism and 50 patients suffering from hypothyroidism were studied. Cutaneous, hair and nail clinical symptoms were studied and registered in a special questionnaire. Mean age of patients suffering from hypothyroidism and hyperthyroidism were 38.24 +/- 14.45 and 25.86 +/- 14.69 years old. Dry and Coarse/rough skin were the most prevalent manifestations in the skin involvement in hypothyroidism since softness was the most prevalent ones in hyperthyroidism. Fragileness was the most prevalent symptom in patients with nail involvement in hypothyroidism since soft skin was the most prevalent ones in hyperthyroidism. Coarse/rough skin was observed more in patients with hair involvement in hypothyroidism since the most prevalent ones was separation of nail from its bed in hyperthyroidism. High prevalence of skin, hair and nail symptoms in thyroid patients, early diagnosis of the signs may be helpful in premature diagnosis and treatment of thyroid diseases.

  13. Optical coherence tomography: imaging architect for dermal microdialysis in psoriasis

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    O'Connell, M.-L.; O'Connor, W.; Ramsay, B.; Guihen, E.; Ho, W. L.; Leahy, M. J.

    2011-03-01

    Optical coherence tomography (OCT) has been used as part of a ground breaking translational study to shed some light on one of the worlds most prevalent autoimmune diseases; psoriasis. The work successfully integrates the fields of optical imaging, biochemistry and dermatology in conducting a dermal microdialysis (DMD) trial for quantitative histamine assessment amongst a group of psoriasis sufferers. The DMD process involves temporary insertion of microscopic hollow tubes into a layer of skin to measure the levels of histamine and other important biological molecules in psoriasis. For comparison purposes, DMD catheters were implanted into healthy, peri-lesional and lesional skin regions. The catheters' entry and exit points and their precise locations in the epidermal layer of the skin were confirmed using OCT thus obtaining high resolution, wide-field images of the affected skin as well as catheter placement whilst local microdialysis enabled a tissue chemistry profile to be obtained from these three skin regions including histamine, a local immune system activator known to contribute towards itch and inflammation. Together these tools offer a synergistic approach in the clinical assessment of the disease. In addition, OCT delivered a non-invasive and rapid method for analyzing the affected skin architecture.

  14. Oral phenotype and variation in focal dermal hypoplasia.

    Science.gov (United States)

    Wright, John Timothy; Puranik, Chaitanya P; Farrington, Frank

    2016-03-01

    Focal dermal hypoplasia (FDH) or Goltz Syndrome (OMIM# 305600) is an X-linked dominant ectodermal dysplasia caused by mutations in the PORCN gene. This gene encodes an endoplasmic reticulum transmembrane protein that is involved in processing the embryonically critical WNT signaling proteins. Individuals diagnosed with FDH were recruited to participate in the study through the National Foundation for Ectodermal Dysplasia. Individuals were evaluated to characterize the FDH phenotype. Each participant completed a brief dental survey and oral evaluation using artificial light. To identify the oral soft and hard tissue findings 19 individuals (16 female and 3 male) participated with a median age of 10 years (range 2-56 years). Soft and hard tissue defects were present in 68% (13) and 94% (18) of the patients, respectively. Dental anomalies were highly prevalent with 68% (13) demonstrating vertical enamel grooving, 52% (10) having peg shaped tooth deformities, and 78% (15) having enamel hypoplasia with or without discoloration. Cleft lip and cleft palate presented in 15% (3) of the participants. Other findings included 57% (11) having intra-oral lipoma or papilloma with no site predilection. Dental malocclusions were common with 63% (12) having some degree of malocclusion with 15% (3) of participants having class III malocclusion with an anterior dental cross bite. Participants frequently reported speech problems or difficulty with chewing (73%; N = 14). This study shows there is marked variation in the oral phenotype of individuals with FDH and underscores the important role of WNT signaling in oro-facial development.

  15. Misdiagnosis and Mistreatment of Post-Kala-Azar Dermal Leishmaniasis

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    Ahmed Mohamed El Hassan

    2013-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is a known complication of visceral leishmaniasis (VL caused by L. donovani. It is rare in VL caused by L. infantum and L. chagasi. In Sudan, it occurs with a frequency of 58% among successfully treated VL patients. In the majority of cases, PKDL can be diagnosed on the basis of clinical appearance, distribution of the lesions, and past history of treated VL. The ideal diagnostic method is to demonstrate the parasite in smears, by culture or PCR. Diagnosis is particularly difficult in patients who develop PKDL in the absence of previous history of visceral leishmaniasis. We describe a case of cutaneous leishmaniasis misdiagnosed as PKDL and 3 cases of PKDL who were either misdiagnosed or mistreated as other dermatoses. This caused exacerbation of their disease leading to high parasite loads in the lesions and dissemination to internal organs in one of the patients, who was also diabetic. The latter patient had L. major infection. A fourth patient with papulonodular lesions on the face and arms of 17-year duration and who was misdiagnosed as having PKDL is also described. He turned out to have cutaneous leishmaniasis due to L. major. Fortunately, he was not treated with steroids. He was cured with intravenous sodium stibogluconate.

  16. Misregulation of iron homeostasis in amyotrophic lateral sclerosis

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    Anna Gajowiak

    2016-06-01

    Full Text Available Iron is essential for all mammalian cells, but it is toxic in excess. Our understanding of molecular mechanisms ensuring iron homeostasis at both cellular and systemic levels has dramatically increased over the past 15 years. However, despite major advances in this field, homeostatic regulation of iron in the central nervous system (CNS requires elucidation. It is unclear how iron moves in the CNS and how its transfer to the CNS across the blood-brain and the blood-cerebrospinal fluid barriers, which separate the CNS from the systemic circulation, is regulated. Increasing evidence indicates the role of iron dysregulation in neuronal cell death observed in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS. ALS is a progressive neurodegenerative disorder characterized by selective cortical czynand spinal motor neuron dysfunction that results from a complex interplay among various pathogenic factors including oxidative stress. The latter is known to strongly affect cellular iron balance, creating a vicious circle to exacerbate oxidative injury. The role of iron in the pathogenesis of ALS is confirmed by therapeutic effects of iron chelation in ALS mouse models. These models are of great importance for deciphering molecular mechanisms of iron accumulation in neurons. Most of them consist of transgenic rodents overexpressing the mutated human superoxide dismutase 1 (SOD1 gene. Mutations in the SOD1 gene constituteone of the most common genetic causes of the inherited form of ALS. However, it should beconsidered that overexpression of the SOD1 gene usually leads to increased SOD1 enzymaticactivity, a condition which does not occur in human pathology and which may itself changethe expression of iron metabolism genes.

  17. Mouse middle ear ion homeostasis channels and intercellular junctions.

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    Lisa M Morris

    Full Text Available HYPOTHESIS: The middle ear contains homeostatic mechanisms that control the movement of ions and fluids similar to those present in the inner ear, and are altered during inflammation. BACKGROUND: The normal middle ear cavity is fluid-free and air-filled to allow for effective sound transmission. Within the inner ear, the regulation of fluid and ion movement is essential for normal auditory and vestibular function. The same ion and fluid channels active in the inner ear may have similar roles with fluid regulation in the middle ear. METHODS: Middle and inner ears from BALB/c mice were processed for immunohistochemistry of 10 specific ion homeostasis factors to determine if similar transport and barrier mechanisms are present in the tympanic cavity. Examination also was made of BALB/c mice middle ears after transtympanic injection with heat-killed Haemophilus influenza to determine if these channels are impacted by inflammation. RESULTS: The most prominent ion channels in the middle ear included aquaporins 1, 4 and 5, claudin 3, ENaC and Na(+,K(+-ATPase. Moderate staining was found for GJB2, KCNJ10 and KCNQ1. The inflamed middle ear epithelium showed increased staining due to expected cellular hypertrophy. Localization of ion channels was preserved within the inflamed middle ear epithelium. CONCLUSIONS: The middle ear epithelium is a dynamic environment with intrinsic mechanisms for the control of ion and water transport to keep the middle ear clear of fluids. Compromise of these processes during middle ear disease may underlie the accumulation of effusions and suggests they may be a therapeutic target for effusion control.

  18. Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis.

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    Tierney, Matthew T; Sacco, Alessandra

    2016-06-01

    The cellular turnover required for skeletal muscle maintenance and repair is mediated by resident stem cells, also termed satellite cells. Satellite cells normally reside in a quiescent state, intermittently entering the cell cycle to fuse with neighboring myofibers and replenish the stem cell pool. However, the mechanisms by which satellite cells maintain the precise balance between self-renewal and differentiation necessary for long-term homeostasis remain unclear. Recent work has supported a previously unappreciated heterogeneity in the satellite cell compartment that may underlie the observed variability in cell fate and function. In this review, we examine the work supporting this notion as well as the potential governing principles, developmental origins, and principal determinants of satellite cell heterogeneity.

  19. The role of macrophages in skin homeostasis.

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    Yanez, Diana A; Lacher, Richard K; Vidyarthi, Aurobind; Colegio, Oscar R

    2017-04-01

    The skin and its appendages comprise the largest and fastest growing organ in the body. It performs multiple tasks and maintains homeostatic control, including the regulation of body temperature and protection from desiccation and from pathogen invasion. The skin can perform its functions with the assistance of different immune cell populations. Monocyte-derived cells are imperative for the completion of these tasks. The comprehensive role of macrophages and Langerhans cells in establishing and maintaining skin homeostasis remains incompletely defined. However, over the past decade, innovations in mouse genetics have allowed for advancements in the field. In this review, we explore different homeostatic roles of macrophages and Langerhans cells, including wound repair, follicle regeneration, salt balance, and cancer regression and progression in the skin. The understanding of the precise functions of myeloid-derived cells in the skin under basal conditions can help develop specific therapies that aid in skin and hair follicle regeneration and cutaneous cancer prevention.

  20. Environmental stresses disrupt telomere length homeostasis.

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    Gal Hagit Romano

    Full Text Available Telomeres protect the chromosome ends from degradation and play crucial roles in cellular aging and disease. Recent studies have additionally found a correlation between psychological stress, telomere length, and health outcome in humans. However, studies have not yet explored the causal relationship between stress and telomere length, or the molecular mechanisms underlying that relationship. Using yeast as a model organism, we show that stresses may have very different outcomes: alcohol and acetic acid elongate telomeres, whereas caffeine and high temperatures shorten telomeres. Additional treatments, such as oxidative stress, show no effect. By combining genome-wide expression measurements with a systematic genetic screen, we identify the Rap1/Rif1 pathway as the central mediator of the telomeric response to environmental signals. These results demonstrate that telomere length can be manipulated, and that a carefully regulated homeostasis may become markedly deregulated in opposing directions in response to different environmental cues.

  1. Blood-Brain Barrier P-Glycoprotein Function in Neurodegenerative Disease

    NARCIS (Netherlands)

    Bartels, A. L.

    2011-01-01

    Protection of the brain is strengthened by active transport and ABC transporters. P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a substrate from the brain, which is important for maintaining loco-regional homeostasis in the brain and protectio

  2. Longitudinal assessment of blood-brain barrier leakage during epileptogenesis in rats. A quantitative MRI study.

    NARCIS (Netherlands)

    van Vliet, E.A.; Otte, W.M.; Gorter, J.A.; Dijkhuizen, R.M.; Wadman, W.J.

    2014-01-01

    The blood-brain barrier (BBB) plays an important role in the homeostasis of the brain. BBB dysfunction has been implicated in the pathophysiology of various neurological disorders, including epilepsy in which it may contribute to disease progression. Precise understanding of BBB dynamics during epil

  3. BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function

    NARCIS (Netherlands)

    Griep, L.M.; Wolbers, F.; de Wagenaar, B.; ter Braak, Paulus Martinus; Weksler, B.B.; Romero, A.; Couraud, P.O.; Vermes, I.; van der Meer, Andries Dirk; van den Berg, Albert

    The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely

  4. BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function

    NARCIS (Netherlands)

    Griep, L.M.; Wolbers, F.; Wagenaar, de B.; Braak, ter P.M.; Weksler, B.B.; Romero, A.; Couraud, P.O.; Vermes, I.; Meer, van der A.D.; Berg, van den A.

    2013-01-01

    The blood-brain barrier (BBB) is a unique feature of the human body, preserving brain homeostasis and preventing toxic substances to enter the brain. However, in various neurodegenerative diseases, the function of the BBB is disturbed. Mechanisms of the breakdown of the BBB are incompletely understo

  5. Cyclophilin A in cardiovascular homeostasis and diseases.

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    Satoh, Kimio

    2015-01-01

    Vascular homeostasis is regulated by complex interactions between many vascular cell components, including endothelial cells, vascular smooth muscle cells (VSMCs), adventitial inflammatory cells, and autonomic nervous system. The balance between oxidant and antioxidant systems determines intracellular redox status, and their imbalance can cause oxidative stress. Excessive oxidative stress is one of the important stimuli that induce cellular damage and dysregulation of vascular cell components, leading to vascular diseases through multiple pathways. Cyclophilin A (CyPA) is one of the causative proteins that mediate oxidative stress-induced cardiovascular dysfunction. CyPA was initially discovered as the intracellular receptor of the immunosuppressive drug cyclosporine 30 years ago. However, recent studies have established that CyPA is secreted from vascular cell components, such as endothelial cells and VSMCs. Extracellular CyPA augments the development of cardiovascular diseases. CyPA secretion is regulated by Rho-kinase, which contributes to the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. We recently reported that plasma CyPA levels are significantly higher in patients with coronary artery disease, which is associated with increased numbers of stenotic coronary arteries and the need for coronary intervention in such patients. Furthermore, we showed that the vascular erythropoietin (Epo)/Epo receptor system plays an important role in production of nitric oxide and maintenance of vascular redox state and homeostasis, with a potential mechanistic link to the Rho-kinase-CyPA pathway. In this article, I review the data on the protective role of the vascular Epo/Epo receptor system and discuss the roles of the CyPA/Rho-kinase system in cardiovascular diseases.

  6. Interference between nanoparticles and metal homeostasis

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    Petit, A. N.; Aude Garcia, C.; Candéias, S.; Casanova, A.; Catty, P.; Charbonnier, P.; Chevallet, M.; Collin-Faure, V.; Cuillel, M.; Douki, T.; Herlin-Boime, N.; Lelong, C.; Luche, S.; Mintz, E.; Moulis, J. M.; Nivière, V.; Ollagnier de Choudens, S.; Rabilloud, T.; Ravanat, J. L.; Sauvaigo, S.; Carrière, M.; Michaud-Soret, I.

    2011-07-01

    The TiO2 nanoparticles (NPs) are now produced abundantly and widely used in a variety of consumer products. Due to the important increase in the production of TiO2-NPs, potential widespread exposure of humans and environment may occur during both the manufacturing process and final use. Therefore, the potential toxicity of TiO2-NPs on human health and environment has attracted particular attention. Unfortunately, the results of the large number of studies on the toxicity of TiO2-NPs differ significantly, mainly due to an incomplete characterization of the used nanomaterials in terms of size, shape and crystalline structure and to their unknown state of agglomeration/aggregation. The purpose of our project entitled NanoBioMet is to investigate if interferences between nanoparticles and metal homeostasis could be observed and to study the toxicity mechanisms of TiO2-NPs with well-characterized physicochemical parameters, using proteomic and molecular approaches. A perturbation of metal homeostasis will be evaluated upon TiO2-NPs exposure which could generate reactive oxygen species (ROS) production. Moreover, oxidative stress consequences such as DNA damage and lipid peroxidation will be studied. The toxicity of TiO2-NPs of different sizes and crystalline structures will be evaluated both in prokaryotic (E. coli) and eukaryotic cells (A549 human pneumocytes, macrophages, and hepatocytes). First results of the project will be presented concerning the dispersion of TiO2-NPs in bacterial medium, proteomic studies on total extracts of macrophages and genotoxicity on pneumocytes.

  7. Interference between nanoparticles and metal homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Petit, A N; Catty, P; Charbonnier, P; Cuillel, M; Mintz, E; Moulis, J M; Niviere, V; Choudens, S Ollagnier de [Laboratoire de Chimie et Biologie des Metaux UMR 5249 CEA-CNRS-UJF, 17 rue des Martyrs, 38054 Grenoble Cedex 09 (France); Garcia, C Aude; Candeias, S; Chevallet, M; Collin-Faure, V; Lelong, C; Luche, S; Rabilloud, T [Laboratoire de Biochimie et Biophysique des Systemes Integres UMR 5092 CNRS-CEA-UJF, 17 rue des martyrs, 38054 Grenoble Cedex 09 (France); Casanova, A; Herlin-Boime, N [Laboratoire Edifices Nanometriques URA 2453 CEA-CNRS-IRAMIS, 91191 Gif-sur-Yvette (France); Douki, T; Ravanat, J L; Sauvaigo, S, E-mail: isabelle.michaud-soret@cea.fr [Laboratoire Lesions des Acides Nucleiques UMR E3 CEA-UJF, 17 rue des Martyrs, 38054 Grenoble Cedex 09 (France)

    2011-07-06

    The TiO{sub 2} nanoparticles (NPs) are now produced abundantly and widely used in a variety of consumer products. Due to the important increase in the production of TiO{sub 2}-NPs, potential widespread exposure of humans and environment may occur during both the manufacturing process and final use. Therefore, the potential toxicity of TiO{sub 2}-NPs on human health and environment has attracted particular attention. Unfortunately, the results of the large number of studies on the toxicity of TiO{sub 2}-NPs differ significantly, mainly due to an incomplete characterization of the used nanomaterials in terms of size, shape and crystalline structure and to their unknown state of agglomeration/aggregation. The purpose of our project entitled NanoBioMet is to investigate if interferences between nanoparticles and metal homeostasis could be observed and to study the toxicity mechanisms of TiO{sub 2}-NPs with well-characterized physicochemical parameters, using proteomic and molecular approaches. A perturbation of metal homeostasis will be evaluated upon TiO{sub 2}-NPs exposure which could generate reactive oxygen species (ROS) production. Moreover, oxidative stress consequences such as DNA damage and lipid peroxidation will be studied. The toxicity of TiO{sub 2}-NPs of different sizes and crystalline structures will be evaluated both in prokaryotic (E. coli) and eukaryotic cells (A549 human pneumocytes, macrophages, and hepatocytes). First results of the project will be presented concerning the dispersion of TiO{sub 2}-NPs in bacterial medium, proteomic studies on total extracts of macrophages and genotoxicity on pneumocytes.

  8. Pathophysiology of the cochlear intrastrial fluid-blood barrier (review).

    Science.gov (United States)

    Shi, Xiaorui

    2016-08-01

    The blood-labyrinth barrier (BLB) in the stria vascularis is a highly specialized capillary network that controls exchanges between blood and the intrastitial space in the cochlea. The barrier shields the inner ear from blood-born toxic substances and selectively passes ions, fluids, and nutrients to the cochlea, playing an essential role in the maintenance of cochlear homeostasis. Anatomically, the BLB is comprised of endothelial cells (ECs) in the strial microvasculature, elaborated tight and adherens junctions, pericytes (PCs), basement membrane (BM), and perivascular resident macrophage-like melanocytes (PVM/Ms), which together form a complex "cochlear-vascular unit" in the stria vascularis. Physical interactions between the ECs, PCs, and PVM/Ms, as well as signaling between the cells, is critical for controlling vascular permeability and providing a proper environment for hearing function. Breakdown of normal interactions between components of the BLB is seen in a wide range of pathological conditions, including genetic defects and conditions engendered by inflammation, loud sound trauma, and ageing. In this review, we will discuss prevailing views of the structure and function of the strial cochlear-vascular unit (also referred to as the "intrastrial fluid-blood barrier"). We will also discuss the disrupted homeostasis seen in a variety of hearing disorders. Therapeutic targeting of the strial barrier may offer opportunities for improvement of hearing health and amelioration of auditory disorders. This article is part of a Special Issue entitled .

  9. The Human Skin Barrier Is Organized as Stacked Bilayers of Fully Extended Ceramides with Cholesterol Molecules Associated with the Ceramide Sphingoid Moiety

    DEFF Research Database (Denmark)

    Iwai, Ichiro; Han, Hongmei; Hollander, Lianne den

    2012-01-01

    The skin barrier is fundamental to terrestrial life and its evolution; it upholds homeostasis and protects against the environment. Skin barrier capacity is controlled by lipids that fill the extracellular space of the skin's surface layer-the stratum corneum. Here we report on the determination...

  10. Dermal dendritic cells” comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages

    OpenAIRE

    Ochoa,Maria Teresa; Loncaric, Anya; Krutzik, Stephan R.; Becker, Todd C.; Modlin, Robert L.

    2008-01-01

    A key cell type of the resident skin immune system is the dendritic cell, which in normal skin is located in two distinct microanatomical compartments: Langerhans cells (LC) mainly in the epidermis and dermal dendritic cells (DDC) in the dermis. Here, the lineage of dermal dendritic cells was investigated using monoclonal antibodies and immunohistology. We provide evidence that “dermal dendritic cells” comprise at least two major phenotypic populations of dendritic appearing cells: immature D...

  11. Cholesterol metabolism and homeostasis in the brain

    OpenAIRE

    Zhang, Juan; Qiang LIU

    2015-01-01

    Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier. The content of cholesterol in brain must be accurately maintained in order to keep brain function well. Defects in brain cholesterol metabolism has been shown to be implicated in neurodegenerative diseases, such as Alzheimer’s disease (AD), Huntington’s disease (HD)...

  12. In vitro dermal absorption rate testing of certain chemicals of interest to the Occupational Safety and Health Administration: summary and evaluation of USEPA's mandated testing.

    Science.gov (United States)

    Fasano, William J; McDougal, James N

    2008-07-01

    In 2004, the United States Environmental Protection Agency (USEPA) published a final test rule in the US Federal Register requiring in vitro dermal penetration rate testing for selected industrial chemicals. The test rule described procedures for determining a permeability coefficient (Kp) and two short-term dermal absorption rates at 10 and 60min using human cadaver skin mounted in an in vitro diffusion cell model. According to the USEPA announcement, the selected chemicals were to be spiked with their radiolabeled form and tested in either water, isopropyl myristate (IPM) or neat depending on their physical character at room temperature, their aqueous solubility, their potential to damage the skin and their ability to achieve the study endpoints as prescribed. Overall, and for the majority of chemicals, the short-term absorption rates were higher at 10min than at 60min and the portion of applied dose remaining in the skin at the end of the exposure period was greater than the portion of dose that had penetrated through the skin and was detected in the receptor solution. In contrast to this, the amount of chemical in the receptor solution at study termination for the Kp (steady-state) experiments was greater than the amount remaining in the skin. For the Kp experiments, which lasted from 2 to 48h, a majority of skins exposed to neat chemical exhibited a reduced barrier function. However, integrity was mostly unaltered for skins from the short-term experiments and Kp experiments using chemicals applied either in water or IPM. Quantitative structure activity relationship (QSAR) model-predicted Kp values were in fair agreement with experimental data for those chemicals that were applied in a water vehicle when the integrity of the skin was not compromised. However, QSAR-derived Kp values were not predictive for those chemicals when applied in IPM vehicle or neat. Absorption predictions, based on the measured Kp and steady-state flux data for chemicals applied in

  13. Optimal Concentrations and Synergistic Effects of Some Herbal Extracts on Viability of Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Zandi

    2016-08-01

    Full Text Available Background Many studies examine the antibacterial effects of medicinal plants; however, little research is done to evaluate their effects on different cell types, especially dermal fibroblasts. Objectives The current study aimed to study the effect of different concentrations of Aloe Vera, henna, chamomile, myrtle, mint, licorice, cinnamon, ginger and cedar extracts and their synergistic effects on the viability of dermal fibroblasts. Methods To evaluate the performance of herbal extracts on dermal fibroblasts, in the first experiment different concentrations (6.25, 12.5, 25, 50, 100, 250, 500 and 1000 µg/mL of the extracts were evaluated by the MTT cell proliferation assay. In the second experiment, the minimum effective concentrations of the plant extracts in triple combination were evaluated in the cells under study. Results The minimum effective concentrations of henna, chamomile, myrtle, mint, cinnamon, ginger and cedar were 12.5, 6.25, 6.25, 6.25, 6.25, 12.5 and 12.5µg/mL, respectively. Results showed that, by comparing the minimum effective concentration of herbal extracts, the viability of dermal fibroblasts significantly increased by cedar extract (P < 0.05. Combination of Aloe Vera, licorice and mint extracts significantly increased the viability of dermal fibroblasts (P < 0.05. Conclusions Based on the results of the current study, it was concluded that Aloe vera, licorice and mint extracts had synergistic effects on the viability of dermal fibroblasts; in addition, the combination of Aloe vera and licorice with either henna or myrtle, and Aloe vera and mint with either cedar or ginger resulted in synergistic effects on viability of dermal fibroblasts. The third category of triple combinations of herbal extracts with synergistic effects on the cells under study was the combination of Aloe Vera and mint with either chamomile or cinnamon and also Aloe vera and licorice with either myrtle or cedar.

  14. Dermal penetration of [14C]captan in young and adult rats.

    Science.gov (United States)

    Fisher, H L; Hall, L L; Sumler, M R; Shah, P V

    1992-07-01

    Age dependence in dermal absorption has been a major concern in risk assessment. Captan, a chloroalkyl thio heterocyclic fungicide, was selected for study of age dependence as representative of this class of pesticides. Dermal penetration of [14C]captan applied at 0.286 mumol/cm2 was determined in young (33-d-old) and adult (82-d-old) female Fischer 344 rats in vivo and by two in vitro methods. Dermal penetration in vivo at 72 h was about 9% of the recovered dose in both young and adult rats. The percentage penetration was found to increase as dosage (0.1, 0.5, 2.7 mumol/cm2) decreased. Two in vitro methods gave variable dermal penetration values compared with in vivo results. A static system yielded twofold higher dermal penetration values compared with in vivo results for both young and adult rats. A flow system yielded higher dermal penetration values in young rats and lower penetration values in adults compared with in vivo results. Concentration in body, kidney, and liver was less in young than in adult rats given the same absorbed dosage. A physiological pharmacokinetic model was developed having a dual compartment for the treated skin and appeared to describe dermal absorption and disposition well. From this model, tissue/blood ratios of captan-derived radioactivity for organs were found to range from 0.35 to 3.4, indicating no large uptake or binding preferences by any organ. This preliminary pharmacokinetic model summarizes the experimental findings and could provide impetus for more complex and realistic models.

  15. Skin physiology in microgravity: a 3-month stay aboard ISS induces dermal atrophy and affects cutaneous muscle and hair follicles cycling in mice.

    Science.gov (United States)

    Neutelings, Thibaut; Nusgens, Betty V; Liu, Yi; Tavella, Sara; Ruggiu, Alessandra; Cancedda, Ranieri; Gabriel, Maude; Colige, Alain; Lambert, Charles

    2015-01-01

    The Mice Drawer System (MDS) Tissue Sharing program was the longest rodent space mission ever performed. It provided 20 research teams with organs and tissues collected from mice having spent 3 months on the International Space Station (ISS). Our participation to this experiment aimed at investigating the impact of such prolonged exposure to extreme space conditions on mouse skin physiology. Mice were maintained in the MDS for 91 days aboard ISS (space group (S)). Skin specimens were collected shortly after landing for morphometric, biochemical, and transcriptomic analyses. An exact replicate of the experiment in the MDS was performed on ground (ground group (G)). A significant reduction of dermal thickness (-15%, P=0.05) was observed in S mice accompanied by an increased newly synthetized procollagen (+42%, P=0.03), likely reflecting an increased collagen turnover. Transcriptomic data suggested that the dermal atrophy might be related to an early degradation of defective newly formed procollagen molecules. Interestingly, numerous hair follicles in growing anagen phase were observed in the three S mice, validated by a high expression of specific hair follicles genes, while only one mouse in the G controls showed growing hairs. By microarray analysis of whole thickness skin, we observed a significant modulation of 434 genes in S versus G mice. A large proportion of the upregulated transcripts encoded proteins related to striated muscle homeostasis. These data suggest that a prolonged exposure to space conditions may induce skin atrophy, deregulate hair follicle cycle, and markedly affect the transcriptomic repertoire of the cutaneous striated muscle panniculus carnosus.

  16. Regulation of intestinal homeostasis and immunity with probiotic lactobacilli

    NARCIS (Netherlands)

    Baarlen, van P.; Wells, J.; Kleerebezem, M.

    2013-01-01

    The gut microbiota provide important stimuli to the human innate and adaptive immune system and co-mediate metabolic and immune homeostasis. Probiotic bacteria can be regarded as part of the natural human microbiota, and have been associated with improving homeostasis, albeit with different levels

  17. A Formal Explication of the Concept of Family Homeostasis.

    Science.gov (United States)

    Ariel, Shlomo; And Others

    1984-01-01

    Presents three articles discussing the concept of family homeostasis and the related concepts of family rules and family feedback. Includes a reply by Paul Dell citing the need for family therapy to go beyond homeostasis and further comments by Ariel, Carel, and Tyano. (JAC)

  18. Development and Validation of the Homeostasis Concept Inventory

    Science.gov (United States)

    McFarland, Jenny L.; Price, Rebecca M.; Wenderoth, Mary Pat; Martinková, Patrícia; Cliff, William; Michael, Joel; Modell, Harold; Wright, Ann

    2017-01-01

    We present the Homeostasis Concept Inventory (HCI), a 20-item multiple-choice instrument that assesses how well undergraduates understand this critical physiological concept. We used an iterative process to develop a set of questions based on elements in the Homeostasis Concept Framework. This process involved faculty experts and undergraduate…

  19. Converse Barrier Certificate Theorems

    DEFF Research Database (Denmark)

    Wisniewski, Rafael; Sloth, Christoffer

    2016-01-01

    This paper shows that a barrier certificate exists for any safe dynamical system. Specifically, we prove converse barrier certificate theorems for a class of structurally stable dynamical systems. Other authors have developed a related result by assuming that the dynamical system has neither sing...

  20. A conceptual framework for homeostasis: development and validation.

    Science.gov (United States)

    McFarland, Jenny; Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

    2016-06-01

    We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis.

  1. Mechanosensitive subcellular rheostasis drives emergent single-cell mechanical homeostasis

    Science.gov (United States)

    Weng, Shinuo; Shao, Yue; Chen, Weiqiang; Fu, Jianping

    2016-09-01

    Mechanical homeostasis--a fundamental process by which cells maintain stable states under environmental perturbations--is regulated by two subcellular mechanotransducers: cytoskeleton tension and integrin-mediated focal adhesions (FAs). Here, we show that single-cell mechanical homeostasis is collectively driven by the distinct, graduated dynamics (rheostasis) of subcellular cytoskeleton tension and FAs. Such rheostasis involves a mechanosensitive pattern wherein ground states of cytoskeleton tension and FA determine their distinct reactive paths through either relaxation or reinforcement. Pharmacological perturbations of the cytoskeleton and molecularly modulated integrin catch-slip bonds biased the rheostasis and induced non-homeostasis of FAs, but not of cytoskeleton tension, suggesting a unique sensitivity of FAs in regulating homeostasis. Theoretical modelling revealed myosin-mediated cytoskeleton contractility and catch-slip-bond-like behaviours in FAs and the cytoskeleton as sufficient and necessary mechanisms for quantitatively recapitulating mechanosensitive rheostasis. Our findings highlight the previously underappreciated physical nature of the mechanical homeostasis of cells.

  2. Deletion of Porcn in mice leads to multiple developmental defects and models human focal dermal hypoplasia (Goltz syndrome.

    Directory of Open Access Journals (Sweden)

    Wei Liu

    Full Text Available BACKGROUND: Focal Dermal Hypoplasia (FDH is a genetic disorder characterized by developmental defects in skin, skeleton and ectodermal appendages. FDH is caused by dominant loss-of-function mutations in X-linked PORCN. PORCN orthologues in Drosophila and mice encode endoplasmic reticulum proteins required for secretion and function of Wnt proteins. Wnt proteins play important roles in embryo development, tissue homeostasis and stem cell maintenance. Since features of FDH overlap with those seen in mouse Wnt pathway mutants, FDH likely results from defective Wnt signaling but molecular mechanisms by which inactivation of PORCN affects Wnt signaling and manifestations of FDH remain to be elucidated. RESULTS: We introduced intronic loxP sites and a neomycin gene in the mouse Porcn locus for conditional inactivation. Porcn-ex3-7flox mice have no apparent developmental defects, but chimeric mice retaining the neomycin gene (Porcn-ex3-7Neo-flox have limb, skin, and urogenital abnormalities. Conditional Porcn inactivation by EIIa-driven or Hprt-driven Cre recombinase results in increased early embryonic lethality. Mesenchyme-specific Prx-Cre-driven inactivation of Porcn produces FDH-like limb defects, while ectodermal Krt14-Cre-driven inactivation produces thin skin, alopecia, and abnormal dentition. Furthermore, cell-based assays confirm that human PORCN mutations reduce WNT3A secretion. CONCLUSIONS: These data indicate that Porcn inactivation in the mouse produces a model for human FDH and that phenotypic features result from defective WNT signaling in ectodermal- and mesenchymal-derived structures.

  3. Skin barrier function

    DEFF Research Database (Denmark)

    2016-01-01

    Renowned experts present the latest knowledge Although a very fragile structure, the skin barrier is probably one of the most important organs of the body. Inward/out it is responsible for body integrity and outward/in for keeping microbes, chemicals, and allergens from penetrating the skin. Since...... the role of barrier integrity in atopic dermatitis and the relationship to filaggrin mutations was discovered a decade ago, research focus has been on the skin barrier, and numerous new publications have become available. This book is an interdisciplinary update offering a wide range of information...... on the subject. It covers new basic research on skin markers, including results on filaggrin and on methods for the assessment of the barrier function. Biological variation and aspects of skin barrier function restoration are discussed as well. Further sections are dedicated to clinical implications of skin...

  4. Effects of dihydrotestosterone on rat dermal papilla cells in vitro.

    Science.gov (United States)

    Kang, Jung-Il; Kim, Sang-Cheol; Kim, Min-Kyoung; Boo, Hye-Jin; Kim, Eun-Ji; Im, Guang-Jin; Kim, Young Ho; Hyun, Jin-Won; Kang, Ji-Hoon; Koh, Young-Sang; Park, Deok-Bae; Yoo, Eun-Sook; Kang, Hee-Kyoung

    2015-06-15

    Androgenetic alopecia involves the action of dihydrotestosterone (DHT) on dermal papilla cells (DPCs) that line the base of the hair follicle. However, the mechanism of DHT action is not completely understood. The effects of DHT on DPCs, regulatory cells that function in follicle growth and the hair cycle, were examined in immortalized cells derived from rat vibrissa follicles. DHT did not affect the proliferation of immortalized DPCs. However, flow cytometry analysis revealed that DHT increased cell-cycle arrest in these cells, which was accompanied by an increase in the p27(kip1) level and by decreases in cyclin E, cyclin D1, and cyclin-dependent kinase 2 levels. DHT treatment resulted in the phosphorylation and nuclear translocation of Smad2/3, a mediator of the transforming growth factor-β (TGF-β) signaling pathway, which leads to the catagen phase of the hair cycle. DHT also induced the phosphorylation and nuclear translocation of heat shock protein 27 (HSP27). Moreover, DHT decreased the levels of total and nuclear β-catenin, an important regulator of hair growth and proliferation, while lithium chloride, a glycogen synthase kinase-3β inhibitor, attenuated the DHT-induced downregulation of the β-catenin level. On the other hand, DHT increased the phosphorylation of mammalian target of rapamycin (mTOR), a regulator of proliferation, in immortalized DPCs. These results illustrate that DHT could shorten the duration of the hair growth cycle by initiating cell-cycle arrest, downregulating the β-catenin level, and upregulating the TGF-β/Smad and HSP27 level, whereas activation of mTOR by DHT could attenuate the inhibition of hair growth cycle in immortalized DPCs. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Generation of human induced pluripotent stem cells from dermal fibroblasts.

    Science.gov (United States)

    Lowry, W E; Richter, L; Yachechko, R; Pyle, A D; Tchieu, J; Sridharan, R; Clark, A T; Plath, K

    2008-02-26

    The generation of patient-specific pluripotent stem cells has the potential to accelerate the implementation of stem cells for clinical treatment of degenerative diseases. Technologies including somatic cell nuclear transfer and cell fusion might generate such cells but are hindered by issues that might prevent them from being used clinically. Here, we describe methods to use dermal fibroblasts easily obtained from an individual human to generate human induced pluripotent stem (iPS) cells by ectopic expression of the defined transcription factors KLF4, OCT4, SOX2, and C-MYC. The resultant cell lines are morphologically indistinguishable from human embryonic stem cells (HESC) generated from the inner cell mass of a human preimplantation embryo. Consistent with these observations, human iPS cells share a nearly identical gene-expression profile with two established HESC lines. Importantly, DNA fingerprinting indicates that the human iPS cells were derived from the donor material and are not a result of contamination. Karyotypic analyses demonstrate that reprogramming of human cells by defined factors does not induce, or require, chromosomal abnormalities. Finally, we provide evidence that human iPS cells can be induced to differentiate along lineages representative of the three embryonic germ layers indicating the pluripotency of these cells. Our findings are an important step toward manipulating somatic human cells to generate an unlimited supply of patient-specific pluripotent stem cells. In the future, the use of defined factors to change cell fate may be the key to routine nuclear reprogramming of human somatic cells.

  6. Dermatologic findings of focal dermal hypoplasia (Goltz syndrome).

    Science.gov (United States)

    Bree, Alanna F; Grange, Dorothy K; Hicks, M John; Goltz, Robert W

    2016-03-01

    Goltz syndrome, caused by mutations in PORCN, is an X-linked dominant ectodermal dysplasia which is also known as focal dermal hypoplasia. This name is derived from the predominant pathologic skin findings of the syndrome. Nineteen Goltz-affected participants attended a multidisciplinary scientific and clinical conference convened by the National Foundation for Ectodermal Dysplasia which allowed further characterization of the features of this very rare condition. At birth, the affected areas of skin are typically erythematous and fragile. The hallmark cutaneous features, which vary widely due to mosacism and X-inactivation, include the previously described skin changes of asymmetric Blaschko-linear and reticulated atrophy, pigmentary changes, and telangectasias. Lipomatous changes and papillomas as characteristically defined were reported in the majority of patients. A newly recognized skin finding was progressive hyperpigmented freckling that occurred within the hypopigmented areas which were noted to be photosensitive. Many patients also had a pebbly texture to the central face, dorsal hands and feet. Punctate erosions within the atrophic areas and hypohidrosis were also common. Most had patchy alopecia and many had diffusely thin hair. Scanning electron microscopy of the hair shafts revealed abnormalities in the majority of participants with several different features identified, including atrophic hairs with reduced diameters, markedly flattened hairs as noted in cross-sectional views, trichorrhexis nodosa, pili torti, and pili trianguli et canaliculi. Nail changes included V-nicking and longitudinal ridging of the nail plate, in addition to micronychia. Early recognition of the dermatologic features, in addition to the variable but universal limb anomalies, of Goltz syndrome will allow early and accurate diagnosis without the need for extensive diagnostic studies, while also allowing for accurate prognosis and appropriate genetic counseling.

  7. Characterization and assessment of dermal and inhalable nickel exposures in nickel production and primary user industries.

    Science.gov (United States)

    Hughson, G W; Galea, K S; Heim, K E

    2010-01-01

    The aim of this study was to measure the levels of nickel in the skin contaminant layer of workers involved in specific processes and tasks within the primary nickel production and primary nickel user industries. Dermal exposure samples were collected using moist wipes to recover surface contamination from defined areas of skin. These were analysed for soluble and insoluble nickel species. Personal samples of inhalable dust were also collected to determine the corresponding inhalable nickel exposures. The air samples were analysed for total inhalable dust and then for soluble, sulfidic, metallic, and oxidic nickel species. The workplace surveys were carried out in five different workplaces, including three nickel refineries, a stainless steel plant, and a powder metallurgy plant, all of which were located in Europe. Nickel refinery workers involved with electrolytic nickel recovery processes had soluble dermal nickel exposure of 0.34 microg cm(-2) [geometric mean (GM)] to the hands and forearms. The GM of soluble dermal nickel exposure for workers involved in packing nickel salts (nickel chloride hexahydrate, nickel sulphate hexahydrate, and nickel hydroxycarbonate) was 0.61 microg cm(-2). Refinery workers involved in packing nickel metal powders and end-user powder operatives in magnet production had the highest dermal exposure (GM = 2.59 microg cm(-2) soluble nickel). The hands, forearms, face, and neck of these workers all received greater dermal nickel exposure compared with the other jobs included in this study. The soluble nickel dermal exposures for stainless steel production workers were at or slightly above the limit of detection (0.02 microg cm(-2) soluble nickel). The highest inhalable nickel concentrations were observed for the workers involved in nickel powder packing (GM = 0.77 mg m(-3)), although the soluble component comprised only 2% of the total nickel content. The highest airborne soluble nickel exposures were associated with refineries using

  8. Regulation of Copper Transport Crossing Brain Barrier Systems by Cu-ATPases: Effect of Manganese Exposure

    OpenAIRE

    Fu, Xue; Zhang, Yanshu; Jiang, Wendy; Monnot, Andrew Donald; Bates, Christopher Alexander; Zheng, Wei

    2014-01-01

    Regulation of cellular copper (Cu) homeostasis involves Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. The question as to how these Cu-ATPases in brain barrier systems transport Cu, i.e., toward brain parenchyma, cerebrospinal fluid (CSF), or blood, remained unanswered. This study was designed to characterize roles of Cu-ATPases in regulating Cu transport at the blood-brain barrier (BBB) and blood-CSF barrier (BCB) and to investigate how exposure to toxic manganese (Mn) altered ...

  9. A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

    Directory of Open Access Journals (Sweden)

    Peipei Zhang

    2014-10-01

    Full Text Available Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration.

  10. Urinary excretion of tetrahydrophtalimide in fruit growers with dermal exposure to captan.

    Science.gov (United States)

    de Cock, J; Heederik, D; Hoek, F; Boleij, J; Kromhout, H

    1995-08-01

    The relation between dermal and respiratory exposure and uptake into the body of captan, measured as 24 hr cumulative tetrahydrophtalimide (THPI) dose, was studied among 14 male fruit growers applying pesticides in orchards in the Netherlands. No contribution of respiratory exposure was observed on THPI in the urine. Dermal exposure, measured with skin pads, showed a clear relation with THPI in urine when exposure was estimated from exposure on skin pads of ankles and neck. No relation was found for total dermal exposure, calculated from measured exposure on skin pads of representative skin areas according to models described in the literature. Determinants of exposure such as use of a cabin on the tractor, use of gloves during mixing and loading, and use of rubber boots also explained THPI in urine very well. This finding corroborated the findings on measured dermal exposure. Results indicate that more attention should be paid to skin areas which are suspected to be most permeable for a chemical under study. It was concluded that dermal exposure data can be linked better to biological monitoring based on empirical findings as gathered in a pilot study on exposure of specific body areas than on estimations of total skin dose.

  11. The Role of Dermal Matrices in Treating Inflammatory and Diabetic Wounds.

    Science.gov (United States)

    Climov, Mihail; Bayer, Lauren R; Moscoso, Andrea V; Matsumine, Hajime; Orgill, Dennis P

    2016-09-01

    Dermal matrices are used to improve healing in both acute and chronic wounds including diabetic and lower extremity wounds, burns, trauma, and surgical reconstruction. The use of dermal matrices for the closure of inflammatory ulcerations is less frequent but growing. Currently available products include decellularized dermis and semisynthetic matrices. A review of the published literature was performed to identify reports that use acellular dermal matrices in diabetic and inflammatory wounds. Studies were evaluated for quality and outcomes, and a level of evidence was assigned according to the American Society of Plastic Surgeons' Rating Levels of Evidence. Case studies from the authors' experience are also presented. Seventeen primary studies evaluating the use of dermal matrices in diabetic ulcers were identified with 2 based on level I data. There are no prospective clinical trial reports of their use in atypical or inflammatory wounds, but there are several case studies. Treatment of diabetic and inflammatory wounds may include both medical and surgical modalities. The use of dermal matrices can be a useful adjunct, but their optimal use will require future clinical studies.

  12. Penile Reconstruction with Skin Grafts and Dermal Matrices: Indications and Management.

    Science.gov (United States)

    Triana Junco, Paloma; Dore, Mariela; Nuñez Cerezo, Vanesa; Jimenez Gomez, Javier; Miguel Ferrero, Miriam; Díaz González, Mercedes; Lopez-Pereira, Pedro; Lopez-Gutierrez, Juan Carlos

    2017-01-01

    Introduction  The penis eventually needs specific cutaneous coverage in the context of reconstructive procedures following trauma or congenital anomalies. Local flaps are the first choice but are not always available after multiple previous procedures. In these cases, skin graft and dermal matrices should be considered. Materials and Methods  This study was a retrospective review of the past 4 years of four patients with severe loss of penile shaft skin who underwent skin reconstruction. Dermal matrices and skin grafts were utilized. Dermal matrices were placed for a median of 4.5 weeks (3.0-6.0 weeks). The skin graft was harvested from the inner thigh region for split-thickness skin graft (STSG) and the inguinal region for full-thickness skin graft (FTSG). Results  The four patients presented with complete loss of skin in the penile shaft. One patient had a vesical exstrophy, one had a buried penis with only one corpus cavernosum, one had a wide congenital lymphedema of the genitalia, and one had a lack of skin following circumcision at home. They underwent reconstruction with three patients undergoing split-thickness skin graft; two dermal matrices; and one full-thickness graft, respectively, thereby achieving a good cosmetic and functional result. There were no complications, and all the patients successfully accepted the graft. Conclusion  Dermal matrices and skin grafts may serve as effective tools in the management of severe penile skin defects unable to be covered with local flaps.

  13. Management of gingival recession with acellular dermal matrix graft: A clinical study

    Directory of Open Access Journals (Sweden)

    V R Balaji

    2016-01-01

    Full Text Available Aims and Objectives: Obtaining root coverage has become an important part of periodontal therapy. The aims of this studyare to evaluate the clinical efficacy of acellular dermal matrix graft in the coverage of denuded roots and also to examine the change in the width of keratinized gingiva. Materials and Methods: A total of 20 sites with more than or equal to 2 mm of recession depth were taken into the study, for treatment with acellular dermal matrix graft. The clinical parameters such as recession depth, recession width, width of keratinized gingiva, probing pocket depth (PD, and clinical attachment level (CAL were measured at the baseline, 8th week, and at the end of the study (16th week. The defects were treated with a coronally positioned pedicle graft combined with acellular dermal matrix graft. Results: Out of 20 sites treated with acellular dermal matrix graft, seven sites showed complete root coverage (100%, and the mean root coverage obtained was 73.39%. There was a statistically significant reduction in recession depth, recession width, and probing PD. There was also a statistically significant increase in width of keratinized gingiva and also gain in CAL. The postoperative results were both clinically and statistically significant (P < 0.0001. Conclusion: The results of this study were esthetically acceptable to the patients and clinically acceptable in all cases. From this study, it may be concluded that acellular dermal matrix graft is an excellent substitute for autogenous graft in coverage of denuded roots.

  14. The Effectiveness of Porcine Dermal Collagen (Permacol(®)) on Wound Healing in the Rat Model.

    Science.gov (United States)

    Kalin, Murat; Kuru, Serdar; Kismet, Kemal; Barlas, Aziz Mutlu; Akgun, Yusuf Akif; Astarci, Hesna Muzeyyen; Ustun, Huseyin; Ertas, Ertugrul

    2015-12-01

    Porcine acellular dermal collagen (PDC), which is a biological material derived from processing porcine dermis, has already been used for urologic, gynecologic, plastic, and general surgery procedures up to now. The aim of this study is to investigate the effectiveness of PDC on wound healing as a dermal substitute in the rat model. Twenty Wistar albino rats were divided into two groups. Standard full-thickness skin defects were created on the back of the rats. In the control group (Group 1), the dressings moisturized with saline were changed daily. In the study group (Group 2), porcine dermal collagen was implanted onto each wound and fixed with 4-0 polypropylene sutures. Contraction percentages of wound areas were calculated on the third, seventh, tenth, and fourteenth days by using the planimetric program. On fourteenth day, the wound areas were excised for histopathological examination, inflammatory scoring, and evaluation of collagen deposition. The study group was superior to the control group in terms of inflammatory scoring, type I/type III collagen ratio, and wound contraction rates. Porcine dermal collagen may be used effectively and safely on full-thickness wounds as a current dermal substitute.

  15. Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function

    DEFF Research Database (Denmark)

    Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis

    2013-01-01

    express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by the following mechanisms: (i) stimulation...... of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion. As barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r...... antagonists likely oppose mast cell-derived histamines. In four immunologically diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic...

  16. Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

    Science.gov (United States)

    Johnson, William M.; Wilson-Delfosse, Amy L.; Mieyal, John. J.

    2012-01-01

    Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases, amyotrophic lateral sclerosis, and Friedreich’s ataxia. In this review background is provided on the steady-state synthesis, regulation, and transport of glutathione, with primary focus on the brain. A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathione-dependent enzymes. Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation. In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status and/or in the activities of glutathione-dependent enzymes. Mechanisms of dysregulation of glutathione and/or glutathione-dependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease. Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions. The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutathione as a biomarker, are critically evaluated. PMID:23201762

  17. Abnormal calcium homeostasis in peripheral neuropathies.

    Science.gov (United States)

    Fernyhough, Paul; Calcutt, Nigel A

    2010-02-01

    Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous diseases of the nervous system. The pathogenesis of two increasingly common disorders of the peripheral nervous system, namely neuropathic pain and diabetic polyneuropathy, has been associated with aberrant Ca2+ channel expression and function. Here we review the current state of knowledge regarding the role of Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic neuropathies. The central impact of both alterations of Ca2+ signalling at the plasma membrane and also intracellular Ca2+ handling on sensory neurone function is discussed and related to abnormal endoplasmic reticulum performance. We also present new data highlighting sub-optimal axonal Ca2+ signalling in diabetic neuropathy and discuss the putative role for this abnormality in the induction of axonal degeneration in peripheral neuropathies. The accumulating evidence implicating Ca2+ dysregulation in both painful and degenerative neuropathies, along with recent advances in understanding of regional variations in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many peripheral neuropathies.

  18. Vitamin A homeostasis endangered by environmental pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Zile, M.H. (Department of Food Science and Human Nutrition, Michigan State University, East Lansing (United States))

    1992-11-01

    Normal vitamin A function depends on adequate stores of the vitamin, a finely regulated supply of the vitamin to target tissues, and an ability of cells to generate functionally active forms of the vitamin. Both endogenous and exogenous factors can adversely affect vitamin A homeostasis. Polyhalogenated aromatic hydrocarbons are ubiquitous environmental pollutants and cause severe disturbances in vitamin A metabolism, manifested by an accelerated metabolism and breakdown of vitamin A and its metabolites and a depletion of vitamin A from the body; this sequence of events accounts for the vitamin A deficiency-like symptoms associated with PHAH intoxication. The mechanism(s) responsible for these events most likely includes altered activities of enzymes that are either directly or indirectly involved in critical vitamin A metabolic pathways. Human populations that continue to be exposed to environmental pollutants, may accumulate critical levels of polyhalogenated aromatic hydrocarbons and will be at risk for inadequate vitamin A function as well as for other health impairments that have been difficult to link to any specific causes. Therefore, it is important to seriously evaluate the similarities in physiological disturbances across species that have become apparent in studies with wildlife inhabiting polluted environments similar to ours; the relevance to human health is evident.197 references.

  19. Dysregulation of glutathione homeostasis in neurodegenerative diseases.

    Science.gov (United States)

    Johnson, William M; Wilson-Delfosse, Amy L; Mieyal, John J

    2012-10-09

    Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are increasingly implicated in the induction and progression of neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, and Friedreich's ataxia. In this review background is provided on the steady-state synthesis, regulation, and transport of glutathione, with primary focus on the brain. A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathione-dependent enzymes. Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation. In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status and/or in the activities of glutathione-dependent enzymes. Mechanisms of dysregulation of glutathione and/or glutathione-dependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease. Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions. The pros and cons of administration of N-acetylcysteine or glutathione as therapeutic agents for neurodegenerative diseases, as well as the potential utility of serum glutathione as a biomarker, are critically evaluated.

  20. DYSREGULATION OF ION HOMEOSTASIS BY ANTIFUNGAL AGENTS

    Directory of Open Access Journals (Sweden)

    Yongqiang eZhang

    2012-04-01

    Full Text Available Ion signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose dependent Ca2+ burst and long lasting pH changes in the model yeast S. cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides.

  1. Cellular Auxin Homeostasis:Gatekeeping Is Housekeeping

    Institute of Scientific and Technical Information of China (English)

    Michel Ruiz Rosquete; Elke Barbez; Jürgen Kleine-Vehn

    2012-01-01

    The phytohormone auxin is essential for plant development and contributes to nearly every aspect of the plant life cycle.The spatio-temporal distribution of auxin depends on a complex interplay between auxin metabolism and cell-to-cell auxin transport.Auxin metabolism and transport are both crucial for plant development;however,it largely remains to be seen how these processes are integrated to ensure defined cellular auxin levels or even gradients within tissues or organs.In this review,we provide a glance at very diverse topics of auxin biology,such as biosynthesis,conjugation,oxidation,and transport of auxin.This broad,but certainly superficial,overview highlights the mutual importance of auxin metabolism and transport.Moreover,it allows pinpointing how auxin metabolism and transport get integrated to jointly regulate cellular auxin homeostasis.Even though these processes have been so far only separately studied,we assume that the phytohormonal crosstalk integrates and coordinates auxin metabolism and transport.Besides the integrative power of the global hormone signaling,we additionally introduce the hypothetical concept considering auxin transport components as gatekeepers for auxin responses.

  2. Neural Control Mechanisms and Body Fluid Homeostasis

    Science.gov (United States)

    Johnson, Alan Kim

    1998-01-01

    The goal of the proposed research was to study the nature of afferent signals to the brain that reflect the status of body fluid balance and to investigate the central neural mechanisms that process this information for the activation of response systems which restore body fluid homeostasis. That is, in the face of loss of fluids from intracellular or extracellular fluid compartments, animals seek and ingest water and ionic solutions (particularly Na(+) solutions) to restore the intracellular and extracellular spaces. Over recent years, our laboratory has generated a substantial body of information indicating that: (1) a fall in systemic arterial pressure facilitates the ingestion of rehydrating solutions and (2) that the actions of brain amine systems (e.g., norepinephrine; serotonin) are critical for precise correction of fluid losses. Because both acute and chronic dehydration are associated with physiological stresses, such as exercise and sustained exposure to microgravity, the present research will aid in achieving a better understanding of how vital information is handled by the nervous system for maintenance of the body's fluid matrix which is critical for health and well-being.

  3. Regulation of energy homeostasis by GPR41

    Directory of Open Access Journals (Sweden)

    Daisuke eInoue

    2014-05-01

    Full Text Available Imbalances in energy regulation lead to metabolic disorders such as obesity and diabetes. Diet plays an essential role in the maintenance of body energy homeostasis by acting not only as energy source but also as a signaling modality. Excess energy increases energy expenditure, leading to a consumption of them. In addition to glucose, mammals utilize short-chain fatty acids (SCFAs, which are produced by colonic bacterial fermentation of dietary fiber, as a metabolic fuel. The roles of SCFAs in energy regulation have remained unclear, although the roles of glucose are well studied. Recently, a G protein-coupled receptor (GPCR deorphanizing strategy successfully identified GPR41 (also called free fatty acid receptor 3 or FFAR3 as a receptor for SCFAs. GPR41 is expressed in adipose tissue, gut, and the peripheral nervous system, and it is involved in SCFA-dependent energy regulation. In this mini-review, we focus on the role of GPR41 in host energy regulation.

  4. Manganese homeostasis in the nervous system.

    Science.gov (United States)

    Chen, Pan; Chakraborty, Sudipta; Mukhopadhyay, Somshuvra; Lee, Eunsook; Paoliello, Monica M B; Bowman, Aaron B; Aschner, Michael

    2015-08-01

    Manganese (Mn) is an essential heavy metal that is naturally found in the environment. Daily intake through dietary sources provides the necessary amount required for several key physiological processes, including antioxidant defense, energy metabolism, immune function and others. However, overexposure from environmental sources can result in a condition known as manganism that features symptomatology similar to Parkinson's disease (PD). This disorder presents with debilitating motor and cognitive deficits that arise from a neurodegenerative process. In order to maintain a balance between its essentiality and neurotoxicity, several mechanisms exist to properly buffer cellular Mn levels. These include transporters involved in Mn uptake, and newly discovered Mn efflux mechanisms. This review will focus on current studies related to mechanisms underlying Mn import and export, primarily the Mn transporters, and their function and roles in Mn-induced neurotoxicity. Though and essential metal, overexposure to manganese may result in neurodegenerative disease analogous to Parkinson's disease. Manganese homeostasis is tightly regulated by transporters, including transmembrane importers (divalent metal transporter 1, transferrin and its receptor, zinc transporters ZIP8 and Zip14, dopamine transporter, calcium channels, choline transporters and citrate transporters) and exporters (ferroportin and SLC30A10), as well as the intracellular trafficking proteins (SPCA1 and ATP12A2). A manganese-specific sensor, GPP130, has been identified, which affords means for monitoring intracellular levels of this metal.

  5. Proposal for the assessment of quantitative dermal exposure limits in occupational environments: Part 2. Feasibility study for application in an exposure scenario for MDA by two different dermal exposure sampling methods

    NARCIS (Netherlands)

    Bos, P.M.J.; Brouwer, D.H.; Stevenson, H.; Hoogendoorn, L.; Boogaard, P.J.; Kort, W.L.A.M. de; Hemmen, J.J. van

    1998-01-01

    Objective. To evaluate two different techniques for assessing dermal exposure to 4,4'-methylene dianiline (MDA) in a field study. The results were used to test the applicability of a recently proposed quantitative dermal occupational exposure limit (DOEL) for MDA in a workplace scenario. Methods. Fo

  6. Ecological Stoichiometry beyond Redfield: An Ionomic Perspective on Elemental Homeostasis

    Science.gov (United States)

    Jeyasingh, Punidan D.; Goos, Jared M.; Thompson, Seth K.; Godwin, Casey M.; Cotner, James B.

    2017-01-01

    Elemental homeostasis has been largely characterized using three important elements that were part of the Redfield ratio (i.e., carbon: nitrogen: phosphorus). These efforts have revealed substantial diversity in homeostasis among taxonomic groups and even within populations. Understanding the evolutionary basis, and ecological consequences of such diversity is a central challenge. Here, we propose that a more complete understanding of homeostasis necessitates the consideration of other elements beyond C, N, and P. Specifically, we posit that physiological complexity underlying maintenance of elemental homeostasis along a single elemental axis impacts processing of other elements, thus altering elemental homeostasis along other axes. Indeed, transcriptomic studies in a wide variety of organisms have found that individuals differentially express significant proportions of the genome in response to variability in supply stoichiometry in order to maintain varying levels of homeostasis. We review the literature from the emergent field of ionomics that has established the consequences of such physiological trade-offs on the content of the entire suite of elements in an individual. Further, we present experimental data on bacteria exhibiting divergent phosphorus homeostasis phenotypes demonstrating the fundamental interconnectedness among elemental quotas. These observations suggest that physiological adjustments can lead to unexpected patterns in biomass stoichiometry, such as correlated changes among suites of non-limiting microelements in response to limitation by macroelements. Including the entire suite of elements that comprise biomass will foster improved quantitative understanding of the links between chemical cycles and the physiology of organisms. PMID:28487686

  7. Ecological Stoichiometry beyond Redfield: An Ionomic Perspective on Elemental Homeostasis

    Directory of Open Access Journals (Sweden)

    Punidan D. Jeyasingh

    2017-04-01

    Full Text Available Elemental homeostasis has been largely characterized using three important elements that were part of the Redfield ratio (i.e., carbon: nitrogen: phosphorus. These efforts have revealed substantial diversity in homeostasis among taxonomic groups and even within populations. Understanding the evolutionary basis, and ecological consequences of such diversity is a central challenge. Here, we propose that a more complete understanding of homeostasis necessitates the consideration of other elements beyond C, N, and P. Specifically, we posit that physiological complexity underlying maintenance of elemental homeostasis along a single elemental axis impacts processing of other elements, thus altering elemental homeostasis along other axes. Indeed, transcriptomic studies in a wide variety of organisms have found that individuals differentially express significant proportions of the genome in response to variability in supply stoichiometry in order to maintain varying levels of homeostasis. We review the literature from the emergent field of ionomics that has established the consequences of such physiological trade-offs on the content of the entire suite of elements in an individual. Further, we present experimental data on bacteria exhibiting divergent phosphorus homeostasis phenotypes demonstrating the fundamental interconnectedness among elemental quotas. These observations suggest that physiological adjustments can lead to unexpected patterns in biomass stoichiometry, such as correlated changes among suites of non-limiting microelements in response to limitation by macroelements. Including the entire suite of elements that comprise biomass will foster improved quantitative understanding of the links between chemical cycles and the physiology of organisms.

  8. Converse Barrier Certificate Theorem

    DEFF Research Database (Denmark)

    Wisniewski, Rafael; Sloth, Christoffer

    2013-01-01

    This paper presents a converse barrier certificate theorem for a generic dynamical system.We show that a barrier certificate exists for any safe dynamical system defined on a compact manifold. Other authors have developed a related result, by assuming that the dynamical system has no singular...... points in the considered subset of the state space. In this paper, we redefine the standard notion of safety to comply with generic dynamical systems with multiple singularities. Afterwards, we prove the converse barrier certificate theorem and illustrate the differences between ours and previous work...

  9. Recycler barrier RF buckets

    Energy Technology Data Exchange (ETDEWEB)

    Bhat, C.M.; /Fermilab

    2011-03-01

    The Recycler Ring at Fermilab uses a barrier rf systems for all of its rf manipulations. In this paper, I will give an overview of historical perspective on barrier rf system, the longitudinal beam dynamics issues, aspects of rf linearization to produce long flat bunches and methods used for emittance measurements of the beam in the RR barrier rf buckets. Current rf manipulation schemes used for antiproton beam stacking and longitudinal momentum mining of the RR beam for the Tevatron collider operation are explained along with their importance in spectacular success of the Tevatron luminosity performance.

  10. Measuring the strength of dermal fibroblast attachment to functionalized titanium alloys in vitro.

    Science.gov (United States)

    Pendegrass, Catherine J; Middleton, Claire A; Gordon, David; Jacob, Josh; Blunn, Gordon W

    2010-03-01

    The success of intraosseous transcutaneous amputation prostheses (ITAP) relies on soft tissue attachment to prevent infection which leads to implant failure. Fibronectin (Fn) has been shown to enhance dermal fibroblast attachment in vitro, however measurement of cell attachment strength has been indirect; using cell area and immunolocalization of focal adhesion components. In this study, we have developed a flow apparatus to assess the biophysical strength of cell attachment to biomaterials used in ITAP. We have demonstrated that dermal fibroblast attachment strength increases significantly up to 96 h and that data from direct and indirect methods of assessing cell attachment strength have a significant positive correlation. Additionally, we have used direct and indirect assessment methods to demonstrate that dermal fibroblast attachment strength is significantly greater on fibronectin-coated titanium alloy compared with uncoated controls at 1, 4, and 24 hours.

  11. Changes in dermal matrix in the absence of Rac1 in keratinocytes

    DEFF Research Database (Denmark)

    Stanley, Alanna; Pedersen, Esben; Brakebusch, Cord

    2016-01-01

    Keratinocytes, in response to irritants, secrete pro-inflammatory mediators which recruit and activate immune and mesenchymal cells, including fibroblasts, to repair the skin. Fibroblasts respond by synthesising collagen and promoting the crosslinking extracellular matrix (ECM). We recently showed...... of ICD on the tissue localisation and arrangements of dermal collagen. Qualitative analysis did not reveal evidence for the formation of pathologies in the dermis. However, quantitative analysis did reveal some perturbations in the dermal matrix, namely that only the combination of the lack of Rac1...... and ICD affects the architectural organisation of the dermal collagen, and that a higher inflammatory state in the tissue (i.e. when Rac1 is deleted in the keratinocytes or ICD is induced in the skin, or a combination of both) influences the diameter of the collagen fibrils. It is proposed...

  12. Clinical evaluation of an acellular dermal allograft for increasing the zone of attached gingiva.

    Science.gov (United States)

    Shulman, J

    1996-03-01

    Grafting with autogenous tissue or freeze-dried skin is the generally accepted method for increasing and/or restoring the width of attached gingiva. This article describes the periodontal use of an acellular dermal allograft previously available for treating burn patients. When used as a gingival graft, this new dermal allograft has major potential advantages over the previously available periodontal graft materials, including improved color and contour match, elimination of multiple surgeries, and unlimited availability. The technique and results of acellular dermal grafting are presented and discussed. The learning objective of this article is to describe the principles and the clinical procedure of this technique. Several cases are used to illustrate this technique.

  13. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    Science.gov (United States)

    Quan, Taihao; Fisher, Gary J

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment (AADM), which contributes to decline of human skin function. PMID:25660807

  14. Attachment of IgG to dermal extracellular matrix in patients with fibromyalgia.

    Science.gov (United States)

    Eneström, S; Bengtson, A; Lindström, F; Johan, K

    1990-01-01

    Deposits of IgG localized to collagen bundles/extracellular matrix components occurred in skin biopsies from patients with primary fibromyalgia (PF). None of these patients demonstrated a positive lupus band test. Control skin biopsies from healthy controls were negative but showed intense reactivity for IgG after collagenase treatment. PF-skin attached both homologous and heterologous serum IgG in indirect immunofluorescence, which may point to a qualitative alteration of dermal matrix components in PF. Skin from patients with systemic lupus erythematosus and rheumatoid arthritis showed a lower dermal fluorescence intensity than in PF patients. The cause of the presence of IgG in dermal tissue from PF patients is unclear. It may be caused by a non-specific attachment of IgG to the extracellular matrix related, for example, to tissue hypoxia and/or increased capillary leakage due to an increased number of mast cells in the PF-skin.

  15. A TRILAYER DERMAL EQUIVALENT CONTAINING SILVER NANOPARTICLES WITH ENHANCED ANTIBACTERIAL PROPERTY

    Institute of Scientific and Technical Information of China (English)

    Ai-bin Huang; Shao-jun Xu; Guo-yang Wei; Lie Ma; Chang-you Gao

    2009-01-01

    A dermal equivalent having a trilayered structure was designed by combining a silver nanoparticles incorporated chitosan film with a bilayer collagen-chitosan/silicon membrane dermal equivalent (BDE). The silver nanoparticles prepared at different conditions were characterized by UV-Vis and transmission electron microscopy (TEM). The macroscopic sharp and the microstructure of the trilayer dermal equivalent (TDE) were also studied. Then, the in vitro antibacterial property of TDE was evaluated by the antibacterial zone test. The effect of the incorporated silver nanoparticles on the resistance of wound infection was further studied by the in vivo animal test. The results prove that the silver nanoparticles incorporated TDE has a better antibacterial property, thus may be potentially applied to a broader field in skin repair such as full thickness defect and burn.

  16. Characterization and evolution of dermal filaments from patients with Morgellons disease.

    Science.gov (United States)

    Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

    2013-01-01

    Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process.

  17. Correction of tear trough deformity with novel porcine collagen dermal filler (Dermicol-P35).

    Science.gov (United States)

    Goldberg, David J

    2009-01-01

    Deformity of the tear trough region, which can occur during the aging process, can result in dark shadows under the eyes and a fatigued appearance. Augmentation of the tear trough is challenging because of the thin skin and lack of fat in the region. Adding volume to the tear trough region with a dermal filler is a nonsurgical procedure with minimal discomfort to the patient. Dermicol-P35 (Evolence; Ortho Dermatologics, Skillman, NJ) is a new, ribose crosslinked, highly purified, porcine-based collagen filler that does not require prior skin testing and has shown improved persistence compared with bovine collagen-based dermal fillers. In this article, we present the clinical outcomes of patients who have received treatment with a novel ribose crosslinked porcine collagen dermal filler for the correction of tear trough deformity.

  18. Immunohistochemical analysis of radiation-induced non-healing dermal wounds of the head and neck.

    Science.gov (United States)

    Riedel, Frank; Philipp, Katrin; Sadick, Haneen; Goessler, Ullrich; Hörmann, Karl; Verse, Thomas

    2005-01-01

    Persistent, poorly healing wounds are a significant clinical problem in patients who have had previous irradiation. The pathology of chronic dermal ulcers is characterised by excessive proteolytic activity which degrades the extracellular matrix (required for cell migration) and growth factors and their receptors. Interestingly, the molecular basis of radiation-induced dermal wounds is poorly understood. The aim of this study was to investigate, by immunohistochemistry, the expression of the endothelial marker vWF, of angiogenic bFGF, VEGF and IL-8, of collagenases MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2, in tissue samples from radiation-induced chronic dermal wounds and healthy control skin. Performing immunohistochemical detection of microvessels, an equivalent density of microvessels was observed within tissue samples from normal healthy skin and from radiation-induced non-healing cutaneous wounds. Investigation of angiogenic bFGF and VEGF demonstrated a decreased expression of both factors in the radiation-induced dermal wounds. The expression of angiogenic IL-8 was weak in both the healthy skin samples and the radiation-induced wounds. In addition, an increased expression of collagenases MMP-2 and MMP-9 protein within the radiation-induced wounds was demonstrated. While the expression of TIMP-1 showed no difference of expression between normal control skin and tissue samples from radiation-induced wounds, TIMP-2 expression was slightly increased compared to healthy controls. Our data suggest that radiation-induced dermal injuries often fail to heal because of decreased angiogenesis and persistently high concentrations of MMPs with an imbalance of their tissue inhibitors. The basic mechanisms of wound healing in radiation-induced dermal wounds at the molecular level need to be understood further for the development of innovative treatment strategies.

  19. Review of data on the dermal penetration of mineral oils and waxes used in cosmetic applications.

    Science.gov (United States)

    Petry, T; Bury, D; Fautz, R; Hauser, M; Huber, B; Markowetz, A; Mishra, S; Rettinger, K; Schuh, W; Teichert, T

    2017-10-05

    Mineral oils and waxes used in cosmetic products, also referred to as "personal care products" outside the European Union, are mixtures of predominantly saturated hydrocarbons consisting of straight-chain, branched and ring structures with carbon chain lengths greater than C16. They are used in skin and lip care cosmetic products due to their excellent skin tolerance as well as their high protecting and cleansing performance and broad viscosity options. Recently, concerns have been raised regarding potential adverse health effects of mineral oils and waxes from dermal application of cosmetics. In order to be able to assess the risk for the consumer the dermal penetration potential of these ingredients has to be evaluated. The scope and objective of this review are to identify and summarize publicly available literature on the dermal penetration of mineral oils and waxes as used in cosmetic products. For this purpose, a comprehensive literature search was conducted. A total of 13 in vivo (human, animal) and in vitro studies investigating the dermal penetration of mineral oils and waxes has been identified and analysed. The majority of the substances were dermally adsorbed to the stratum corneum and only a minor fraction reached deeper skin layers. Overall, there is no evidence from the various studies that mineral oils and waxes are percutaneously absorbed and become systemically available. Thus, given the absence of dermal uptake, mineral oils and waxes as used in cosmetic products do not present a risk to the health of the consumer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Histology of the heterostracan dermal skeleton: Insight into the origin of the vertebrate mineralised skeleton.

    Science.gov (United States)

    Keating, Joseph N; Marquart, Chloe L; Donoghue, Philip C J

    2015-06-01

    Living vertebrates are divided into those that possess a fully formed and fully mineralised skeleton (gnathostomes) versus those that possess only unmineralised cartilaginous rudiments (cyclostomes). As such, extinct phylogenetic intermediates of these living lineages afford unique insights into the evolutionary assembly of the vertebrate mineralised skeleton and its canonical tissue types. Extinct jawless and jawed fishes assigned to the gnathostome stem evidence the piecemeal assembly of skeletal systems, revealing that the dermal skeleton is the earliest manifestation of a homologous mineralised skeleton. Yet the nature of the primitive dermal skeleton, itself, is poorly understood. This is principally because previous histological studies of early vertebrates lacked a phylogenetic framework required to derive evolutionary hypotheses. Nowhere is this more apparent than within Heterostraci, a diverse clade of primitive jawless vertebrates. To this end, we surveyed the dermal skeletal histology of heterostracans, inferred the plesiomorphic heterostracan skeleton and, through histological comparison to other skeletonising vertebrate clades, deduced the ancestral nature of the vertebrate dermal skeleton. Heterostracans primitively possess a four-layered skeleton, comprising a superficial layer of odontodes composed of dentine and enameloid; a compact layer of acellular parallel-fibred bone containing a network of vascular canals that supply the pulp canals (L1); a trabecular layer consisting of intersecting radial walls composed of acellular parallel-fibred bone, showing osteon-like development (L2); and a basal layer of isopedin (L3). A three layered skeleton, equivalent to the superficial layer L2 and L3 and composed of enameloid, dentine and acellular bone, is possessed by the ancestor of heterostracans + jawed vertebrates. We conclude that an osteogenic component is plesiomorphic with respect to the vertebrate dermal skeleton. Consequently, we interpret the

  1. Protective effect of oat bran extracts on human dermal fibroblast injury induced by hydrogen peroxide

    Institute of Scientific and Technical Information of China (English)

    Bing FENG; Lai-ji MA; Jin-jing YAO; Yun FANG; Yan-ai MEI; Shao-min WEI

    2013-01-01

    Oat contains different components that possess antioxidant properties;no study to date has addressed the antioxidant effect of the extract of oat bran on the cellular level.Therefore,the present study focuses on the investigation of the protective effect of oat bran extract by enzymatic hydrolysates on human dermal fibroblast injury induced by hydrogen peroxide(H2O2).Kjeldahl determination,phenol-sulfuric acid method,and high-performance liquid chromatography(HPLC)analysis indicated that the enzymatic products of oat bran contain a protein amount of 71.93%,of which 97.43% are peptides with a molecular range from 438.56 to 1301.01 Da.Assays for 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging activity indicate that oat peptide-rich extract has a direct and concentration-dependent antioxidant activity.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)colorimetric assay and the TdT-mediated digoxigenin-dUTP nick-end labeling(TUNEL)assay for apoptosis showed that administration of H2O2 in human dermal fibroblasts caused cell damage and apoptosis.Pre-incubation of human dermal fibroblasts with the Oatp for 24 h markedly inhibited human dermal fibroblast injury induced by H2O2,but application oat peptides with H2O2 at same time did not.Pre-treatment of human dermal fibroblasts with Oatp significantly reversed the H2O2-induced decrease of superoxide dismutase(SOD)and the inhibition of malondialdehyde(MDA).The results demonstrate that oat peptides possess antioxidant activity and are effective against H2O2-induced human dermal fibroblast injury by the enhanced activity of SOD and decrease in MDA level.Our results suggest that oat bran will have the potential to be further explored as an antioxidant functional food in the prevention of aging-related skin injury.

  2. REDUCED WOUND CONTRACTION AND SCAR FORMATION IN PUNCH BIOPSY WOUNDS - NATIVE COLLAGEN DERMAL SUBSTITUTES - A CLINICAL-STUDY

    NARCIS (Netherlands)

    DEVRIES, HJC; ZEEGELAAR, JE; MIDDELKOOP, E; GIJSBERS, G; VANMARLE, J; WILDEVUUR, CHR; WESTERHOF, W

    In full-thickness skin wounds dermal regeneration usually fails, resulting in scar formation and wound contraction. We studied dermal regeneration by implantation of collagenous matrices in a human punch biopsy wound model. Matrices were made of native bovine collagen I fibres, and either hyaluronic

  3. Dermatokinetics of didecyldimethylammonium chloride and the influence of some commercial biocidal formulations on its dermal absorption in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Heer, C. de; Burgsteden, J.A. van; Sandt, J.J.M. van de

    2007-01-01

    The in vitro dermal absorption kinetics of didecyldimethylammonium chloride (DDAC) was studied after single and multiple exposure. In addition, the influence of biocidal formulations on the absorption of DDAC was investigated. Following dermal exposure to DDAC in aqueous solution, less than 0.5% of

  4. The evolving role of the NAD+/nicotinamide metabolome in skin homeostasis, cellular bioenergetics, and aging.

    Science.gov (United States)

    Oblong, John E

    2014-11-01

    Human skin is exposed to daily environmental insults, particularly solar radiation, that triggers a range of molecular responses. These perturbations to the normal homeostatic state can lead to cellular dysfunction and, ultimately, impacts tissue integrity and accelerates skin aging (photoaging). One of the responses is increased oxidative stress which has been shown to disrupt cellular bioenergetics. This can be detected by depletion of the nucleotide energy metabolites NAD+ and ATP as both an acute transient decrease and, over time, a more permanent chronic reduction due in part to cumulative damage of mitochondria. NAD+ and its primary precursor nicotinamide have been known for some time to impact skin homeostasis based on linkages to dietary requirements, treatment of various inflammatory conditions, photoaging, and prevention of cancer. Cellular NAD+ pools are known to be lower in aged skin and treatment with nicotinamide is hypothesized to restore these levels, thereby mitigating cellular bioenergetics dysfunction. In dermal fibroblasts, nicotinamide is able to protect against oxidative stress to glycolysis, oxidative phosphorylation as well as increase mitochondrial efficiency via sirtuin-dependent selective mitophagy. Recent research has found that NAD+ cellular pools are more dynamic than previously thought, oscillating in tandem with free nicotinamide, and serves as a regulatory point and feedback loop in cellular metabolism regulation, maintenance of mitochondrial efficiency, and circadian rhythmicity. Since UV-induced oxidative stress in skin can disrupt these processes, continued molecular understanding of the role of NAD+ and nicotinamide in skin biology is important to identify interventions that would help maintain its normal homeostatic functions and efficient cellular bioenergetics.

  5. [Vascular endothelial Barrier Function].

    Science.gov (United States)

    Ivanov, A N; Puchinyan, D M; Norkin, I A

    2015-01-01

    Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

  6. Barriers to Effective Listening.

    Science.gov (United States)

    Hulbert, Jack E.

    1989-01-01

    Discusses the following barriers which interfere with listening efficiency: content, speaker, medium, distractions, mindset, language, listening speed, and feedback. Suggests ways to combat these obstacles to accurate comprehension. (MM)

  7. Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections.

    Science.gov (United States)

    Draughn, G Logan; Allen, C Leigh; Routh, Patricia A; Stone, Maria R; Kirker, Kelly R; Boegli, Laura; Schuchman, Ryan M; Linder, Keith E; Baynes, Ronald E; James, Garth; Melander, Christian; Pollard, Angela; Cavanagh, John

    2017-01-01

    2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

  8. Autologous smashed dermal graft with epidermal re-closure: Modified technique for acne scars

    Directory of Open Access Journals (Sweden)

    Umashankar Nagaraju

    2016-01-01

    Full Text Available Conventional technique of dermal grafting for acne scars where the source of filler material used is the patient′s own dermis requires longer surgical time, recovery period and can result in unsightly scars at the donor area. Hence, it is not suitable for treating a larger number of scars. Furthermore, these dermal grafts are firm and cannot be contoured to fit all types of acne scars. Occurrence of epidermal cyst and secondary infection is another complication if epidermis is not completely removed. Enzymatic techniques need trypsinisation which is expensive and requires laboratory facilities.

  9. Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans

    DEFF Research Database (Denmark)

    Grimbaldeston, Michele A; Skov, Lone; Finlay-Jones, John J

    2002-01-01

    Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic factor associated with the development of basal cell carcinoma (BCC). The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise...... by sun exposure. Two sections (4 microm) per biopsy were immunohistochemically stained for detection of histamine-containing dermal mast cells. Computer-generated image analysis evaluated dermal mast cell prevalence in both sections by quantifying the total number of mast cells according to the total...

  10. Rat hair follicle dermal papillae have an extracellular matrix containing basement membrane components

    DEFF Research Database (Denmark)

    Couchman, J R

    1986-01-01

    Dermal papillae are small mesenchymally derived zones at the bases of hair follicles which have an important role in hair morphogenesis in the embryo and control of the hair growth cycle in postnatal mammals. The cells of the papilla are enmeshed in a dense extracellular matrix which undergoes...... extensive changes in concert with the hair cycle. Here it is shown that this matrix in anagen pelage follicles of postnatal rats contains an abundance of basement membrane components rather than dermal components such as interstitial collagens. In particular, type IV collagen, laminin, and basement membrane...

  11. Coverage of Megaprosthesis with Human Acellular Dermal Matrix after Ewing's Sarcoma Resection: A Case Report

    Directory of Open Access Journals (Sweden)

    Robert M. Whitfield

    2011-01-01

    Full Text Available A 23-year-old female with Ewing's Sarcoma underwent tibial resection and skeletal reconstruction using proximal tibial allograft prosthetic reconstruction with distal femur endoprosthetic reconstruction and rotating hinge. Human acellular dermal matrix, (Alloderm, LifeCell, Branchburg, NJ, USA, was used to wrap the skeletal reconstruction. Soft tissue reconstruction was completed with a rotational gastrocnemius muscle flap and skin graft. Despite prolonged immobilization, the patient quickly regained full range of motion of her skeletal reconstruction. Synthetic mesh, tapes and tubes are used to perform capsule reconstruction of megaprosthesis. This paper describes the role of human acellular dermal matrix in capsule reconstruction around a megaprosthesis.

  12. Coverage of Megaprosthesis with Human Acellular Dermal Matrix after Ewing's Sarcoma Resection: A Case Report.

    Science.gov (United States)

    Whitfield, Robert M; Rinard, Jeremy; King, David

    2011-01-01

    A 23-year-old female with Ewing's Sarcoma underwent tibial resection and skeletal reconstruction using proximal tibial allograft prosthetic reconstruction with distal femur endoprosthetic reconstruction and rotating hinge. Human acellular dermal matrix, (Alloderm, LifeCell, Branchburg, NJ, USA), was used to wrap the skeletal reconstruction. Soft tissue reconstruction was completed with a rotational gastrocnemius muscle flap and skin graft. Despite prolonged immobilization, the patient quickly regained full range of motion of her skeletal reconstruction. Synthetic mesh, tapes and tubes are used to perform capsule reconstruction of megaprosthesis. This paper describes the role of human acellular dermal matrix in capsule reconstruction around a megaprosthesis.

  13. Role of presenilins in neuronal calcium homeostasis.

    Science.gov (United States)

    Zhang, Hua; Sun, Suya; Herreman, An; De Strooper, Bart; Bezprozvanny, Ilya

    2010-06-23

    Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Familial AD (FAD) mutations in presenilins have been linked to calcium (Ca(2+)) signaling abnormalities. To explain these results, we previously proposed that presenilins function as endoplasmic reticulum (ER) passive Ca(2+) leak channels. To directly investigate the role of presenilins in neuronal ER Ca(2+) homeostasis, we here performed a series of Ca(2+) imaging experiments with primary neuronal cultures from conditional presenilin double-knock-out mice (PS1(dTAG/dTAG), PS2(-/-)) and from triple-transgenic AD mice (KI-PS1(M146V), Thy1-APP(KM670/671NL), Thy1-tau(P301L)). Obtained results provided additional support to the hypothesis that presenilins function as ER Ca(2+) leak channels in neurons. Interestingly, we discovered that presenilins play a major role in ER Ca(2+) leak function in hippocampal but not in striatal neurons. We further discovered that, in hippocampal neurons, loss of presenilin-mediated ER Ca(2+) leak function was compensated by an increase in expression and function of ryanodine receptors (RyanRs). Long-term feeding of the RyanR inhibitor dantrolene to amyloid precursor protein-presenilin-1 mice (Thy1-APP(KM670/671NL), Thy1-PS1(L166P)) resulted in an increased amyloid load, loss of synaptic markers, and neuronal atrophy in hippocampal and cortical regions. These results indicate that disruption of ER Ca(2+) leak function of presenilins may play an important role in AD pathogenesis.

  14. Effect of lysosomotropic molecules on cellular homeostasis.

    Science.gov (United States)

    Kuzu, Omer F; Toprak, Mesut; Noory, M Anwar; Robertson, Gavin P

    2017-03-01

    Weak bases that readily penetrate through the lipid bilayer and accumulate inside the acidic organelles are known as lysosomotropic molecules. Many lysosomotropic compounds exhibit therapeutic activity and are commonly used as antidepressant, antipsychotic, antihistamine, or antimalarial agents. Interestingly, studies also have shown increased sensitivity of cancer cells to certain lysosomotropic agents and suggested their mechanism of action as a promising approach for selective destruction of cancer cells. However, their chemotherapeutic utility may be limited due to various side effects. Hence, understanding the homeostatic alterations mediated by lysosomotropic compounds has significant importance for revealing their true therapeutic potential as well as toxicity. In this review, after briefly introducing the concept of lysosomotropism and classifying the lysosomotropic compounds into two major groups according to their cytotoxicity on cancer cells, we focused on the subcellular alterations mediated by class-II lysosomotropic compounds. Briefly, their effect on intracellular cholesterol homeostasis, autophagy and lysosomal sphingolipid metabolism was discussed. Accordingly, class-II lysosomotropic molecules inhibit intracellular cholesterol transport, leading to the accumulation of cholesterol inside the late endosomal-lysosomal cell compartments. However, the accumulated lysosomal cholesterol is invisible to the cellular homeostatic circuits, hence class-II lysosomotropic molecules also upregulate cholesterol synthesis pathway as a downstream event. Considering the fact that Niemann-Pick disease, a lysosomal cholesterol storage disorder, also triggers similar pathologic abnormalities, this review combines the knowledge obtained from the Niemann-Pick studies and lysosomotropic compounds. Taken together, this review is aimed at allowing readers a better understanding of subcellular alterations mediated by lysosomotropic drugs, as well as their potential

  15. Barriers to SCM implementing

    OpenAIRE

    M.E. Rosli; B. Md Dero; A. R. Ismail; M. N. Ab Rahman

    2008-01-01

    Purpose: This paper explores the barriers faced by Malaysian manufacturing companies in successfullyimplementing the Supply Chain Management (SCM). The study has highlighted some pertinent factorsperforming the barriers that are most frequently reported by the studied companies. Sixteen companies, fromservice and manufacturing companies were studied over a period of two years to assess their SCM practicesthrough survey and interview processes.Design/methodology/approach: This part discusses t...

  16. Intestinal barrier and gut microbiota: Shaping our immune responses throughout life.

    Science.gov (United States)

    Takiishi, Tatiana; Fenero, Camila Ideli Morales; Câmara, Niels Olsen Saraiva

    2017-09-06

    The gastrointestinal (GI) tract is considered the largest immunological organ in the body having a central role in regulating immune homeostasis. Contrary to earlier belief, the intestinal epithelial barrier is not a static physical barrier but rather strongly interacts with the gut microbiome and cells of the immune system. This intense communication between epithelial cells, immune cells and microbiome will shape specific immune responses to antigens, balancing tolerance and effector immune functions. Recent studies indicate that composition of the gut microbiome affects immune system development and modulates immune mediators, which in turn affect the intestinal barrier. Moreover, dysbiosis may favor intestinal barrier disruption and could be related to increased susceptibility to certain diseases. This review will be focused on the development of the intestinal barrier and its function in host immune defense and how gut microbiome composition throughout life can affect this role.

  17. Magnetic Nanoparticles Cross the Blood-Brain Barrier: When Physics Rises to a Challenge

    Directory of Open Access Journals (Sweden)

    Maria Antònia Busquets

    2015-12-01

    Full Text Available The blood-brain barrier is a physical and physiological barrier that protects the brain from toxic substances within the bloodstream and helps maintain brain homeostasis. It also represents the main obstacle in the treatment of many diseases of the central nervous system. Among the different approaches employed to overcome this barrier, the use of nanoparticles as a tool to enhance delivery of therapeutic molecules to the brain is particularly promising. There is special interest in the use of magnetic nanoparticles, as their physical characteristics endow them with additional potentially useful properties. Following systemic administration, a magnetic field applied externally can mediate the capacity of magnetic nanoparticles to permeate the blood-brain barrier. Meanwhile, thermal energy released by magnetic nanoparticles under the influence of radiofrequency radiation can modulate blood-brain barrier integrity, increasing its permeability. In this review, we present the strategies that use magnetic nanoparticles, specifically iron oxide nanoparticles, to enhance drug delivery to the brain.

  18. Eicosanoid receptors: Targets for the treatment of disrupted intestinal epithelial homeostasis.

    Science.gov (United States)

    Moreno, Juan J

    2017-02-05

    The importance of cyclooxygenase and lipoxygenase pathways and the consequent eicosanoid synthesis in the physiology and pathophysiology of the intestinal epithelium is currently being established. Each eicosanoid (prostanoid, leukotriene, hydroxyeicosatetraenoic acid) preferentially recognizes one or more receptors coupled to one or more signal-transduction processes. This overview focuses on the role of eicosanoid receptors in the maintenance of intestinal epithelium physiology through the control of proliferation/differentiation/apoptosis processes. Furthermore, it is reported that the role of these receptors on the regulation of the barrier function of the intestinal epithelium have arisen through the regulation of absorption/secretion processes, tight-junction state and the control of the intestinal immune response. Also, this review considers the implication of AA cascade in the disruption of epithelial homeostasis during inflammatory bowel diseases and colorectal cancer as well as the therapeutic values and potential of the eicosanoid receptors as novel targets for the treatments of the pathologies above mentioned.

  19. A key role for E-cadherin in intestinal homeostasis and Paneth cell maturation.

    Science.gov (United States)

    Schneider, Marlon R; Dahlhoff, Maik; Horst, David; Hirschi, Benjamin; Trülzsch, Konrad; Müller-Höcker, Josef; Vogelmann, Roger; Allgäuer, Michael; Gerhard, Markus; Steininger, Sylvia; Wolf, Eckhard; Kolligs, Frank T

    2010-12-14

    E-cadherin is a major component of adherens junctions. Impaired expression of E-cadherin in the small intestine and colon has been linked to a disturbed intestinal homeostasis and barrier function. Down-regulation of E-cadherin is associated with the pathogenesis of infections with enteropathogenic bacteria and Crohn's disease. To genetically clarify the function of E-cadherin in intestinal homeostasis and maintenance of the epithelial defense line, the Cdh1 gene was conditionally inactivated in the mouse intestinal epithelium. Inactivation of the Cdh1 gene in the small intestine and colon resulted in bloody diarrhea associated with enhanced apoptosis and cell shedding, causing life-threatening disease within 6 days. Loss of E-cadherin led cells migrate faster along the crypt-villus axis and perturbed cellular differentiation. Maturation and positioning of goblet cells and Paneth cells, the main cell lineage of the intestinal innate immune system, was severely disturbed. The expression of anti-bacterial cryptidins was reduced and mice showed a deficiency in clearing enteropathogenic bacteria from the intestinal lumen. These results highlight the central function of E-cadherin in the maintenance of two components of the intestinal epithelial defense: E-cadherin is required for the proper function of the intestinal epithelial lining by providing mechanical integrity and is a prerequisite for the proper maturation of Paneth and goblet cells.

  20. A key role for E-cadherin in intestinal homeostasis and Paneth cell maturation.

    Directory of Open Access Journals (Sweden)

    Marlon R Schneider

    Full Text Available BACKGROUND: E-cadherin is a major component of adherens junctions. Impaired expression of E-cadherin in the small intestine and colon has been linked to a disturbed intestinal homeostasis and barrier function. Down-regulation of E-cadherin is associated with the pathogenesis of infections with enteropathogenic bacteria and Crohn's disease. METHODS AND FINDINGS: To genetically clarify the function of E-cadherin in intestinal homeostasis and maintenance of the epithelial defense line, the Cdh1 gene was conditionally inactivated in the mouse intestinal epithelium. Inactivation of the Cdh1 gene in the small intestine and colon resulted in bloody diarrhea associated with enhanced apoptosis and cell shedding, causing life-threatening disease within 6 days. Loss of E-cadherin led cells migrate faster along the crypt-villus axis and perturbed cellular differentiation. Maturation and positioning of goblet cells and Paneth cells, the main cell lineage of the intestinal innate immune system, was severely disturbed. The expression of anti-bacterial cryptidins was reduced and mice showed a deficiency in clearing enteropathogenic bacteria from the intestinal lumen. CONCLUSION: These results highlight the central function of E-cadherin in the maintenance of two components of the intestinal epithelial defense: E-cadherin is required for the proper function of the intestinal epithelial lining by providing mechanical integrity and is a prerequisite for the proper maturation of Paneth and goblet cells.

  1. ERR gamma Regulates Cardiac, Gastric, and Renal Potassium Homeostasis

    NARCIS (Netherlands)

    Alaynick, William A.; Way, James M.; Wilson, Stephanie A.; Benson, William G.; Pei, Liming; Downes, Michael; Yu, Ruth; Jonker, Johan W.; Holt, Jason A.; Rajpal, Deepak K.; Li, Hao; Stuart, Joan; McPherson, Ruth; Remlinger, Katja S.; Chang, Ching-Yi; McDonnell, Donald P.; Evans, Ronald M.; Billin, Andrew N.

    2010-01-01

    Energy production by oxidative metabolism in kidney, stomach, and heart, is primarily expended in establishing ion gradients to drive renal electrolyte homeostasis, gastric acid secretion, and cardiac muscle contraction, respectively. In addition to orchestrating transcriptional control of oxidative

  2. Matriptase zymogen supports epithelial development, homeostasis and regeneration

    DEFF Research Database (Denmark)

    Friis, Stine; Tadeo, Daniel; Le-Gall, Sylvain M.

    2017-01-01

    Background Matriptase is a membrane serine protease essential for epithelial development, homeostasis, and regeneration, as well as a central orchestrator of pathogenic pericellular signaling in the context of inflammatory and proliferative diseases. Matriptase is an unusual protease in that its...

  3. Disruption of iron homeostasis in mesothelial cells following talc pleurodesis

    Science.gov (United States)

    The mechanism for biological effect following particle exposure is incompletely understood. One postulate proposed to explain biological effect after particles is an altered iron homeostasis in the host. The fibro-inflammatory properties of particles are exploited therapeutically...

  4. Induction and detection of disturbed homeostasis in cardiopulmonary bypass

    NARCIS (Netherlands)

    de Vroege, R; Meerman, FT; Eijsman, L; Wildevuur, WR; Wildevuur, CRH; van Oeveren, W

    2004-01-01

    During cardiopulmonary bypass (CPB) haemodynamic alterations, haemostasis and the inflammatory response are the main causes of homeostatic disruption. Even with CPB procedures of short duration, the homeostasis of a patient is disrupted and, in many cases, requires intensive postoperative treatment

  5. Redox homeostasis: The Golden Mean of healthy living.

    Science.gov (United States)

    Ursini, Fulvio; Maiorino, Matilde; Forman, Henry Jay

    2016-08-01

    The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve "reactive oxygen species" rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles (parahormesis). In summary

  6. Redox homeostasis: The Golden Mean of healthy living

    Directory of Open Access Journals (Sweden)

    Fulvio Ursini

    2016-08-01

    Full Text Available The notion that electrophiles serve as messengers in cell signaling is now widely accepted. Nonetheless, major issues restrain acceptance of redox homeostasis and redox signaling as components of maintenance of a normal physiological steady state. The first is that redox signaling requires sudden switching on of oxidant production and bypassing of antioxidant mechanisms rather than a continuous process that, like other signaling mechanisms, can be smoothly turned up or down. The second is the misperception that reactions in redox signaling involve “reactive oxygen species” rather than reaction of specific electrophiles with specific protein thiolates. The third is that hormesis provides protection against oxidants by increasing cellular defense or repair mechanisms rather than by specifically addressing the offset of redox homeostasis. Instead, we propose that both oxidant and antioxidant signaling are main features of redox homeostasis. As the redox shift is rapidly reversed by feedback reactions, homeostasis is maintained by continuous signaling for production and elimination of electrophiles and nucleophiles. Redox homeostasis, which is the maintenance of nucleophilic tone, accounts for a healthy physiological steady state. Electrophiles and nucleophiles are not intrinsically harmful or protective, and redox homeostasis is an essential feature of both the response to challenges and subsequent feedback. While the balance between oxidants and nucleophiles is preserved in redox homeostasis, oxidative stress provokes the establishment of a new radically altered redox steady state. The popular belief that scavenging free radicals by antioxidants has a beneficial effect is wishful thinking. We propose, instead, that continuous feedback preserves nucleophilic tone and that this is supported by redox active nutritional phytochemicals. These nonessential compounds, by activating Nrf2, mimic the effect of endogenously produced electrophiles

  7. Symbiotic physiology promotes homeostasis in Daisyworld.

    Science.gov (United States)

    Boyle, Richard A; Lenton, Timothy M; Watson, Andrew J

    2011-04-07

    A connection is hypothesized between the physiological consequences of mutualistic symbiosis and life's average long-term impact on certain highly biologically conserved environmental variables. This hypothesis is developed analytically and with a variant of the Daisyworld model. Biological homeostasis is frequently effective due to co-ordination between opposing physiological "rein" functions, which buffer an organism in response to an external (often environmental) perturbation. It is proposed that during evolutionary history the pooling of different species' physiological functions in mutualistic symbioses increased the range of suboptimal environmental conditions that could be buffered against--a mutual tolerance benefit sometimes sufficient to outweigh the cost of cooperation. A related argument is that for a small number of biologically-crucial physical variables (i) the difference between organism interiors and the life-environment interface is relatively low, and (ii) the biologically optimum level of that variable is relatively highly conserved across different species. For such variables, symbiosis tends to cause (at a cost) an increase in the number of environmental buffering functions per unit of selection, which in turn biases the overall impact of the biota on the state of the variable towards the biological optimum. When a costly but more temperature-tolerant and physiologically versatile symbiosis between one black (warming) and one white (cooling) "daisy" is added to the (otherwise unaltered) Daisyworld parable, four new results emerge: (1) The extension of habitability to a wider luminosity range, (2) resistance to the impact of "cheater" white daisies with cold optima, that derive short-term benefit from environmental destabilisation, (3) the capacity to maintain residual, oscillatory regulation in response to forcings that change more rapidly than allele frequencies and (crucially) (4) "succession"-type dynamics in which the tolerant symbiosis

  8. 黄褐斑:表皮屏障与黑素屏障失衡%Melasma: the imbalance between epidermal barrier and melanin barrier

    Institute of Scientific and Technical Information of China (English)

    宋秀祖; 许爱娥

    2012-01-01

    黄褐斑是一种面部获得性色素增加性皮肤病,发病机制尚不清,概述黄褐斑的表皮屏障及黑素屏障的变化,以及真皮血管的变化.在此基础上推测黄褐斑的可能发病机制为紫外线、化妆品、避孕药等不良刺激导致表皮屏障功能障碍,代偿性引起黑素细胞功能活跃,黑素屏障增强,形成临床上表现为色素沉着为主的皮肤病.进一步导致真皮毛细血管扩张,血管内皮生长因子表达增加,促进色素沉着发生.%Melasma is an acquired skin disease characterized by facial hyperpigmentation of unclear pathogenesis.This paper describes the changes of epidermal barrier,melanin barrier and dermal blood vessels in melasma.On this basis,the pathogenesis of melasma is speculated to be associated with ultraviolet,cosmetics,contraceptives and other adverse stimuli,which cause epidermal barrier dysfunction,lead to a compensatory increase in melanocyte activity and melanin barrier followed by the occurrence of diseases characterized by skin pigmentation.Moreover,dermal telangiectasis is induced and vascular endothelial growth factor expression is enhanced,which accelerate skin pigmentation accordingly.

  9. Na+/K+-ATPase α1 identified as an abundant protein in the blood-labyrinth barrier that plays an essential role in the barrier integrity.

    Directory of Open Access Journals (Sweden)

    Yue Yang

    Full Text Available The endothelial-blood/tissue barrier is critical for maintaining tissue homeostasis. The ear harbors a unique endothelial-blood/tissue barrier which we term "blood-labyrinth-barrier". This barrier is critical for maintaining inner ear homeostasis. Disruption of the blood-labyrinth-barrier is closely associated with a number of hearing disorders. Many proteins of the blood-brain-barrier and blood-retinal-barrier have been identified, leading to significant advances in understanding their tissue specific functions. In contrast, capillaries in the ear are small in volume and anatomically complex. This presents a challenge for protein analysis studies, which has resulted in limited knowledge of the molecular and functional components of the blood-labyrinth-barrier. In this study, we developed a novel method for isolation of the stria vascularis capillary from CBA/CaJ mouse cochlea and provided the first database of protein components in the blood-labyrinth barrier as well as evidence that the interaction of Na(+/K(+-ATPase α1 (ATP1A1 with protein kinase C eta (PKCη and occludin is one of the mechanisms of loud sound-induced vascular permeability increase.Using a mass-spectrometry, shotgun-proteomics approach combined with a novel "sandwich-dissociation" method, more than 600 proteins from isolated stria vascularis capillaries were identified from adult CBA/CaJ mouse cochlea. The ion transporter ATP1A1 was the most abundant protein in the blood-labyrinth barrier. Pharmacological inhibition of ATP1A1 activity resulted in hyperphosphorylation of tight junction proteins such as occludin which increased the blood-labyrinth-barrier permeability. PKCη directly interacted with ATP1A1 and was an essential mediator of ATP1A1-initiated occludin phosphorylation. Moreover, this identified signaling pathway was involved in the breakdown of the blood-labyrinth-barrier resulting from loud sound trauma.The results presented here provide a novel method for

  10. Hedging Double Barriers with Singles

    NARCIS (Netherlands)

    Sbuelz, A.

    2000-01-01

    Double barrier options provide risk managers with good-deal flexibility in tailoring portfolio returns.Their hedges offer full protection only if unwound along the barriers.This work provides non-dynamic hedges that project the risk of double barriers on to single barriers.Non-dynamic hedges overcom

  11. Vacuum barrier for excimer lasers

    Energy Technology Data Exchange (ETDEWEB)

    Shurter, Roger P. (Jemez Springs, NM)

    1992-01-01

    A barrier for separating the vacuum area of a diode from the pressurized gas area of an excimer laser. The barrier is a composite material comprising layers of a metal such as copper, along with layers of polyimide, and a matrix of graphite fiber yarns impregnated with epoxy. The barrier is stronger than conventional foil barriers, and allows greater electron throughput.

  12. Vacuum barrier for excimer lasers

    Energy Technology Data Exchange (ETDEWEB)

    Shurter, R.P.

    1992-09-15

    A barrier for separating the vacuum area of a diode from the pressurized gas area of an excimer laser. The barrier is a composite material comprising layers of a metal such as copper, along with layers of polyimide, and a matrix of graphite fiber yarns impregnated with epoxy. The barrier is stronger than conventional foil barriers, and allows greater electron throughput. 3 figs.

  13. Epithelial Barrier Regulation by Hypoxia-Inducible Factor.

    Science.gov (United States)

    Glover, Louise E; Colgan, Sean P

    2017-09-01

    Mucosal tissues represent surfaces that are exposed to the outside world and provide a conduit for internal and external communication. Tissues such as the intestine and the lung are lined by layer(s) of epithelial cells that, when organized in three dimensions, provide a critical barrier to the flux of luminal contents. This selective barrier is provided through the regulated expression of junctional proteins and mucins. Tissue oxygen metabolism is central to the maintenance of homeostasis in the mucosa. In some organs (e.g., the colon), low baseline Po2 determines tissue metabolism and results in basal expression of the transcription factor, hypoxia-inducible factor (HIF), which is enhanced after ischemia/inflammation. Recent studies have indicated that HIF contributes fundamentally to the expression of barrier-related genes and in the regulation of barrier-adaptive responses within the mucosa. Here, we briefly review recent literature on the topic of hypoxia and HIF regulation of barrier in mucosal health and during disease.

  14. Cadherin 11 Involved in Basement Membrane Damage and Dermal Changes in Melasma.

    Science.gov (United States)

    Kim, Nan-Hyung; Choi, Soo-Hyun; Lee, Tae Ryong; Lee, Chang-Hoon; Lee, Ai-Young

    2016-06-15

    Basement membrane (BM) disruption and dermal changes (elastosis, collagenolysis, vascular ectasia) have been reported in melasma. Although ultraviolet (UV) irradiation can induce these changes, UV is not always necessary for melasma development. Cadherin 11 (CDH11), which is upregulated in some melasma patients, has previously been shown to stimulate melanogenesis. Because CDH11 action requires cell-cell adhesion between fibroblasts and melanocytes, BM disruption in vivo should facilitate this. The aim of this study was to examine whether CDH11 overexpression leads to BM disruption and dermal changes, independent of UV irradiation. Immunohistochemistry/immunofluorescence, real-time PCR, Western blotting, and zymography suggested that BM disruption/dermal changes and related factors were present in the hyperpigmented skin of CDH11-upregulated melasma patients and in CDH11-overexpressing fibroblasts/keratinocytes. The opposite was seen in CDH11-knockdown cells. UV irradiation of the cultured cells did not increase CDH11 expression. Collectively, these data demonstrate that CDH11 overexpression could induce BM disruption and dermal changes in melasma, regardless of UV exposure.

  15. BIOCOMPATIBILITY AND TISSUE REGENERATING CAPACITY OF CROSS-LINKED DERMAL SHEEP COLLAGEN

    NARCIS (Netherlands)

    VANWACHEM, PB; VANLUYN, MJA; DAMINK, LHHO; DIJKSTRA, PJ; FEIJEN, J; NIEUWENHUIS, P

    1994-01-01

    The biocompatibility and tissue regenerating capacity of four crosslinked dermal sheep collagens (DSC) was studied. In vitro, the four DSC versions were found to be noncytotoxic or very low in cytoxicity. After subcutaneous implantation in rats, hexamethylenediisocyanate-crosslinked DSC (HDSC) seldo

  16. TFE-PLASMA POLYMERIZED DERMAL SHEEP COLLAGEN FOR THE REPAIR OF ABDOMINAL-WALL DEFECTS

    NARCIS (Netherlands)

    VANDERLAAN, JS; LOPEZ, GP; VANWACHEM, PB; NIEUWENHUIS, P; RATNER, BD; BLEICHRODT, RP; SCHAKENRAAD, JM

    1991-01-01

    The aim of this study was to design and evaluate a degradable biomaterial for the repair of abdominal wall defects. Hexamethylenediisocyanate-tanned dermal sheep collagen (HDSC) was plasma-polymerized with tetrafluoroethylene (TFE) which resulted in a hydrophobic surface on the visceral side (TFE-HD

  17. Role of clothing in both accelerating and impeding dermal absorption of airborne SVOCs

    DEFF Research Database (Denmark)

    Morrison, Glenn C.; Weschler, Charles J.; Bekö, Gabriel

    2016-01-01

    .5, respectively. Even for non-occupational environments, wearing clothing that has adsorbed/absorbed indoor air pollutants can increase dermal uptake of SVOCs by substantial amounts relative to bare skin.Journal of Exposure Science and Environmental Epidemiology advance online publication, 10 June 2015; doi:10.1038...

  18. Water permeability parameters of dermal fibroblast employed in tissue engineering in subzero temperatures

    Institute of Scientific and Technical Information of China (English)

    WANG; Xin; CHENG; Qikang; GAO; Cai; YANG; Pengfei; HUA; Tse

    2005-01-01

    Fibroblast is a crucial kind of cell in the construction of the tissue engineered dermal equivalent. In order to optimize the cryopreservation protocols of the tissue- engineered dermis, the characteristics of dermal fibroblast in subzero temperatures are required, which include the water permeability of the cell membrane and the apparent activation energy. Using the differential scanning calorimeter (DSC), the volumetric shrinkage during freezing of human dermal fibroblast suspensions was obtained at the cooling rate of 5℃·min-1 in the presence of extracellular ice. To ensure the presence of extracellular ice, a small quantity of ice nucleation bacteria (INA bacteria), pseudomonas syringae was added in the samples. And based on the Karlsson's model, a nonlinear- least-squares curve fitting technique was implemented to calculate the cryogenic parameters. At the reference temperature TR (= 0℃), the water permeability of membrane Lpg = 0.578μm·min-1·atm-1 and the apparent activation energy ELP = 308.8 kJ·mol-1. These parameters were then used to simulate water transport of fibroblast during constant cooling at rates between 0.01―50℃·min-1. The simulation results were analyzed to predict the amount of water left in the cell after dehydration and the "optimal cooling rate" for fibroblast cryopreservation. For the dermal fibroblast with DMEM solution, a cooling rate of 4.6℃·min-1 was optimal.

  19. Pengujian Toksisitas Akut Oral Dan Dermal pada Biolarvasida Metarhizium anisopliae terhadap Tikus Putih Spraque Dawley

    Directory of Open Access Journals (Sweden)

    Deni Zulfiana

    2016-03-01

    Full Text Available Acute oral and dermal toxicity test against white rats was conducted to determine the toxicity and side effects of bio-larvacide (Metarhizium anisopliae crude extract on humans. In the oral test used a maximum dose 5000 mg/kg and dermal testing used a maximum dose of 2000 mg/kg. Dose treatment and control tested to 5 Spraque Dawley male rats. The results showed that oral treatment with a dose of 5000 mg/kg did not cause mortality and did not cause changes in anatomic pathology of viceral organs. In the dermal treatment with a dose of 2000 mg/kg did not cause mortality and did not cause changes in anatomic pathology of viceral organs. Based on these results LD50 acute oral M. anisopliae biolarvacide above 5000 mg/kg and the acute dermal is above 2000 mg/kg. It was therefore concluded that the formulation of Metarhizium anisopliae biolarvasida classified as not hazardous when used in accordance with the recommendation of the class I (WHO, 2003.

  20. Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

    NARCIS (Netherlands)

    Rennen, M.A.J.; Nordheim, K.; Houben, G.F.; Heer, C. de

    2002-01-01

    Health risks resulting from occupational exposure to chemicals are controlled by the establishment of acceptable dermal and respiratory exposure levels. Due to a lack of route-specific toxicity data, acceptable levels are frequently established by means of route-to-route extrapolation. A pitfall in

  1. Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal explants

    Science.gov (United States)

    Methicillin-resistant Staphylococcus aureus (MRSA) can infect wounds and produce difficult-to- treat biofilms. To determine the extent that MRSA biofilms can deplete oxygen, change pH and damage host tissue, we developed a porcine dermal explant model on which we cultured GFP-labeled MRSA biofilms. ...

  2. Dermal Absorption of Nanomaterials Titanium Dioxide and Zinc Oxide Based Sunscreen

    DEFF Research Database (Denmark)

    Beer, Christiane; Dokkedahl, Karin Stenderup; Wang, Jing

    of nanomaterials in products on the Danish market and their consequences on consumers and the environment. Furthermore, the aim is to clarify possible risks that might be associated with nanomaterials for consumers and the environment. The current project ’Dermal Absorption of Nanomaterials Titanium Dioxide...

  3. In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

    NARCIS (Netherlands)

    Olde damink, L.H.H.; Olde Damink, L.H.H.; Dijkstra, Pieter J.; van Luyn, M.J.A.; van Wachem, P.B.; Nieuwenhuis, P.; Feijen, Jan

    1996-01-01

    Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) crosslinked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide hydrochloride and N-hydroxysuccinimide (E/N-DSC) towards enzymatic degradation. Contrary to

  4. In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

    NARCIS (Netherlands)

    Damink, LHHO; Dijkstra, PJ; vanLuyn, MJA; vanWachem, PB; Nieuwenhuis, P; Feijen, J

    Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) cross-inked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide (EIN-DSC) towards enzymatic degradation. Contrary to

  5. High prevalence of dermal parasites among coral reef fishes of Curaçao

    NARCIS (Netherlands)

    M.A. Bernal; S.R. Floeter; M.R. Gaither; G.O. Longo; R. Morais; C.E.L. Ferreira; M.J.A. Vermeij; L.A. Rocha

    2015-01-01

    During expeditions to Curaçao in August and October of 2013, a large number of fish infected with dermal parasites was observed. Infected individuals presented black spots and white blemishes on their skin and fins that were easily observed by divers, and which have been associated with infections b

  6. Assessment of dermal exposure during airless spray painting using a quantitative visualisation technique

    NARCIS (Netherlands)

    Brouwer, D.H.; Lansink, C.M.; Cherrie, J.W.; Hemmen, J.J. van

    2000-01-01

    The range of dermal exposure to non-volatile compounds during spray painting was studied in a semi-experimental study involving three enterprises and 12 painters. A fluorescent tracer was added to the paint and deposition of the tracer on clothing and uncovered parts of the skin was assessed using v

  7. In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

    NARCIS (Netherlands)

    Damink, LHHO; Dijkstra, PJ; vanLuyn, MJA; vanWachem, PB; Nieuwenhuis, P; Feijen, J

    1996-01-01

    Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) cross-inked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide (EIN-DSC) towards enzymatic degradation. Contrary to non-cross-

  8. Changes in the mechanical properties of dermal sheep collagen during in vitro degradation

    NARCIS (Netherlands)

    Olde Damink, L.H.H.; Dijkstra, P.J.; Luyn, van M.J.A.; Wachem, van P.B.; Nieuwenhuis, P.; Feijen, J.

    1995-01-01

    The changes in tensile strength, elongation at break, and high strain modulus of dermal sheep collagen (DSC) during in vitro degradation using bacterial collagenase were studied. The changes in mechanical properties were compared with the change in weight of the samples as a function of degradation

  9. CHANGES IN THE MECHANICAL-PROPERTIES OF DERMAL SHEEP COLLAGEN DURING IN-VITRO DEGRADATION

    NARCIS (Netherlands)

    DAMINK, LHHO; DIJKSTRA, PJ; VANLUYN, MJA; VANWACHEM, PB; NIEUWENHUIS, P; FEIJEN, J

    1995-01-01

    The changes in tensile strength, elongation at break, and high strain modulus of dermal sheep collagen (DSC) during in vitro degradation using bacterial collagenase were studied. The changes in mechanical properties were compared with the change in weight of the samples as a function of degradation

  10. In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

    NARCIS (Netherlands)

    Olde Damink, L.H.H.; Dijkstra, P.J.; Luyn, van M.J.A.; Wachem, van P.B.; Nieuwenhuis, P.; Feijen, J.

    1996-01-01

    Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) crosslinked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide hydrochloride and N-hydroxysuccinimide (E/N-DSC) towards enzymatic degradation. Contrary to non-cross

  11. Dermal pharmacokinetics of Terpinen-4-ol following topical administration of Zingiber cassumunar (plai) oil.

    Science.gov (United States)

    Chooluck, Kotchaphan; Singh, Rajendra P; Sathirakul, Korbtham; Derendorf, Hartmut

    2012-11-01

    The purpose of this study was to investigate dermal pharmacokinetics of terpinen-4-ol in rats following topical administration of plai oil derived from the rhizomes of Zingiber cassumunar Roxb. Unbound terpinen-4-ol concentrations in dermal tissue were measured by microdialysis. The dermal pharmacokinetic study of terpinen-4-ol was performed under non-occlusive conditions. The oil was topically applied at a dose of 2, 4, and 8 mg/cm2 plai oil corresponding to the amount of 1.0, 1.9, and 3.8 mg/cm2 terpinen-4-ol, respectively. Following topical application of the oil, terpinen-4-ol rapidly distributed into the dermis and demonstrated linear pharmacokinetics with no changes in the dose-normalized area under the concentration-time curves across the investigated dosage range. The mean percentages of free terpinen-4-ol distributed in the dermis per amount of administered were 0.39 ± 0.06 %, 0.41 ± 0.08 %, and 0.30 ± 0.03 % for 2, 4, and 8 mg/cm2 doses, respectively. The dermal pharmacokinetics of terpinen-4-ol could provide information for its further formulation development and therapy schedules. Georg Thieme Verlag KG Stuttgart · New York.

  12. High prevalence of dermal parasites among coral reef fishes of Curaçao

    NARCIS (Netherlands)

    Bernal, M.A.; Floeter, S.R.; Gaither, M.R.; Longo, G.O.; Morais, R.; Ferreira, C.E.L.; Vermeij, M.J.A.; Rocha, L.A.

    2016-01-01

    During expeditions to Curaçao in August and October of 2013, a large number of fish infected with dermal parasites was observed. Infected individuals presented black spots and white blemishes on their skin and fins that were easily observed by divers, and which have been associated with infections b

  13. Crosslinking and modification of dermal sheep collagen using 1,4-butanediol diglycidyl ether

    NARCIS (Netherlands)

    Zeeman, R; Dijkstra, PJ; van Wachem, PB; van Luyn, MJA; Hendriks, M; Cahalan, PT; Feijen, J

    1999-01-01

    Crosslinking of dermal sheep collagen (DSC) was accomplished using 1,4-butanediol diglycidyl ether (BDDGE). At pH values > 8.0, epoxide groups of BDDGE will react with amine groups of collagen. The effects of BDDGE concentration, pH, time, and temperature were studied. Utilization of a 4-wt % BDDGE

  14. RELATIONS BETWEEN INVITRO CYTOTOXICITY AND CROSS-LINKED DERMAL SHEEP COLLAGENS

    NARCIS (Netherlands)

    VANLUYN, MJA; VANWACHEM, PB; DAMINK, LO; DIJKSTRA, PJ; FEIJEN, J; NIEUWENHUIS, P

    Collagen-based biomaterials have found various applications in the biomedical field. However, collagen-based biomaterials may induce cytotoxic effects. This study evaluated possible cytotoxic effects of (crosslinked) dermal sheep collagen (DSC) using a 7-d-methylcellulose cell culture with human

  15. Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

    NARCIS (Netherlands)

    Rennen, M.A.J.; Nordheim, K.; Houben, G.F.; Heer, C. de

    2002-01-01

    Health risks resulting from occupational exposure to chemicals are controlled by the establishment of acceptable dermal and respiratory exposure levels. Due to a lack of route-specific toxicity data, acceptable levels are frequently established by means of route-to-route extrapolation. A pitfall in

  16. Reliability of a semi-quantitative method for dermal exposure assessment (DREAM)

    NARCIS (Netherlands)

    Wendel de Joode, B. van; Hemmen, J.J. van; Meijster, T.; Major, V.; London, L.; Kromhout, H.

    2005-01-01

    Valid and reliable semi-quantitative dermal exposure assessment methods for epidemiological research and for occupational hygiene practice, applicable for different chemical agents, are practically nonexistent. The aim of this study was to assess the reliability of a recently developed semi-quantita

  17. Immunopathology of post kala-azar dermal leishmaniasis (PKDL): T-cell phenotypes and cytokine profile

    DEFF Research Database (Denmark)

    Ismail, A; El Hassan, A M; Kemp, K

    1999-01-01

    In Sudan, post kala-azar dermal leishmaniasis (PKDL) caused by Leishmania donovani develops in half of the patients treated for visceral leishmaniasis (kala-azar). In most patients lesions heal spontaneously, but in others symptoms are severe and persist for years. This study examined...

  18. Exposure to fungicides in fruit growing: Re-entry time as a predictor for dermal exposure

    NARCIS (Netherlands)

    Tielemans, E.; Louwerse, E.; Cock, J. de; Brouwer, D.; Zielhuis, G.; Heederik, D.

    1999-01-01

    As part of a European Concerted Action on Male Reproduction Capability an exposure assessment survey was conducted among seasonal workers in the fruit growing sector in the Netherlands. Dermal exposure to the fungicides captan and tolylfluanid was measured using cotton gloves (12 persons) and skin p

  19. Red blood cell lysate modulates the expression of extracellular matrix proteins in dermal fibroblasts.

    Science.gov (United States)

    Akbari, Amir; Li, Yunyuan; Kilani, Ruhangiz T; Ghahary, Aziz

    2012-11-01

    During the early stage of wound healing process, blood clots can be served as a temporary extracellular matrix (ECM) to let skin cell migration and proliferation. The red blood cells are generally thought as inert bystanders in the early and inflammatory phase of wound healing. Here, we provide evidence that red blood cells (RBC) also play an important role in modulation of key ECM components such as type-I collagen, α-smooth muscle actin, fibronectin, and matrix metalloproteinases (MMPs). In this study, we used western blot analysis and showed a significant increase in the level of MMP-1, 2, 3. Furthermore, we found that RBC lysate significantly down-regulates type-I collagen and α-smooth muscle actin while up-regulates fibronectin expression in dermal fibroblasts. To further explore the mechanism by which RBC lysate modulates MMP-1 expression, the effect of inhibitors for three MAPK signaling pathways on RBC inducing MMP-1 expression by dermal fibroblasts were tested. The result showed that the inhibitor of ERK1/2 could abrogate the stimulatory effect of RBC lysate on MMP-1 expression in dermal fibroblasts. Consistently, RBC treatment results in an increase of ERK1/2 phosphorylation in dermal fibroblast. In conclusion, these findings suggest that RBC lysate can modulate the expression of MMPs and key ECM components which are important in healing process.

  20. Factors influencing success of pelvic organ prolapse repair using porcine dermal implant Pelvicol.

    NARCIS (Netherlands)

    Boer, T.A. de; Gietelink, D.A.; Hendriks, J.C.M.; Vierhout, M.E.

    2010-01-01

    OBJECTIVE: To evaluate factors influencing pelvic organ prolapse (POP) recurrence after repair surgery with a porcine dermal collagen implant (Pelvicol). STUDY DESIGN: From December 2003 to August 2005, 78 patients with mainly stage 3 pelvic organ prolapse by the Pelvic Organ Prolapse Quantification

  1. Dermal Matrices and Bioengineered Skin Substitutes: A Critical Review of Current Options

    Directory of Open Access Journals (Sweden)

    Heidi Debels, MD

    2015-01-01

    Conclusions: Skin substitutes are a useful tool in plastic and reconstructive surgery practices as an alternative to skin grafts. In the choice of substitute, the general plastic surgery principle of replacing like tissue with like tissue seems to be still standing, and products most resembling the natural dermal extracellular matrix should be preferred.

  2. Outcome of dermal grafting in the management of atrophic facial scars

    Directory of Open Access Journals (Sweden)

    Kanathur Shilpa

    2016-01-01

    Full Text Available Background: Scars over the face are cosmetically and psychologically disturbing. Various techniques have been described and are being practiced in the management of these scars. Aims and Objectives: This study was undertaken to study the safety, effectiveness of using dermal grafts as fillers in the management of facial scars due to acne, chickenpox, trauma or any others. Materials and Methods: Fifteen patients with atrophic facial scars of varied aetiology and willing for surgery were considered for dermal graft technique. After pre-operative workup, subcision was done 2 weeks before planned surgery. Depending on the type of scar, grafts were inserted using pocket or road railing techniques. Scar improvement was assessed based on patient satisfaction. Results: Linear scars showed excellent improvement. Acne, varicella and traumatic scars also showed good improvement. However, two patients did not appreciate improvement due to marked surface irregularities as the scars were elevated. They were further subjected to LASER and chemical peel resurfacing. Conclusion: Dermal grafting can be used in the management of any round to oval facial scar which is soft, prominent and at least 4-5 mm across; linear scars at least 2-3 mm across and 3-4 cm in length. However, scars with prominent surface irregularities need further resurfacing techniques along with dermal grafting. Limitations: Limitations of the study include small sample size, and only subjective assessment of the scar has been taken into consideration to assess the outcome.

  3. Determinants of Dermal Exposure Relevant for Exposure Modelling in Regulatory Risk Assessment

    NARCIS (Netherlands)

    Marquart, J.; Brouwer, D.H.; Gijsbers, J.H.J.; Links, I.H.M.; Warren, N.; Hemmen, J.J. van

    2003-01-01

    Risk assessment of chemicals requires assessment of the exposure levels of workers. In the absence of adequate specific measured data, models are often used to estimate exposure levels. For dermal exposure only a few models exist, which are not validated externally. In the scope of a large European

  4. Experimental dermatological surgery: An animal model for developing skills with dermal fillers

    Directory of Open Access Journals (Sweden)

    Juliana Catucci Boza

    2011-01-01

    Full Text Available The importance of laboratory experiments in the formation of physicians is well recognized since they facilitate scientific development and enhance technical skills. Dermal filling procedures are performed for the correction of wrinkles, rhytids, scars, and lipodystrophy. Till date, experimental models for the training of dermal filling techniques have not been studied. To demonstrate an experimental laboratory model for the training of dermal filling techniques in an animal model. The heads of pigs were used for this purpose, together with Carbopol gel at different densities, which was used to simulate the fillers available in the market. Needles and specific cannulas were used to apply the fillers into the creases and other areas of the pig skin. The pig head appears to be a suitable model for this training. Carbopol gel is a good choice for simulating fillers. This model of laboratory experiment requires a minimum of infrastructure; it is a low-cost alternative and facilitates practical training in the application of dermal fillers.

  5. Soil organic matter content effects on dermal pesticide bioconcentration in American toads (Bufo americanus).

    Science.gov (United States)

    Pesticides have been implicated as a major factor in global amphibian declines and may pose great risk to terrestrial phase amphibians moving to and from breeding ponds on agricultural landscapes. Dermal uptake from soil is known to occur in amphibians, but predicting pesticide a...

  6. A Toolkit for Dermal Risk Assessment: Toxicological Approach for Hazard Characterization

    NARCIS (Netherlands)

    Schuhmacher-Wolz, U.; Kalberlah, F.; Oppl, R.; Hemmen, J.J. van

    2003-01-01

    The toxicological background for hazard assessment using a simple to use toolkit for assessment and management of health risks from occupational dermal exposure is presented. Hazard assessment is intended to answer the following questions: (i) is the substance under consideration capable of damaging

  7. Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

    Science.gov (United States)

    Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular, and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and fou...

  8. Dermal connective tissue development in mice: an essential role for tenascin-X.

    NARCIS (Netherlands)

    Egging, D.; Vlijmen-Willems, I.M.J.J. van; Starcher, B.; Gijsen, Y.; Zweers, M.C.; Blankevoort, L.; Bristow, J.; Schalkwijk, J.

    2006-01-01

    Deficiency of the extracellular matrix protein tenascin-X (TNX) causes a recessive form of Ehlers-Danlos syndrome (EDS) characterized by hyperextensible skin and hypermobile joints. It is not known whether the observed alterations of dermal collagen fibrils and elastic fibers in these patients are c

  9. Deficiency of tenascin-X causes abnormalities in dermal elastic fiber morphology

    NARCIS (Netherlands)

    Zweers, MC; van Vlijmen-Willems, IM; van Kuppevelt, TH; Mecham, RP; Steijlen, PM; Bristow, J; Schalkwijk, J

    2004-01-01

    Deficiency of the extracellular matrix protein tenascin-X (TNX) was recently described as the molecular basis of a new, recessive type of Ehlers-Danlos syndrome. Here we report gross abnormalities of the elastic fibers and microfibrils in the dermis of these patients, and reduced dermal collagen con

  10. Dermal connective tissue development in mice: an essential role for tenascin-X

    NARCIS (Netherlands)

    D.F. Egging; I. van Vlijmen; B. Starcher; Y. Gijsen; M.C. Zweers; L. Blankevoort; J. Bristow; J. Schalkwijk

    2006-01-01

    Deficiency of the extracellular matrix protein tenascin-X (TNX) causes a recessive form of Ehlers-Danlos syndrome (EDS) characterized by hyperextensible skin and hypermobile joints. It is not known whether the observed alterations of dermal collagen fibrils and elastic fibers in these patients are c

  11. Deficiency of tenascin-X causes abnormalities in dermal elastic fiber morphology

    NARCIS (Netherlands)

    Zweers, MC; van Vlijmen-Willems, IM; van Kuppevelt, TH; Mecham, RP; Steijlen, PM; Bristow, J; Schalkwijk, J

    2004-01-01

    Deficiency of the extracellular matrix protein tenascin-X (TNX) was recently described as the molecular basis of a new, recessive type of Ehlers-Danlos syndrome. Here we report gross abnormalities of the elastic fibers and microfibrils in the dermis of these patients, and reduced dermal collagen con

  12. Teratogenicity study of N-methylpyrrolidone after dermal application to Sprague-Dawley rats.

    Science.gov (United States)

    Becci, P J; Knickerbocker, M J; Reagan, E L; Parent, R A; Burnette, L W

    1982-01-01

    Teratogenicity studies were performed in rats given N-methylpyrrolidone, a solvent used in chemical processing. Dosages of 75,237 and 750 mg of N-methylpyrrolidone/kg body weight/day were administered dermally to groups of 25 pregnant Sprague-Dawley rats on days 6 through 15 of gestation. Additionally, the study used a positive dermal control. Hexafluoroacetone, was chosen based on its dermal teratogenic activity. An oral positive control, aspirin, was included in order to add significance to the data generated in the experimental positive dermal control group. All animals were killed and subjected to uterine examination on day 20 of gestation. Maternal toxicity was indicated at 750 mg of N-methylpyrrolidone/kg by reduced body weight gain during gestation. Treatment with N-methylpyrrolidone resulted in dose-dependent brightly colored yellow urine and dry skin. Treatment at the high dosage level resulted in fewer live fetuses per dam, an increase in the percentage of resorption sites and skeletal abnormalities. These effects could be the result of maternal toxicity. There was no evidence of teratogenic effects nor effects on the dams at 75 and 237 mg/kg of body weight.

  13. Multipotent adult progenitor cells : their role in wound healing and the treatment of dermal wounds

    NARCIS (Netherlands)

    Herdrich, B. J.; Lind, R. C.; Liechty, K. W.

    2008-01-01

    The use of cellular therapy in the treatment of dermal wounds is currently an active area of investigation. Multipotent adult progenitor cells (MAPC) are an attractive choice for cytotherapy because they have a large proliferative potential, the ability to differentiate into different cell types and

  14. Skin permeability and pharmacokinetics of diclofenac epolamine administered by dermal patch in Yorkshire-Landrace pigs

    Directory of Open Access Journals (Sweden)

    Tse S

    2012-10-01

    Full Text Available Susanna Tse,1 Kendall D Powell,2 Stephen MacLennan,3 Allan R Moorman,4 Craig Paterson,5 Rosonald R Bell11Pfizer Inc, Groton, CT, USA; 2Tandem Labs, Durham, NC, USA; 3BioCryst Pharmaceuticals Inc, Durham, NC, USA; 4Alta Vetta Pharmaceutical Consulting LLC, Durham, NC, USA; 5Salix Pharmaceuticals Inc, Raleigh, NC, USAPurpose: This study compared the pharmacokinetic profile, and systemic and local absorption of diclofenac, following dermal patch application and oral administration in Yorkshire- Landrace pigs.Patients and methods: Twelve anesthetized, female, Yorkshire-Landrace pigs were randomized to receive either the dermal patch (FLECTOR® patch, 10 × 14 cm; Alpharma Pharmaceuticals, a subsidiary of Pfizer Inc, New York, NY or 50 mg oral diclofenac (Voltaren®; Novartis, East Hanover, NJ. Tissue (skin area of 2 × 2 cm and underlying muscles approximately 2–3 cm in depth and blood (10 mL samples were collected at timed intervals up to 11.5 hours after initial patch application or oral administration. The concentrations of diclofenac in plasma, skin, and muscle samples were analyzed using validated ultra performance liquid chromatography tandem mass spectrometric methods.Results: Peak systemic exposure of diclofenac was very low by dermal application compared with oral administration (maximum concentration [Cmax] values of 3.5 vs 9640 ng/mL, respectively. Absorption of diclofenac into underlying muscles beneath the dermal patch was sustained, and followed apparently zero-order kinetics, with the skin serving as a depot with elevated concentrations of diclofenac. Concentrations of diclofenac in muscles beneath the patch application site were similar to corresponding tissues after oral administration (Cmax values of 879 and 1160 ng/mL, respectively. In contrast to the wide tissue distribution of diclofenac after oral administration, dermal patch application resulted in high concentrations of diclofenac only on the treated skin and immediate

  15. Dermal substitution with Matriderm(®) in burns on the dorsum of the hand.

    Science.gov (United States)

    Ryssel, H; Germann, G; Kloeters, O; Gazyakan, E; Radu, C A

    2010-12-01

    Dermal substitutes are used increasingly in deep partial and full-thickness burn wounds in order to enhance elasticity and pliability. In particular, the dorsum of the hand is an area requiring extraordinary mobility for full range of motion. The aim of this comparative study was to evaluate intra-individual outcomes among patients with full-thickness burns of the dorsum of both hands. One hand was treated with split-thickness skin grafts (STSG) alone, and the other with the dermal substitute Matriderm(®) and split-thickness skin grafts. In this study 36 burn wounds of the complete dorsum of both hands in 18 patients with severe burns (age 45.1±17.4 years, 43.8±11.8% TBSA) were treated with the simultaneous application of Matriderm(®), a bovine based collagen I, III, V and elastin-hydrolysate based dermal substitute, and split-thickness skin grafting (STSG) in the form of sheets on one hand, and STSG in the form of sheets alone on the other hand. The study was designed as a prospective comparative study. Using both objective and subjective assessments, data were collected at one week and 6 months after surgery. The following parameters were included: After one week all wounds were assessed for autograft survival. Skin quality was measured 6 months postoperatively using the Vancouver Burn Skin Score (VBSS). Range of motion was measured by Finger-Tip-Palmar-Crease-Distance (FPD) and Finger-Nail-Table-Distance (FNTD). Autograft survival was not altered by simultaneous application of the dermal matrix (p>0.05). The VBSS demonstrated a significant increase in skin quality in the group with dermal substitutes (p=0.02) compared to the control group with non-substituted wounds. Range of motion was significantly improved in the group treated with the dermal substitute (p=0.04). From our results it can be concluded that simultaneous use of Matriderm(®) and STSG is safe and feasible, leading to significantly better results in respect to skin quality of the dorsum of the

  16. Inflammation and the Intestinal Barrier: Leukocyte–Epithelial Cell Interactions, Cell Junction Remodeling, and Mucosal Repair

    Science.gov (United States)

    Luissint, Anny-Claude; Parkos, Charles A.; Nusrat, Asma

    2017-01-01

    The intestinal tract is lined by a single layer of columnar epithelial cells that forms a dynamic, permeable barrier allowing for selective absorption of nutrients, while restricting access to pathogens and food-borne antigens. Precise regulation of epithelial barrier function is therefore required for maintaining mucosal homeostasis and depends, in part, on barrier-forming elements within the epithelium and a balance between pro- and anti-inflammatory factors in the mucosa. Pathologic states, such as inflammatory bowel disease, are associated with a leaky epithelial barrier, resulting in excessive exposure to microbial antigens, recruitment of leukocytes, release of soluble mediators, and ultimately mucosal damage. An inflammatory microenvironment affects epithelial barrier properties and mucosal homeostasis by altering the structure and function of epithelial intercellular junctions through direct and indirect mechanisms. We review our current understanding of complex interactions between the intestinal epithelium and immune cells, with a focus on pathologic mucosal inflammation and mechanisms of epithelial repair. We discuss leukocyte–epithelial interactions, as well as inflammatory mediators that affect the epithelial barrier and mucosal repair. Increased knowledge of communication networks between the epithelium and immune system will lead to tissue-specific strategies for treating pathologic intestinal inflammation. PMID:27436072

  17. Gastric barrier function and toxic damage.

    Science.gov (United States)

    Niv, Yaron; Banić, Marko

    2014-01-01

    Gastric epithelium is the first significant barrier between the inner body and the potentially toxic material in the lumen. Nutrients affect gastric barrier continuously--alcohol, coffee, spices, salted food, etc. Also, very potent noxious agents are widely prescribed drugs--nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin and selective serotonin reuptake inhibitors. Helicobacter pylori is a well-known and well-investigated pathogen associated with serious gastric damage and gastric carcinoma. For its defense and maintenance of homeostasis and integrity, except acid secretion and maintenance of low luminal pH, gastric mucosa also has a specific structure, and its function is influenced by different control mechanisms. These include control of mucosal blood flow, control of mucus and bicarbonate secretion, constant cell renewal, and neuronal and hormonal control of defense mechanisms. These mechanisms are mediated by prostaglandins, nitric oxide, growth factors, heat-shock proteins and a neuropeptide called calcitonin gene-related protein. Adrenal glucocorticoids and the central nervous system also play an important role in regulating gastro-protection, especially hypothalamus and the dorsal vagal complex. Gastric mucosa is also an important component of the body's immune system and gut-associated lymphoid tissue which serves as the initiation site for antigen-specific humoral and cell-mediated immune response. Treatment options for gastric barrier dysfunction and damage due to aforementioned noxious agents are guided by the nature of damage and our understanding of the pathophysiological mechanisms involved. Currently, management is guideline driven and depends upon eradication treatment in patients infected with H. pylori and treatment or prevention of aspirin or NSAID ulceration. © 2014 S. Karger AG, Basel.

  18. Dermal permeation of biocides and aromatic chemicals in three generic formulations of metalworking fluids.

    Science.gov (United States)

    Vijay, Vikrant; White, Eugene M; Kaminski, Michael D; Riviere, Jim E; Baynes, Ronald E

    2009-01-01

    Metalworking fluids (MWF) are complex mixtures consisting of a variety of components and additives. A lack of scientific data exists regarding the dermal permeation of its components, particularly biocides. The aim of this study was to evaluate the dermal permeation of biocides and other aromatic chemicals in water and in three generic soluble oil, semi-synthetic, and synthetic MWF types in order to evaluate any differences in their permeation profiles. An in vitro flow-through diffusion cell study was performed to determine dermal permeation. An infinite dose of different groups of chemicals (6 biocides and 29 aromatic chemicals) was applied to porcine skin, with perfusate samples being collected over an 8-h period. Perfusate samples were analyzed by gas chromatography/mass spectrometry (GC-MS) and ultra-performance liquid chromatography/mass spectroscopy (UPLC-MS), and permeability was calculated from the analysis of the permeated chemical concentration-time profile. In general, the permeation of chemicals was highest in aqueous solution, followed by synthetic, semi-synthetic, and soluble oil MWF. The absorption profiles of most of the chemicals including six biocides were statistically different among the synthetic and soluble oil MWF formulations, with reduced permeation occurring in oily formulations. Permeation of almost all chemicals was statistically different between aqueous and three MWF formulation types. Data from this study show that permeation of chemicals is higher in a generic synthetic MWF when compared to a soluble oil MWF. This indicates that a soluble oil MWF may be safer than a synthetic MWF in regard to dermal permeation of chemicals to allow for an increased potential of systemic toxicity. Therefore, one may conclude that a synthetic type of formulation has more potential to produce contact dermatitis and induce systemic toxicological effects. The dilution of these MWF formulations with water may increase dermal permeability of biocides

  19. 11β-hydroxysteroid dehydrogenase 1 specific inhibitor increased dermal collagen content and promotes fibroblast proliferation.

    Directory of Open Access Journals (Sweden)

    Mika Terao

    Full Text Available Glucocorticoids (GCs are one of the most effective anti-inflammatory drugs for treating acute and chronic inflammatory diseases. However, several studies have shown that GCs alter collagen metabolism in the skin and induce skin atrophy. Cortisol is the endogenous GC that is released in response to various stressors. Over the last decade, extraadrenal cortisol production in various tissues has been reported. Skin also synthesizes cortisol through a de novo pathway and through an activating enzyme. 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1 is the enzyme that catalyzes the conversion of hormonally inactive cortisone to active cortisol in cells. We previously found that 11β-HSD1 negatively regulates proliferation of keratinocytes. To determine the function of 11β-HSD1 in dermal fibroblasts and collagen metabolism, the effect of a selective 11β-HSD1 inhibitor was studied in mouse tissues and dermal fibroblasts. The expression of 11β-HSD1 increased with age in mouse skin. Subcutaneous injection of a selective 11β-HSD1 inhibitor increased dermal thickness and collagen content in the mouse skin. In vitro, proliferation of dermal fibroblasts derived from 11β-HSD1 null mice (Hsd11b1(-/- mice was significantly increased compared with fibroblasts from wild-type mice. However, in vivo, dermal thickness of Hsd11b1(-/- mice was not altered in 3-month-old and 1-year-old mouse skin compared with wild-type mouse skin. These in vivo findings suggest the presence of compensatory mechanisms in Hsd11b1(-/- mice. Our findings suggest that 11β-HSD1 inhibition may reverse the decreased collagen content observed in intrinsically and extrinsically aged skin and in skin atrophy that is induced by GC treatment.

  20. Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal explants.

    Science.gov (United States)

    Lone, Abdul G; Atci, Erhan; Renslow, Ryan; Beyenal, Haluk; Noh, Susan; Fransson, Boel; Abu-Lail, Nehal; Park, Jeong-Jin; Gang, David R; Call, Douglas R

    2015-06-01

    We developed a porcine dermal explant model to determine the extent to which Staphylococcus aureus biofilm communities deplete oxygen, change pH, and produce damage in underlying tissue. Microelectrode measurements demonstrated that dissolved oxygen (DO) in biofilm-free dermal tissue was 4.45 ± 1.17 mg/liter, while DO levels for biofilm-infected tissue declined sharply from the surface, with no measurable oxygen detectable in the underlying dermal tissue. Magnetic resonance imaging demonstrated that biofilm-free dermal tissue had a significantly lower relative effective diffusion coefficient (0.26 ± 0.09 to 0.30 ± 0.12) than biofilm-infected dermal tissue (0.40 ± 0.12 to 0.48 ± 0.12; P < 0.0001). Thus, the difference in DO level was attributable to biofilm-induced oxygen demand rather than changes in oxygen diffusivity. Microelectrode measures showed that pH within biofilm-infected explants was more alkaline than in biofilm-free explants (8.0 ± 0.17 versus 7.5 ± 0.15, respectively; P < 0.002). Cellular and nuclear details were lost in the infected explants, consistent with cell death. Quantitative label-free shotgun proteomics demonstrated that both proapoptotic programmed cell death protein 5 and antiapoptotic macrophage migration inhibitory factor accumulated in the infected-explant spent medium, compared with uninfected-explant spent media (1,351-fold and 58-fold, respectively), consistent with the cooccurrence of apoptosis and necrosis in the explants. Biofilm-origin proteins reflected an extracellular matrix-adapted lifestyle of S. aureus. S. aureus biofilms deplete oxygen, increase pH, and induce cell death, all factors that contribute to impede wound healing.

  1. Patterns of dermal exposure to hazardous substances in European union workplaces.

    Science.gov (United States)

    Rajan-Sithamparanadarajah, R; Roff, M; Delgado, P; Eriksson, K; Fransman, W; Gijsbers, J H J; Hughson, G; Mäkinen, M; van Hemmen, J J

    2004-04-01

    Workplace dermal exposure assessment is a complex task that aims to understand the dynamic interaction between the skin and the hazardous substances present in the surrounding environment. A European project known as RISKOFDERM gathered dermal exposure data in 85 workplaces (industrial and other types) in five countries in Europe. In order to optimize data collection and to develop a representative picture of dermal exposure, scenarios (tasks made up of a series of activities) were grouped together into dermal exposure operation units (DEOs). The allocation of scenarios to relevant DEOs was achieved on the basis of similarities of exposure routes, tasks and professional judgement. Sampling and quantification procedures were based on the approaches recommended by the OECD protocol. The laboratories involved in the analysis of the samples participated in quality assurance programmes. This exercise resulted in 419 body measurements and 437 measurements on hands expressed in terms of formulation (product) in use. Exposures for a given scenario varied by several orders of magnitude. The extent and patterns of exposure were found to be dependent on various exposure determinants, including inter- and intra-scenario variations. Hands were found to be the most contaminated parts of the body. Exposure patterns for liquid and solid contaminants were different. On the basis of the analysis of the data presented here, the averaged results (median and 95th percentile) for a given DEO unit should not be used as a representative measure of dermal exposure for all scenarios within that DEO without taking the exposure determinants into account. However, the data could be used to develop an exposure matrix (indicative exposure distributions) for different types of scenario and workplace, using determinants of exposure and a Bayesian approach to integrating expert opinion.

  2. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Puente, Pilar de la, E-mail: pilardelapuentegarcia@gmail.com [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain); Ludeña, Dolores [Pathology Service, University Hospital of Salamanca, P/San Vicente 58-182, 37007 Salamanca (Spain); López, Marta; Ramos, Jennifer; Iglesias, Javier [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain)

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  3. Novel Mechanisms of Compromised Lymphatic Endothelial Cell Homeostasis in Obesity: The Role of Leptin in Lymphatic Endothelial Cell Tube Formation and Proliferation.

    Directory of Open Access Journals (Sweden)

    Akinori Sato

    Full Text Available Leptin is a hormone produced by adipose tissue that regulates various physiological processes. Recent studies have shown that the level of circulating leptin is elevated in obese patients and have suggested a relationship between obesity and postoperative lymphedema. However, the mechanisms by which postoperative lymphedema develops in obese patients and the mechanisms by which leptin regulates lymphatic endothelial cell homeostasis such as tube formation and cell proliferation remain unknown. Here we report that leptin regulates tube formation and cell proliferation in human dermal lymphatic endothelial cells (HDLECs by activation of the signal transducer and activator of transcription 3 pathway, which is downstream signaling of the leptin receptor. Additionally, we found that upregulation of suppressor of cytokine signaling 3 underlies the mechanisms by which a high dose of leptin inhibits cell proliferation and tube formation. Leptin also enhanced expression of the proinflammatory cytokine IL-6 in HDLECs. Interestingly, IL-6 rescues the compromised cell proliferation and tube formation caused by treatment with a high dose of leptin in an autocrine or paracrine manner. Taken together, our findings reveal a novel mechanism by which compromised HDLECs maintain their homeostasis during inflammation mediated by leptin and IL-6. Thus, regulating the level of leptin or IL-6 may be a viable strategy to reduce the incidence of postoperative lymphedema.

  4. Barriers to cancer screening.

    Science.gov (United States)

    Womeodu, R J; Bailey, J E

    1996-01-01

    Many barriers to cancer screening have been summarized and discussed. Barriers have been documented in all patient populations, but some groups such as ethnic minorities and the elderly face unique barriers. The barriers to cancer screening, are multifactorial, but much of the responsibility for change must lie with health care providers and the health care delivery industry. This is not to free the patient of all responsibility, but some significant barriers are beyond their direct control. Take, for example, socioeconomic status, disease knowledge, and culturally related perceptions and myths about cancer detection and treatment. The health care industry must do a better job identifying and overcoming these barriers. The significant effects of provider counseling and advice must not be underestimated. Patients must first be advised, and then further actions must be taken if they reject the screening advice. Did they refuse adherence to recommendations because they do not view themselves as susceptible, because of overwhelming personal barriers, or because of a fatalistic attitude toward cancer detection and treatment? If that is the case, physicians and health care institutions must attempt to change perceptions, educate, and personalize the message so that patients accept their disease susceptibility [table: see text]. Multiple patient and provider risk factors have been identified that can be used to target patients particularly at high risk for inadequate cancer screening and providers at high risk for performing inadequate screening. Research has clearly demonstrated the effectiveness of interventions to improve tracking of patient and physician compliance with screening recommendations. Further research is needed to show the impact of managed-care penetration and payer status on screening efforts, and incentive schemes need to be tested that reward institutions and third-party payers who develop uniform standards and procedures for cancer screening. The

  5. The blood-nerve barrier: structure and functional significance.

    Science.gov (United States)

    Weerasuriya, Ananda; Mizisin, Andrew P

    2011-01-01

    The blood-nerve barrier (BNB) defines the physiological space within which the axons, Schwann cells, and other associated cells of a peripheral nerve function. The BNB consists of the endoneurial microvessels within the nerve fascicle and the investing perineurium. The restricted permeability of these two barriers protects the endoneurial microenvironment from drastic concentration changes in the vascular and other extracellular spaces. It is postulated that endoneurial homeostatic mechanisms regulate the milieu intérieur of peripheral axons and associated Schwann cells. These mechanisms are discussed in relation to nerve development, Wallerian degeneration and nerve regeneration, and lead neuropathy. Finally, the putative factors responsible for the cellular and molecular control of BNB permeability are discussed. Given the dynamic nature of the regulation of the permeability of the perineurium and endoneurial capillaries, it is suggested that the term blood-nerve interface (BNI) better reflects the functional significance of these structures in the maintenance of homeostasis within the endoneurial microenvironment.

  6. Delayed repair in a case of forearm fascial muscle herniation using non-cross-linked acellular porcine dermal matrix.

    Science.gov (United States)

    Hartmann, Christoph E A; Branford, Olivier A; Floyd, David

    2012-09-01

    The options for treatment of symptomatic muscle herniation in the limbs traditionally include fasciotomy, direct repair, tendon weave graft (palmaris longus), fascial graft (tensor fascia lata), and synthetic mesh (prolene). A recent case report has described the use of acellular cadaveric dermal matrix to reconstruct fascial defects in 2 cases. We describe the use of Strattice, a non-cross-linked acellular porcine dermal matrix, as a fascial underlay graft in a case of symptomatic upper limb muscle herniation. We propose that Strattice has the advantages over cadaveric dermal matrices in terms of avoiding the use of human donor tissue. It has suitable tensile properties to be used for reconstructing fascial defects.

  7. Culture of Dermal Papilla Cells from Ovine Wool Follicles: An In Vitro Model for Papilla Size Determination.

    Science.gov (United States)

    Rufaut, Nicholas W; Nixon, Allan J; Sinclair, Rodney D

    2016-01-01

    Common human balding or hair loss is driven by follicle miniaturization. Miniaturization is thought to be caused by a reduction in dermal papilla size. The molecular mechanisms that regulate papilla size are poorly understood, and their elucidation would benefit from a tractable experimental model. We have found that dermal papilla cells from sheep spontaneously aggregate in culture to form papilla-like structures. Here, we describe methods for microdissecting dermal papillae from wool follicles, for initiating and maintaining cultures of ovine papilla cells, and for using these cells in an in vitro assay to measure the effect of bioactive molecules on aggregate size.

  8. Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation

    Science.gov (United States)

    Vladar, Eszter K.; Nayak, Jayakar V.; Milla, Carlos E.; Axelrod, Jeffrey D.

    2016-01-01

    Motile airway cilia that propel contaminants out of the lung are oriented in a common direction by planar cell polarity (PCP) signaling, which localizes PCP protein complexes to opposite cell sides throughout the epithelium to orient cytoskeletal remodeling. In airway epithelia, PCP is determined in a 2-phase process. First, cell-cell communication via PCP complexes polarizes all cells with respect to the proximal-distal tissue axis. Second, during ciliogenesis, multiciliated cells (MCCs) undergo cytoskeletal remodeling to orient their cilia in the proximal direction. The second phase not only directs cilium polarization, but also consolidates polarization across the epithelium. Here, we demonstrate that in airway epithelia, PCP depends on MCC differentiation. PCP mutant epithelia have misaligned cilia, and also display defective barrier function and regeneration, indicating that PCP regulates multiple aspects of airway epithelial homeostasis. In humans, MCCs are often sparse in chronic inflammatory diseases, and these airways exhibit PCP dysfunction. The presence of insufficient MCCs impairs mucociliary clearance in part by disrupting PCP-driven polarization of the epithelium. Consistent with defective PCP, barrier function and regeneration are also disrupted. Pharmacological stimulation of MCC differentiation restores PCP and reverses these defects, suggesting its potential for broad therapeutic benefit in chronic inflammatory disease. PMID:27570836

  9. Support or Barrier?

    DEFF Research Database (Denmark)

    Sanden, Guro Refsum; Lønsmann, Dorte

    This study offers a critical look at how corporate-level language management influences front-line language practices among employees in three multinational corporations (MNCs) headquartered in Scandinavia. Based on interview and document data, we examine, firstly, what front-line practices emplo...... to a discussion of how a company’s language policy may be seen as both support and a barrier....

  10. Overcoming Language Barriers

    Science.gov (United States)

    De Buda, Yvonne

    1976-01-01

    Many family physicians in Canada experience language and cultural barriers between themselves and their patients. Several aspects of the ensuing problems are described and some practical suggestions for solutions are made. The importance of health education for new Canadians in the family physician's office as well as through the media and community projects is stressed. Imagesp68-ap68-bp70-a PMID:21308059

  11. Barriers to obesity treatment.

    Science.gov (United States)

    Mauro, Marina; Taylor, Valerie; Wharton, Sean; Sharma, Arya M

    2008-05-01

    Obesity, one of the most prevalent health problems in the Western world, is a chronic and progressive condition. Therefore, as with other chronic diseases, patients with obesity require lifelong treatment. Long-term efficacy and effectiveness of obesity treatments is notoriously poor. This may in part be attributable to the substantial barriers that undermine long-term obesity management strategies. These can include lack of recognition of obesity as a chronic condition, low socioeconomic status, time constraints, intimate saboteurs, and a wide range of comorbidities including mental health, sleep, chronic pain, musculoskeletal, cardiovascular, respiratory, digestive and endocrine disorders. Furthermore, medications used to treat some of these disorders may further undermine weight-loss efforts. Lack of specific obesity training of health professionals, attitudes and beliefs as well as coverage and availability of obesity treatments can likewise pose important barriers. Health professionals need to take care to identify, acknowledge and address these barriers where possible to increase patient success as well as compliance and adherence with treatments. Failure to do so may further undermine the sense of failure, low self esteem and self efficacy already common among obese individuals. Addressing treatment barriers can save resources and increase the prospect of long-term success.

  12. Effects of Gliadin consumption on the Intestinal Microbiota and Metabolic Homeostasis in Mice Fed a High-fat Diet

    Science.gov (United States)

    Zhang, Li; Andersen, Daniel; Roager, Henrik Munch; Bahl, Martin Iain; Hansen, Camilla Hartmann Friis; Danneskiold-Samsøe, Niels Banhos; Kristiansen, Karsten; Radulescu, Ilinca Daria; Sina, Christian; Frandsen, Henrik Lauritz; Hansen, Axel Kornerup; Brix, Susanne; Hellgren, Lars I.; Licht, Tine Rask

    2017-01-01

    Dietary gluten causes severe disorders like celiac disease in gluten-intolerant humans. However, currently understanding of its impact in tolerant individuals is limited. Our objective was to test whether gliadin, one of the detrimental parts of gluten, would impact the metabolic effects of an obesogenic diet. Mice were fed either a defined high-fat diet (HFD) containing 4% gliadin (n = 20), or a gliadin-free, isocaloric HFD (n = 20) for 23 weeks. Combined analysis of several parameters including insulin resistance, histology of liver and adipose tissue, intestinal microbiota in three gut compartments, gut barrier function, gene expression, urinary metabolites and immune profiles in intestinal, lymphoid, liver and adipose tissues was performed. Mice fed the gliadin-containing HFD displayed higher glycated hemoglobin and higher insulin resistance as evaluated by the homeostasis model assessment, more hepatic lipid accumulation and smaller adipocytes than mice fed the gliadin-free HFD. This was accompanied by alterations in the composition and activity of the gut microbiota, gut barrier function, urine metabolome, and immune phenotypes within liver and adipose tissue. Our results reveal that gliadin disturbs the intestinal environment and affects metabolic homeostasis in obese mice, suggesting a detrimental effect of gluten intake in gluten-tolerant subjects consuming a high-fat diet. PMID:28300220

  13. [Activation of the neuroendocrine system during changes in homeostasis during stress conditions].

    Science.gov (United States)

    Vigas, M; Jezová, D

    1996-02-01

    Neuroendocrine response to stress stimuli is aimed to maintain body homeostasis. The activation of the neuroendocrine system is accomplished mainly by two ways: by feedback regulation based on the recognition of altered metabolic homeostasis by appropriate receptors sending the signal into the CNS, and by forward regulation involving a direct stimulation of the neuroendocrine system by a central command coming from an activated brain regulatory center. With regard to mechanisms of neuroendocrine activation, the signal specificity and site of its origin are of particular importance. The significance of the signal in neuroendocrine responses has been evaluated in three different stress conditions: hypoglycemia, surgical trauma and dynamic physical exercise. The stimulus inducing neuroendocrine response during hypoglycemia is the glucopenia. The signal for the activation of the neuroendocrine response is generated in glucosensitive cells which are not located in a single brain structure (hypothetical glucostat). The signal for growth hormone, vasopressin and oxytocin release is produced in brain structures protected by the blood-brain barrier, that for ACTH release in regions both protected and unprotected by the barrier, while the signal for prolactin release is generated in tissues lacking the blood-brain barrier. The neuroendocrine response during surgical trauma is activated by a signal formed in the damaged tissue reaching the CNS by neural pathways. Moreover, cytokins may participate on endocrine stimulation in those surgical interventions in which a large amount of bacterial endotoxins is released. During a complicated surgery, e.g. during a bypass other signals and modifying factors, such as hypothermia, dilution of blood, hypoperfusion of organs, rewarming of the body and hormone degradation in the oxygenator are important. On the On the other hand, during a short-term dynamic exercise, a forward regulation by a central signal from the activated CNS motor

  14. Barrier mechanisms in the Drosophila blood-brain barrier

    OpenAIRE

    Samantha Jane Hindle; Roland Jerome Bainton

    2014-01-01

    The invertebrate blood-brain barrier field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through GPCR signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate blood-brain barrier has recently been shown to require coordinated funct...

  15. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Ryu HJ

    2014-12-01

    Full Text Available Hwa Jung Ryu,1,* Mu Yeb Seo,2,* Sung Kyu Jung,1 Eun Ho Maeng,2 Seung-Young Lee,2 Dong-Hyouk Jang,2 Taek-Jin Lee,2 Ki-Yeon Jo,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Meyoung-Kon Kim,3 Beom Jun Lee,5 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, 2Korea Testing and Research Institute, Gyunggido, 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, 5College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea *These authors contributed equally to this work and both should be considered first authors Abstract: Zinc oxide (ZnO works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there

  16. Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes.

    Science.gov (United States)

    Murray, A R; Kisin, E; Leonard, S S; Young, S H; Kommineni, C; Kagan, V E; Castranova, V; Shvedova, A A

    2009-03-29

    Single-walled carbon nanotubes (SWCNT) represent a novel material with unique electronic and mechanical properties. The extremely small size ( approximately 1 nm diameter) renders their chemical and physical properties unique. A variety of different techniques are available for the production of SWCNT; however, the most common is via the disproportionation of gaseous carbon molecules supported on catalytic iron particles (high-pressure CO conversion, HiPCO). The physical nature of SWCNT may lead to dermal penetration following deposition on exposed skin. This dermal deposition provides a route of exposure which is important to consider when evaluating SWCNT toxicity. The dermal effects of SWCNT are largely unknown. We hypothesize that SWCNT may be toxic to the skin. We further hypothesize that SWCNT toxicity may be dependent upon the metal (particularly iron) content of SWCNT via the metal's ability to interact with the skin, initiate oxidative stress, and induce redox-sensitive transcription factors thereby affecting/leading to inflammation. To test this hypothesis, the effects of SWCNT were assessed both in vitro and in vivo using EpiDerm FT engineered skin, murine epidermal cells (JB6 P+), and immune-competent hairless SKH-1 mice. Engineered skin exposed to SWCNT showed increased epidermal thickness and accumulation and activation of dermal fibroblasts which resulted in increased collagen as well as release of pro-inflammatory cytokines. Exposure of JB6 P+ cells to unpurified SWCNT (30% iron) resulted in the production of ESR detectable hydroxyl radicals and caused a significant dose-dependent activation of AP-1. No significant changes in AP-1 activation were detected when partially purified SWCNT (0.23% iron) were introduced to the cells. However, NFkappaB was activated in a dose-dependent fashion by exposure to both unpurified and partially purified SWCNT. Topical exposure of SKH-1 mice (5 days, with daily doses of 40 microg/mouse, 80 microg/mouse, or 160

  17. Geophysical characterization of subsurface barriers

    Energy Technology Data Exchange (ETDEWEB)

    Borns, D.J.

    1995-08-01

    An option for controlling contaminant migration from plumes and buried waste sites is to construct a subsurface barrier of a low-permeability material. The successful application of subsurface barriers requires processes to verify the emplacement and effectiveness of barrier and to monitor the performance of a barrier after emplacement. Non destructive and remote sensing techniques, such as geophysical methods, are possible technologies to address these needs. The changes in mechanical, hydrologic and chemical properties associated with the emplacement of an engineered barrier will affect geophysical properties such a seismic velocity, electrical conductivity, and dielectric constant. Also, the barrier, once emplaced and interacting with the in situ geologic system, may affect the paths along which electrical current flows in the subsurface. These changes in properties and processes facilitate the detection and monitoring of the barrier. The approaches to characterizing and monitoring engineered barriers can be divided between (1) methods that directly image the barrier using the contrasts in physical properties between the barrier and the host soil or rock and (2) methods that reflect flow processes around or through the barrier. For example, seismic methods that delineate the changes in density and stiffness associated with the barrier represents a direct imaging method. Electrical self potential methods and flow probes based on heat flow methods represent techniques that can delineate the flow path or flow processes around and through a barrier.

  18. TCR down-regulation controls T cell homeostasis

    DEFF Research Database (Denmark)

    Boding, Lasse; Bonefeld, Charlotte Menné; Nielsen, Bodil L

    2009-01-01

    was caused by the combination of reduced thymic output, decreased T cell apoptosis, and increased transition of naive T cells to memory T cells. Experiments with bone marrow chimeric mice confirmed that the CD3gammaLLAA mutation exerted a T cell intrinsic effect on T cell homeostasis that resulted...... in an increased transition of CD3gammaLLAA naive T cells to memory T cells and a survival advantage of CD3gammaLLAA T cells compared with wild-type T cells. The experimental observations were further supported by mathematical modeling of T cell homeostasis. Our study thus identifies an important role of CD3gamma......-mediated TCR down-regulation in T cell homeostasis....

  19. Histamine Induces Vascular Hyperpermeability by Increasing Blood Flow and Endothelial Barrier Disruption In Vivo.

    Science.gov (United States)

    Ashina, Kohei; Tsubosaka, Yoshiki; Nakamura, Tatsuro; Omori, Keisuke; Kobayashi, Koji; Hori, Masatoshi; Ozaki, Hiroshi; Murata, Takahisa

    2015-01-01

    Histamine is a mediator of allergic inflammation released mainly from mast cells. Although histamine strongly increases vascular permeability, its precise mechanism under in vivo situation remains unknown. We here attempted to reveal how histamine induces vascular hyperpermeability focusing on the key regulators of vascular permeability, blood flow and endothelial barrier. Degranulation of mast cells by antigen-stimulation or histamine treatment induced vascular hyperpermeability and tissue swelling in mouse ears. These were abolished by histamine H1 receptor antagonism. Intravital imaging showed that histamine dilated vasculature, increased blood flow, while it induced hyperpermeability in venula. Whole-mount staining showed that histamine disrupted endothelial barrier formation of venula indicated by changes in vascular endothelial cadherin (VE-cadherin) localization at endothelial cell junction. Inhibition of nitric oxide synthesis (NOS) by L-NAME or vasoconstriction by phenylephrine strongly inhibited the histamine-induced blood flow increase and hyperpermeability without changing the VE-cadherin localization. In vitro, measurements of trans-endothelial electrical resistance of human dermal microvascular endothelial cells (HDMECs) showed that histamine disrupted endothelial barrier. Inhibition of protein kinase C (PKC) or Rho-associated protein kinase (ROCK), NOS attenuated the histamine-induced barrier disruption. These observations suggested that histamine increases vascular permeability mainly by nitric oxide (NO)-dependent vascular dilation and subsequent blood flow increase and maybe partially by PKC/ROCK/NO-dependent endothelial barrier disruption.

  20. Embryonic Blood-Cerebrospinal Fluid Barrier Formation and Function

    Directory of Open Access Journals (Sweden)

    David eBueno

    2014-10-01

    Full Text Available During embryonic development and adult life, brain cavities and ventricles are filled with cerebrospinal fluid (CSF. CSF has attracted interest as an active signaling medium that regulates brain development, homeostasis and disease. CSF is a complex protein-rich fluid containing growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS. The composition and substance concentrations of CSF are tightly controlled. In recent years, it has been demonstrated that embryonic CSF (eCSF has a key function as a fluid pathway for delivering diffusible signals to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. From fetal stages through to adult life, CSF is primarily produced by the choroid plexus. The development and functional activities of the choroid plexus and other blood–brain barrier (BBB systems in adults and fetuses have been extensively analyzed. However, eCSF production and control of its homeostasis in embryos, from the closure of the anterior neuropore when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus, has not been studied in as much depth and remains open to debate. This review brings together the existing literature, some of which is based on experiments conducted by our research group, concerning the formation and function of a temporary embryonic blood–CSF barrier in the context of the crucial roles played by the molecules in eCSF.