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Sample records for skin tissue heterogeneity

  1. Biothermomechanics of skin tissues

    NASA Astrophysics Data System (ADS)

    Xu, F.; Lu, T. J.; Seffen, K. A.

    Biothermomechanics of skin is highly interdisciplinary involving bioheat transfer, burn damage, biomechanics and neurophysiology. During heating, thermally induced mechanical stress arises due to the thermal denaturation of collagen, resulting in macroscale shrinkage. Thus, the strain, stress, temperature and thermal pain/damage are highly correlated; in other words, the problem is fully coupled. The aim of this study is to develop a computational approach to examine the heat transfer process and the heat-induced mechanical response, so that the differences among the clinically applied heating modalities can be quantified. Exact solutions for temperature, thermal damage and thermal stress for a single-layer skin model were first derived for different boundary conditions. For multilayer models, numerical simulations using the finite difference method (FDM) and finite element method (FEM) were used to analyze the temperature, burn damage and thermal stress distributions in the skin tissue. The results showed that the thermomechanical behavior of skin tissue is very complex: blood perfusion has little effect on thermal damage but large influence on skin temperature distribution, which, in turn, influences significantly the resulting thermal stress field; the stratum corneum layer, although very thin, has a large effect on the thermomechanical behavior of skin, suggesting that it should be properly accounted for in the modeling of skin thermal stresses; the stress caused by non-uniform temperature distribution in the skin may also contribute to the thermal pain sensation.

  2. Skin tissue engineering.

    PubMed

    Mansbridge, Jonathan

    2008-01-01

    The major applications of tissue-engineered skin substitutes are in promoting the healing of acute and chronic wounds. Several approaches have been taken by commercial companies to develop products to address these conditions. Skin substitutes include both acellular and cellular devices. While acellular skin substitutes act as a template for dermal formation, this discussion mainly covers cellular devices. In addressing therapeutic applications in tissue engineering generally, a valuable precursor is an understanding of the mechanism of the underlying pathology. While this is straightforward in many cases, it has not been available for wound healing. Investigation of the mode of action of the tissue-engineered skin substitutes has led to considerable insight into the mechanism of formation, maintenance and treatment of chronic wounds. Four aspects mediating healing are considered here for their mechanism of action: (i) colonization of the wound bed by live fibroblasts in the implant, (ii) the secretion of growth factors, (iii) provision of a suitable substrate for cell migration, particularly keratinocytes and immune cells, and (iv) modification of the immune system by secretion of neutrophil recruiting chemokines. An early event in acute wound healing is an influx of neutrophils that destroy planktonic bacteria. However, if the bacteria are able to form biofilm, they become resistant to neutrophil action and prevent reepithelialization. In this situation the wound becomes chronic. In chronic wounds, fibroblasts show a senescence-like phenotype with decreased secretion of neutrophil chemoattractants that make it more likely that biofilms become established. Treatment of the chronic wounds involves debridement to eliminate biofilm, and the use of antimicrobials. A role of skin substitutes is to provide non-senescent fibroblasts that attract and activate neutrophils to prevent biofilm re-establishment. The emphasis of the conclusion is the importance of preventing

  3. Tissue Engineered Human Skin Equivalents

    PubMed Central

    Zhang, Zheng; Michniak-Kohn, Bozena B.

    2012-01-01

    Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed. PMID:24300178

  4. Tissue-engineered skin substitutes.

    PubMed

    Mansbridge, Jonathan

    2002-01-01

    The last two years have seen new tissue-engineered skin substitutes come onto the market and begin to resolve the various roles to which each is best suited. It is becoming evident that some of the very expensive cell-based products have cost-benefit advantage despite their high price and are valuable within the restricted applications for which they are intended. The use of skin substitutes for testing purposes has extended from epidermal keratinocytes to other integumentary epithelia and into preparations containing multiple cell types in which reactions resulting from paracrine interactions can be examined. Challenges remain in the application of gene therapy techniques to skin substitutes, both the control of transgene expression and in the selection of suitable genes to transfect. A coming challenge is the production of tissue-engineered products without the use of animal products other than human cells. A challenge that may be diminishing is the importance of acute rejection of allogeneic tissue-engineered skin substitutes.

  5. Tissue engineering of skin for wound coverage.

    PubMed

    Biedermann, Thomas; Boettcher-Haberzeth, Sophie; Reichmann, Ernst

    2013-10-01

    Over the past few decades, important milestones have been reached in the field of skin tissue engineering, bringing the ultimate goal of fabricating an autologous dermoepidermal skin substitute with all its cellular components and skin appendages closer to reality. Yet, scientific progress alone is not enough, clinical demands must be addressed and commercial interests need to be fulfilled. This review gives an overview of commercially available skin substitutes for skin replacement therapies and an insight into the recent development of an autologous full-thickness skin substitute that can readily be transplanted in large quantities onto the patient. Georg Thieme Verlag KG Stuttgart · New York.

  6. Macrophage heterogeneity and tissue lipids.

    PubMed

    Gordon, Siamon

    2007-01-01

    Macrophages are present as resident cells in adipose tissue, and blood monocytes are recruited in increased numbers to sites of lipid accumulation in atherosclerosis, a modified form of inflammation in the arterial wall. Recent findings reported by 3 separate groups in this issue of the JCI provide evidence for distinct monocyte subsets, differential chemokine receptor usage, and phenotypic modulation of macrophages in murine models of genetic and high-fat diet-induced disease (see the related articles beginning on pages 175, 185, and 195). These studies raise prospects for selective therapeutic targets to ameliorate macrophage hyperinflammatory responses, while sparing host defense and repair mechanisms.

  7. Fibroblast heterogeneity: more than skin deep.

    PubMed

    Sorrell, J Michael; Caplan, Arnold I

    2004-02-15

    Dermal fibroblasts are a dynamic and diverse population of cells whose functions in skin in many respects remain unknown. Normal adult human skin contains at least three distinct subpopulations of fibroblasts, which occupy unique niches in the dermis. Fibroblasts from each of these niches exhibit distinctive differences when cultured separately. Specific differences in fibroblast physiology are evident in papillary dermal fibroblasts, which reside in the superficial dermis, and reticular fibroblasts, which reside in the deep dermis. Both of these subpopulations of fibroblasts differ from the fibroblasts that are associated with hair follicles. Fibroblasts engage in fibroblast-epidermal interactions during hair development and in interfollicular regions of skin. They also play an important role in cutaneous wound repair and an ever-increasing role in bioengineering of skin. Bioengineered skin currently performs important roles in providing (1) a basic understanding of skin biology, (2) a vehicle for testing topically applied products and (3) a resource for skin replacement.

  8. Skin connective tissue and ageing.

    PubMed

    Calleja-Agius, Jean; Brincat, Mark; Borg, Marika

    2013-10-01

    Collagen atrophy is a major factor in skin ageing. A strong correlation exists between skin collagen loss and oestrogen deficiency caused by the menopause. Skin ageing is associated with a progressive increase in extensibility and a reduction in elasticity. With increasing age, the skin also becomes more fragile and susceptible to trauma, leading to more lacerations and bruising. Furthermore, wound healing is impaired in older women. Oestrogen use after the menopause increases collagen content, dermal thickness and elasticity, and it decreases the likelihood of senile dry skin. Large-scale clinical trials are necessary to help make informed recommendations about postmenopausal oestrogen use and its role in preventing skin ageing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Nanomaterials and nanotechnology for skin tissue engineering

    PubMed Central

    Mohamed, Aezeden; Xing, Malcolm (Mengqiu)

    2012-01-01

    A recent literature review of the field shows that tissue-engineered skin has been in clinical use for the last several decades and that, over this time the technology has advanced rapidly. Despite this progress no synthetic skin yet produced has completely replicated normal, healthy skin. Therefore, researchers must continue to develop materials that successfully overcome the problems with current skin tissue substitutes. This paper is a comprehensive review of the prospects for nanotechnology and nanomaterials to close this gap by mimicking surface properties for reconstruction of a variety of skin tissues. In addition, a number of commercially available products that regenerate different layers of the burn-damaged or chronically wounded skin are reviewed. PMID:22928165

  10. Advances in Skin Regeneration Using Tissue Engineering

    PubMed Central

    Vig, Komal; Chaudhari, Atul; Tripathi, Shweta; Dixit, Saurabh; Sahu, Rajnish; Pillai, Shreekumar; Dennis, Vida A.; Singh, Shree R.

    2017-01-01

    Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application. PMID:28387714

  11. MicroRNAs in skin tissue engineering.

    PubMed

    Miller, Kyle J; Brown, David A; Ibrahim, Mohamed M; Ramchal, Talisha D; Levinson, Howard

    2015-07-01

    35.2 million annual cases in the U.S. require clinical intervention for major skin loss. To meet this demand, the field of skin tissue engineering has grown rapidly over the past 40 years. Traditionally, skin tissue engineering relies on the "cell-scaffold-signal" approach, whereby isolated cells are formulated into a three-dimensional substrate matrix, or scaffold, and exposed to the proper molecular, physical, and/or electrical signals to encourage growth and differentiation. However, clinically available bioengineered skin equivalents (BSEs) suffer from a number of drawbacks, including time required to generate autologous BSEs, poor allogeneic BSE survival, and physical limitations such as mass transfer issues. Additionally, different types of skin wounds require different BSE designs. MicroRNA has recently emerged as a new and exciting field of RNA interference that can overcome the barriers of BSE design. MicroRNA can regulate cellular behavior, change the bioactive milieu of the skin, and be delivered to skin tissue in a number of ways. While it is still in its infancy, the use of microRNAs in skin tissue engineering offers the opportunity to both enhance and expand a field for which there is still a vast unmet clinical need. Here we give a review of skin tissue engineering, focusing on the important cellular processes, bioactive mediators, and scaffolds. We further discuss potential microRNA targets for each individual component, and we conclude with possible future applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Tissue engineering of cultured skin substitutes.

    PubMed

    Horch, Raymund E; Kopp, Jürgen; Kneser, Ulrich; Beier, Justus; Bach, Alexander D

    2005-01-01

    Skin replacement has been a challenging task for surgeons ever since the introduction of skin grafts by Reverdin in 1871. Recently, skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements. This has been fostered by the dramatically improved survival rates of major burns where the availability of autologous normal skin for grafting has become one of the limiting factors. The ideal properties of a temporary and a permanent skin substitute have been well defined. Tissue-engineered skin replacements: cultured autologous keratinocyte grafts, cultured allogeneic keratinocyte grafts, autologous/allogeneic composites, acellular biological matrices, and cellular matrices including such biological substances as fibrin sealant and various types of collagen, hyaluronic acid etc. have opened new horizons to deal with such massive skin loss. In extensive burns it has been shown that skin substitution with cultured grafts can be a life-saving measure where few alternatives exist. Future research will aim to create skin substitutes with cultured epidermis that under appropriate circumstances may provide a wound cover that could be just as durable and esthetically acceptable as conventional split-thickness skin grafts. Genetic manipulation may in addition enhance the performance of such cultured skin substitutes. If cell science, molecular biology, genetic engineering, material science and clinical expertise join their efforts to develop optimized cell culture techniques and synthetic or biological matrices then further technical advances might well lead to the production of almost skin like new tissue-engineered human skin products resembling natural human skin.

  13. Tissue macrophage heterogeneity: issues and prospects.

    PubMed

    Gordon, Siamon; Plűddemann, Annette

    2013-09-01

    The vast majority of macrophages in the body are present in tissues outside the circulation, yet their remarkable phenotypic heterogeneity within different anatomical compartments in the steady state and disease remains essentially unexplored. The development of immunocytochemical and fluorescent histological methods has revealed the presence and morphological diversity of macrophages within tissues, especially in the mouse, but functional specialisation in situ is difficult to establish and their mechanistic basis remains unknown, particularly in humans, in spite of the rich material available. In this review, we consider some of the technical issues that hamper investigation, assess the contribution of cell differentiation and modulation to macrophage heterogeneity within tissues and illustrate variation of macrophages and closely related cells in selected organs in mouse and man.

  14. Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro.

    PubMed

    Sriram, Gopu; Bigliardi, Paul Lorenz; Bigliardi-Qi, Mei

    2015-11-01

    Advances in cell culture methods, multidisciplinary research, clinical need to replace lost skin tissues and regulatory need to replace animal models with alternative test methods has led to development of three dimensional models of human skin. In general, these in vitro models of skin consist of keratinocytes cultured over fibroblast-populated dermal matrices. Accumulating evidences indicate that mesenchyme-derived signals are essential for epidermal morphogenesis, homeostasis and differentiation. Various studies show that fibroblasts isolated from different tissues in the body are dynamic in nature and are morphologically and functionally heterogeneous subpopulations. Further, these differences seem to be dictated by the local biological and physical microenvironment the fibroblasts reside resulting in "positional identity or memory". Furthermore, the heterogeneity among the fibroblasts play a critical role in scarless wound healing and complete restoration of native tissue architecture in fetus and oral mucosa; and excessive scar formation in diseased states like keloids and hypertrophic scars. In this review, we summarize current concepts about the heterogeneity among fibroblasts and their role in various wound healing environments. Further, we contemplate how the insights on fibroblast heterogeneity could be applied for the development of next generation organotypic skin models. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

  15. Videofetoscopically assisted fetal tissue engineering: skin replacement.

    PubMed

    Fauza, D O; Fishman, S J; Mehegan, K; Atala, A

    1998-02-01

    Treatment of several congenital anomalies is frequently hindered by lack of enough tissue for surgical reconstruction in the neonatal period. The purposes of this study were (1) introduction of a novel concept in perinatal surgery, involving minimally invasive harvest of fetal tissue, which is then processed through tissue engineering techniques in vitro while pregnancy is allowed to continue, so that, at delivery, the newborn can benefit from having autologous, expanded tissue promptly available for surgical implantation at birth; (2) analysis of the progress of an engineered fetal skin graft with time, after implantation in the neonate; and (3) study of the effects of current tissue engineering techniques on fetal keratinocytes and fetal dermal fibroblasts. Ten 90- to 95-day-gestation fetal lambs underwent surgical creation of two large paramedian excisional skin defects on the posterior body wall. Subsequently, fetal skin specimens no larger than 1.5 x 1.5 cm were videofetoscopically harvested. Fetal keratinocytes and dermal fibroblasts were then separately cultivated and expanded in vitro for 45 to 50 days, resulting in a total of approximately 250 to 300 million cells. Seven to 10 days before fetal delivery, all cells were seeded in two layers on a 16 to 20-cm2, 3-mm thick biodegradable polyglycolic acid polymer matrix. One to 4 days after delivery, the autologous engineered skin was implanted over one of two previously created skin defects. The second skin defect region received an absorbable polymer scaffold without cells as a control. If necessary, the original skin wounds were further amplified before implantation. Each animal provided at least one time-point for histological analysis of both types of repair through excisional biopsies performed at weekly intervals, up to 8 weeks postimplantation. Normal skin specimens were also used as controls. Fetal and neonatal survival rates were 100%. Based on previous postnatal skin engineering studies, fetal dermal

  16. Building Epithelial Tissues from Skin Stem Cells

    PubMed Central

    Fuchs, E.; Nowak, J.A.

    2009-01-01

    The skin epidermis and its appendages provide a protective barrier that guards against loss of fluids, physical trauma, and invasion by harmful microbes. To perform these functions while confronting the harsh environs of the outside world, our body surface undergoes constant rejuvenation through homeostasis. In addition, it must be primed to repair wounds in response to injury. The adult skin maintains epidermal homeostasis, hair regeneration, and wound repair through the use of its stem cells. What are the properties of skin stem cells, when do they become established during embryogenesis, and how are they able to build tissues with such remarkably distinct architectures? How do stem cells maintain tissue homeostasis and repair wounds and how do they regulate the delicate balance between proliferation and differentiation? What is the relationship between skin cancer and mutations that perturbs the regulation of stem cells? In the past 5 years, the field of skin stem cells has bloomed as we and others have been able to purify and dissect the molecular properties of these tiny reservoirs of goliath potential. We report here progress on these fronts, with emphasis on our laboratory’s contributions to the fascinating world of skin stem cells. PMID:19022769

  17. Transport lattice models of heat transport in skin with spatially heterogeneous, temperature-dependent perfusion.

    PubMed

    Gowrishankar, T R; Stewart, Donald A; Martin, Gregory T; Weaver, James C

    2004-11-17

    Investigation of bioheat transfer problems requires the evaluation of temporal and spatial distributions of temperature. This class of problems has been traditionally addressed using the Pennes bioheat equation. Transport of heat by conduction, and by temperature-dependent, spatially heterogeneous blood perfusion is modeled here using a transport lattice approach. We represent heat transport processes by using a lattice that represents the Pennes bioheat equation in perfused tissues, and diffusion in nonperfused regions. The three layer skin model has a nonperfused viable epidermis, and deeper regions of dermis and subcutaneous tissue with perfusion that is constant or temperature-dependent. Two cases are considered: (1) surface contact heating and (2) spatially distributed heating. The model is relevant to the prediction of the transient and steady state temperature rise for different methods of power deposition within the skin. Accumulated thermal damage is estimated by using an Arrhenius type rate equation at locations where viable tissue temperature exceeds 42 degrees C. Prediction of spatial temperature distributions is also illustrated with a two-dimensional model of skin created from a histological image. The transport lattice approach was validated by comparison with an analytical solution for a slab with homogeneous thermal properties and spatially distributed uniform sink held at constant temperatures at the ends. For typical transcutaneous blood gas sensing conditions the estimated damage is small, even with prolonged skin contact to a 45 degrees C surface. Spatial heterogeneity in skin thermal properties leads to a non-uniform temperature distribution during a 10 GHz electromagnetic field exposure. A realistic two-dimensional model of the skin shows that tissue heterogeneity does not lead to a significant local temperature increase when heated by a hot wire tip. The heat transport system model of the skin was solved by exploiting the mathematical

  18. Transport lattice models of heat transport in skin with spatially heterogeneous, temperature-dependent perfusion

    PubMed Central

    Gowrishankar, TR; Stewart, Donald A; Martin, Gregory T; Weaver, James C

    2004-01-01

    Background Investigation of bioheat transfer problems requires the evaluation of temporal and spatial distributions of temperature. This class of problems has been traditionally addressed using the Pennes bioheat equation. Transport of heat by conduction, and by temperature-dependent, spatially heterogeneous blood perfusion is modeled here using a transport lattice approach. Methods We represent heat transport processes by using a lattice that represents the Pennes bioheat equation in perfused tissues, and diffusion in nonperfused regions. The three layer skin model has a nonperfused viable epidermis, and deeper regions of dermis and subcutaneous tissue with perfusion that is constant or temperature-dependent. Two cases are considered: (1) surface contact heating and (2) spatially distributed heating. The model is relevant to the prediction of the transient and steady state temperature rise for different methods of power deposition within the skin. Accumulated thermal damage is estimated by using an Arrhenius type rate equation at locations where viable tissue temperature exceeds 42°C. Prediction of spatial temperature distributions is also illustrated with a two-dimensional model of skin created from a histological image. Results The transport lattice approach was validated by comparison with an analytical solution for a slab with homogeneous thermal properties and spatially distributed uniform sink held at constant temperatures at the ends. For typical transcutaneous blood gas sensing conditions the estimated damage is small, even with prolonged skin contact to a 45°C surface. Spatial heterogeneity in skin thermal properties leads to a non-uniform temperature distribution during a 10 GHz electromagnetic field exposure. A realistic two-dimensional model of the skin shows that tissue heterogeneity does not lead to a significant local temperature increase when heated by a hot wire tip. Conclusions The heat transport system model of the skin was solved by

  19. Skin tissue generation by laser cell printing.

    PubMed

    Koch, Lothar; Deiwick, Andrea; Schlie, Sabrina; Michael, Stefanie; Gruene, Martin; Coger, Vincent; Zychlinski, Daniela; Schambach, Axel; Reimers, Kerstin; Vogt, Peter M; Chichkov, Boris

    2012-07-01

    For the aim of ex vivo engineering of functional tissue substitutes, Laser-assisted BioPrinting (LaBP) is under investigation for the arrangement of living cells in predefined patterns. So far three-dimensional (3D) arrangements of single or two-dimensional (2D) patterning of different cell types have been presented. It has been shown that cells are not harmed by the printing procedure. We now demonstrate for the first time the 3D arrangement of vital cells by LaBP as multicellular grafts analogous to native archetype and the formation of tissue by these cells. For this purpose, fibroblasts and keratinocytes embedded in collagen were printed in 3D as a simple example for skin tissue. To study cell functions and tissue formation process in 3D, different characteristics, such as cell localisation and proliferation were investigated. We further analysed the formation of adhering and gap junctions, which are fundamental for tissue morphogenesis and cohesion. In this study, it was demonstrated that LaBP is an outstanding tool for the generation of multicellular 3D constructs mimicking tissue functions. These findings are promising for the realisation of 3D in vitro models and tissue substitutes for many applications in tissue engineering. Copyright © 2012 Wiley Periodicals, Inc.

  20. [Skin and tissue bank: Operational model for the recovery and preservation of tissues and skin allografts].

    PubMed

    Martínez-Flores, Francisco; Sandoval-Zamora, Hugo; Machuca-Rodriguez, Catalina; Barrera-López, Araceli; García-Cavazos, Ricardo; Madinaveitia-Villanueva, Juan Antonio

    2016-01-01

    Tissue storage is a medical process that is in the regulation and homogenisation phase in the scientific world. The international standards require the need to ensure safety and efficacy of human allografts such as skin and other tissues. The activities of skin and tissues banks currently involve their recovery, processing, storage and distribution, which are positively correlated with technological and scientific advances present in current biomedical sciences. A description is presented of the operational model of Skin and Tissue Bank at INR as successful case for procurement, recovery and preservation of skin and tissues for therapeutic uses, with high safety and biological quality. The essential and standard guidelines are presented as keystones for a tissue recovery program based on scientific evidence, and within an ethical and legal framework, as well as to propose a model for complete overview of the donation of tissues and organ programs in Mexico. Finally, it concludes with essential proposals for improving the efficacy of transplantation of organs and tissue programs. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  1. Progress and opportunities for tissue-engineered skin

    NASA Astrophysics Data System (ADS)

    MacNeil, Sheila

    2007-02-01

    Tissue-engineered skin is now a reality. For patients with extensive full-thickness burns, laboratory expansion of skin cells to achieve barrier function can make the difference between life and death, and it was this acute need that drove the initiation of tissue engineering in the 1980s. A much larger group of patients have ulcers resistant to conventional healing, and treatments using cultured skin cells have been devised to restart the wound-healing process. In the laboratory, the use of tissue-engineered skin provides insight into the behaviour of skin cells in healthy skin and in diseases such as vitiligo, melanoma, psoriasis and blistering disorders.

  2. Fibrotic remodeling of tissue-engineered skin with deep dermal fibroblasts is reduced by keratinocytes.

    PubMed

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

    2014-02-01

    Two-thirds of burn patients with deep dermal injuries are affected by hypertrophic scars, and currently, there are no clinically effective therapies. Tissue-engineered skin is a very promising model for the elucidation of the role of matrix microenvironment and biomechanical characteristics and could help in the identification of new therapeutic targets for hypertrophic scars. Conventionally, tissue-engineered skin is made of heterogeneous dermal fibroblasts and keratinocytes; however, recent work has shown that superficial and deep dermal fibroblasts are antifibrotic and profibrotic, respectively. Furthermore, keratinocytes are believed to regulate the development and remodeling of fibrosis in skin. This study aimed to assess the influence of keratinocytes and layered fibroblasts on the characteristics of tissue-engineered skin. Layered fibroblasts and keratinocytes isolated from superficial and deep dermis and epidermis, respectively, of the lower abdominal tissue were independently co-cultured on collagen-glycosaminoglycan scaffolds, and the resulting tissue-engineered skin was assessed for differences in tissue remodeling based on the underlying specific dermal fibroblast subpopulation. Collagen production by deep fibroblasts but not by superficial fibroblasts was significantly reduced upon co-culture with keratinocytes. Also, keratinocytes in the tissue-engineered skin resulted in significantly reduced expression of profibrotic connective tissue growth factor and fibronectin, and increased expression of the antifibrotic matrix metalloproteinase-1 by deep fibroblasts but not by superficial fibroblasts. Tissue-engineered skin made of deep fibroblasts and keratinocytes had lower levels of small proteoglycans, decorin, and fibromodulin, and higher levels of large proteoglycan, versican, compared to tissue-engineered skin made of superficial fibroblasts and keratinocytes. Tissue-engineered skin made of deep fibroblasts and keratinocytes had lower expression of

  3. Heterogeneities in Leishmania infantum Infection: Using Skin Parasite Burdens to Identify Highly Infectious Dogs

    PubMed Central

    Calvo-Bado, Leo; Garcez, Lourdes M.; Quinnell, Rupert J.

    2014-01-01

    Background The relationships between heterogeneities in host infection and infectiousness (transmission to arthropod vectors) can provide important insights for disease management. Here, we quantify heterogeneities in Leishmania infantum parasite numbers in reservoir and non-reservoir host populations, and relate this to their infectiousness during natural infection. Tissue parasite number was evaluated as a potential surrogate marker of host transmission potential. Methods Parasite numbers were measured by qPCR in bone marrow and ear skin biopsies of 82 dogs and 34 crab-eating foxes collected during a longitudinal study in Amazon Brazil, for which previous data was available on infectiousness (by xenodiagnosis) and severity of infection. Results Parasite numbers were highly aggregated both between samples and between individuals. In dogs, total parasite abundance and relative numbers in ear skin compared to bone marrow increased with the duration and severity of infection. Infectiousness to the sandfly vector was associated with high parasite numbers; parasite number in skin was the best predictor of being infectious. Crab-eating foxes, which typically present asymptomatic infection and are non-infectious, had parasite numbers comparable to those of non-infectious dogs. Conclusions Skin parasite number provides an indirect marker of infectiousness, and could allow targeted control particularly of highly infectious dogs. PMID:24416460

  4. Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

    PubMed

    Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

    2016-10-01

    In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Adipose tissue: cell heterogeneity and functional diversity.

    PubMed

    Esteve Ràfols, Montserrat

    2014-02-01

    There are two types of adipose tissue in the body whose function appears to be clearly differentiated. White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat. A good balance between them is important to maintain energy homeostasis. The concept of white adipose tissue has radically changed in the past decades, and is now considered as an endocrine organ that secretes many factors with autocrine, paracrine, and endocrine functions. In addition, we can no longer consider white adipose tissue as a single tissue, because it shows different metabolic profiles in its different locations, with also different implications. Although the characteristic cell of adipose tissue is the adipocyte, this is not the only cell type present in adipose tissue, neither the most abundant. Other cell types in adipose tissue described include stem cells, preadipocytes, macrophages, neutrophils, lymphocytes, and endothelial cells. The balance between these different cell types and their expression profile is closely related to maintenance of energy homeostasis. Increases in adipocyte size, number and type of lymphocytes, and infiltrated macrophages are closely related to the metabolic syndrome diseases. The study of regulation of proliferation and differentiation of preadipocytes and stem cells, and understanding of the interrelationship between the different cell types will provide new targets for action against these diseases. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  6. Determination of Tumor Heterogeneity in Colorectal Cancers Using Heterogeneity Tissue Microarrays.

    PubMed

    Stahl, Phillip R; Schnellert, Jessica; Koop, Christina; Simon, Ronald; Marx, Andreas; Izbicki, Jakob R; Sauter, Guido; Quaas, Alexander

    2015-09-01

    Cancer is often heterogeneous both on a morphological and on a genetic level. Though resected tumors are often large, molecular tumor analysis is usually restricted to one tissue block. In this project we introduce a new tool for a high-throughput heterogeneity analysis of colorectal cancer. A heterogeneity tissue microarray (TMA) was manufactured from tissues of 340 patients with colorectal cancer. For this purpose 8 different tissue spots were taken from as many different cancer blocks per patient as possible (at least 4 different blocks). Additional tissue samples from 1 to 4 corresponding lymph node metastases were added from 134 patients. The system was then validated by analysing one parameter each known for minimal (p53) or substantial (HER2) heterogeneity in colorectal cancer. P53 alterations as detected by immunohistochemistry were seen in 174 (51.3 %) of 339 analyzable primary tumors of which 23 (13.2 % of positive cases) showed a heterogeneous distribution pattern. HER2 overexpression was seen in 18 (5.4 %) of 336 evaluable tumors. HER2 amplification occurred in 6 (33.3 %) of the 18 cases with HER2 overexpression. Genomic heterogeneity was more prevalent for HER2 alterations than for p53 alterations. For immunohistochemical expression analysis, 16 of 18 positive cases were heterogeneous (88.9 %) and for amplification 3 of 6 cases (50 %) were heterogeneous. Large section validation revealed, however a considerable fraction of heterogeneous cases were due to technical artifacts. In summary, our data suggest, that heterogeneity TMAs are a powerful tool to rapidly screen for molecular heterogeneity in colorectal cancer.

  7. In vitro skin models and tissue engineering protocols for skin graft applications.

    PubMed

    Naves, Lucas B; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram

    2016-11-30

    In this review, we present a brief introduction of the skin structure, a concise compilation of skin-related disorders, and a thorough discussion of different in vitro skin models, artificial skin substitutes, skin grafts, and dermal tissue engineering protocols. The advantages of the development of in vitro skin disorder models, such as UV radiation and the prototype model, melanoma model, wound healing model, psoriasis model, and full-thickness model are also discussed. Different types of skin grafts including allografts, autografts, allogeneic, and xenogeneic are described in detail with their associated applications. We also discuss different tissue engineering protocols for the design of various types of skin substitutes and their commercial outcomes. Brief highlights are given of the new generation three-dimensional printed scaffolds for tissue regeneration applications. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  8. Heterogeneity of Scaffold Biomaterials in Tissue Engineering

    PubMed Central

    Edgar, Lauren; McNamara, Kyle; Wong, Theresa; Tamburrini, Riccardo; Katari, Ravi; Orlando, Giuseppe

    2016-01-01

    Tissue engineering (TE) offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal. PMID:28773457

  9. Tumors of the skin and soft tissues

    SciTech Connect

    Weller, R.E.

    1991-10-01

    The majority of the body surface is covered by the skin. Many internal disorders are reflected in the condition of the skin. One of the major functions of the skin is protection of the other organ systems from a variety of environmental insults. In this role, the skin itself is exposed to factors that can ultimately cause chronic diseases and cancer. Since it is relatively easy to recognize skin abnormalities, most skin cancers are brought to professional attention sooner than other types of cancer. However, due to the close resemblance between many skin neoplasms and noncancerous dermatologic disorders, these neoplasms may be mistreated for months or even years. In veterinary oncology, as in human medicine, most cancers can be effectively treated or cured following an accurate diagnosis. Once diagnosed, skin neoplasms should be aggressively treated. If causal factors are known, exposure to these factors should be limited through removal of the agent (for chemical carcinogens) or limiting exposure to the agent (for other carcinogens such as sunlight). 10 tabs. (MHB)

  10. Measurement of diffusion coefficient of propylene glycol in skin tissue

    NASA Astrophysics Data System (ADS)

    Genin, Vadim D.; Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, Valery V.

    2015-03-01

    Optical clearing of the rat skin under the action of propylene glycol was studied ex vivo. It was found that collimated transmittance of skin samples increased, whereas weight and thickness of the samples decreased during propylene glycol penetration in skin tissue. A mechanism of the optical clearing under the action of propylene glycol is discussed. Diffusion coefficient of propylene glycol in skin tissue ex vivo has been estimated as (1.35±0.95)×10-7 cm2/s with the taking into account of kinetics of both weight and thickness of skin samples. The presented results can be useful for enhancement of many methods of laser therapy and optical diagnostics of skin diseases and localization of subcutaneous neoplasms.

  11. Pharmacokinetics and skin-tissue penetration of daptomycin in rats

    PubMed Central

    Matsumoto, Kazuaki; Kitaoka, Masashi; Kuroda, Yuko; Ikawa, Kazuro; Morikawa, Norifumi; Sasaki, Junichi; Iketani, Osamu; Iwata, Satoshi; Horino, Tetsuya; Hori, Seiji; Kizu, Junko

    2015-01-01

    Background Daptomycin is recommended for complicated skin and skin-structure infections. However, information on the penetration of daptomycin into skin is limited. Therefore, the aim of this in vivo investigation was to determine the pharmacokinetics and skin penetration of daptomycin in rats. Materials and methods Concentrations of daptomycin were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was conducted to estimate the rate and extent of daptomycin penetration from the systemic circulation into skin tissue. Since protein binding of daptomycin in rat serum was 89.3%, the free maximum concentration (Cmax) and free area under the curve from time 0 to infinity (AUC0–∞) for plasma were calculated as follows: fCmax, plasma = (1 – 0.893) × Cmax, plasma, fAUC0–∞, plasma = (1 – 0.893) × AUC0–∞, plasma. Results The following values (mean ± standard deviation) were obtained: 0.06±0 L/h/kg for total clearance (CLtotal), 0.44±0.06 hours for elimination-rate constant, 1.58±0.23 hours for half-life, 0.14±0.02 L/kg for steady-state volume distribution, and 2.28±0.33 hours for mean residence time. Time to Cmax was 3.0 hours for plasma and skin tissue. Cmax and AUC0–∞ for plasma were 175.8±5.1 μg/mL and 811.8±31.9 μg × h/mL, respectively. Cmax and AUC0–∞ for skin tissue were 19.1±1.7 μg/mL and 113.9±21.8 μg × h/mL, respectively. Furthermore, fCmax and fAUC0–∞ for plasma were 18.8 μg/mL and 86.9 μg × h/mL, respectively. The degrees of skin-tissue penetration, defined as the Cmax, skin tissue/fCmax, plasma ratio and AUC0–∞, skin tissue/fAUC0–∞, plasma ratio, were 1.0 and 1.3, respectively. Conclusion Daptomycin exhibited good penetration into skin tissue, supporting its use for the treatment of complicated skin and skin-structure infections. However, further studies are needed in infected patients in order to investigate the relationship between the antimicrobial efficacy

  12. [Tissue engineering and construction of human skin in vitro].

    PubMed

    Arvelo, Francisco

    2007-09-01

    Tissue engineering is the new science that has come to make possible the growth of new organ tissue from small fragments of healthy tissue, thus partially or totally restoring the lost functions of ill tissues or organs, as shown by the achievements made with the culture of skin, cornea or cartilage. Thus far, this new science is able to ensure the recovery of lost functions and, doubtlessly, in a near future will be capable of developing tissues and organs not unlike natural ones. In our laboratory we have began the development of tissue engineering techniques for the successful construction of in vitro skin with the aim at mid term of producing cornea and cartilage. In a first clinical trial, these techniques were applied in the treatment of chronic skin lesions and the advantages and reach of these new tools were demonstrated for the effective solution of problems with would otherwise not be easily solved through the use of conventional treatments.

  13. Heterogeneity of white adipose tissue: molecular basis and clinical implications

    PubMed Central

    Kwok, Kelvin H M; Lam, Karen S L; Xu, Aimin

    2016-01-01

    Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability and vascularization. Additional factors that influence adipose tissue heterogeneity are genetic predisposition, environment, gender and age. Under obese condition, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. For instance, individuals with central obesity are more susceptible to developing diabetes and cardiovascular complications, whereas those with peripheral obesity are more metabolically healthy. This review summarizes the clinical and mechanistic evidence for the depot-specific differences that give rise to different metabolic consequences, and provides therapeutic insights for targeted treatment of obesity. PMID:26964831

  14. Macrophage heterogeneity in tissues: phenotypic diversity and functions

    PubMed Central

    Gordon, Siamon; Plüddemann, Annette; Martinez Estrada, Fernando

    2014-01-01

    During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue-resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults. We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment. In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation. PMID:25319326

  15. Heterogeneity assessment of histological tissue sections in whole slide images.

    PubMed

    Belhomme, Philippe; Toralba, Simon; Plancoulaine, Benoît; Oger, Myriam; Gurcan, Metin N; Bor-Angelier, Catherine

    2015-06-01

    Computerized image analysis (IA) can provide quantitative and repeatable object measurements by means of methods such as segmentation, indexation, classification, etc. Embedded in reliable automated systems, IA could help pathologists in their daily work and thus contribute to more accurate determination of prognostic histological factors on whole slide images. One of the key concept pathologists want to dispose of now is a numerical estimation of heterogeneity. In this study, the objective is to propose a general framework based on the diffusion maps technique for measuring tissue heterogeneity in whole slide images and to apply this methodology on breast cancer histopathology digital images.

  16. Strain rate sensitivity of skin tissue under thermomechanical loading.

    PubMed

    Zhou, B; Xu, F; Chen, C Q; Lu, T J

    2010-02-13

    There have been limited studies addressing the thermally dependent mechanical properties of skin tissue, although this can contribute to a variety of medical applications. To address this, an experimental study on the tensile behaviour of pig skin tissue under different thermal loading conditions and different mechanical stretching rates was performed. The results indicate that there is a significant variation among skin tensile behaviours under different temperatures and loading rates, which is correlated with dermal collagen denaturation. The Ogden model was used to summarize the effect of the strain rate and the temperature upon the measured constitutive response through two parameters (alpha and mu). These results can be used in future models to improve clinical thermal treatments for skin tissue.

  17. Growing skin: Tissue expansion in pediatric forehead reconstruction

    PubMed Central

    Zollner, Alexander M.; Buganza Tepole, Adrian; Gosain, Arun K.; Kuhl, Ellen

    2011-01-01

    Tissue expansion is a common surgical procedure to grow extra skin through controlled mechanical over-stretch. It creates skin that matches the color, texture, and thickness of the surrounding tissue, while minimizing scars and risk of rejection. Despite intense research in tissue expansion and skin growth, there is a clear knowledge gap between heuristic observation and mechanistic understanding of the key phenomena that drive the growth process. Here, we show that a continuum mechanics approach, embedded in a custom-designed finite element model, informed by medical imaging, provides valuable insight into the biomechanics of skin growth. In particular, we model skin growth using the concept of an incompatible growth configuration. We characterize its evolution in time using a second-order growth tensor parameterized in terms of a scalar-valued internal variable, the in-plane area growth. When stretched beyond the physiological level, new skin is created, and the in-plane area growth increases. For the first time, we simulate tissue expansion on a patient-specific geometric model, and predict stress, strain, and area gain at three expanded locations in a pediatric skull: in the scalp, in the forehead, and in the cheek. Our results may help the surgeon to prevent tissue over-stretch and make informed decisions about expander geometry, size, placement, and inflation. We anticipate our study to open new avenues in reconstructive surgery, and enhance treatment for patients with birth defects, burn injuries, or breast tumor removal. PMID:22052000

  18. Growing skin: tissue expansion in pediatric forehead reconstruction.

    PubMed

    Zöllner, Alexander M; Buganza Tepole, Adrian; Gosain, Arun K; Kuhl, Ellen

    2012-07-01

    Tissue expansion is a common surgical procedure to grow extra skin through controlled mechanical over-stretch. It creates skin that matches the color, texture, and thickness of the surrounding tissue, while minimizing scars and risk of rejection. Despite intense research in tissue expansion and skin growth, there is a clear knowledge gap between heuristic observation and mechanistic understanding of the key phenomena that drive the growth process. Here, we show that a continuum mechanics approach, embedded in a custom-designed finite element model, informed by medical imaging, provides valuable insight into the biomechanics of skin growth. In particular, we model skin growth using the concept of an incompatible growth configuration. We characterize its evolution in time using a second-order growth tensor parameterized in terms of a scalar-valued internal variable, the in-plane area growth. When stretched beyond the physiological level, new skin is created, and the in-plane area growth increases. For the first time, we simulate tissue expansion on a patient-specific geometric model, and predict stress, strain, and area gain at three expanded locations in a pediatric skull: in the scalp, in the forehead, and in the cheek. Our results may help the surgeon to prevent tissue over-stretch and make informed decisions about expander geometry, size, placement, and inflation. We anticipate our study to open new avenues in reconstructive surgery and enhance treatment for patients with birth defects, burn injuries, or breast tumor removal.

  19. Bioglass Activated Skin Tissue Engineering Constructs for Wound Healing.

    PubMed

    Yu, Hongfei; Peng, Jinliang; Xu, Yuhong; Chang, Jiang; Li, Haiyan

    2016-01-13

    Wound healing is a complicated process, and fibroblast is a major cell type that participates in the process. Recent studies have shown that bioglass (BG) can stimulate fibroblasts to secrete a multitude of growth factors that are critical for wound healing. Therefore, we hypothesize that BG can stimulate fibroblasts to have a higher bioactivity by secreting more bioactive growth factors and proteins as compared to untreated fibroblasts, and we aim to construct a bioactive skin tissue engineering graft for wound healing by using BG activated fibroblast sheet. Thus, the effects of BG on fibroblast behaviors were studied, and the bioactive skin tissue engineering grafts containing BG activated fibroblasts were applied to repair the full skin lesions on nude mouse. Results showed that BG stimulated fibroblasts to express some critical growth factors and important proteins including vascular endothelial growth factor, basic fibroblast growth factor, epidermal growth factor, collagen I, and fibronectin. In vivo results revealed that fibroblasts in the bioactive skin tissue engineering grafts migrated into wound bed, and the migration ability of fibroblasts was stimulated by BG. In addition, the bioactive BG activated fibroblast skin tissue engineering grafts could largely increase the blood vessel formation, enhance the production of collagen I, and stimulate the differentiation of fibroblasts into myofibroblasts in the wound site, which would finally accelerate wound healing. This study demonstrates that the BG activated skin tissue engineering grafts contain more critical growth factors and extracellular matrix proteins that are beneficial for wound healing as compared to untreated fibroblast cell sheets.

  20. Nanofibrous structured biomimetic strategies for skin tissue regeneration.

    PubMed

    Jayarama Reddy, Venugopal; Radhakrishnan, Sridhar; Ravichandran, Rajeswari; Mukherjee, Shayanti; Balamurugan, Ramalingam; Sundarrajan, Subramanian; Ramakrishna, Seeram

    2013-01-01

    Mimicking porous topography of natural extracellular matrix is advantageous for successful regeneration of damaged tissues or organs. Nanotechnology being one of the most promising and growing technology today shows an extremely huge potential in the field of tissue engineering. Nanofibrous structures that mimic the native extracellular matrix and promote the adhesion of various cells are being developed as tissue-engineered scaffolds for skin, bone, vasculature, heart, cornea, nervous system, and other tissues. A range of novel biocomposite materials has been developed to enhance the bioactive or therapeutic properties of these nanofibrous scaffolds via surface modifications, including the immobilization of functional cell-adhesive ligands and bioactive molecules such as drugs, enzymes, and cytokines. In skin tissue engineering, usage of allogeneic skin is avoided to reestablish physiological continuity and also to address the challenge of curing acute and chronic wounds, which remains as the area of exploration with various biomimetic approaches. Two-dimensional, three-dimensional scaffolds and stem cells are presently used as dermal regeneration templates for the treatment of full-thickness skin defects resulting from injuries and severe burns. The present review elaborates specifically on the fabrication of nanofibrous structured strategies for wound dressings, wound healing, and controlled release of growth factors for skin tissue regeneration.

  1. CONNECTIVE TISSUE SYNTHESIS BY SCLERODERMA SKIN FIBROBLASTS IN CELL CULTURE

    PubMed Central

    Leroy, E. Carwile

    1972-01-01

    Skin fibroblasts from subjects with scleroderma and control subjects were grown in tissue culture to compare the characteristics of connective tissue metabolism. A striking increase in soluble collagen (media hydroxyproline) was observed in eight of nine scleroderma cultures when they were compared with identically handled control cultures matched for the age and sex of the donor and the anatomic site of the donor skin. Glycoprotein content as estimated by hexosamine and sialic acid was also significantly increased in the scleroderma cultures. Estimations of protein-polysaccharide content by uronic acid determinations were low in all cultures and not significantly increased in scleroderma cultures. This report demonstrates the feasibility of using fibroblast cell cultures to study chronic rheumatic and connective tissue disorders. The initial results suggest a net increase in collagen and glycoprotein synthesis in scleroderma fibroblast cultures. The implications of an abnormality of connective tissue metabolism by skin fibroblasts propagated in vitro in the acquired disorder scleroderma are discussed. PMID:4260235

  2. 3D printing method for freeform fabrication of optical phantoms simulating heterogeneous biological tissue

    NASA Astrophysics Data System (ADS)

    Wang, Minjie; Shen, Shuwei; Yang, Jie; Dong, Erbao; Xu, Ronald

    2014-03-01

    The performance of biomedical optical imaging devices heavily relies on appropriate calibration. However, many of existing calibration phantoms for biomedical optical devices are based on homogenous materials without considering the multi-layer heterogeneous structures observed in biological tissue. Using such a phantom for optical calibration may result in measurement bias. To overcome this problem, we propose a 3D printing method for freeform fabrication of tissue simulating phantoms with multilayer heterogeneous structure. The phantom simulates not only the morphologic characteristics of biological tissue but also absorption and scattering properties. The printing system is based on a 3D motion platform with coordinated control of the DC motors. A special jet nozzle is designed to mix base, scattering, and absorption materials at different ratios. 3D tissue structures are fabricated through layer-by-layer printing with selective deposition of phantom materials of different ingredients. Different mixed ratios of base, scattering and absorption materials have been tested in order to optimize the printing outcome. A spectrometer and a tissue spectrophotometer are used for characterizing phantom absorption and scattering properties. The goal of this project is to fabricate skin tissue simulating phantoms as a traceable standard for the calibration of biomedical optical spectral devices.

  3. The effect of age on skin color and color heterogeneity in four ethnic groups.

    PubMed

    de Rigal, Jean; Des Mazis, Isabelle; Diridollou, Stephane; Querleux, Bernard; Yang, Grace; Leroy, Frederce; Barbosa, Vietoria Holloway

    2010-05-01

    Few comparative data are available on age-related changes in skin color among different ethnic groups. The aim of the study was to measure and analyze the skin color and color heterogeneity in four different ethnic groups living in the same local environment and to determine the effects of age on these skin color characteristics. Female volunteers (385) from four ethnic populations (African-American, Caucasian, Chinese and Mexicans) living in the same city were enrolled after informed consent. Skin color was measured on two facial areas, forehead and cheek. The subjects were further divided into six age ranges: 19-30, 31-40, 41-50, 51-60, 61-70 and 71-87 years to determine any age-related effects on the skin color and color heterogeneity in both areas. According to the L(*)a(*)b(*) CIE system, clarity (fairness/lightness) was found to be lower in the African-American group whereas the hue was lower in Caucasians, which means more red skin. A clear, statistically significant darkening of the skin with age was observed in all ethnic groups, while evidence of yellowing of the skin was shown in the Chinese volunteers. Overall, the skin color of the face of African-Americans was more heterogeneous than in the other ethnic groups, but showed the least increase with age. Our study revealed interesting differences in skin color and color heterogeneity with respect to ethnicity and age-related alterations. Data obtained are very useful in improving our knowledge about the skin of people of different origins and helps in the development of specific cosmetic products that are well adapted to all these populations.

  4. Polarized Reflectance Measurement of Burned Skin Tissues

    NASA Astrophysics Data System (ADS)

    de Pedro, Hector Michael; Chang, Chuan-I.; Zarnani, Faranak; Glosser, Robert; Maas, D.; Idris, A.

    2011-10-01

    In the US, there are over 400,000 burn victims with 3,500 deaths in 2010. Recent evidence suggests that early removal of burn tissues can significantly increase the success of their recovery, since burns continue to spread and damage surrounding tissues after hours of injury. The rationale behind this procedure is that burns trigger the body's immune system to overreact, causing additional damage. Therefore, it is important to distinguish burn areas so that it can be removed. The problem with this is that it is difficult to recognize the margins of the burn area. In our project, we use polarized reflectance as a tool to identify the burned tissues from unburned ones.

  5. Unexpected complication associated with balneotherapy: Skin and soft tissue infection

    NASA Astrophysics Data System (ADS)

    Alım, Bülent; Bostancı, Fahrettin; Servi, M. Alperen; Ćetinel, Sinan; Bingöl, M. Ozan

    2017-04-01

    Balneotherapy cure is an ongoing process, but patients can benefit most when cure is complete. For these reason, patients should be closely monitored and necessary precautions should be taken in terms of the complications that may occur in order to prevent the interruption or discontinuation of balneotherapy. Here, we wanted to represent a case that developed left leg soft tissue infection during the application of balneotherapy and because of this reason we stopped the balneotherapy As a result, when balneotherapy is planned for patients with risk factors such as diabetes and obesity, frequent examination of the skin and the application of skin moisturizers will be beneficial to prevent itching and skin dryness.

  6. Skin Tissue Engineering: Application of Adipose-Derived Stem Cells

    PubMed Central

    Zimoch, Jakub; Biedermann, Thomas

    2017-01-01

    Perception of the adipose tissue has changed dramatically over the last few decades. Identification of adipose-derived stem cells (ASCs) ultimately transformed paradigm of this tissue from a passive energy depot into a promising stem cell source with properties of self-renewal and multipotential differentiation. As compared to bone marrow-derived stem cells (BMSCs), ASCs are more easily accessible and their isolation yields higher amount of stem cells. Therefore, the ASCs are of high interest for stem cell-based therapies and skin tissue engineering. Currently, freshly isolated stromal vascular fraction (SVF), which may be used directly without any expansion, was also assessed to be highly effective in treating skin radiation injuries, burns, or nonhealing wounds such as diabetic ulcers. In this paper, we review the characteristics of SVF and ASCs and the efficacy of their treatment for skin injuries and disorders. PMID:28337463

  7. Optimization of permanent breast seed implant dosimetry incorporating tissue heterogeneity

    NASA Astrophysics Data System (ADS)

    Mashouf, Shahram

    Seed brachytherapy is currently used for adjuvant radiotherapy of early stage prostate and breast cancer patients. The current standard for calculation of dose around brachytherapy sources is based on the AAPM TG43 formalism, which generates the dose in homogeneous water medium. Recently, AAPM task group no. 186 (TG186) emphasized the importance of accounting for heterogeneities. In this work we introduce an analytical dose calculation algorithm in heterogeneous media using CT images. The advantages over other methods are computational efficiency and the ease of integration into clinical use. An Inhomogeneity Correction Factor (ICF) is introduced as the ratio of absorbed dose in tissue to that in water medium. ICF is a function of tissue properties and independent of the source structure. The ICF is extracted using CT images and the absorbed dose in tissue can then be calculated by multiplying the dose as calculated by the TG43 formalism times ICF. To evaluate the methodology, we compared our results with Monte Carlo simulations as well as experiments in phantoms with known density and atomic compositions. The dose distributions obtained through applying ICF to TG43 protocol agreed very well with those of Monte Carlo simulations and experiments in all phantoms. In all cases, the mean relative error was reduced by at least a factor of two when ICF correction factor was applied to the TG43 protocol. In conclusion we have developed a new analytical dose calculation method, which enables personalized dose calculations in heterogeneous media using CT images. The methodology offers several advantages including the use of standard TG43 formalism, fast calculation time and extraction of the ICF parameters directly from Hounsfield Units. The methodology was implemented into our clinical treatment planning system where a cohort of 140 patients were processed to study the clinical benefits of a heterogeneity corrected dose.

  8. Macrophage heterogeneity in tissues: phenotypic diversity and functions.

    PubMed

    Gordon, Siamon; Plüddemann, Annette; Martinez Estrada, Fernando

    2014-11-01

    During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue-resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults. We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment. In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation. © 2014 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.

  9. Complicated skin, skin structure and soft tissue infections - are we threatened by multi-resistant pathogens?

    PubMed Central

    2010-01-01

    Tissue infections or skin, skin structure, and deep seated soft tissue infections are general terms for infections of the entire skin layer including the subcutaneous and muscle tissue layers and their respective fascia structures. Infections of the different mediastinal fascias (mediastinitis) and retroperitoneal fascia infections also belong to this category. Due to the variability of their clinical presentation, skin and soft tissue infections can be classified according to different features. The following aspects can be used for classification: - anatomical structures - pathogens - necessity for urgent treatment - extent of infection The incidence of skin and soft tissue infections in which MRSA (methicillin-resistent Staphylococcus aureus) is involved has been steadily increasing over the past 15 years. These wounds should be treated according to the same open treatment principles as other infected wounds. Since these infections are often superficial contaminations, antibiotic therapy is not indicated. If systemic infection occurs in form of MRSA sepsis, antibiotic therapy is indicated. Several recent reports identified MRSA as the leading pathogen in SSTIs. It also causes 20% to 50% of diabetes-associated foot infections in several countries and is associated with worse outcomes than other pathogens. PMID:21163729

  10. A review of tissue-engineered skin bioconstructs available for skin reconstruction

    PubMed Central

    Shevchenko, Rostislav V.; James, Stuart L.; James, S. Elizabeth

    2010-01-01

    Situations where normal autografts cannot be used to replace damaged skin often lead to a greater risk of mortality, prolonged hospital stay and increased expenditure for the National Health Service. There is a substantial need for tissue-engineered skin bioconstructs and research is active in this field. Significant progress has been made over the years in the development and clinical use of bioengineered components of the various skin layers. Off-the-shelf availability of such constructs, or production of sufficient quantities of biological materials to aid rapid wound closure, are often the only means to help patients with major skin loss. The aim of this review is to describe those materials already commercially available for clinical use as well as to give a short insight to those under development. It seeks to provide skin scientists/tissue engineers with the information required to not only develop in vitro models of skin, but to move closer to achieving the ultimate goal of an off-the-shelf, complete full-thickness skin replacement. PMID:19864266

  11. Dosimetric effect of tissue heterogeneity for (125)I prostate implants.

    PubMed

    Oliveira, Susana Maria; Teixeira, Nuno José; Fernandes, Lisete; Teles, Pedro; Vaz, Pedro

    2014-11-01

    To use Monte Carlo (MC) together with voxel phantoms to analyze the tissue heterogeneity effect in the dose distributions and equivalent uniform dose (EUD) for (125)I prostate implants. Dose distribution calculations in low dose-rate brachytherapy are based on the dose deposition around a single source in a water phantom. This formalism does not take into account tissue heterogeneities, interseed attenuation, or finite patient dimensions effects. Tissue composition is especially important due to the photoelectric effect. The computed tomographies (CT) of two patients with prostate cancer were used to create voxel phantoms for the MC simulations. An elemental composition and density were assigned to each structure. Densities of the prostate, vesicles, rectum and bladder were determined through the CT electronic densities of 100 patients. The same simulations were performed considering the same phantom as pure water. Results were compared via dose-volume histograms and EUD for the prostate and rectum. The mean absorbed doses presented deviations of 3.3-4.0% for the prostate and of 2.3-4.9% for the rectum, when comparing calculations in water with calculations in the heterogeneous phantom. In the calculations in water, the prostate D 90 was overestimated by 2.8-3.9% and the rectum D 0.1cc resulted in dose differences of 6-8%. The EUD resulted in an overestimation of 3.5-3.7% for the prostate and of 7.7-8.3% for the rectum. The deposited dose was consistently overestimated for the simulation in water. In order to increase the accuracy in the determination of dose distributions, especially around the rectum, the introduction of the model-based algorithms is recommended.

  12. Dosimetric effect of tissue heterogeneity for 125I prostate implants

    PubMed Central

    Oliveira, Susana Maria; Teixeira, Nuno José; Fernandes, Lisete; Teles, Pedro; Vaz, Pedro

    2014-01-01

    Aim To use Monte Carlo (MC) together with voxel phantoms to analyze the tissue heterogeneity effect in the dose distributions and equivalent uniform dose (EUD) for 125I prostate implants. Background Dose distribution calculations in low dose-rate brachytherapy are based on the dose deposition around a single source in a water phantom. This formalism does not take into account tissue heterogeneities, interseed attenuation, or finite patient dimensions effects. Tissue composition is especially important due to the photoelectric effect. Materials and methods The computed tomographies (CT) of two patients with prostate cancer were used to create voxel phantoms for the MC simulations. An elemental composition and density were assigned to each structure. Densities of the prostate, vesicles, rectum and bladder were determined through the CT electronic densities of 100 patients. The same simulations were performed considering the same phantom as pure water. Results were compared via dose–volume histograms and EUD for the prostate and rectum. Results The mean absorbed doses presented deviations of 3.3–4.0% for the prostate and of 2.3–4.9% for the rectum, when comparing calculations in water with calculations in the heterogeneous phantom. In the calculations in water, the prostate D90 was overestimated by 2.8–3.9% and the rectum D0.1cc resulted in dose differences of 6–8%. The EUD resulted in an overestimation of 3.5–3.7% for the prostate and of 7.7–8.3% for the rectum. Conclusions The deposited dose was consistently overestimated for the simulation in water. In order to increase the accuracy in the determination of dose distributions, especially around the rectum, the introduction of the model-based algorithms is recommended. PMID:25337412

  13. Fabricating optical phantoms to simulate skin tissue properties and microvasculatures

    NASA Astrophysics Data System (ADS)

    Sheng, Shuwei; Wu, Qiang; Han, Yilin; Dong, Erbao; Xu, Ronald

    2015-03-01

    This paper introduces novel methods to fabricate optical phantoms that simulate the morphologic, optical, and microvascular characteristics of skin tissue. The multi-layer skin-simulating phantom was fabricated by a light-cured 3D printer that mixed and printed the colorless light-curable ink with the absorption and the scattering ingredients for the designated optical properties. The simulated microvascular network was fabricated by a soft lithography process to embed microchannels in polydimethylsiloxane (PDMS) phantoms. The phantoms also simulated vascular anomalies and hypoxia commonly observed in cancer. A dual-modal multispectral and laser speckle imaging system was used for oxygen and perfusion imaging of the tissue-simulating phantoms. The light-cured 3D printing technique and the soft lithography process may enable freeform fabrication of skin-simulating phantoms that embed microvessels for image and drug delivery applications.

  14. Tissue viability imaging for quantification of skin erythema and blanching

    NASA Astrophysics Data System (ADS)

    Nilsson, Gert E.; Leahy, Martin J.

    2010-02-01

    Naked eye observation has up to recently been the main method of determining skin erythema (vasodilatation) and blanching (vasoconstriction) in skin testing. Since naked eye observation is a highly subjective and investigatordependent method, it is difficult to attain reproducibility and to compare results reported by different researchers performing their studies at different laboratories. Consequently there is a need for more objective, quantitative and versatile methods in the assessment of alterations in skin erythema and blanching caused by internal and external factors such as the intake of vasoactive drugs, application of agents on the skin surface and by constituents in the environment. Since skin microcirculation is sensitive to applied pressure and heat, such methods should preferably be noninvasive and designed for remote use without touching the skin. As skin microcirculation further possesses substantial spatial variability, imaging techniques are to be preferred before single point measurements. An emerging technology based on polarization digital camera spectroscopy - Tissue Viability Imaging (TiVi) - fulfills these requirements. The principles of TiVi (1) and some of its early applications (2-5) are addressed in this paper.

  15. Skin and Soft Tissue Infections (Patera Foot) in Immigrants, Spain

    PubMed Central

    Ternavasio-de la Vega, Hugo-Guillermo; Ángel-Moreno, Alfonso; Hernández-Cabrera, Michele; Pisos-Álamo, Elena; Bolaños-Rivero, Margarita; Carranza-Rodriguez, Cristina; Calderín-Ortega, Antonio; Pérez-Arellano, José-Luis

    2009-01-01

    An unusual skin and soft tissue infection of the lower limbs has been observed in immigrants from sub-Saharan Africa who cross the Atlantic Ocean crowded on small fishing boats (pateras). Response to conventional treatment is usually poor. Extreme extrinsic factors (including new pathogens) may contribute to the etiology of the infection and its pathogenesis. PMID:19331742

  16. Investigation of normal human skin tissue and acupuncture points of human skin tissue using fiberoptical FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Brooks, Angelique L.; Bruch, Reinhard F.; Afanasyeva, Natalia I.; Kolyakov, Sergei F.; Butvina, Leonid N.; Ma, Lixing

    1998-06-01

    An innovative spectroscopic diagnostic method has been developed for investigation of different regions of normal human skin tissue. This new method is a combination of Fourier transform IR fiberoptic evanescent wave (FTIR-FEW) spectroscopy and fiber optic techniques for the middle IR (MIR) wavelength range. The fiber optical sensors we have used are characterized by low optical losses and high flexibility for remote analysis. Our fiber optical accessories and method allows for direct interaction of the skin tissue with the fiber probe and can be utilized with a diversity of standard commercial Fourier transform spectrometers. The FTIR-FEW technique, using nontoxic unclad fibers in the attenuated total reflection regime, is suitable for noninvasive, fast, sensitive investigations of normal skin in vivo for various medical diagnostics applications including studies of acupuncture points. Here we present the first data on IR spectra of skin tissue in vivo for normal skin and several acupuncture points in the range of 1300 to 1800 cm-1 and 2600 to 4000 cm-1.

  17. Use of diathermy for weeding heterogeneous tissue cultures.

    PubMed

    Marks, R M; Penny, R

    1986-06-01

    Cultures generated from tissues consisting of multiple types of cells are often heterogeneous. Unless the cell type of interest has or can be given some selective growth advantage it may be overgrown by other cells. While developing techniques for the tissue culture of microvascular endothelial cells we evaluated an electrosurgical generator (diathermy) to selectively kill nonendothelial cells. Primary cell cultures were observed at X 100 magnification under phase contrast microscopy and a needle electrode apposed to the cell to be destroyed. A return electrode was constructed by placing a sterile clip in contact with the culture medium. The diathermy power setting controlled the area of lysis. Use of this technique allowed weeding of unwanted cells without damage to endothelial cells, which were able to grow to confluence in pure culture.

  18. A liquid optical phantom with tissue-like heterogeneities for confocal microscopy

    PubMed Central

    Wang, Danni; Chen, Ye; Liu, Jonathan T. C.

    2012-01-01

    Phantoms play an important role in the development, standardization, and calibration of biomedical imaging devices in laboratory and clinical settings, serving as standards to assess the performance of such devices. Here we present the design of a liquid optical phantom to facilitate the assessment of optical-sectioning microscopes that are being developed to enable point-of-care pathology. This phantom, composed of silica microbeads in an Intralipid base, is specifically designed to characterize a reflectance-based dual-axis confocal (DAC) microscope for skin imaging. The phantom mimics the scattering properties of normal human epithelial tissue in terms of an effective scattering coefficient and a depth-dependent degradation in spatial resolution due to beam steering caused by tissue micro-architectural heterogeneities. PMID:23243566

  19. Skin shedding and tissue regeneration in African spiny mice (Acomys).

    PubMed

    Seifert, Ashley W; Kiama, Stephen G; Seifert, Megan G; Goheen, Jacob R; Palmer, Todd M; Maden, Malcolm

    2012-09-27

    Evolutionary modification has produced a spectrum of animal defence traits to escape predation, including the ability to autotomize body parts to elude capture. After autotomy, the missing part is either replaced through regeneration (for example, in urodeles, lizards, arthropods and crustaceans) or permanently lost (such as in mammals). Although most autotomy involves the loss of appendages (legs, chelipeds, antennae or tails, for example), skin autotomy can occur in certain taxa of scincid and gekkonid lizards. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing showed a propensity for skin to tear under very low tension and the absence of a fracture plane. After skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Notably, we found that regenerative capacity in Acomys was extended to ear holes, where the mice exhibited complete regeneration of hair follicles, sebaceous glands, dermis and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells) after limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through the assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of conventional model organisms, and suggests that mammals may retain a higher capacity for regeneration than was previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.

  20. Skin shedding and tissue regeneration in African spiny mice (Acomys)

    PubMed Central

    Seifert, Ashley W.; Kiama, Stephen G.; Seifert, Megan G.; Goheen, Jacob R.; Palmer, Todd M.; Maden, Malcolm

    2012-01-01

    SUMMARY Evolutionary modification has produced a spectrum of animal defense traits to escape predation, including the ability to autotomize body parts to elude capture1,2. Following autotomy, the missing part is either replaced through regeneration (e.g. urodeles, lizards, arthropods, crustaceans) or is permanently lost (mammals). While most autotomy involves the loss of appendages (e.g. leg, cheliped, antennae, tail), skin autotomy can occur in certain taxa of scincid and gekkonid lizards3. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing revealed a propensity for skin to tear under very low tension and the absence of a fracture plane. Following skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Surprisingly, we found regenerative capacity in Acomys extended to ear holes where they exhibited complete regeneration of hair follicles, sebaceous glands, dermis, and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells4) following limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of traditional model organisms and suggests that mammals may retain a higher capacity for regeneration than previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring. PMID:23018966

  1. Electrophysiological heterogeneity and stability of reentry in simulated cardiac tissue.

    PubMed

    Xie, F; Qu, Z; Garfinkel, A; Weiss, J N

    2001-02-01

    Generation of wave break is a characteristic feature of cardiac fibrillation. In this study, we investigated how dynamic factors and fixed electrophysiological heterogeneity interact to promote wave break in simulated two-dimensional cardiac tissue, by using the Luo-Rudy (LR1) ventricular action potential model. The degree of dynamic instability of the action potential model was controlled by varying the maximal amplitude of the slow inward Ca(2+) current to produce spiral waves in homogeneous tissue that were either nearly stable, meandering, hypermeandering, or in breakup regimes. Fixed electrophysiological heterogeneity was modeled by randomly varying action potential duration over different spatial scales to create dispersion of refractoriness. We found that the degree of dispersion of refractoriness required to induce wave break decreased markedly as dynamic instability of the cardiac model increased. These findings suggest that reducing the dynamic instability of cardiac cells by interventions, such as decreasing the steepness of action potential duration restitution, may still have merit as an antifibrillatory strategy.

  2. Macro- to microscale strain transfer in fibrous tissues is heterogeneous and tissue-specific.

    PubMed

    Han, Woojin M; Heo, Su-Jin; Driscoll, Tristan P; Smith, Lachlan J; Mauck, Robert L; Elliott, Dawn M

    2013-08-06

    Mechanical deformation applied at the joint or tissue level is transmitted through the macroscale extracellular matrix to the microscale local matrix, where it is transduced to cells within these tissues and modulates tissue growth, maintenance, and repair. The objective of this study was to investigate how applied tissue strain is transferred through the local matrix to the cell and nucleus in meniscus, tendon, and the annulus fibrosus, as well as in stem cell-seeded scaffolds engineered to reproduce the organized microstructure of these native tissues. To carry out this study, we developed a custom confocal microscope-mounted tensile testing device and simultaneously monitored strain across multiple length scales. Results showed that mean strain was heterogeneous and significantly attenuated, but coordinated, at the local matrix level in native tissues (35-70% strain attenuation). Conversely, freshly seeded scaffolds exhibited very direct and uniform strain transfer from the tissue to the local matrix level (15-25% strain attenuation). In addition, strain transfer from local matrix to cells and nuclei was dependent on fiber orientation and tissue type. Histological analysis suggested that different domains exist within these fibrous tissues, with most of the tissue being fibrous, characterized by an aligned collagen structure and elongated cells, and other regions being proteoglycan (PG)-rich, characterized by a dense accumulation of PGs and rounder cells. In meniscus, the observed heterogeneity in strain transfer correlated strongly with cellular morphology, where rounder cells located in PG-rich microdomains were shielded from deformation, while elongated cells in fibrous microdomains deformed readily. Collectively, these findings suggest that different tissues utilize distinct strain-attenuating mechanisms according to their unique structure and cellular phenotype, and these differences likely alter the local biologic response of such tissues and constructs in

  3. Mechanisms underlying heterologous skin scaffold-mediated tissue remodeling

    PubMed Central

    Mimura, Kallyne K. O.; Moraes, Andréia R.; Miranda, Aline C.; Greco, Rebecca; Ansari, Tahera; Sibbons, Paul; Greco, Karin V.; Oliani, Sonia M.

    2016-01-01

    Biocompatibility of two newly developed porcine skin scaffolds was assessed after 3, 14, 21 and 90 days of implantation in rats. Both scaffolds showed absence of cells, preservation of ECM and mechanical properties comparable to non-decellularised skin before implantation. Host cell infiltration was much prominent on both scaffolds when compared to Permacol (surgical control). At day 3, the grafts were surrounded by polymorphonuclear cells, which were replaced by a notable number of IL-6-positive cells at day 14. Simultaneously, the number of pro-inflammatory M1-macrophage was enhanced. Interestingly, a predominant pro-remodeling M2 response, with newly formed vessels, myofibroblasts activation and a shift on the type of collagen expression was sequentially delayed (around 21 days). The gene expression of some trophic factors involved in tissue remodeling was congruent with the cellular events. Our findings suggested that the responsiveness of macrophages after non-crosslinked skin scaffolds implantation seemed to intimately affect various cell responses and molecular events; and this range of mutually reinforcing actions was predictive of a positive tissue remodeling that was essential for the long-standing success of the implants. Furthermore, our study indicates that non-crosslinked biologic scaffold implantation is biocompatible to the host tissue and somehow underlying molecular events involved in tissue repair. PMID:27725772

  4. [Microbiological diagnosis of infections of the skin and soft tissues].

    PubMed

    Burillo, Almudena; Moreno, Antonio; Salas, Carlos

    2007-11-01

    Skin and soft tissue infections are often seen in clinical practice, yet their microbiological diagnosis is among the most complex of laboratory tasks. The diagnosis of a skin and a soft tissue infection is generally based on clinical criteria and not microbiological results. A microbiological diagnosis is reserved for cases in which the etiology of infection is required, e.g., when the infection is particularly severe, when less common microorganisms are suspected as the causative agent (e.g. in immunocompromised patients), when response to antimicrobial treatment is poor, or when a longstanding wound does not heal within a reasonable period of time. We report the indications, sampling and processing techniques, and interpretation criteria for various culture types, including quantitative cultures from biopsy or tissue specimens and semiquantitative and qualitative cultures performed on all types of samples. For non-invasive samples taken from open wounds, application of the Q index to Gram stains is a cost-effective way to standardize sample quality assessment and interpretation of the pathogenic involvement of the different microorganisms isolated from cultures. All these issues are covered in the SEIMC microbiological procedure number 22: Diagnóstico microbiológico de las infecciones de piel y tejidos blandos (Microbiological diagnosis of infections of the skin and soft tissues) (2nd ed., 2006, www.seimc.org/protocolos/microbiologia).

  5. Quantifying thermal modifications on laser welded skin tissue

    NASA Astrophysics Data System (ADS)

    Tabakoglu, Hasim Ö.; Gülsoy, Murat

    2011-02-01

    Laser tissue welding is a potential medical treatment method especially on closing cuts implemented during any kind of surgery. Photothermal effects of laser on tissue should be quantified in order to determine optimal dosimetry parameters. Polarized light and phase contrast techniques reveal information about extend of thermal change over tissue occurred during laser welding application. Change in collagen structure in skin tissue stained with hematoxilen and eosin samples can be detected. In this study, three different near infrared laser wavelengths (809 nm, 980 nm and 1070 nm) were compared for skin welding efficiency. 1 cm long cuts were treated spot by spot laser application on Wistar rats' dorsal skin, in vivo. In all laser applications, 0.5 W of optical power was delivered to the tissue, 5 s continuously, resulting in 79.61 J/cm2 energy density (15.92 W/cm2 power density) for each spot. The 1st, 4th, 7th, 14th, and 21st days of recovery period were determined as control days, and skin samples needed for histology were removed on these particular days. The stained samples were examined under a light microscope. Images were taken with a CCD camera and examined with imaging software. 809 Nm laser was found to be capable of creating strong full-thickness closure, but thermal damage was evident. The thermal damage from 980 nm laser welding was found to be more tolerable. The results showed that 1070 nm laser welding produced noticeably stronger bonds with minimal scar formation.

  6. Cell-based vascularization strategies for skin tissue engineering.

    PubMed

    Hendrickx, Benoit; Vranckx, Jan J; Luttun, Aernout

    2011-02-01

    Providing a blood-vascular network to promote survival and integration of cells in thick dermal substitutes for application in full-thickness wounds is essential for the successful outcome of skin tissue engineering. Nevertheless, promoting vascularization also represents a critical bottleneck in today's skin tissue engineering practice. Several cell types have been considered and tested, mostly in preclinical studies, to increase vascularization. When the clinical situation allows delayed reconstruction of the defect, an autologous approach is preferable, whereas in acute cases allogeneic therapy is needed. In both cases, the cells should be harvested with minimal donor-site morbidity and should be available in large amounts and safe in terms of tumor formation and transmission of animal diseases. Here, we outline the different mechanisms of cell-based vascularization and subsequently elaborate in more detail on the candidate cell types and their pros and cons in terms of clinical application and regulation of the wound healing process.

  7. Risk of residual breast tissue after skin-sparing mastectomy.

    PubMed

    Dreadin, Julie; Sarode, Venetia; Saint-Cyr, Michel; Hynan, Linda S; Rao, Roshni

    2012-01-01

    Skin-sparing mastectomy (SSM) is an accepted surgical option for breast cancer treatment. SSM allows for preservation of the skin envelope and improved cosmesis. Despite initial concerns, large series have not revealed higher recurrence rates. There is, however, a paucity of data regarding the rates of residual breast tissue (RBT) left behind after SSM, what factors influence this, and the oncologic implications of RBT. Retrospective review identified 288 total mastectomies. Patients who had undergone SSM with excision of additional skin for reconstructive purposes, either at the initial oncologic surgery or at subsequent revision, were included in the final study group. Pathologic analysis was performed to evaluate excised skin. Data regarding demographics, tumor type, and treatment were collected. Comparison between patients who had pathologically confirmed RBT in the excised skin and those who did not was performed. Of 288 total mastectomies, 92 were SSM's, and 66 had skin specimens removed for nononcologic reasons, of these, 4 (6%) had RBT. Age at diagnosis (p = 0.806), BMI (p = 0.531), tumor size (p = 0.922), and estrogen receptor status (p > 0.999) did not contribute to increased RBT risk. At median follow-up of 33.5 months, there have been no recurrences. In addition, cost analysis reveals it is likely not cost-effective to perform pathologic evaluation of these specimens. SSM, performed at an academic medical center by fellowship-trained surgeons, has a very low rate of RBT, and does not compromise oncologic outcomes. Routine pathologic assessment of these skin specimens, removed for nononcologic reasons, may not be required. © 2012 Wiley Periodicals, Inc.

  8. Monte Carlo Method in optical diagnostics of skin and skin tissues

    NASA Astrophysics Data System (ADS)

    Meglinski, Igor V.

    2003-12-01

    A novel Monte Carlo (MC) technique for photon migration through 3D media with the spatially varying optical properties is presented. The employed MC technique combines the statistical weighting variance reduction and real photon paths tracing schemes. The overview of the results of applications of the developed MC technique in optical/near-infrared reflectance spectroscopy, confocal microscopy, fluorescence spectroscopy, OCT, Doppler flowmetry and Diffusing Wave Spectroscopy (DWS) are presented. In frame of the model skin represents as a complex inhomogeneous multi-layered medium, where the spatial distribution of blood and chromophores are variable within the depth. Taking into account variability of cells structure we represent the interfaces of skin layers as a quasi-random periodic wavy surfaces. The rough boundaries between the layers of different refractive indices play a significant role in the distribution of photons within the medium. The absorption properties of skin tissues in visible and NIR spectral region are estimated by taking into account the anatomical structure of skin as determined from histology, including the spatial distribution of blood vessels, water and melanin content. Model takes into account spatial distribution of fluorophores following the collagen fibers packing, whereas in epidermis and stratum corneum the distribution of fluorophores assumed to be homogeneous. Reasonable estimations for skin blood oxygen saturation and haematocrit are also included. The model is validated against analytic solution of the photon diffusion equation for semi-infinite homogeneous highly scattering medium. The results demonstrate that matching of the refractive index of the medium significantly improves the contrast and spatial resolution of the spatial photon sensitivity profile. It is also demonstrated that when model supplied with reasonable physical and structural parameters of biological tissues the results of skin reflectance spectra simulation

  9. Tissue Expanders in Skin Deficient Ventral Hernias Utilizing Component Separation

    PubMed Central

    Molinar, Vanessa E.; Molinar, Alonso; Palladino, Humberto

    2015-01-01

    Summary: Skin deficient complex ventral hernias are complicated surgical cases that have multimodal approaches. There is no current consensus on the management of those patients who also have concomitant stomas or enterocutaneous fistula. We present 2 cases in which the senior authors were able to apply tissue expanders above and between the abdominal wall in patients with an enterocutaneous fistula or stoma. After expansion and final closure, the patients did not experience recurrent hernias. PMID:26893988

  10. Heterogeneity characterization of immunohistochemistry stained tissue using convolutional autoencoder

    NASA Astrophysics Data System (ADS)

    Zerhouni, Erwan; Prisacari, Bogdan; Zhong, Qing; Wild, Peter; Gabrani, Maria

    2017-03-01

    The focus of this paper is to illustrate how computational image processing and machine learning can help address two of the challenges of histological image analysis, namely, the cellular heterogeneity, and the imprecise labeling. We propose an unsupervised method of generating representative image signatures based on an autoencoder architecture which reduces the dependency on labels that tend to be imprecise and tedious to get. We have modified and enhanced the architecture to simultaneously produce representative image features as well as perform dictionary learning on these features to enable robust characterization of the cellular phenotypes. We integrate the extracted features in a disease grading framework, test it in prostate tissues immunostained for different protein visualization and show significant improvement in terms of grading accuracy compared to alternative supervised feature-extraction methods.

  11. Mechanism study of skin tissue ablation by nanosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Fang, Qiyin

    Understanding the fundamental mechanisms in laser tissue ablation is essential to improve clinical laser applications by reducing collateral damage and laser pulse energy requirement. The motive of this dissertation is to study skin tissue ablation by nanosecond laser pulses in a wide spectral region from near-infrared to ultraviolet for a clear understanding of the mechanism that can be used to improve future design of the pulsed lasers for dermatology and plastic surgery. Multiple laser and optical configurations have been constructed to generate 9 to 12ns laser pulses with similar profiles at 1064. 532, 266 and 213nm for this study of skin tissue ablation. Through measurements of ablation depth as a function cf laser pulse energy, the 589nm spectral line in the secondary radiation from ablated skin tissue samples was identified as the signature of the occurrence of ablation. Subsequently, this spectral signature has been used to investigate the probabilistic process of the ablation near the threshold at the four wavelengths. Measurements of the ablation probability were conducted as a function of the electrical field strength of the laser pulse and the ablation thresholds in a wide spectral range from 1064nm to 213nm were determined. Histology analysis and an optical transmission method were applied in assessing of the ablation depth per pulse to study the ablation process at irradiance levels higher than threshold. Because more than 70% of the wet weight of the skin tissue is water, optical breakdown and backscattering in water was also investigated along with a nonlinear refraction index measurement using a z-scan technique. Preliminary studies on ablation of a gelatin based tissue phantom are also reported. The current theoretical models describing ablation of soft tissue ablation by short laser pulses were critically reviewed. Since none of the existing models was found capable of explaining the experimental results, a new plasma-mediated model was developed

  12. [Research of pressure of skin soft tissue expander].

    PubMed

    Xu, Kunming; Li, Hongmian; Luo, Zhijun; Li, Qingfeng

    2013-03-01

    To investigate the change law of the intracapsular pressure in vitro without outside force and the pressure of the expander upon the skin soft tissue in vivo during clinical routine expansion so as to provide some references for the safe application of the expander. The rectangle expanders of 50, 80, 100, 150, 200, 250, 300, and 400 mL were used for in vitro expansion at room temperature to 400% volume of the expander capacity. The pressures before and after saline injection were recorded. Twelve patients who needed scar plastic surgery were enrolled; 17 rectangle expanders were implanted in 5 areas (cheek, trunk, forehead and temporal, limb, and head) and expanded routinely. The pressures before and after saline injection were recorded. The pressure of the expander upon the skin soft tissue was calculated and the values of the pressure at 50%, 100%, 150%, and 200% volume of 5 areas were chosen and analyzed statistically. The intracapsular pressure of the expanders at different volumes in vitro without outside force during routine expansion before and after saline injection was beyond 0 mm Hg (1 mm Hg=0.133 kPa) at around 100% volume, increased rapidly from 100% to 250% volume, and kept stable from 250% to 400% volume. In vivo, 16 expanders within 200% volume had the maximum pressure before saline injection, 15 had the maximum pressure after saline injection. Before saline injection, the pressure of the expander upon the skin soft tissue was lowest in the cheek, showing significant difference when compared with those of the forehead and temporal and head (P < 0.05); the pressure in the trunk was significantly lower than that in the head (P < 0.05); and there was no significant difference between the other body sites (P > 0.05). After saline injection, the pressure of the expander upon the skin soft tissue was lowest in the cheek, and showed an increasing trend in the trunk, the limb, the forehead and temporal, and the head; no significant difference was found

  13. Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

    PubMed Central

    Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

    2015-01-01

    Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

  14. Combining platelet-rich plasma and tissue-engineered skin in the treatment of large skin wound.

    PubMed

    Han, Tong; Wang, Hao; Zhang, Ya Qin

    2012-03-01

    The objective of the study was to observe the effects of tissue-engineered skin in combination with platelet-rich plasma (PRP) and other preparations on the repair of large skin wound on nude mice.We first prepared PRP from venous blood by density-gradient centrifugation. Large skin wounds were created surgically on the dorsal part of nude mice. The wounds were then treated with either artificial skin, tissue-engineered skin, tissue-engineered skin combined with basic fibroblast growth factor, tissue-engineered skin combined with epidermal growth factor, or tissue-engineered skin combined with PRP. Tissue specimens were collected at different time intervals after surgery. Hematoxylin-eosin and periodic acid-Schiff staining and immunohistochemistry were performed to assess the rate of wound healing.Macroscopic observations, hematoxylin-eosin/periodic acid-Schiff staining, and immunohistochemistry revealed that the wounds treated with tissue-engineered skin in combination with PRP showed the most satisfactory wound recovery, among the 5 groups.

  15. A parametric study of thermal therapy of skin tissue.

    PubMed

    Nóbrega, Simão; Coelho, Pedro J

    2017-01-01

    A thermal therapy for cancer in skin tissue is numerically investigated using three bioheat conduction models, namely Pennes, thermal wave and dual-phase lag models. A laser is applied at the surface of the skin for cancer ablation, and the temperature and thermal damage distributions are predicted using the three bioheat models and two different modeling approaches of the laser effect. The first one is a prescribed surface heat flux, in which the tissue is assumed to be highly absorbent, while the second approach is a volumetric heat source, which is reasonable if the scattering and absorption skin effects are of similar magnitude. The finite volume method is applied to solve the governing bioheat equation. A parametric study is carried out to ascertain the effects of the thermophysical properties of the cancer on the thermal damage. The temperature distributions predicted by the three models exhibit significant differences, even though the temperature distributions are similar when the laser is turned off. The type of bioheat model has more influence on the predicted thermal damage than the type of modeling approach used for the laser. The phase lags of heat flux and temperature gradient have an important influence on the results, as well as the thermal conductivity of the cancer. In contrast, the uncertainty in the specific heat and blood perfusion rate has a minor influence on the thermal damage.

  16. Analytical model of diffuse reflectance spectrum of skin tissue

    SciTech Connect

    Lisenko, S A; Kugeiko, M M; Firago, V A; Sobchuk, A N

    2014-01-31

    We have derived simple analytical expressions that enable highly accurate calculation of diffusely reflected light signals of skin in the spectral range from 450 to 800 nm at a distance from the region of delivery of exciting radiation. The expressions, taking into account the dependence of the detected signals on the refractive index, transport scattering coefficient, absorption coefficient and anisotropy factor of the medium, have been obtained in the approximation of a two-layer medium model (epidermis and dermis) for the same parameters of light scattering but different absorption coefficients of layers. Numerical experiments on the retrieval of the skin biophysical parameters from the diffuse reflectance spectra simulated by the Monte Carlo method show that commercially available fibre-optic spectrophotometers with a fixed distance between the radiation source and detector can reliably determine the concentration of bilirubin, oxy- and deoxyhaemoglobin in the dermis tissues and the tissue structure parameter characterising the size of its effective scatterers. We present the examples of quantitative analysis of the experimental data, confirming the correctness of estimates of biophysical parameters of skin using the obtained analytical expressions. (biophotonics)

  17. Analytical model of diffuse reflectance spectrum of skin tissue

    NASA Astrophysics Data System (ADS)

    Lisenko, S. A.; Kugeiko, M. M.; Firago, V. A.; Sobchuk, A. N.

    2014-01-01

    We have derived simple analytical expressions that enable highly accurate calculation of diffusely reflected light signals of skin in the spectral range from 450 to 800 nm at a distance from the region of delivery of exciting radiation. The expressions, taking into account the dependence of the detected signals on the refractive index, transport scattering coefficient, absorption coefficient and anisotropy factor of the medium, have been obtained in the approximation of a two-layer medium model (epidermis and dermis) for the same parameters of light scattering but different absorption coefficients of layers. Numerical experiments on the retrieval of the skin biophysical parameters from the diffuse reflectance spectra simulated by the Monte Carlo method show that commercially available fibre-optic spectrophotometers with a fixed distance between the radiation source and detector can reliably determine the concentration of bilirubin, oxy- and deoxyhaemoglobin in the dermis tissues and the tissue structure parameter characterising the size of its effective scatterers. We present the examples of quantitative analysis of the experimental data, confirming the correctness of estimates of biophysical parameters of skin using the obtained analytical expressions.

  18. Genetic heterogeneity in leiomyomas of deep soft tissue.

    PubMed

    Panagopoulos, Ioannis; Gorunova, Ludmila; Brunetti, Marta; Agostini, Antonio; Andersen, Hege Kilen; Lobmaier, Ingvild; Bjerkehagen, Bodil; Heim, Sverre

    2017-07-25

    Leiomyoma of deep soft tissue is a rare type of benign smooth muscle tumor that mostly occurs in the retroperitoneum or abdominal cavity of women, and about which very little genetic information exists. In the present study, eight leiomyomas of deep soft tissue were genetically analyzed. G-banding showed that three tumors carried rearrangements of the long arm of chromosome 12, three others had 8q rearrangements, the 7th tumor had deletion of the long arm of chromosome 7, del(7)(q22), and the 8th had aberrations of chromosome bands 3q21~23 and 11q21~22. The target genes of the 12q and 8q aberrations were HMGA2 and PLAG1, respectively. In the leiomyomas with 12q rearrangements, both HMGA2 and PLAG1 were expressed whereas in the tumors with 8q aberrations, only PLAG1 was expressed. In the cases without 12q or 8q aberrations, the expression of HMGA2 was very low and PLAG1 was expressed only in the case with del(7)(q22). All eight leiomyomas of deep soft tissue expressed MED12 but none of them had mutation in exon 2 of that gene. In two tumors with 12q rearrangements, RPSAP52 on 12q14.3 was fused with non-coding RNA (accession number XR_944195) from 14q32.2 or ZFP36L1 from14q24.1. In a tumor with inv(12), exon 3 of HMGA2 was fused to a sequence in intron 1 of the CRADD gene from 12q22. The present data together with those of our two previous studies in which the fusions KAT6B-KANSL1 and EWSR1-PBX3 were described in two retroperitoneal leiomyomas carrying a t(10;17)(q22;q21) and a t(9;22)(q33;q12) translocation, respectively, show that leiomyomas of deep soft tissue are genetically heterogenous but have marked similarities to uterine leiomyomas.

  19. Genetic heterogeneity in leiomyomas of deep soft tissue

    PubMed Central

    Panagopoulos, Ioannis; Gorunova, Ludmila; Brunetti, Marta; Agostini, Antonio; Andersen, Hege Kilen; Lobmaier, Ingvild; Bjerkehagen, Bodil; Heim, Sverre

    2017-01-01

    Leiomyoma of deep soft tissue is a rare type of benign smooth muscle tumor that mostly occurs in the retroperitoneum or abdominal cavity of women, and about which very little genetic information exists. In the present study, eight leiomyomas of deep soft tissue were genetically analyzed. G-banding showed that three tumors carried rearrangements of the long arm of chromosome 12, three others had 8q rearrangements, the 7th tumor had deletion of the long arm of chromosome 7, del(7)(q22), and the 8th had aberrations of chromosome bands 3q21∼23 and 11q21∼22. The target genes of the 12q and 8q aberrations were HMGA2 and PLAG1, respectively. In the leiomyomas with 12q rearrangements, both HMGA2 and PLAG1 were expressed whereas in the tumors with 8q aberrations, only PLAG1 was expressed. In the cases without 12q or 8q aberrations, the expression of HMGA2 was very low and PLAG1 was expressed only in the case with del(7)(q22). All eight leiomyomas of deep soft tissue expressed MED12 but none of them had mutation in exon 2 of that gene. In two tumors with 12q rearrangements, RPSAP52 on 12q14.3 was fused with non-coding RNA (accession number XR_944195) from 14q32.2 or ZFP36L1 from14q24.1. In a tumor with inv(12), exon 3 of HMGA2 was fused to a sequence in intron 1 of the CRADD gene from 12q22. The present data together with those of our two previous studies in which the fusions KAT6B-KANSL1 and EWSR1-PBX3 were described in two retroperitoneal leiomyomas carrying a t(10;17)(q22;q21) and a t(9;22)(q33;q12) translocation, respectively, show that leiomyomas of deep soft tissue are genetically heterogenous but have marked similarities to uterine leiomyomas. PMID:28591699

  20. Ablation of skin tissue by holmium:YAG laser

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Holt, Andrew; Nordquist, Robert E.

    1994-08-01

    Surface epithelial damage by Ho:YAG laser and recovery were studied using histology and electron microscopy. Rabbit skin was irradiated with fluence varying from 55 J/cm2 to 680 J/cm2. Laser damage was determined by histological measurement of three major injury indicators: surface lesion width, depth of photocoagulation, and depth of thermal damage. When the fluence increased, the surface lesion widened and the photocoagulation zone extended deeper into the dermis. The thermally damaged zone (60 degree(s)C < T < 100 degree(s)C) remained at a relatively unchanged depth (about 1 mm) throughout our fluence range. The muscle and nerve tissues appeared to remain intact under most of our irradiance except at 500 J/cm2 and greater. Thermally injured tissues began recovery within a short period and eventually returned to normal; electron microscopic findings indicated that severe swelling occurred in the individual collagen fibrils, but they were not disrupted and usually recovered to appear normal. A layer of new epithelium started growing underneath the photocoagulated zone around day 3. After 7 days, most photocoagulated tissue was partially, in some cases completely, separated from the skin by the new epithelium. The damage and recovery parameters established should aid in the clinical use of Holmium laser in treating lesions, benign or malignant, in hollow tubular organs and on surface epithelia.

  1. Naturally derived biofunctional nanofibrous scaffold for skin tissue regeneration.

    PubMed

    Suganya, S; Venugopal, J; Ramakrishna, S; Lakshmi, B S; Dev, V R Giri

    2014-07-01

    Significant wound healing activity of Aloe vera (AV) and higher elastic strength of Silk fibroin (SF) along with mammalian cell compatibility makes AV and SF an attractive material for tissue engineering. The purpose of the present work was to combine their unique properties, with the advantage of electrospinning to prepare a hybrid transdermal biomaterial for dermal substitutes. The physico-chemical characterization of the developed scaffold showed finer morphology expressing amino and esteric groups with improved hydrophilic properties and favorable tensile strain of 116% desirable for skin tissue engineering. Their biological response showed favorable fibroblast proliferation compared to control which almost increased linearly by (p<0.01) 34.68% on day 3, (p<0.01) 19.13% on day 6, and (p<0.001) 97.86% on day 9 with higher expression of CMFDA, collagen and F-actin proteins. The obtained results prove that the nanofibrous scaffold with synergistic property of AV and SF would be a potential biomaterial for skin tissue regeneration.

  2. Caprine (goat) collagen: a potential biomaterial for skin tissue engineering.

    PubMed

    Banerjee, Indranil; Mishra, Debasish; Das, Tamal; Maiti, Swatilekha; Maiti, Tapas K

    2012-01-01

    Collagens presently used in tissue engineering are primarily of bovine or porcine origin. However, a risk of a spongiform encephalopathy epidemic has limited the use of collagen from these sources. Keeping the aforementioned perspective in mind, we explored the possibility of using domestic goat available in the subcontinent as a potential source of collagen for tissue-engineering application. This article delineates the isolation, physico-chemical characterization, biocompatibility study and wound healing application of acid soluble caprine (goat) tendon collagen (GTC). Physico-chemical characterization of 1% acetic acid extracted GTC was done by SDS-PAGE, amino-acid composition analysis, FT-IR and CD spectroscopy. Results revealed that GTC was comprised of type-I collagen. Biocompatibility study showed that GTC augmented cell adhesion, cell cycle progression and proliferation. Immuno-cytochemical analysis in conjugation with traction force microscopy further confirmed a superior focal adhesion complex mediated cell-substrate interaction in GTC. Finally, in vivo study in mice model revealed that GTC has low immunogenicity and it augments healing process significantly. Throughout the study, calf skin collagen (CSC) was used as standard for comparative evaluation. In conclusion, it can be said that GTC may find its application as biomaterial in skin tissue engineering.

  3. Evaluating elastic properties of heterogeneous soft tissue by surface acoustic waves detected by phase-sensitive optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Li, Chunhui; Guan, Guangying; Li, Sinan; Huang, Zhihong; Wang, Ruikang K.

    2012-05-01

    The combined use of surface acoustic wave (SAW) and phase-sensitive optical coherence tomography (PhS-OCT) is useful to evaluate the elasticity of layered biological tissues, such as normal skin. However, the pathological tissue is often originated locally, leading to the alternation of mechanical properties along both axial and lateral directions. We present a feasibility study on whether the SAW technique is sensitive to detect the alternation of mechanical property along the lateral direction within tissue, which is important for clinical utility of this technique to localize diseased tissue. Experiments are carried out on purposely designed tissue phantoms and ex vivo chicken breast samples, simulating the localized change of elasticity. A PhS-OCT system is employed not only to provide the ultra-high sensitive measurement of the generated surface waves on the tissue surface, but also to provide the real time imaging of the tissue to assist the elasticity evaluation of the heterogeneous tissue. The experimental results demonstrate that with PhS-OCT used as a pressure sensor, the SAW is highly sensitive to the elasticity change of the specimen in both vertical and lateral directions with a sensing depth of ˜5 mm with our current system setup, thus promising its useful clinical applications where the quantitative elasticity of localized skin diseases is needed to aid in diagnosis and treatment.

  4. Skin and soft tissue infections in the military.

    PubMed

    Lamb, Lucy; Morgan, M

    2013-09-01

    Skin and soft tissue infections (SSTI) are common in military populations regularly living and training in close contact with each other. The majority of such infections are simple and can be easily treated with antibiotics and appropriate infection control practices. Some, however, can progress to become complex and even life threatening, such as Panton-Valentine Leukocidin (PVL)-associated staphylococcus aureus pneumonia, or Streptococcus pyogenes necrotising fasciitis, which carry a mortality rate of up to 65% and 30%, respectively. This review focuses on the most important SSTIs and those more commonly affecting military personnel with advice on how they are best managed.

  5. Nanostructured materials from hydroxyethyl cellulose for skin tissue engineering.

    PubMed

    Zulkifli, Farah Hanani; Hussain, Fathima Shahitha Jahir; Rasad, Mohammad Syaiful Bahari Abdull; Mohd Yusoff, Mashitah

    2014-12-19

    In this study, a novel fibrous membrane of hydroxyethyl cellulose (HEC)/poly(vinyl alcohol) blend was successfully fabricated by electrospinning technique and characterized. The concentration of HEC (5%) with PVA (15%) was optimized, blended in different ratios (30-50%) and electrospun to get smooth nanofibers. Nanofibrous membranes were made water insoluble by chemically cross-linking by glutaraldehyde and used as scaffolds for the skin tissue engineering. The microstructure, morphology, mechanical and thermal properties of the blended HEC/PVA nanofibrous scaffolds were characterized by scanning electron microscope, Fourier transform infrared spectroscopy, differential scanning colorimetry, universal testing machine and thermogravimetric analysis. Cytotoxicity studies on these nanofibrous scaffolds were carried out using human melanoma cells by the MTT assays. The cells were able to attach and spread in the nanofibrous scaffolds as shown by the SEM images. These preliminary results show that these nanofibrous scaffolds that supports cell adhesion and proliferation is promising for skin tissue engineering. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Plant-derived human collagen scaffolds for skin tissue engineering.

    PubMed

    Willard, James J; Drexler, Jason W; Das, Amitava; Roy, Sashwati; Shilo, Shani; Shoseyov, Oded; Powell, Heather M

    2013-07-01

    Tissue engineering scaffolds are commonly formed using proteins extracted from animal tissues, such as bovine hide. Risks associated with the use of these materials include hypersensitivity and pathogenic contamination. Human-derived proteins lower the risk of hypersensitivity, but possess the risk of disease transmission. Methods engineering recombinant human proteins using plant material provide an alternate source of these materials without the risk of disease transmission or concerns regarding variability. To investigate the utility of plant-derived human collagen (PDHC) in the development of engineered skin (ES), PDHC and bovine hide collagen were formed into tissue engineering scaffolds using electrospinning or freeze-drying. Both raw materials were easily formed into two common scaffold types, electrospun nonwoven scaffolds and lyophilized sponges, with similar architectures. The processing time, however, was significantly lower with PDHC. PDHC scaffolds supported primary human cell attachment and proliferation at an equivalent or higher level than the bovine material. Interleukin-1 beta production was significantly lower when activated THP-1 macrophages where exposed to PDHC electrospun scaffolds compared to bovine collagen. Both materials promoted proper maturation and differentiation of ES. These data suggest that PDHC may provide a novel source of raw material for tissue engineering with low risk of allergic response or disease transmission.

  7. Plant-Derived Human Collagen Scaffolds for Skin Tissue Engineering

    PubMed Central

    Willard, James J.; Drexler, Jason W.; Das, Amitava; Roy, Sashwati; Shilo, Shani; Shoseyov, Oded

    2013-01-01

    Tissue engineering scaffolds are commonly formed using proteins extracted from animal tissues, such as bovine hide. Risks associated with the use of these materials include hypersensitivity and pathogenic contamination. Human-derived proteins lower the risk of hypersensitivity, but possess the risk of disease transmission. Methods engineering recombinant human proteins using plant material provide an alternate source of these materials without the risk of disease transmission or concerns regarding variability. To investigate the utility of plant-derived human collagen (PDHC) in the development of engineered skin (ES), PDHC and bovine hide collagen were formed into tissue engineering scaffolds using electrospinning or freeze-drying. Both raw materials were easily formed into two common scaffold types, electrospun nonwoven scaffolds and lyophilized sponges, with similar architectures. The processing time, however, was significantly lower with PDHC. PDHC scaffolds supported primary human cell attachment and proliferation at an equivalent or higher level than the bovine material. Interleukin-1 beta production was significantly lower when activated THP-1 macrophages where exposed to PDHC electrospun scaffolds compared to bovine collagen. Both materials promoted proper maturation and differentiation of ES. These data suggest that PDHC may provide a novel source of raw material for tissue engineering with low risk of allergic response or disease transmission. PMID:23298216

  8. Skin color correction for tissue spectroscopy: demonstration of a novel approach with tissue-mimicking phantoms.

    PubMed

    Soyemi, Olusola O; Landry, Michelle R; Yang, Ye; Idwasi, Patrick O; Soller, Babs R

    2005-02-01

    The application of partial least squares (PLS) regression to visible-near-infrared (VIS-NIR) spectroscopy for modeling important blood and tissue parameters is generally complicated by the variation in skin pigmentation (melanin) across the human population. An orthogonal correction method for removing the influence of skin pigmentation has been demonstrated in diffuse reflectance spectra from two-layer tissue-mimicking phantoms. The absorption properties of the phantoms were defined by lyophilized human hemoglobin (bottom layer) and synthetic melanin (top layer). Tissue-like scattering was simulated in both layers with intralipid. The approach uses principal components analysis (PCA) loading vectors from a separate set of phantom spectra that encode the unwanted melanin variation to remove the effect of melanin from the test phantoms. The preprocessing of phantom spectra using this orthogonal correction method resulted in PLS models with reduced complexity and enhanced prediction performance. Preliminary results from a separate study that evaluates the feasibility of defining skin color variation in an experiment with a single human subject are also presented.

  9. Influence of heterogeneous and anisotropic tissue conductivity on electric field distribution in deep brain stimulation.

    PubMed

    Aström, Mattias; Lemaire, Jean-Jacques; Wårdell, Karin

    2012-01-01

    The aim was to quantify the influence of heterogeneous isotropic and heterogeneous anisotropic tissue on the spatial distribution of the electric field during deep brain stimulation (DBS). Three finite element tissue models were created of one patient treated with DBS. Tissue conductivity was modelled as (I) homogeneous isotropic, (II) heterogeneous isotropic based on MRI, and (III) heterogeneous anisotropic based on diffusion tensor MRI. Modelled DBS electrodes were positioned in the subthalamic area, the pallidum, and the internal capsule in each tissue model. Electric fields generated during DBS were simulated for each model and target-combination and visualized with isolevels at 0.20 (inner), and 0.05 V mm(-1) (outer). Statistical and vector analysis was used for evaluation of the distribution of the electric field. Heterogeneous isotropic tissue altered the spatial distribution of the electric field by up to 4% at inner, and up to 10% at outer isolevel. Heterogeneous anisotropic tissue influenced the distribution of the electric field by up to 18 and 15% at each isolevel, respectively. The influence of heterogeneous and anisotropic tissue on the electric field may be clinically relevant in anatomic regions that are functionally subdivided and surrounded by multiple fibres of passage.

  10. Assisting Main Task Learning by Heterogeneous Auxiliary Tasks with Applications to Skin Cancer Screening.

    PubMed

    Situ, Ning; Yuan, Xiaojing; Zouridakis, George

    2011-01-01

    In typical classification problems, high level concept features provided by a domain expert are usually available during classifier training but not during its deployment. We address this problem from a multitask learning (MTL) perspective by treating these features as auxiliary learning tasks. Previous efforts in MTL have mostly assumed that all tasks have the same input space. However, auxiliary tasks can have different input spaces, since their learning targets are different. Thus, to handle cases with heterogeneous input, in this paper we present a newly developed model using heterogeneous auxiliary tasks to help main task learning. First, we formulate a convex optimization problem for the proposed model, and then, we analyze its hypothesis class and derive true risk bounds. Finally, we compare the proposed model with other relevant methods when applied to the problem of skin cancer screening and public datasets. Our results show that the performance of the proposed method is highly competitive compared to other relevant methods.

  11. Immediate Changes to Skin and Subcutaneous Tissue Strains Following Manual Lymph Drainage in Legs with Lymphedema

    PubMed Central

    Kakutani, Hiromi; Nakamura, Kaori; Morikage, Noriyasu; Yamashita, Osamu; Harada, Takasuke; Ueda, Koshiro; Samura, Makoto; Tanaka, Yuya; Takeuchi, Yuriko; Hamano, Kimikazu

    2016-01-01

    Objectives: To study the immediate impact of manual lymph drainage (MLD) on skin and subcutaneous tissue strains in legs with lymphedema using free-hand real-time tissue elastography (RTE). Methods: Skin and subcutaneous tissue strain measurements were taken at the middle of the inner thigh and calf by RTE in 20 legs with lymphedema of 18 patients (stage II: 11, late stage II: 7, stage III: 2) and in 70 legs of 35 normal subjects. In patients with lymphedema, the same measurements were repeated immediately following MLD. Results: Significant negative correlations were found between pre-MLD strains and the MLD-induced changes in thigh and calf skin strains (thigh skin: p <0.01, calf skin: p = 0.05), but not in subcutaneous tissue strains. Pre-MLD intercepts of these regression lines were closer to normal values as compared to mean pre-MLD values (normal thigh skin: 0.54% ± 0.30%, calf skin: 0.25% ± 0.18%, Pre-MLD thigh skin: 0.39% ± 0.20%, calf skin: 0.17% ± 0.12%, Pre-MLD intercept of thigh skin: 0.48%, Pre-MLD intercept of calf skin: 0.31%). Conclusions: It appears that MLD did not simply soften the skin, but rather normalized it in terms of strain. However, this was not confirmed in the subcutaneous tissue. PMID:27087870

  12. Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps.

    PubMed

    Zhang, Qixu; Johnson, Joshua A; Dunne, Lina W; Chen, Youbai; Iyyanki, Tejaswi; Wu, Yewen; Chang, Edward I; Branch-Brooks, Cynthia D; Robb, Geoffrey L; Butler, Charles E

    2016-04-15

    Using a perfusion decellularization protocol, we developed a decellularized skin/adipose tissue flap (DSAF) comprising extracellular matrix (ECM) and intact vasculature. Our DSAF had a dominant vascular pedicle, microcirculatory vascularity, and a sensory nerve network and retained three-dimensional (3D) nanofibrous structures well. DSAF, which was composed of collagen and laminin with well-preserved growth factors (e.g., vascular endothelial growth factor, basic fibroblast growth factor), was successfully repopulated with human adipose-derived stem cells (hASCs) and human umbilical vein endothelial cells (HUVECs), which integrated with DSAF and formed 3D aggregates and vessel-like structures in vitro. We used microsurgery techniques to re-anastomose the recellularized DSAF into nude rats. In vivo, the engineered flap construct underwent neovascularization and constructive remodeling, which was characterized by the predominant infiltration of M2 macrophages and significant adipose tissue formation at 3months postoperatively. Our results indicate that DSAF co-cultured with hASCs and HUVECs is a promising platform for vascularized soft tissue flap engineering. This platform is not limited by the flap size, as the entire construct can be immediately perfused by the recellularized vascular network following simple re-integration into the host using conventional microsurgical techniques. Significant soft tissue loss resulting from traumatic injury or tumor resection often requires surgical reconstruction using autologous soft tissue flaps. However, the limited availability of qualitative autologous flaps as well as the donor site morbidity significantly limits this approach. Engineered soft tissue flap grafts may offer a clinically relevant alternative to the autologous flap tissue. In this study, we engineered vascularized soft tissue free flap by using skin/adipose flap extracellular matrix scaffold (DSAF) in combination with multiple types of human cells. Following

  13. Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review

    PubMed Central

    Chaudhari, Atul A.; Vig, Komal; Baganizi, Dieudonné Radé; Sahu, Rajnish; Dixit, Saurabh; Dennis, Vida; Singh, Shree Ram; Pillai, Shreekumar R.

    2016-01-01

    Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts. PMID:27898014

  14. Changes of color coordinates of biological tissue with superficial skin damage due to mechanical trauma

    NASA Astrophysics Data System (ADS)

    Pteruk, Vail; Mokanyuk, Olexander; Kvaternuk, Olena; Yakenina, Lesya; Kotyra, Andrzej; Romaniuk, Ryszard S.; Dussembayeva, Shynar

    2015-12-01

    Change of color coordinates of normal and pathological biological tissues is based on calculated spectral diffuse reflection. The proposed color coordinates of normal and pathological biological tissues of skin provided using standard light sources, allowing accurately diagnose skin damage due to mechanical trauma with a blunt object for forensic problems.

  15. Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review.

    PubMed

    Chaudhari, Atul A; Vig, Komal; Baganizi, Dieudonné Radé; Sahu, Rajnish; Dixit, Saurabh; Dennis, Vida; Singh, Shree Ram; Pillai, Shreekumar R

    2016-11-25

    Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

  16. Deformations experienced in the human skin, adipose tissue, and fascia in osteopathic manipulative medicine.

    PubMed

    Chaudhry, Hans; Bukiet, Bruce; Ji, Zhiming; Stecco, Antonio; Findley, Thomas W

    2014-10-01

    Osteopathic manipulative medicine techniques involve compressive and tangential forces to target the fascia. These forces are transmitted to the skin and adipose tissue before the fascia is encountered. Knowing the extent of deformation of these 2 tissue layers relative to the fascia will assist osteopathic physicians in evaluating techniques for manual therapies and adjusting these therapies to reduce patient discomfort and improve results. To determine the magnitude of the forces transmitted to the skin, adipose tissue, and fascia, and to determine the magnitude of deformation produced in the skin and adipose tissue relative to the fascia using a mathematical model. The large deformation theory of elasticity, valid for 3-dimensional deformations, was used to evaluate the forces that need to be applied such that a specified deformation is produced in any region of the skin, adipose tissue, or fascia layers. Similarly, if the forces are specified, then the deformation produced can be determined. The normal and tangential forces required to produce a deformation of 9% compression and 4% shear for the skin were 50 N and 11 N, respectively. Normal and tangential forces of about 100 N and 22 N were found for a similar deformation of fascia. For adipose tissue, these forces were 36 N and 8 N, respectively. In addition, the skin experienced more compression and shear-about 1.5 times as much as the fascia, and the adipose tissue experienced about 2.5 to 3.5 times the deformation of the fascia and 50% more than the skin when a given force was applied to the skin. The forces applied to the surface of the skin were transmitted through this layer and the adipose layer entirely to the fascia. Therefore, the skin and adipose tissue experienced the same magnitude of force as the fascia. However, the skin and adipose tissue experienced more compression and shear than the fascia. © 2014 The American Osteopathic Association.

  17. Neutrophilic Skin Lesions in Autoimmune Connective Tissue Diseases

    PubMed Central

    Hau, Estelle; Vignon Pennamen, Marie-Dominique; Battistella, Maxime; Saussine, Anne; Bergis, Maud; Cavelier-Balloy, Benedicte; Janier, Michel; Cordoliani, Florence; Bagot, Martine; Rybojad, Michel; Bouaziz, Jean-David

    2014-01-01

    Abstract The pathophysiology of neutrophilic dermatoses (NDs) and autoimmune connective tissue diseases (AICTDs) is incompletely understood. The association between NDs and AICTDs is rare; recently, however, a distinctive subset of cutaneous lupus erythematosus (LE, the prototypical AICTD) with neutrophilic histological features has been proposed to be included in the spectrum of lupus. The aim of our study was to test the validity of such a classification. We conducted a monocentric retrospective study of 7028 AICTDs patients. Among these 7028 patients, a skin biopsy was performed in 932 cases with mainly neutrophilic infiltrate on histology in 9 cases. Combining our 9 cases and an exhaustive literature review, pyoderma gangrenosum, Sweet syndrome (n = 49), Sweet-like ND (n = 13), neutrophilic urticarial dermatosis (n = 6), palisaded neutrophilic granulomatous dermatitis (n = 12), and histiocytoid neutrophilic dermatitis (n = 2) were likely to occur both in AICTDs and autoinflammatory diseases. Other NDs were specifically encountered in AICTDs: bullous LE (n = 71), amicrobial pustulosis of the folds (n = 28), autoimmunity-related ND (n = 24), ND resembling erythema gyratum repens (n = 1), and neutrophilic annular erythema (n = 1). The improvement of AICTDS neutrophilic lesions under neutrophil targeting therapy suggests possible common physiopathological pathways between NDs and AICTDs. PMID:25546688

  18. Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs.

    PubMed

    Colosi, Cristina; Costantini, Marco; Barbetta, Andrea; Dentini, Mariella

    2017-01-01

    3D bioprinting is an emerging field that can be described as a robotic additive biofabrication technology that has the potential to build tissues or organs. In general, bioprinting uses a computer-controlled printing device to accurately deposit cells and biomaterials into precise architectures with the goal of creating on demand organized multicellular tissue structures and eventually intra-organ vascular networks. The latter, in turn, will promote the host integration of the engineered tissue/organ in situ once implanted. Existing biofabrication techniques still lay behind this goal. Here, we describe a novel microfluidic printing head-integrated within a custom 3D bioprinter-that allows for the deposition of multimaterial and/or multicellular within a single scaffold by extruding simultaneously different bioinks or by rapidly switching between one bioink and another. The designed bioprinting method effectively moves toward the direction of creating viable tissues and organs for implantation in clinic and research in lab environments.

  19. Comparison of the histological morphology between normal skin and scar tissue.

    PubMed

    Yang, Shao-wei; Geng, Zhi-jun; Ma, Kui; Sun, Xiao-yan; Fu, Xiao-bing

    2016-04-01

    Skin wound healing is a complex event, and interrupted wound healing process could lead to scar formation. The aim of this study was to examine the morphological changes of scar tissue. Pathological staining (HE staining, Masson's trichrome staining, methenamine silver staining) was used to evaluate the morphological changes of regenerating epidermis in normal skin and scar tissue, and immunofluorescence staining to detect the expression of collagen IV, a component of basement membrane (BM), and the expression of integrinβ4, a receptor for BM laminins. Additionally, the expression of CK14, CK5, and CK10 was measured to evaluate the proliferation and differentiation of keratinocytes in normal skin and scar tissue. The results showed that the structure of the skin was histologically changed in scar tissue. Collagen IV, expressed under the epidermis of normal skin, was reduced distinctly in scar tissue. Integrinβ4, expressed in the basal layer of normal skin, was found absent in the basal layer of scar tissue. Additionally, it was found that keratinocytes in scarring epidermis were more proliferative than in normal skin. These results indicate that during the skin wound healing, altered formation of BM may affect the proliferation of keratinocytes, reepithelial and tissue remodeling, and then result in scar formation. Thus, remodeling BM structure during wound repair may be beneficial for improving healing in cutaneous wounds during clinical practice.

  20. Skin and soft tissue necrosis from calcium chloride in a deicer.

    PubMed

    Kim, Min P; Raho, Vittorio J; Mak, John; Kaynar, A Murat

    2007-01-01

    Calcium chloride salt is the principle ingredient of many commercially available deicers. Calcium chloride melts snow and ice by its osmotic action. We present a case of skin and soft tissue necrosis associated with the use of a calcium chloride-containing deicer. Although calcium chloride is known to produce soft tissue necrosis if it extravasates during intravenous administration, necrosis and skin sloughing has rarely been described after topical exposure to this salt. Calcium chloride likely produces tissue injury from the heat liberated by mixing calcium chloride with water (exothermic reaction) and from direct calcium deposits in the skin (calcinosis cutis) and soft tissue.

  1. In vivo skin treatment with tissue-tolerable plasma influences skin physiology and antioxidant profile in human stratum corneum.

    PubMed

    Fluhr, Joachim W; Sassning, Sven; Lademann, Olaf; Darvin, Maxim E; Schanzer, Sabine; Kramer, Axel; Richter, Heike; Sterry, Wolfram; Lademann, Juergen

    2012-02-01

    The antimicrobial treatment of wounds is still a major problem. Tissue-tolerable electrical plasma (TTP) is a new approach for topical microbial disinfection of the skin surface. The aim of the present study was to investigate the influence of TTP on a carotenoid profile in relation to skin physiology parameters (epidermal barrier function, stratum corneum (SC) hydration, surface temperature and irritation parameters). We were interested in the interaction of TTP and the antioxidative network, as well as the consequences for skin physiology parameters. These parameters are also indicative of TTP safety in vivo. For plasma application, 'Kinpen 09' was used (surface exposure 30-43°C) for 3 s. Beta-carotene and water profiles were assessed by in vivo Raman microspectroscopy (skin composition analyzer 3510). Skin physiology parameters were measured with Tewameter TM 300, Corneometer CM 825, skin thermometer and Chromameter CR 300. All parameters were assessed non-invasively on seven healthy volunteers before and after plasma application in vivo. We could show that TTP application leads to a decrease in beta-carotene especially in the superficial SC. Skin-surface temperature increased by 1.74°C, while the transepidermal water loss (TEWL) increase indicated an impaired barrier function. SC hydration decreased as seen in water profile especially in the superficial layers and capacitance values. A slight increase in skin redness was measurable. The induction of reactive oxygen species is probably the major contributor of TTP efficacy in skin disinfection. Skin physiology parameters were influenced without damaging the skin or skin functions, indicating the safety of TTP under in vivo conditions.

  2. Measurement of the axial and circumferential mechanical properties of rat skin tissue at different anatomical locations.

    PubMed

    Karimi, Alireza; Haghighatnama, Maedeh; Navidbakhsh, Mahdi; Haghi, Afsaneh Motevalli

    2015-04-01

    Skin tissue is not only responsible for thermoregulation but also for protecting the human body from mechanical, bacterial, and viral insults. The mechanical properties of skin tissue may vary according to the anatomical locations in the body. However, the linear elastic and nonlinear hyperelastic mechanical properties of the skin in different anatomical regions and at different loading directions (axial and circumferential) so far have not been determined. In this study, the mechanical properties during tension of the rat abdomen and back were calculated at different loading directions using linear elastic and nonlinear hyperelastic material models. The skin samples were subjected to a series of tensile tests. The elastic modulus and maximum stress of the skin tissues were measured before the incidence of failure. The nonlinear mechanical behavior of the skin tissues was also computationally investigated through a constitutive equation. Hyperelastic strain energy density function was calibrated using the experimental data. The results revealed the anisotropic mechanical behavior of the abdomen and the isotropic mechanical response of the back skin. The highest elastic modulus was observed in the abdomen skin under the axial direction (10 MPa), while the lowest one was seen in the back skin under axial loading (5 MPa). The Mooney-Rivlin material model closely addressed the nonlinear mechanical behavior of the skin at different loading directions, which can be implemented in the future biomechanical models of skin tissue. The results might have implications not only for understanding of the isotropic and anisotropic mechanical behavior of skin tissue at different anatomical locations but also for providing more information for a diversity of disciplines, including dermatology, cosmetics industry, clinical decision making, and clinical intervention.

  3. Application of collagen-chitosan/fibrin glue asymmetric scaffolds in skin tissue engineering.

    PubMed

    Han, Chun-mao; Zhang, Li-ping; Sun, Jin-zhang; Shi, Hai-fei; Zhou, Jie; Gao, Chang-you

    2010-07-01

    To create a scaffold that is suitable for the construction of tissue-engineered skin, a novel asymmetric porous scaffold with different pore sizes on either side was prepared by combining a collagen-chitosan porous membrane with fibrin glue. Tissue-engineered skin was fabricated using this asymmetric scaffold, fibroblasts, and a human keratinocyte line (HaCaT). Epidermal cells could be seen growing easily and achieved confluence on the fibrin glue on the upper surface of the scaffold. Scanning electron microscopy showed typical shuttle-like fibroblasts adhering to the wall of the scaffold and fluorescence microscopy showed them growing in the dermal layer of the scaffold. The constructed composite skin substitute had a histological structure similar to that of normal skin tissue after three weeks of culture. The results of our study suggest that the asymmetric scaffold is a promising biologically functional material for skin tissue engineering, with prospects for clinical applications.

  4. Application of collagen-chitosan/fibrin glue asymmetric scaffolds in skin tissue engineering*

    PubMed Central

    Han, Chun-mao; Zhang, Li-ping; Sun, Jin-zhang; Shi, Hai-fei; Zhou, Jie; Gao, Chang-you

    2010-01-01

    To create a scaffold that is suitable for the construction of tissue-engineered skin, a novel asymmetric porous scaffold with different pore sizes on either side was prepared by combining a collagen-chitosan porous membrane with fibrin glue. Tissue-engineered skin was fabricated using this asymmetric scaffold, fibroblasts, and a human keratinocyte line (HaCaT). Epidermal cells could be seen growing easily and achieved confluence on the fibrin glue on the upper surface of the scaffold. Scanning electron microscopy showed typical shuttle-like fibroblasts adhering to the wall of the scaffold and fluorescence microscopy showed them growing in the dermal layer of the scaffold. The constructed composite skin substitute had a histological structure similar to that of normal skin tissue after three weeks of culture. The results of our study suggest that the asymmetric scaffold is a promising biologically functional material for skin tissue engineering, with prospects for clinical applications. PMID:20593518

  5. Thermally-induced change in the relaxation behavior of skin tissue.

    PubMed

    Xu, F; Lu, T J; Seffen, K A

    2009-07-01

    Skin biothermomechanics is highly interdisciplinary, involving bioheat transfer, burn damage, biomechanics, and physiology. Characterization of the thermomechanical behavior of skin tissue is of great importance and can contribute to a variety of medical applications. However, few quantitative studies have been conducted on the thermally-dependent mechanical properties of skin tissue. The aim of the present study is to experimentally examine the thermally-induced change in the relaxation behavior of skin tissue in both hyperthermal and hypothermic ranges. The results show that temperature has great influence on the stress-relaxation behavior of skin tissue under both hyperthermal and hypothermic temperatures; the quantitative relationship that has been found between temperature and the viscoelastic parameter (the elastic fraction or fractional energy dissipation) was temperature dependent, with greatest dissipation at high temperature levels.

  6. CD49a Expression Defines Tissue-Resident CD8(+) T Cells Poised for Cytotoxic Function in Human Skin.

    PubMed

    Cheuk, Stanley; Schlums, Heinrich; Gallais Sérézal, Irène; Martini, Elisa; Chiang, Samuel C; Marquardt, Nicole; Gibbs, Anna; Detlofsson, Ebba; Introini, Andrea; Forkel, Marianne; Höög, Charlotte; Tjernlund, Annelie; Michaëlsson, Jakob; Folkersen, Lasse; Mjösberg, Jenny; Blomqvist, Lennart; Ehrström, Marcus; Ståhle, Mona; Bryceson, Yenan T; Eidsmo, Liv

    2017-02-21

    Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8(+)CD49a(+) Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8(+)CD49a(-) Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8(+) Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases.

  7. Optical coherence tomography investigation of growth cycles of engineered skin tissue

    NASA Astrophysics Data System (ADS)

    Schmitt, Robert; Marx, Ulrich; Walles, Heike; Heymer, Andrea

    2010-02-01

    Engineered skin tissues are widely used in dermatological, pharmacological and toxicological studies and as autologous transplants in wound healing. Due to the high demand for artificial skin equivalents, there is a need for an automation of the manual production process to achieve a high-grade product. Thus, non-invasive monitoring of engineered tissue during the growth cycles is of major significance to understand and consequently improve the growth characteristics of in vitro tissue. Prior to the framework of the automation of artificial humanoid 3d-skin tissue engineering, optimal growth parameters need to be determined. The successful engineering of humanoid tissue is strongly coupled to the composition and structure of the upper epidermal and dermal skin layers. The layers are based on primary humanoid keratinocytes and a collagen - fibroblasts matrix. We applied optical coherence tomography as tissue imaging technology, which offers great potential to detect and characterize the differentiation processes of engineered skin. OCT provides a high resolution in the micron range with an imaging depth of about 1.5mm in semitransparent tissue. Due to a high quality signal to noise ratio, even small changes in signal at the boundary of the skin layers are detectable. In a study, OCT tomograms were taken after each production step of the skin equivalents and compared to the images of histologies.

  8. MALDI imaging in human skin tissue sections: focus on various matrices and enzymes.

    PubMed

    Enthaler, Bernd; Trusch, Maria; Fischer, Markus; Rapp, Claudius; Pruns, Julia K; Vietzke, Jens-Peter

    2013-02-01

    Matrix-assisted laser/desorption ionization (MALDI) mass-spectrometric imaging (MSI), also known as MALDI imaging, is a powerful technique for mapping biological molecules such as endogenous proteins and peptides in human skin tissue sections. A few groups have endeavored to apply MALDI-MSI to the field of skin research; however, a comprehensive article dealing with skin tissue sections and the application of various matrices and enzymes is not available. Our aim is to present a multiplex method, based on MALDI-MSI, to obtain the maximum information from skin tissue sections. Various matrices were applied to skin tissue sections: (1) 9-aminoacridine for imaging metabolites in negative ion mode; (2) sinapinic acid to obtain protein distributions; (3) α-cyano-4-hydroxycinnamic acid subsequent to on-tissue enzymatic digestion by trypsin, elastase, and pepsin, respectively, to localize the resulting peptides. Notably, substantial amounts of data were generated from the distributions retrieved for all matrices applied. Several primary metabolites, e.g. ATP, were localized and subsequently identified by on-tissue postsource decay measurements. Furthermore, maps of proteins and peptides derived from on-tissue digests were generated. Identification of peptides was achieved by elution with different solvents, mixing with α-cyano-4-hydroxycinnamic acid, and subsequent tandem mass spectrometry (MS/MS) measurements, thereby avoiding on-tissue MS/MS measurements. Highly abundant peptides were identified, allowing their use as internal calibrants in future MALDI-MSI analyses of human skin tissue sections. Elastin as an endogenous skin protein was identified only by use of elastase, showing the high potential of alternative enzymes. The results show the versatility of MALDI-MSI in the field of skin research. This article containing a methodological perspective depicts the basics for a comprehensive comparison of various skin states.

  9. [Modified method of constructing tissue microarray which contains keloid and normal skin].

    PubMed

    Zhang, Zhenyu; Chen, Junjie; Cen, Ying; Zhao, Sha; Liao, Dianying; Gong, Jing

    2010-08-01

    To seek for a method of constructing the tissue microarray which contains keloid, skin around keloid, and normal skin. The specimens were gained from patients of voluntary donation between March and May 2009, including the tissues of keloid (27 cases), skin around keloid (13 cases), and normal skin (27 cases). The specimens were imbedded by paraffin as donor blocks. The traditional method of constructing the tissue microarray and section were modified according to the histological characteristics of the keloid and skin tissue and the experimental requirement. The tissue cores were drilled from donor blocks and attached securely on the adhesive platform which was prepared. The adhesive platform with tissue cores in situ was placed into an imbedding mold, which then was preheated briefly. Paraffin at approximately 70 degrees C was injected to fill the mold and then cooled to room temperature. Then HE staining, immunohistochemistry staining were performed and the results were observed by microscope. The constructed tissue microarray block contained 67 cores as designed and displayed smooth surface with no crack. All the cores distributed regularly, had no disintegration or manifest shift. HE staining of tissue microarray section showed that all cores had equal thickness, distinct layer, manifest contradistinction, well-defined edge, and consistent with original pathological diagnosis. Immunohistochemistry staining results demonstrated that all cores contained enough tissue dose to apply group comparison. However, in tissue microarray which was made as traditional method, many cores missed and a few cores shifted obviously. Applying modified method can successfully construct tissue microarray which is composed of keloid, skin around keloid, and normal skin. This tissue microarray will become an effective tool of researching the pathogenesis of keloid.

  10. Improved Methods to Produce Tissue-Engineered Skin Substitutes Suitable for the Permanent Closure of Full-Thickness Skin Injuries

    PubMed Central

    Larouche, Danielle; Cantin-Warren, Laurence; Desgagné, Maxime; Guignard, Rina; Martel, Israël; Ayoub, Akram; Lavoie, Amélie; Gauvin, Robert; Auger, François A.; Moulin, Véronique J.; Germain, Lucie

    2016-01-01

    Abstract There is a clinical need for skin substitutes to replace full-thickness skin loss. Our group has developed a bilayered skin substitute produced from the patient's own fibroblasts and keratinocytes referred to as Self-Assembled Skin Substitute (SASS). After cell isolation and expansion, the current time required to produce SASS is 45 days. We aimed to optimize the manufacturing process to standardize the production of SASS and to reduce production time. The new approach consisted in seeding keratinocytes on a fibroblast-derived tissue sheet before its detachment from the culture plate. Four days following keratinocyte seeding, the resulting tissue was stacked on two fibroblast-derived tissue sheets and cultured at the air–liquid interface for 10 days. The resulting total production time was 31 days. An alternative method adapted to more contractile fibroblasts was also developed. It consisted in adding a peripheral frame before seeding fibroblasts in the culture plate. SASSs produced by both new methods shared similar histology, contractile behavior in vitro and in vivo evolution after grafting onto mice when compared with SASSs produced by the 45-day standard method. In conclusion, the new approach for the production of high-quality human skin substitutes should allow an earlier autologous grafting for the treatment of severely burned patients. PMID:27872793

  11. Humanized tissue pharmacodynamics of cefazolin against commonly isolated pathogens in skin and skin structure infections.

    PubMed

    Jain, Jami G; Housman, Seth T; Nicolau, David P

    2014-09-01

    The objective of this study was to assess the efficacy of humanized cefazolin tissue concentrations against methicillin-susceptible Staphylococcus aureus (MSSA) and Enterobacteriaceae in an in vitro pharmacodynamic model. Nine clinical isolates [five MSSA (cefazolin MIC range 0.5-2.0 mg/L), two Escherichia coli (cefazolin MICs 1.0 and 2.0 mg/L) and two Klebsiella pneumoniae (cefazolin MICs of 1.0 and 2.0 mg/L)] were evaluated with a starting inoculum (0 h) of 10(6) cfu/mL. Time-kill curves were built and the area under the bacterial killing and regrowth curve (AUBC) was calculated. The starting inoculum had a mean ± SD of 6.3 ± 0.28 log10 cfu/mL. Cefazolin human simulated targets for peak, trough and half-life were 13.0 mg/L, 2.6 mg/L and 2.6 h, respectively. Control isolates grew to 8.5 ± 0.2 log10 cfu/mL. Against MSSA, cefazolin achieved a reduction from 0 h of -1.18 ± 0.67 and -3.58 ± 1.24 log10 cfu/mL, at 4 and 24 h, respectively. Cefazolin achieved a reduction in bacterial density of -3.45 ± 0.35 and -2.68 ± 0.99 log10 cfu/mL at 4 and 24 h, respectively, when tested against Enterobacteriaceae. No significant difference was observed when comparing AUBC based on MIC values. The rate of initial bacterial reduction of Enterobacteriaceae was rapid, with a decrease of >3 log10 cfu/mL by 4 h, while MSSA exhibited a gradual reduction in bacterial density over one dosing interval. The observed antibacterial effects of cefazolin support its continued utility against susceptible S. aureus, E. coli and K. pneumoniae in skin and skin structure infections. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Photoprotection by pistachio bioactives in a 3-dimensional human skin equivalent tissue model.

    PubMed

    Chen, C-Y Oliver; Smith, Avi; Liu, Yuntao; Du, Peng; Blumberg, Jeffrey B; Garlick, Jonathan

    2017-01-25

    Reactive oxygen species (ROS) generated during ultraviolet (UV) light exposure can induce skin damage and aging. Antioxidants can provide protection against oxidative injury to skin via "quenching" ROS. Using a validated 3-dimensional (3D) human skin equivalent (HSE) tissue model that closely mimics human skin, we examined whether pistachio antioxidants could protect HSE against UVA-induced damage. Lutein and γ-tocopherol are the predominant lipophilic antioxidants in pistachios; treatment with these compounds prior to UVA exposure protected against morphological changes to the epithelial and connective tissue compartments of HSE. Pistachio antioxidants preserved overall skin thickness and organization, as well as fibroblast morphology, in HSE exposed to UVA irradiation. However, this protection was not substantiated by the analysis of the proliferation of keratinocytes and apoptosis of fibroblasts. Additional studies are warranted to elucidate the basis of these discordant results and extend research into the potential role of pistachio bioactives promoting skin health.

  13. CCN1 contributes to skin connective tissue aging by inducing age-associated secretory phenotype in human skin dermal fibroblasts.

    PubMed

    Quan, Taihao; Qin, Zhaoping; Robichaud, Patrick; Voorhees, John J; Fisher, Gary J

    2011-08-01

    Dermal connective tissue collagen is the major structural protein in skin. Fibroblasts within the dermis are largely responsible for collagen production and turnover. We have previously reported that dermal fibroblasts, in aged human skin in vivo, express elevated levels of CCN1, and that CCN1 negatively regulates collagen homeostasis by suppressing collagen synthesis and increasing collagen degradation (Quan et al. Am J Pathol 169:482-90, 2006, J Invest Dermatol 130:1697-706, 2010). In further investigations of CCN1 actions, we find that CCN1 alters collagen homeostasis by promoting expression of specific secreted proteins, which include matrix metalloproteinases and proinflammatory cytokines. We also find that CCN1-induced secretory proteins are elevated in aged human skin in vivo. We propose that CCN1 induces an "Age-Associated Secretory Phenotype", in dermal fibroblasts, which mediates collagen reduction and fragmentation in aged human skin.

  14. Heating simulations of pulsed high-intensity focused ultrasound in the presence of heterogeneous tissue

    NASA Astrophysics Data System (ADS)

    Zhou, Hao; Zheng, Yinfei; Duan, Huilong

    2017-03-01

    A numerical model for evaluating the distribution of the acoustic pressure and temperature beneath the abdominal wall or the chest wall under nonablative high-intensity ultrasound treatments is proposed. The nonlinear propagation of the ultrasound wave was simulated using a k-space pseudo-spectral method. The abdominal wall (heterogeneous medium) was presented by the digital tissue cross sections. The heating process was modeled by solving the bioheat equation using a finite difference time domain (FDTD) method. As indicated in the simulation, the presents of the heterogeneous tissue can influence the distribution of the acoustic intensity. The intensity beneath the abdominal wall was decreased by 2.2 dB on the focal point compared with homogeneous tissue and the temperature of the focused region in the tissue is reduced as a result. Furthermore, compared with conventional 2-order FDTD methods, the proposed model is still stable when the high dissipative tissue (e.g., bone) presents.

  15. Reentry Near the Percolation Threshold in a Heterogeneous Discrete Model for Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Alonso, Sergio; Bär, Markus

    2013-04-01

    Arrhythmias in cardiac tissue are related to irregular electrical wave propagation in the heart. Cardiac tissue is formed by a discrete cell network, which is often heterogeneous. A localized region with a fraction of nonconducting links surrounded by homogeneous conducting tissue can become a source of reentry and ectopic beats. Extensive simulations in a discrete model of cardiac tissue show that a wave crossing a heterogeneous region of cardiac tissue can disintegrate into irregular patterns, provided the fraction of nonconducting links is close to the percolation threshold of the cell network. The dependence of the reentry probability on this fraction, the system size, and the degree of excitability can be inferred from the size distribution of nonconducting clusters near the percolation threshold.

  16. Skin donors and human skin allografts: evaluation of an 11-year practice and discard in a referral tissue bank.

    PubMed

    Gaucher, Sonia; Khaznadar, Zena; Gourevitch, Jean-Claude; Jarraya, Mohamed

    2016-03-01

    The Saint Louis hospital tissue bank provides skin allografts to pediatric and adult burn units in the Paris area. The aim of this study was to analyze our activity during the last 11 years focusing on the reasons for skin discard. Skin is procured solely from the back of the body, which is divided into 10 zones that are harvested and processed separately. This retrospective study included all skin donors harvested between June 2002 and June 2013, representing a total of 336 donors and 2770 zones. The donors were multiorgan heart-beating donors in 91 % of cases (n = 307). The main reason for discarding harvested skin was microbial contamination, detected in 99 donors (29 %). Most contaminants were of low pathogenicity. Other reasons for discard included positive serologic tests for 2 donors [17 zones (0.61 %)], unsuitable physical skin characteristics for 3 zones (0.11 %), the donor's medical history for 53 zones (1.91 %), and technical issues with processing or distribution for 61 zones (2.2 %). In our experience, microbial contamination continues to be the main reason for discarding potential skin allografts. However, discards are limited by separate harvesting and processing of multiple zones in each donor.

  17. Simulated Sunlight-Mediated Photodynamic Therapy for Melanoma Skin Cancer by Titanium-Dioxide-Nanoparticle-Gold-Nanocluster-Graphene Heterogeneous Nanocomposites.

    PubMed

    Cheng, Yan; Chang, Yun; Feng, Yanlin; Liu, Ning; Sun, Xiujuan; Feng, Yuqing; Li, Xi; Zhang, Haiyuan

    2017-05-01

    Simulated sunlight has promise as a light source able to alleviate the severe pain associated with patients during photodynamic therapy (PDT); however, low sunlight utilization efficiency of traditional photosensitizers dramatically limits its application. Titanium-dioxide-nanoparticle-gold-nanocluster-graphene (TAG) heterogeneous nanocomposites are designed to efficiently utilize simulated sunlight for melanoma skin cancer PDT. The narrow band gap in gold nanoclusters (Au NCs), and staggered energy bands between Au NCs, titanium dioxide nanoparticles (TiO2 NPs), and graphene can result in efficient utilization of simulated sunlight and separation of electron-hole pairs, facilitating the production of abundant hydroxyl and superoxide radicals. Under irradiation of simulated sunlight, TAG nanocomposites can trigger a series of toxicological responses in mouse B16F1 melanoma cells, such as intracellular reactive oxygen species production, glutathione depletion, heme oxygenase-1 expression, and mitochondrial dysfunctions, resulting in severe cell death. Furthermore, intravenous or intratumoral administration of biocompatible TAG nanocomposites in B16F1-tumor-xenograft-bearing mice can significantly inhibit tumor growth and cause severe pathological tumor tissue changes. All of these results demonstrate prominent simulated sunlight-mediated PDT effects. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. A simplified analytical dose calculation algorithm accounting for tissue heterogeneity for low-energy brachytherapy sources.

    PubMed

    Mashouf, Shahram; Lechtman, Eli; Beaulieu, Luc; Verhaegen, Frank; Keller, Brian M; Ravi, Ananth; Pignol, Jean-Philippe

    2013-09-21

    The American Association of Physicists in Medicine Task Group No. 43 (AAPM TG-43) formalism is the standard for seeds brachytherapy dose calculation. But for breast seed implants, Monte Carlo simulations reveal large errors due to tissue heterogeneity. Since TG-43 includes several factors to account for source geometry, anisotropy and strength, we propose an additional correction factor, called the inhomogeneity correction factor (ICF), accounting for tissue heterogeneity for Pd-103 brachytherapy. This correction factor is calculated as a function of the media linear attenuation coefficient and mass energy absorption coefficient, and it is independent of the source internal structure. Ultimately the dose in heterogeneous media can be calculated as a product of dose in water as calculated by TG-43 protocol times the ICF. To validate the ICF methodology, dose absorbed in spherical phantoms with large tissue heterogeneities was compared using the TG-43 formalism corrected for heterogeneity versus Monte Carlo simulations. The agreement between Monte Carlo simulations and the ICF method remained within 5% in soft tissues up to several centimeters from a Pd-103 source. Compared to Monte Carlo, the ICF methods can easily be integrated into a clinical treatment planning system and it does not require the detailed internal structure of the source or the photon phase-space.

  19. A simplified analytical dose calculation algorithm accounting for tissue heterogeneity for low-energy brachytherapy sources

    NASA Astrophysics Data System (ADS)

    Mashouf, Shahram; Lechtman, Eli; Beaulieu, Luc; Verhaegen, Frank; Keller, Brian M.; Ravi, Ananth; Pignol, Jean-Philippe

    2013-09-01

    The American Association of Physicists in Medicine Task Group No. 43 (AAPM TG-43) formalism is the standard for seeds brachytherapy dose calculation. But for breast seed implants, Monte Carlo simulations reveal large errors due to tissue heterogeneity. Since TG-43 includes several factors to account for source geometry, anisotropy and strength, we propose an additional correction factor, called the inhomogeneity correction factor (ICF), accounting for tissue heterogeneity for Pd-103 brachytherapy. This correction factor is calculated as a function of the media linear attenuation coefficient and mass energy absorption coefficient, and it is independent of the source internal structure. Ultimately the dose in heterogeneous media can be calculated as a product of dose in water as calculated by TG-43 protocol times the ICF. To validate the ICF methodology, dose absorbed in spherical phantoms with large tissue heterogeneities was compared using the TG-43 formalism corrected for heterogeneity versus Monte Carlo simulations. The agreement between Monte Carlo simulations and the ICF method remained within 5% in soft tissues up to several centimeters from a Pd-103 source. Compared to Monte Carlo, the ICF methods can easily be integrated into a clinical treatment planning system and it does not require the detailed internal structure of the source or the photon phase-space.

  20. Inference of Cell Mechanics in Heterogeneous Epithelial Tissue Based on Multivariate Clone Shape Quantification

    PubMed Central

    Tsuboi, Alice; Umetsu, Daiki; Kuranaga, Erina; Fujimoto, Koichi

    2017-01-01

    Cell populations in multicellular organisms show genetic and non-genetic heterogeneity, even in undifferentiated tissues of multipotent cells during development and tumorigenesis. The heterogeneity causes difference of mechanical properties, such as, cell bond tension or adhesion, at the cell–cell interface, which determine the shape of clonal population boundaries via cell sorting or mixing. The boundary shape could alter the degree of cell–cell contacts and thus influence the physiological consequences of sorting or mixing at the boundary (e.g., tumor suppression or progression), suggesting that the cell mechanics could help clarify the physiology of heterogeneous tissues. While precise inference of mechanical tension loaded at each cell–cell contacts has been extensively developed, there has been little progress on how to distinguish the population-boundary geometry and identify the cause of geometry in heterogeneous tissues. We developed a pipeline by combining multivariate analysis of clone shape with tissue mechanical simulations. We examined clones with four different genotypes within Drosophila wing imaginal discs: wild-type, tartan (trn) overexpression, hibris (hbs) overexpression, and Eph RNAi. Although the clones were previously known to exhibit smoothed or convoluted morphologies, their mechanical properties were unknown. By applying a multivariate analysis to multiple criteria used to quantify the clone shapes based on individual cell shapes, we found the optimal criteria to distinguish not only among the four genotypes, but also non-genetic heterogeneity from genetic one. The efficient segregation of clone shape enabled us to quantitatively compare experimental data with tissue mechanical simulations. As a result, we identified the mechanical basis contributed to clone shape of distinct genotypes. The present pipeline will promote the understanding of the functions of mechanical interactions in heterogeneous tissue in a non-invasive manner. PMID

  1. Imaging-guided two-photon excitation-emission-matrix measurements of human skin tissues

    NASA Astrophysics Data System (ADS)

    Yu, Yingqiu; Lee, Anthony M. D.; Wang, Hequn; Tang, Shuo; Zhao, Jianhua; Lui, Harvey; Zeng, Haishan

    2012-07-01

    There are increased interests on using multiphoton imaging and spectroscopy for skin tissue characterization and diagnosis. However, most studies have been done with just a few excitation wavelengths. Our objective is to perform a systematic study of the two-photon fluorescence (TPF) properties of skin fluorophores, normal skin, and diseased skin tissues. A nonlinear excitation-emission-matrix (EEM) spectroscopy system with multiphoton imaging guidance was constructed. A tunable femtosecond laser was used to vary excitation wavelengths from 730 to 920 nm for EEM data acquisition. EEM measurements were performed on excised fresh normal skin tissues, seborrheic keratosis tissue samples, and skin fluorophores including: NADH, FAD, keratin, melanin, collagen, and elastin. We found that in the stratum corneum and upper epidermis of normal skin, the cells have large sizes and the TPF originates from keratin. In the lower epidermis, cells are smaller and TPF is dominated by NADH contributions. In the dermis, TPF is dominated by elastin components. The depth resolved EEM measurements also demonstrated that keratin structure has intruded into the middle sublayers of the epidermal part of the seborrheic keratosis lesion. These results suggest that the imaging guided TPF EEM spectroscopy provides useful information for the development of multiphoton clinical devices for skin disease diagnosis.

  2. Microbiome Heterogeneity Characterizing Intestinal Tissue and Inflammatory Bowel Disease Phenotype.

    PubMed

    Tyler, Andrea D; Kirsch, Richard; Milgrom, Raquel; Stempak, Joanne M; Kabakchiev, Boyko; Silverberg, Mark S

    2016-04-01

    Inflammatory bowel disease has been associated with differential abundance of numerous organisms when compared to healthy controls (HCs); however, few studies have investigated variability in the microbiome across intestinal locations and how this variability might be related to disease location and phenotype. In this study, we have analyzed the microbiome of a large cohort of individuals recruited at Mount Sinai Hospital in Toronto, Canada. Biopsies were taken from subjects with Crohn's disease, ulcerative colitis, and HC, and also individuals having undergone ileal pouch-anal anastomosis for treatment of ulcerative colitis or familial adenomatous polyposis. Microbial 16S rRNA was sequenced using the Illumina MiSeq platform. We observed a great deal of variability in the microbiome characterizing different sampling locations. Samples from pouch and afferent limb were comparable in microbial composition. When comparing sigmoid and terminal ileum samples, more differences were observed. The greatest number of differentially abundant microbes was observed when comparing either pouch or afferent limb samples to sigmoid or terminal ileum. Despite these differences, we were able to observe modest microbial variability between inflammatory bowel disease phenotypes and HCs, even when controlling for sampling location and additional experimental factors. Most detected associations were observed between HCs and Crohn's disease, with decreases in specific genera in the families Ruminococcaceae and Lachnospiraceae characterizing tissue samples from individuals with Crohn's disease. This study highlights important considerations when analyzing the composition of the microbiome and also provides useful insight into differences in the microbiome characterizing these seemingly related phenotypes.

  3. Fat tissue histological study at NIR laser treatment of the skin in vivo

    NASA Astrophysics Data System (ADS)

    Yanina, Irina Y.; Tuchin, Valery V.; Navolokin, Nikita A.; Matveeva, Olga V.; Bucharskaya, Alla B.; Maslyakova, Galina N.

    2011-07-01

    Histological slices of skin samples with the subcutaneous adipose tissue after laser irradiation at different doses are analyzed. These data may be used at carrying out of the analysis of histological slices of skin samples with the subcutaneous adipose tissue after photodynamic therapy. The obtained data are important for safe layer-by-layer dosimetry of laser irradiation used in the treatment of obesity and cellulite.

  4. Optical clearing of skin tissue ex vivo with polyethylene glycol

    NASA Astrophysics Data System (ADS)

    Tuchina, D. K.; Genin, V. D.; Bashkatov, A. N.; Genina, E. A.; Tuchin, V. V.

    2016-01-01

    Alterations of the optical and structural (weight, thickness, and square) parameters of skin caused by polyethylene glycol (PEG) with molecular weights of 300 and 400 Da were studied experimentally. The objects of the study were ex vivo skin samples of albino laboratory rats. Collimated transmittance of the skin was measured in the wavelength range 500-900 nm. As a result of exposure to the agents, an increase in the collimated transmittance and a decrease in weight, thickness, and square of skin samples were observed. Analysis of the kinetics of parameters alterations allowed us to measure the diffusion coefficient of the agents in the skin as (1.83 ± 2.22) × 10-6 and (1.70 ± 1.47) × 10-6 cm2/s for PEG-300 and PEG-400, respectively, and the rate of alterations of the structural parameters. The results obtained in this study can be used for the improvement of existing and development of new methods of noninvasive diagnostics and therapy of subcutaneous diseases.

  5. Mapping the cellular and molecular heterogeneity of normal and malignant breast tissues and cultured cell lines

    PubMed Central

    2010-01-01

    Introduction Normal and neoplastic breast tissues are comprised of heterogeneous populations of epithelial cells exhibiting various degrees of maturation and differentiation. While cultured cell lines have been derived from both normal and malignant tissues, it remains unclear to what extent they retain similar levels of differentiation and heterogeneity as that found within breast tissues. Methods We used 12 reduction mammoplasty tissues, 15 primary breast cancer tissues, and 20 human breast epithelial cell lines (16 cancer lines, 4 normal lines) to perform flow cytometry for CD44, CD24, epithelial cell adhesion molecule (EpCAM), and CD49f expression, as well as immunohistochemistry, and in vivo tumor xenograft formation studies to extensively analyze the molecular and cellular characteristics of breast epithelial cell lineages. Results Human breast tissues contain four distinguishable epithelial differentiation states (two luminal phenotypes and two basal phenotypes) that differ on the basis of CD24, EpCAM and CD49f expression. Primary human breast cancer tissues also contain these four cellular states, but in altered proportions compared to normal tissues. In contrast, cultured cancer cell lines are enriched for rare basal and mesenchymal epithelial phenotypes, which are normally present in small numbers within human tissues. Similarly, cultured normal human mammary epithelial cell lines are enriched for rare basal and mesenchymal phenotypes that represent a minor fraction of cells within reduction mammoplasty tissues. Furthermore, although normal human mammary epithelial cell lines exhibit features of bi-potent progenitor cells they are unable to differentiate into mature luminal breast epithelial cells under standard culture conditions. Conclusions As a group breast cancer cell lines represent the heterogeneity of human breast tumors, but individually they exhibit increased lineage-restricted profiles that fall short of truly representing the intratumoral

  6. Pivotal role for skin transendothelial radio-resistant anti-inflammatory macrophages in tissue repair

    PubMed Central

    Barreiro, Olga; Cibrian, Danay; Clemente, Cristina; Alvarez, David; Moreno, Vanessa; Valiente, Íñigo; Bernad, Antonio; Vestweber, Dietmar; Arroyo, Alicia G; Martín, Pilar; von Andrian, Ulrich H; Sánchez Madrid, Francisco

    2016-01-01

    Heterogeneity and functional specialization among skin-resident macrophages are incompletely understood. In this study, we describe a novel subset of murine dermal perivascular macrophages that extend protrusions across the endothelial junctions in steady-state and capture blood-borne macromolecules. Unlike other skin-resident macrophages that are reconstituted by bone marrow-derived progenitors after a genotoxic insult, these cells are replenished by an extramedullary radio-resistant and UV-sensitive Bmi1+ progenitor. Furthermore, they possess a distinctive anti-inflammatory transcriptional profile, which cannot be polarized under inflammatory conditions, and are involved in repair and remodeling functions for which other skin-resident macrophages appear dispensable. Based on all their properties, we define these macrophages as Skin Transendothelial Radio-resistant Anti-inflammatory Macrophages (STREAM) and postulate that their preservation is important for skin homeostasis. DOI: http://dx.doi.org/10.7554/eLife.15251.001 PMID:27304075

  7. [Obtention of human skin sheets by means of tissue engineering].

    PubMed

    Arvelo, Francisco; Pérez, Pedro; Cotte, Carlos

    2004-01-01

    The aim of this "in vitro" study was to develop a new system for keratinocyte culture on a dermal equivalent that enables treatment of different skin injuries. The keratinocyte where obtained from primary cell cultures derived from skin biopsies, seeded over a fibrin matrix enhanced with live human fibroblast. Cells growing over the dermal equivalent, rapidly confluences and a stratified epithelium was obtained within 20-25 days culture. Detachment of composite culture from flask is a simple and quick procedure with no need for chemical or enzyme treatments. The method described provides a number of advantages which include the large expansion of keratinocyte from the primary cell cultures without the need of a feeder layer, the availability of plasma from blood banks, and the versatile and safe manipulation of composite obtained "in vitro". All these facts allow to assure that this system could result very efficient for the treatment of all type of skin injuries.

  8. A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity.

    PubMed

    Cerchiari, Alec E; Garbe, James C; Jee, Noel Y; Todhunter, Michael E; Broaders, Kyle E; Peehl, Donna M; Desai, Tejal A; LaBarge, Mark A; Thomson, Matthew; Gartner, Zev J

    2015-02-17

    Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue-ECM boundary, rather than by differential homo- and heterotypic energies of cell-cell interaction. Surprisingly, interactions with the tissue-ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell-cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell-cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell-ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer.

  9. Full-field bulge test for planar anisotropic tissues: part I--experimental methods applied to human skin tissue.

    PubMed

    Tonge, Theresa K; Atlan, Lorre S; Voo, Liming M; Nguyen, Thao D

    2013-04-01

    The nonlinear anisotropic properties of human skin tissue were investigated using bulge testing. Full-field displacement data were obtained during testing of human skin tissues procured from the lower back of post-mortem human subjects using 3-D digital image correlation. To measure anisotropy, the dominant fiber direction of the tissue was determined from the deformed geometry of the specimen. Local strains and stress resultants were calculated along both the dominant fiber direction and the perpendicular direction. Variation in anisotropy and stiffness was observed between specimens. The use of stress resultants rather than the membrane stress approximation accounted for bending effects, which are significant for a thick nonlinear tissue. Of the six specimens tested, it was observed that specimens from older donors exhibited a stiffer and more isotropic response than those from younger donors. It was seen that the mechanical response of the tissue was negligibly impacted by preconditioning or the ambient humidity. The methods presented in this work for skin tissue are sufficiently general to be applied to other planar tissues, such as pericardium, gastrointestinal tissue, and fetal membranes. The stress resultant-stretch relations will be used in a companion paper to obtain material parameters for a nonlinear anisotropic hyperelastic model.

  10. Differential expression of antimicrobial peptides in psoriasis and psoriatic arthritis as a novel contributory mechanism for skin and joint disease heterogeneity.

    PubMed

    Bierkarre, H; Harder, J; Cuthbert, R; Emery, P; Leuschner, I; Mrowietz, U; Hedderich, J; McGonagle, D; Gläser, R

    2016-01-01

    This study tested the hypothesis that a differential innate immune antimicrobial peptide (AMP) profile was evident between the skin and joints in psoriasis and psoriatic arthritis (PsA) and that PsA synovitis may have a distinct AMP pattern compared to other arthropathies. Twenty-two cases had knee biopsies [10 PsA, eight rheumatoid arthritis (RA), and four osteoarthritis (OA)]. Lesional and non-lesional skin biopsies in psoriasis and control tissue were also obtained (n = 4 each). Immunohistochemistry with semi-quantitative scoring of both synovium and skin was performed using the following panel of AMPs: S100 A8, S100 A9, human neutrophil peptides 1-3 (HNP1-3), human β-defensins 2 and 3 (hBD-2 and hBD-3), cathelicidin LL-37, psoriasin (S100 A7), and ribonuclease 7 (RNase 7). Similar expression of S100 A8, S100 A9, and HNP1-3 was detectable in PsA and RA synovium but only in the synovium sublining layer (SSL). No expression of psoriasin, RNase 7, hBD-2, and hBD-3 could be detected in the synovial tissue of PsA, RA, or OA. All psoriasis skin samples exhibited broad expression of all investigated AMPs, with strong keratinocyte expression. Given that some AMPs, especially hBD-2, are genetically linked to psoriasis and are only expressed in the skin, these findings show how differential AMP expression in innate immune responses may contribute to disease heterogeneity between PsA and psoriasis and provides a genetic basis for the non-progression of psoriasis subgroups to PsA.

  11. Tissue engineered fetal skin constructs for pediatric burns

    PubMed Central

    Norbury, William B; Jeschke, Marc G; Herndon, David N

    2005-01-01

    The management of patients with partial thickness (second degree) burns is problematic due to the different treatments needed for varying depths of injury. A report recently published in The Lancet describes a novel treatment for deep second degree burns using a fetal skin construct (FSC). The authors included eight pediatric patients with small second degree burns. They showed that FSCs reduced the need for autografting of deep second degree burns, with little hypertrophy of new skin and no skin contraction. This technology is new and exciting, but in our opinion several issues must be addressed before FSCs can enter the clinical arena. All of the patients were included in the treatment group, and therefore no comparison with conventional skin substitutes was possible. There is no mention of the use of laser Doppler in any initial assessment of patients. The debridement carried out before application of the FSC is not elaborated upon, and the surface areas involved in the study were very small in most cases, which limits the relevance to patients with larger burns. The use of FSCs gives us an additional option in a range of possible treatments for this notoriously difficult-to-treat patient group. PMID:16356232

  12. Microwave Radar Imaging of Heterogeneous Breast Tissue Integrating A Priori Information

    PubMed Central

    Kelly, Thomas N.; Sarafianou, Mantalena; Craddock, Ian J.

    2014-01-01

    Conventional radar-based image reconstruction techniques fail when they are applied to heterogeneous breast tissue, since the underlying in-breast relative permittivity is unknown or assumed to be constant. This results in a systematic error during the process of image formation. A recent trend in microwave biomedical imaging is to extract the relative permittivity from the object under test to improve the image reconstruction quality and thereby to enhance the diagnostic assessment. In this paper, we present a novel radar-based methodology for microwave breast cancer detection in heterogeneous breast tissue integrating a 3D map of relative permittivity as a priori information. This leads to a novel image reconstruction formulation where the delay-and-sum focusing takes place in time rather than range domain. Results are shown for a heterogeneous dense (class-4) and a scattered fibroglandular (class-2) numerical breast phantom using Bristol's 31-element array configuration. PMID:25435861

  13. Impaired Tissue Oxygenation in Metabolic Syndrome Requires Increased Microvascular Perfusion Heterogeneity.

    PubMed

    Mason McClatchey, P; Wu, Fan; Olfert, I Mark; Ellis, Christopher G; Goldman, Daniel; Reusch, Jane E B; Frisbee, Jefferson C

    2017-02-01

    Metabolic syndrome (MS) in obese Zucker rats (OZR) is associated with impaired skeletal muscle performance and blunted hyperemia. Studies suggest that reduced O2 diffusion capacity is required to explain compromised muscle performance and that heterogeneous microvascular perfusion distribution is critical. We modeled tissue oxygenation during muscle contraction in control and OZR skeletal muscle using physiologically realistic relationships. Using a network model of Krogh cylinders with increasing perfusion asymmetry and increased plasma skimming, we predict increased perfusion heterogeneity and decreased muscle oxygenation in OZR, with partial recovery following therapy. Notably, increasing O2 delivery had less impact on VO2 than equivalent decreases in O2 delivery, providing a mechanism for previous empirical work associating perfusion heterogeneity and impaired O2 extraction. We demonstrate that increased skeletal muscle perfusion asymmetry is a defining characteristic of MS and must be considered to effectively model and understand blood-tissue O2 exchange in this model of human disease.

  14. Skin autofluorescence as marker of tissue advanced glycation end-products accumulation in formerly preeclamptic women.

    PubMed

    Coffeng, Sophie M; Blaauw, Judith; Souwer, Esteban T D; Rakhorst, Gerhard; Smit, Andries J; Graaff, Reindert; van Doormaal, Jasper J; Aarnoudse, Jan G; Faas, Marijke M; van Pampus, Maria G

    2011-01-01

    In women with a history of preeclampsia skin autofluorescence as marker of tissue AGEs accumulation is increased, supporting a common causal metabolic or vascular link between preeclampsia and cardiovascular diseases. To investigate whether skin autofluorescence (AF), as marker of tissue accumulation of advanced glycation end-products (AGEs), is elevated in women with a 4-year history of severe preeclampsia. About 17 formerly preeclamptic women and 16 controls were included. Skin AF and several traditional cardiovascular risk factors were recorded. In comparison to controls, formerly preeclamptic women had higher skin AF of the legs, body mass index (BMI), blood pressure, and high-sensitivity C-reactive protein (hsCRP), HbA1C, and triglycerides in serum. Skin AF as well as cardiovascular risk factors is elevated in formerly preeclamptic women. These results suggest a common causal vascular link between preeclampsia and cardiovascular diseases.

  15. Comparison of therapeutic antibiotic treatments on tissue-engineered human skin substitutes.

    PubMed

    Gibson, Angela L; Schurr, Michael J; Schlosser, Sandy J; Comer, Allen R; Allen-Hoffmann, B Lynn

    2008-05-01

    For regenerative medicine to gain clinical acceptance, the effects of commonly used treatment regimens on bioengineered organs must be considered. The antibiotics mafenide acetate (mafenide) and neomycin plus polymyxin (neo/poly) are routinely used to irrigate postoperative skin grafts on contaminated wounds. The effects of these clinically used antibiotics were investigated using tissue-engineered human skin substitutes generated with primary human keratinocytes or the near-diploid human keratinocyte cell line, Near-diploid Immortal Keratinocytes. Following topical or dermal treatment, the skin substitutes were assayed for viability, tissue morphology, glycogen content, and the expression of active caspase 3. Mafenide, but not neo/poly, induced morphological and biochemical changes in tissue-engineered skin substitutes. Keratinocytes in all histological layers of mafenide-treated skin substitutes exhibited ballooning degeneration and glycogen depletion. Mafenide-treatment also triggered separation of basal keratinocytes from the underlying dermis. None of the antibiotic treatments induced apoptosis, as measured by active caspase 3 immunostaining. The results demonstrate that mafenide, but not neo/poly, is detrimental to the viability and structural integrity of tissue-engineered human skin substitutes. These findings highlight the need to identify treatment regimens that are compatible with and hence enable the therapeutic efficacy of first-generation bioengineered organs such as skin.

  16. In vitro fluorescence measurements and Monte Carlo simulation of laser irradiation propagation in porcine skin tissue.

    PubMed

    Drakaki, E; Makropoulou, M; Serafetinides, A A

    2008-07-01

    In dermatology, the in vivo spectral fluorescence measurements of human skin can serve as a valuable supplement to standard non-invasive techniques for diagnosing various skin diseases. However, quantitative analysis of the fluorescence spectra is complicated by the fact that skin is a complex multi-layered and inhomogeneous organ, with varied optical properties and biophysical characteristics. In this work, we recorded, in vitro, the laser-induced fluorescence emission signals of healthy porcine skin, one of the animals, which is considered as one of the most common models for investigations related to medical diagnostics of human cutaneous tissues. Differences were observed in the form and intensity of the fluorescence signal of the porcine skin, which can be attributed to the different concentrations of the native fluorophores and the variable physical and biological conditions of the skin tissue. As the light transport in the tissue target is directly influencing the absorption and the fluorescence emission signals, we performed Monte Carlo simulation of the light distribution in a five-layer model of human skin tissue, with a pulsed ultraviolet laser beam.

  17. Computational methods for predicting drug transport in anisotropic and heterogeneous brain tissue.

    PubMed

    Linninger, Andreas A; Somayaji, Mahadevabharath R; Erickson, Terrianne; Guo, Xiaodong; Penn, Richard D

    2008-07-19

    Effective drug delivery for many neurodegenerative diseases or tumors of the central nervous system is challenging. Targeted invasive delivery of large macromolecules such as trophic factors to desired locations inside the brain is difficult due to anisotropy and heterogeneity of the brain tissue. Despite much experimental research, prediction of bio-transport phenomena inside the brain remains unreliable. This article proposes a rigorous computational approach for accurately predicting the fate of infused therapeutic agents inside the brain. Geometric and physiological properties of anisotropic and heterogeneous brain tissue affecting drug transport are accounted for by in-vivo diffusion tensor magnetic resonance imaging data. The three-dimensional brain anatomy is reconstructed accurately from subject-specific medical images. Tissue anisotropy and heterogeneity are quantified with the help of diffusion tensor imaging (DTI). Rigorous first principles physical transport phenomena are applied to predict the fate of a high molecular weight trophic factor infused into the midbrain. Computer prediction of drug distribution in humans accounting for heterogeneous and anisotropic brain tissue properties have not been adequately researched in open literature before.

  18. [Research Progress of Collagen-based Three-dimensional Porous Scaffolds Used in Skin Tissue Engineering].

    PubMed

    Zhang, Jing; Tang, Qiwei; Zhou, Aimei; Yang, Shulin

    2015-08-01

    Collagen is a kind of natural biomedical material and collagen based three-dimensional porous scaffolds have been widely used in skin tissue engineering. However, these scaffolds do not meet the requirements for artificial skin substitutes in terms of their poor mechanical properties, short supply, and rejection in the bodies. All of these factors limit their further application in skin tissue engineering. A variety of methods have been chosen to meliorate the situation, such as cross linking and blending other substance for improving mechanical properties. The highly biomimetic scaffolds either in structure or in function can be prepared through culturing cells and loading growth factors. To avoid the drawbacks of unsafety attributing to animals, investigators have fixed their eyes on the recombinant collagen. This paper reviews the the progress of research and application of collagen-based 3-dimensional porous scaffolds in skin tissue engineering.

  19. [Application of skin and soft tissue expansion in treatment of burn injury].

    PubMed

    Wang, N Z; Shen, Z Y; Ma, C X

    2000-09-01

    To evaluate the application of skin and soft tissue expansion in the treatment of deformity due to extensive severe burn injury and repair of severe deep electrical burned scalp and skull with fresh wound. From 1988, 83 cases of application of skin and soft tissue expansion were reported. In those patients with deformity due to severe burn of large area and with whole nasal defect, soft tissue expander was used under the forehead skin graft and venter frontalis, followed by reconstruction of nose with the expanded vascularized skin flap and carved cartilago costalis as nasal frame. In patients of severe deep electrical burned scalp and skull with fresh wound, skin and soft tissue expansion were used to repair the wound simultaneously with scalp burn alopecia, anesthetics and antibiotics injected into the extracapsular space of the expander in case of pain and infection. All of the cases were successfully treated with little pain and minimized infection. Skin and soft tissue expansion in a safe and reliable measure in the treatment of deformity due to extensive severe burn injury and repair of severe deep electrical burned scalp and skull with fresh wound.

  20. [Effects of linear alkylbenzenesulfonate on oxidative stress and collagen fiber in skin tissue of mice].

    PubMed

    Zhao, Wenhong; Wang, Jinhua; Wang, Kailei; Zhang, Wen

    2015-06-01

    To observe the effect of linear alkylbenzenesulfonate (LAS) on oxidative stress and collagen fiber in skin tissue of mice and to explore the correlation between oxidative stress and collagen metabolism.
 Forty healthy Kunming mice (male) were randomly divided into 4 groups: a control group, a low-, middle- and high-dose group of LAS (LD, MD and HD groups), treated with LAS at 150, 300 and 600 mg/L respectively (n=10 per group). The skin on the back of mice was smeared with distilled water or different dosage of LAS for 60 days. The measured indexes included general condition of mice, HE and Masson staining of skin, the content of hydroxyproline (Hyp) in skin tissue, the activity of super oxidase dismutase (SOD) and the content of malondialdehyde (MDA) in skin tissue and serum, and the activity of lactate dehydrogenase (LDH) in serum.
 Compared with the control group, the changes of diet, daily activities and mental state of mice with different dose of LAS were not obvious during the experiment, but the body weight of mice in the experimental groups reduced obviously after 4 weeks of experiment (P<0.01), and their skin tissue was thinner, some of epidermis of skin contained areas with cellular necrosis and abscission. Superficial layer of dermis was infiltrated by inflammatory cells. The collagen fibers were looser and dimmer. At the same time, the content of MDA and the activity of LDH increased remarkably (P<0.01), while the activity of SOD and the content of Hyp decreased obviously (P<0.01).
 LAS can induce oxidative stress in the skin tissue of mice, which can destroy the integrity of skin structure and collagen fiber and reduce the content of collagen fiber. The oxidative damage might be the primary cause for disorders of collagen fiber.
.

  1. Stimulation of the penetration of particles into the skin by plasma tissue interaction

    NASA Astrophysics Data System (ADS)

    Lademann, O.; Richter, H.; Kramer, A.; Patzelt, A.; Meinke, M. C.; Graf, C.; Gao, Q.; Korotianskiy, E.; Rühl, E.; Weltmann, K.-D.; Lademann, J.; Koch, S.

    2011-10-01

    A high number of treatments in dermatology are based on the penetration of topically applied drugs through the skin barrier. This process is predominantly inefficient, on account of the strong protection properties of the upper skin layer - the stratum corneum. If the skin barrier is damaged, the penetration efficiency of topically applied drugs increases. Therefore, different methods have been developed to influence the barrier properties of the skin. Recently, it could be demonstrated that a cold tissue tolerable plasma (TTP) produced by a plasma-jet can strongly enhance drug delivery through the skin. These investigations were performed by using a solution of fluorescent dye as a model drug. In the present study, these investigations were carried out using fluorescent silica particles at different sizes. The aim of the study was to investigate whether or not there is a limitation in size for topically applied substances to pass through the skin barrier after plasma treatment.

  2. Textural analysis of optical coherence tomography skin images: quantitative differentiation between healthy and cancerous tissues

    NASA Astrophysics Data System (ADS)

    Adabi, Saba; Conforto, Silvia; Hosseinzadeh, Matin; Noe, Shahryar; Daveluy, Steven; Mehregan, Darius; Nasiriavanaki, Mohammadreza

    2017-02-01

    Optical Coherence Tomography (OCT) offers real-time high-resolution three-dimensional images of tissue microstructures. In this study, we used OCT skin images acquired from ten volunteers, neither of whom had any skin conditions addressing the features of their anatomic location. OCT segmented images are analyzed based on their optical properties (attenuation coefficient) and textural image features e.g., contrast, correlation, homogeneity, energy, entropy, etc. Utilizing the information and referring to their clinical insight, we aim to make a comprehensive computational model for the healthy skin. The derived parameters represent the OCT microstructural morphology and might provide biological information for generating an atlas of normal skin from different anatomic sites of human skin and may allow for identification of cell microstructural changes in cancer patients. We then compared the parameters of healthy samples with those of abnormal skin and classified them using a linear Support Vector Machines (SVM) with 82% accuracy.

  3. Constitutive modeling of stress softening and permanent set in a porcine skin tissue: Impact of the storage preservation.

    PubMed

    Caro-Bretelle, A S; Ienny, P; Leger, R; Corn, S; Bazin, I; Bretelle, F

    2016-09-06

    Prior to testing, soft tissues are usually maintained in different media and additives (solution, air, cryopreservant…) under various environment conditions (temperature, storage duration….). In many cases, results from mechanical tests performed on these stored tissues are supposed to be as closed as possible to the fresh ones. In the present work, cyclic tensile tests were performed with increasing values of strain on porcine skin tissues (excised following the Langer's lines) to enhance tissues mechanical nonlinearity such as softening behavior and permanent set. Optical methods were used to follow the in-plane strains evolution. These latest values were used as data to simulate the structural behavior of these heterogeneous materials. The numerical simulation is based on the constitutive pseudo-elastic model accounting for the softening behavior as well as the permanent set. As a result, reliable material parameters were extracted from the experiments/model comparison for each storage solution. The result of this study reveals that preservation conditions must be carefully chosen: at low strain the tissues store in fridge in a saline solution during a short time, or in freezer (-80°C) in water with cryopreservant and the fresh one lead to a similar mechanical response. For larger strain, the freezing (-80°C) in water with cryopreservant is the only procedure for which the tissue recovers its initial behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Noninvasive detection of skin cancers by measuring optical properties of tissues

    NASA Astrophysics Data System (ADS)

    Wang, Lihong V.; Jacques, Steven L.

    1995-05-01

    Skin cancer is the most frequently occurring cancer of all cancers. Each yea rover 500,000 new cases of skin cancer will be detected. A high percentage of skin cancers are diseases in which fatalities can be all but eliminated and morbidity reduced if detected early and treated properly. These skin lesions are distinguished generally by subjective visual inspection and their definitive diagnosis requires time-consuming expensive histopathological evaluation of excisional or incisional biopsies. In vivo experimental evidence published in the literature has shown that cancerous skin lesions have different total diffuse reflectance spectra than non- cancerous lesions or normal skin. Therefore, cancerous skin lesions may be differentiated from non-cancerous skin lesions by comparing the optical properties of the skin lesions with those of the surrounding normal skin sites, where the optical properties of the normal skin sites are used to account for different types of skin or different areas of skin. We have demonstrated that the effect of melanin concentration on the diffuse reflectance may be removed by extrapolating the reflectance at different wavelengths to an apparent pivot point. Because the concentration of melanin does not indicate malignancy, the removal of its effect is important to avoid false detection. The total diffuse reflectance depends on the albedo and anisotropy of tissues. Therefore, the total diffuse reflectance will remain the same as long as the anisotropy and the ratio between the absorption coefficient and the reduced scattering coefficient remain the same. Separating the absorption and scattering effects should enhance the detection sensitivity of skin cancers.

  5. Tattoo ink nanoparticles in skin tissue and fibroblasts

    PubMed Central

    Twigg, Peter C; Baker, Richard; Tobin, Desmond J

    2015-01-01

    Summary Tattooing has long been practised in various societies all around the world and is becoming increasingly common and widespread in the West. Tattoo ink suspensions unquestionably contain pigments composed of nanoparticles, i.e., particles of sub-100 nm dimensions. It is widely acknowledged that nanoparticles have higher levels of chemical activity than their larger particle equivalents. However, assessment of the toxicity of tattoo inks has been the subject of little research and ink manufacturers are not obliged to disclose the exact composition of their products. This study examines tattoo ink particles in two fundamental skin components at the nanometre level. We use atomic force microscopy and light microscopy to examine cryosections of tattooed skin, exploring the collagen fibril networks in the dermis that contain ink nanoparticles. Further, we culture fibroblasts in diluted tattoo ink to explore both the immediate impact of ink pigment on cell viability and also to observe the interaction between particles and the cells. PMID:26171294

  6. Tattoo ink nanoparticles in skin tissue and fibroblasts.

    PubMed

    Grant, Colin A; Twigg, Peter C; Baker, Richard; Tobin, Desmond J

    2015-01-01

    Tattooing has long been practised in various societies all around the world and is becoming increasingly common and widespread in the West. Tattoo ink suspensions unquestionably contain pigments composed of nanoparticles, i.e., particles of sub-100 nm dimensions. It is widely acknowledged that nanoparticles have higher levels of chemical activity than their larger particle equivalents. However, assessment of the toxicity of tattoo inks has been the subject of little research and ink manufacturers are not obliged to disclose the exact composition of their products. This study examines tattoo ink particles in two fundamental skin components at the nanometre level. We use atomic force microscopy and light microscopy to examine cryosections of tattooed skin, exploring the collagen fibril networks in the dermis that contain ink nanoparticles. Further, we culture fibroblasts in diluted tattoo ink to explore both the immediate impact of ink pigment on cell viability and also to observe the interaction between particles and the cells.

  7. Terahertz pulse imaging in reflection geometry of skin tissue using time-domain analysis techniques

    NASA Astrophysics Data System (ADS)

    Woodward, Ruth M.; Wallace, Vincent P.; Cole, Bryan E.; Pye, Richard J.; Arnone, Donald D.; Linfield, Edmund H.; Pepper, Michael

    2002-06-01

    We demonstrate the application of Terahertz Pulse Imaging (TPI) in reflection geometry for the study of skin tissue and related cancers. The terahertz frequency regime of 0.1-100THz excites the vibrational modes of molecules, allowing for spectroscopic investigation. The sensitivity of terahertz to polar molecules, such as water, makes TPI suitable for studying the hydration levels in the stratum corneum and the determination of the lateral spread of skin cancer pre-operatively. By studying the terahertz pulse shape in the time domain we have been able to differentiate between diseased and normal tissue for the study of basal cell carcinoma (BCC). Measurements on scar tissue, which is known to contain less water than the surrounding skin, and on regions of inflammation, show a clear contrast in the THz image compared to normal skin. We discuss the time domain analysis techniques used to classify the different tissue types. Basal cell carcinoma shows a positive terahertz contrast, and inflammation and scar tissue shows a negative terahertz contrast compared to normal tissue. This demonstrates for the first time the potential of TPI both in the study of skin cancer and inflammatory related disorders.

  8. Self-reported incidence of skin and soft tissue infections among deployed US military.

    PubMed

    May, Larissa; Porter, Chad; Tribble, David; Armstrong, Adam; Mostafa, Manal; Riddle, Mark

    2011-07-01

    The incidence of skin and soft tissue infections has steadily increased over the past decade, and military populations, particularly recruits, have been affected. However, the epidemiology of skin and soft tissue infections in deployed personnel has not previously been described. We conducted a cross-sectional study of United States military personnel in mid-deployment using self-reported questionnaire data containing 11 demographic questions and 20 questions related to skin and soft tissue infections. The primary outcome was self-reported incident SSTI. Descriptive analyses were conducted and incidence estimates calculated. Multivariable regression models were developed to evaluate the association between SSTI and important covariates. Self-reported treatment modalities and effect on work performance were also assessed. The study was approved by the Institutional Review Board. 2125 questionnaires were completed over 12 months using convenience sampling. 110 personnel (5%) reported one or more skin and soft tissue infection during their most recent employment, for an incidence of 52 cases per 100,000 person-days. The majority reported a single infection. A higher proportion of individuals reporting skin and soft tissue infection were female, reported antibiotic use in the 6 months prior to completing the survey, had a family member in the healthcare occupation, and were senior enlisted or officers. 40 (36%) were treated with antibiotics and 24 (22%) underwent incision and drainage. Less than 5% (3 patients) required admission. Eighty eight respondents (81%), reported no days of lost job performance. There is a higher than expected incidence of skin and soft tissue infections in deployed military personnel. Although fewer than 20% of patients report missing at least one day of work, this can have a significant impact on the military mission. Further study should be conducted into how to prevent skin and soft tissue infections in military populations. Copyright

  9. Photodamage in deep tissue two-photon optical biopsy of human skin.

    PubMed

    Dalbosco, Luca; Zanini, Giulia; D'Amato, Elvira; Tessarolo, Francesco; Boi, Sebastiana; Bauer, Paolo; Haase, Albrecht; Antolini, Renzo

    2015-10-01

    Photodamage, induced by femtosecond laser radiation, was studied in thick samples of human skin tissue (healthy skin and neoplastic lesions). Photobleaching, photoionization, and thermomechanical damage effects were characterized comparatively. The laser power dependence of the damage rates allowed to connect macroscopic effects to underlying molecular processes. Optical effects were correlated to histopathological changes. Tissue alterations were found only from thermomechanical cavitation and limited to superficial layers of the epidermis. From the depth-dependencies of all damage thresholds a depth-dependent power-compensation scheme was defined allowing for damage-free deep tissue optical biopsy. Damage-induced luminescence pattern for different excitation powers and a corresponding threshold analysis.

  10. Optical diffuse reflectance accessory for measurements of skin tissue by near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Marbach, R.; Heise, H. M.

    1995-02-01

    An optimized accessory for measuring the diffuse reflectance spectra of human skin tissue in the near-infrared spectral range is presented. The device includes an on-axis ellipsoidal collecting mirror with efficient illumination optics for small sampling areas of bulky body specimens. The optical design is supported by the results of a Monte Carlo simulation study of the reflectance characteristics of skin tissue. Because the results evolved from efforts to measure blood glucose noninvasively, the main emphasis is placed on the long-wavelength near-infrared range where sufficient penetration depth for radiation into tissue is still available. The accessory is applied for in vivo diffuse reflectance measurements.

  11. Optical diffuse reflectance accessory for measurements of skin tissue by near-infrared spectroscopy.

    PubMed

    Marbach, R; Heise, H M

    1995-02-01

    An optimized accessory for measuring the diffuse reflectance spectra of human skin tissue in the near-infrared spectral range is presented. The device includes an on-axis ellipsoidal collecting mirror with efficient illumination optics for small sampling areas of bulky body specimens. The optical design is supported by the results of a Monte Carlo simulation study of the reflectance characteristics of skin tissue. Because the results evolved from efforts to measure blood glucose noninvasively, the main emphasis is placed on the long-wavelength near-infrared range where sufficient penetration depth for radiation into tissue is still available. The accessory is applied for in vivo diffuse reflectance measurements.

  12. Heterogeneous Deformable Modeling of Bio-Tissues and Haptic Force Rendering for Bio-Object Modeling

    NASA Astrophysics Data System (ADS)

    Lin, Shiyong; Lee, Yuan-Shin; Narayan, Roger J.

    This paper presents a novel technique for modeling soft biological tissues as well as the development of an innovative interface for bio-manufacturing and medical applications. Heterogeneous deformable models may be used to represent the actual internal structures of deformable biological objects, which possess multiple components and nonuniform material properties. Both heterogeneous deformable object modeling and accurate haptic rendering can greatly enhance the realism and fidelity of virtual reality environments. In this paper, a tri-ray node snapping algorithm is proposed to generate a volumetric heterogeneous deformable model from a set of object interface surfaces between different materials. A constrained local static integration method is presented for simulating deformation and accurate force feedback based on the material properties of a heterogeneous structure. Biological soft tissue modeling is used as an example to demonstrate the proposed techniques. By integrating the heterogeneous deformable model into a virtual environment, users can both observe different materials inside a deformable object as well as interact with it by touching the deformable object using a haptic device. The presented techniques can be used for surgical simulation, bio-product design, bio-manufacturing, and medical applications.

  13. Skin indentation firmness and tissue dielectric constant assessed in face, neck, and arm skin of young healthy women.

    PubMed

    Mayrovitz, Harvey N; Corbitt, Kelly; Grammenos, Alexandra; Abello, Allen; Mammino, Jason

    2017-02-01

    Our goal was to test the hypothesis that skin firmness correlates with skin hydration. Dermal water was assessed by tissue dielectric constant (TDC) at 0.5 mm (TDC0.5 ) and 2.5 mm (TDC2.5 ) depths on four face sites and two arm sites of 35 women (25.0 ± 1.6 years). Firmness was determined by force (mN) to indent skin to 0.3 mm (F0.3 ) and 1.3 mm (F1.3 ). F0.3 was similar among face sites (avg = 16.2 ± 7.2 mN) but F1.3 varied (avg = 32.5 ± 4.1 mN). TDC2.5 was similar among face sites (avg = 37.7 ± 4.2) but TDC0.5 varied (avg = 36.2 ± 4.8). F1.3 of arm sites was similar (avg = 60.2 ± 18.6 mN) and both greater than F1.3 of neck (28.3 ± 7.1 mN) and face. Regression analysis showed a near-zero correlation between forces and TDC at all sites. The near-zero correlation may be due to low skin interstitial hydraulic resistance to mobile water movement in healthy young skin. If true, then conditions in which dermal hydraulic conductance is reduced as in lymphedematous, diabetic, or aged skin are more likely show the hypothesized relationship. Our findings provide normalized reference values and suggest that such persons are an important population to study to test for a possible skin water-indentation force relationship and its utilization for early diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. New derivation method and simulation of skin effect in biological tissue.

    PubMed

    Fan, Xiaoli; Zhou, Qianxiang; Liu, Zhongqi; Xie, Fang

    2015-01-01

    Based on the electrical properties of biological tissues, bioimpedance measurement technology can be employed to collect physiologic and pathologic information by measuring changes in human bioimpedance. When an alternating current (AC) is applied as a detection signal to a tissue, the current field distribution, which is affected by skin effect, is related to both the bioimpedance of the tissue and the AC frequency. These relations would possibly reduce the accuracy and reliability of the measurement. In this study, an electromagnetic theory-based method, in which cylindrical conductor were divided into layers, was used to obtain current field distribution models of human limbs. Model simulations were conducted in MATLAB. The skin effect phenomenon and its characteristics in human tissues at different frequencies were observed, thus providing essential data on skin effect, which are useful in the development of bioimpedance measurement technology.

  15. A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

    PubMed Central

    Cerchiari, Alec E.; Garbe, James C.; Jee, Noel Y.; Todhunter, Michael E.; Broaders, Kyle E.; Peehl, Donna M.; Desai, Tejal A.; LaBarge, Mark A.; Thomson, Matthew; Gartner, Zev J.

    2015-01-01

    Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue–ECM boundary, rather than by differential homo- and heterotypic energies of cell–cell interaction. Surprisingly, interactions with the tissue–ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell–cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell–cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell–ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer. PMID:25633040

  16. Pattern analysis of dynamic susceptibility contrast-enhanced MR imaging demonstrates peritumoral tissue heterogeneity.

    PubMed

    Akbari, Hamed; Macyszyn, Luke; Da, Xiao; Wolf, Ronald L; Bilello, Michel; Verma, Ragini; O'Rourke, Donald M; Davatzikos, Christos

    2014-11-01

    To augment the analysis of dynamic susceptibility contrast material-enhanced magnetic resonance (MR) images to uncover unique tissue characteristics that could potentially facilitate treatment planning through a better understanding of the peritumoral region in patients with glioblastoma. Institutional review board approval was obtained for this study, with waiver of informed consent for retrospective review of medical records. Dynamic susceptibility contrast-enhanced MR imaging data were obtained for 79 patients, and principal component analysis was applied to the perfusion signal intensity. The first six principal components were sufficient to characterize more than 99% of variance in the temporal dynamics of blood perfusion in all regions of interest. The principal components were subsequently used in conjunction with a support vector machine classifier to create a map of heterogeneity within the peritumoral region, and the variance of this map served as the heterogeneity score. The calculated principal components allowed near-perfect separability of tissue that was likely highly infiltrated with tumor and tissue that was unlikely infiltrated with tumor. The heterogeneity map created by using the principal components showed a clear relationship between voxels judged by the support vector machine to be highly infiltrated and subsequent recurrence. The results demonstrated a significant correlation (r = 0.46, P < .0001) between the heterogeneity score and patient survival. The hazard ratio was 2.23 (95% confidence interval: 1.4, 3.6; P < .01) between patients with high and low heterogeneity scores on the basis of the median heterogeneity score. Analysis of dynamic susceptibility contrast-enhanced MR imaging data by using principal component analysis can help identify imaging variables that can be subsequently used to evaluate the peritumoral region in glioblastoma. These variables are potentially indicative of tumor infiltration and may become useful tools in

  17. Effects of heterogeneities on the partitioning of airway and tissue properties in normal mice.

    PubMed

    Ito, Satoru; Lutchen, Kenneth R; Suki, Béla

    2007-03-01

    We measured the mechanical properties of the respiratory system of C57BL/6 mice using the optimal ventilation waveform method in closed- and open-chest conditions at different positive end-expiratory pressures. The tissue damping (G), tissue elastance (H), airway resistance (Raw), and hysteresivity were obtained by fitting the impedance data to three different models: a constant-phase model by Hantos et al. (Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ. J Appl Physiol 72: 168-178, 1992), a heterogeneous Raw model by Suki et al. (Suki B, Yuan H, Zhang Q, Lutchen KR. J Appl Physiol 82: 1349-1359, 1997), and a heterogeneous H model by Ito et al. (Ito S, Ingenito EP, Arold SP, Parameswaran H, Tgavalekos NT, Lutchen KR, Suki B. J Appl Physiol 97: 204-212, 2004). Both in the closed- and open-chest conditions, G and hysteresivity were the lowest and Raw the highest in the heterogeneous Raw model, and G and H were the largest in the heterogeneous H model. Values of G, Raw, and hysteresivity were significantly higher in the closed-chest than in the open-chest condition. However, H was not affected by the conditions. When the tidal volume of the optimal ventilation waveform was decreased from 8 to 4 ml/kg in the closed-chest condition, G and hysteresivity significantly increased, but there were smaller changes in H or Raw. In summary, values of the obtained mechanical properties varied among these models, primarily due to heterogeneity. Moreover, the mechanical parameters were significantly affected by the chest wall and tidal volume in mice. Contribution of the chest wall and heterogeneity to the mechanical properties should be carefully considered in physiological studies in which partitioning of airway and tissue properties are attempted.

  18. Effect of lipopolysaccharide on the biological characteristics of human skin fibroblasts and hypertrophic scar tissue formation.

    PubMed

    Yang, Hongming; Hu, Chao; Li, Fengyu; Liang, Liming; Liu, Lingying

    2013-06-01

    Burn injury-mediated destruction of the skin barrier normally induces microbial invasion, in turn leading to the development of systemic infection and occasional septic shock by the release of endotoxins. The objective of this work was to study the influence of lipopolysaccharide (LPS) on the biological characteristics of normal skin fibroblasts and to elucidate the influence of LPS in the initial stage of skin wound healing. Twenty patients with hypertrophic scar in proliferative stage were selected randomly and primary cultures were established from fibroblasts derived from their hypertrophic scar tissue and normal skin. Normal skin fibroblasts of passage 3 were stimulated with different concentrations of LPS. LPS stimulated the proliferation and collagen synthesis of fibroblasts within a certain extent of concentrations (0.005-0.5 μg/mL) (P < 0.05), whereas at a concentration of 1 μg/mL inhibited the proliferation and collagen synthesis of fibroblasts (P < 0.05). Collagen synthesis by normal skin fibroblasts after LPS stimulation mimicked those derived from hypertrophic scar tissue. LPS of 0.1 μg/mL had significant effect on normal skin fibroblasts-continuous passage of these fibroblasts resulted in ultrastructural pattern similar to fibroblasts derived from hypertrophic scar tissue, and the findings was substantiated by hematoxylin and eosin staining and immunohistochemistry detection of proliferation cell nuclear antigen, type I procollagen and α-smooth muscle actin. Our results suggest that LPS might convert normal skin fibroblasts to hypertrophic scar tissue fibroblasts and participate in the formation of hypertrophic scar; hence, appropriate concentration of LPS may have no effect or be beneficial to skin wound healing, whereas excessive concentration of LPS may delay the time of wound healing. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  19. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity

    PubMed Central

    Plikus, Maksim V.; Van Spyk, Elyse Noelani; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S.; Andersen, Bogi

    2015-01-01

    Historically work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as liver, fat and muscle. In recent years, skin is emerging as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging and carcinogenesis. Morphologically skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration -- the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell-type specific circadian mutants. Also, due to the accessibility of the skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar UV radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. The skin also provides opportunities to interrogate clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model for investigating the

  20. The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity.

    PubMed

    Plikus, Maksim V; Van Spyk, Elyse N; Pham, Kim; Geyfman, Mikhail; Kumar, Vivek; Takahashi, Joseph S; Andersen, Bogi

    2015-06-01

    Historically, work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as the liver, fat, and muscle. In recent years, skin has emerged as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging, and carcinogenesis. Morphologically, skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable, and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell type-specific circadian mutants. Also, due to the accessibility of skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV) radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it also represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. Skin also provides opportunities to interrogate the clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model

  1. Pointwise mutual information quantifies intratumor heterogeneity in tissue sections labeled with multiple fluorescent biomarkers

    PubMed Central

    Spagnolo, Daniel M.; Gyanchandani, Rekha; Al-Kofahi, Yousef; Stern, Andrew M.; Lezon, Timothy R.; Gough, Albert; Meyer, Dan E.; Ginty, Fiona; Sarachan, Brion; Fine, Jeffrey; Lee, Adrian V.; Taylor, D. Lansing; Chennubhotla, S. Chakra

    2016-01-01

    Background: Measures of spatial intratumor heterogeneity are potentially important diagnostic biomarkers for cancer progression, proliferation, and response to therapy. Spatial relationships among cells including cancer and stromal cells in the tumor microenvironment (TME) are key contributors to heterogeneity. Methods: We demonstrate how to quantify spatial heterogeneity from immunofluorescence pathology samples, using a set of 3 basic breast cancer biomarkers as a test case. We learn a set of dominant biomarker intensity patterns and map the spatial distribution of the biomarker patterns with a network. We then describe the pairwise association statistics for each pattern within the network using pointwise mutual information (PMI) and visually represent heterogeneity with a two-dimensional map. Results: We found a salient set of 8 biomarker patterns to describe cellular phenotypes from a tissue microarray cohort containing 4 different breast cancer subtypes. After computing PMI for each pair of biomarker patterns in each patient and tumor replicate, we visualize the interactions that contribute to the resulting association statistics. Then, we demonstrate the potential for using PMI as a diagnostic biomarker, by comparing PMI maps and heterogeneity scores from patients across the 4 different cancer subtypes. Estrogen receptor positive invasive lobular carcinoma patient, AL13-6, exhibited the highest heterogeneity score among those tested, while estrogen receptor negative invasive ductal carcinoma patient, AL13-14, exhibited the lowest heterogeneity score. Conclusions: This paper presents an approach for describing intratumor heterogeneity, in a quantitative fashion (via PMI), which departs from the purely qualitative approaches currently used in the clinic. PMI is generalizable to highly multiplexed/hyperplexed immunofluorescence images, as well as spatial data from complementary in situ methods including FISSEQ and CyTOF, sampling many different components

  2. Tissue Myeloid Progenitors Differentiate into Pericytes through TGF-β Signaling in Developing Skin Vasculature.

    PubMed

    Yamazaki, Tomoko; Nalbandian, Ani; Uchida, Yutaka; Li, Wenling; Arnold, Thomas D; Kubota, Yoshiaki; Yamamoto, Seiji; Ema, Masatsugu; Mukouyama, Yoh-Suke

    2017-03-21

    Mural cells (pericytes and vascular smooth muscle cells) are essential for the regulation of vascular networks and maintenance of vascular integrity, but their origins are diverse in different tissues and not known in the organs that arise from the ectoderm, such as skin. Here, we show that tissue-localized myeloid progenitors contribute to pericyte development in embryonic skin vasculature. A series of in vivo fate-mapping experiments indicates that tissue myeloid progenitors differentiate into pericytes. Furthermore, depletion of tissue myeloid cells and their progenitors in PU.1 (also known as Spi1) mutants results in defective pericyte development. Fluorescence-activated cell sorting (FACS)-isolated myeloid cells and their progenitors from embryonic skin differentiate into pericytes in culture. At the molecular level, transforming growth factor-β (TGF-β) induces pericyte differentiation in culture. Furthermore, type 2 TGF-β receptor (Tgfbr2) mutants exhibit deficient pericyte development in skin vasculature. Combined, these data suggest that pericytes differentiate from tissue myeloid progenitors in the skin vasculature through TGF-β signaling.

  3. Characterizing optical properties and spatial heterogeneity of human ovarian tissue using spatial frequency domain imaging

    NASA Astrophysics Data System (ADS)

    Nandy, Sreyankar; Mostafa, Atahar; Kumavor, Patrick D.; Sanders, Melinda; Brewer, Molly; Zhu, Quing

    2016-10-01

    A spatial frequency domain imaging (SFDI) system was developed for characterizing ex vivo human ovarian tissue using wide-field absorption and scattering properties and their spatial heterogeneities. Based on the observed differences between absorption and scattering images of different ovarian tissue groups, six parameters were quantitatively extracted. These are the mean absorption and scattering, spatial heterogeneities of both absorption and scattering maps measured by a standard deviation, and a fitting error of a Gaussian model fitted to normalized mean Radon transform of the absorption and scattering maps. A logistic regression model was used for classification of malignant and normal ovarian tissues. A sensitivity of 95%, specificity of 100%, and area under the curve of 0.98 were obtained using six parameters extracted from the SFDI images. The preliminary results demonstrate the diagnostic potential of the SFDI method for quantitative characterization of wide-field optical properties and the spatial distribution heterogeneity of human ovarian tissue. SFDI could be an extremely robust and valuable tool for evaluation of the ovary and detection of neoplastic changes of ovarian cancer.

  4. Reentry produced by small-scale heterogeneities in a discrete model of cardiac tissue

    NASA Astrophysics Data System (ADS)

    Alonso, Sergio; Bär, Markus

    2016-06-01

    Reentries are reexcitations of cardiac tissue after the passing of an excitation wave which can cause dangerous arrhythmias like tachycardia or life-threatening heart failures like fibrillation. The heart is formed by a network of cells connected by gap junctions. Under ischemic conditions some of the cells lose their connections, because gap junctions are blocked and the excitability is decreased. We model a circular region of the tissue where a fraction of connections among individual cells are removed and substituted by non-conducting material in a two-dimensional (2D) discrete model of a heterogeneous excitable medium with local kinetics based on electrophysiology. Thus, two neighbouring cells are connected (disconnected) with a probability ϕ (1 - ϕ). Such a region is assumed to be surrounded by homogeneous tissue. The circular heterogeneous area is shown to act as a source of new waves which reenter into the tissue and reexcitate the whole domain. We employ the Fenton-Karma equations to model the action potential for the local kinetics of the discrete nodes to study the statistics of the reentries in two dimensional networks with different topologies. We conclude that the probability of reentry is determined by the proximity of the fraction of disrupted connections between neighboring nodes (“cells”) in the heterogeneous region to the percolation threshold.

  5. Characterizing optical properties and spatial heterogeneity of human ovarian tissue using spatial frequency domain imaging

    PubMed Central

    Nandy, Sreyankar; Mostafa, Atahar; Kumavor, Patrick D; Sanders, Melinda; Brewer, Molly; Zhu, Quing

    2016-01-01

    Abstract. A spatial frequency domain imaging (SFDI) system was developed for characterizing ex vivo human ovarian tissue using wide-field absorption and scattering properties and their spatial heterogeneities. Based on the observed differences between absorption and scattering images of different ovarian tissue groups, six parameters were quantitatively extracted. These are the mean absorption and scattering, spatial heterogeneities of both absorption and scattering maps measured by a standard deviation, and a fitting error of a Gaussian model fitted to normalized mean Radon transform of the absorption and scattering maps. A logistic regression model was used for classification of malignant and normal ovarian tissues. A sensitivity of 95%, specificity of 100%, and area under the curve of 0.98 were obtained using six parameters extracted from the SFDI images. The preliminary results demonstrate the diagnostic potential of the SFDI method for quantitative characterization of wide-field optical properties and the spatial distribution heterogeneity of human ovarian tissue. SFDI could be an extremely robust and valuable tool for evaluation of the ovary and detection of neoplastic changes of ovarian cancer. PMID:26822943

  6. 3D reconstruction of skin pathological tissue: the understanding of microrelief pattern and dermal ridge.

    PubMed

    Oh, Ga Na; Yoon, Jung Hee; Kye, Hee Sang; Kim, Dai Hyun; Kim, Jong Yeob; Choi, Jae Eun; Seo, Soo Hong; Kye, Young Chul; Ahn, Hyo Hyun; Rhyu, Im Joo

    2014-05-01

    Most studies about the structures of the human skin have been on the general histologic features of the skin. The purpose of this study was to understand the relationship between the microrelief (MR) pattern and histologic structure of the human skin, and to find the usefulness of the three-dimensional reconstruction (3DR) technique of pathological skin tissue. Human skin specimens were obtained from the medial forearm, abdomen, and volar aspects of the finger tips of cadavers. Two-dimensional surface-viewed images of the skin showing MR patterns were obtained using dry dermoscopy. Histologic structures of the skin were evaluated by 3D images obtained using the 3DR technique. MR was deeper and wider in the abdomen than in the medial side of the forearm. In the medial side of the forearm, 10.27 rete ridges were distributed in a plateau, on average. In the abdomen, about 14.37 rete ridges were distributed in a plateau. From 3DR technique, MR pattern thought to be a superordinate concept to rete ridges. The 3DR technique was useful and may allow a better understanding of the pathogenetic changes in the skin surface in aging skin. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Quantifying Heterogeneity in Emphysema from High Resolution Computed Tomography: A Lung Tissue Research Consortium Study

    PubMed Central

    Yilmaz, Cuneyt; Dane, Dan M.; Patel, Nova C.; Hsia, Connie C.W.

    2012-01-01

    Rationale and Objective To quantify spatial distribution of emphysema using high-resolution computed tomography (HRCT), we applied semi-automated analysis with internal attenuation calibration to measure regional air volume, tissue volume, and fractional tissue volume (FTV=tissue/[air+tissue] volume) in well-characterized patients studied by the Lung Tissue Research Consortium (LTRC). Methods HRCT was obtained at supine end-inspiration and end-expiration, and prone end-inspiration from 31 patients with mild, moderate, severe, or very severe emphysema (stages II–V, FEV1>75%, 51–75%, 21–50% and ≤20% predicted, respectively). Control data were from 20 healthy non-smokers (stage I). Each lobe was analyzed separately. Heterogeneity of FTV was assessed from coefficients of variation (CV) within and among lobes, and the kurtosis and skewness of FTV histograms. Results In emphysema, lobar air volume increased up to 177% except in the right middle lobe. Lobar tissue volume increased up to 107% in mild-moderate stages then normalized in advanced stages. Normally, FTV was up to 82% higher in lower than upper lobes. In mild-moderate emphysema, lobar FTV increased by up to 74% above normal at supine inspiration. In severe emphysema FTV declined below normal in all lobes and positions in correlation with pulmonary function (p<0.05). Markers of FTV heterogeneity increased steadily with disease stage in correlation with pulmonary function (p<0.05); the pattern is distinct from that seen in interstitial lung disease (ILD). Conclusion CT-derived biomarkers differentiate the spatial patterns of emphysema distribution and heterogeneity from that in ILD. Early emphysema is associated with elevated tissue volume and FTV, consistent with hyperemia, inflammation or atelectasis. PMID:23122057

  8. MRI analyses show that kinesio taping affects much more than just the targeted superficial tissues and causes heterogeneous deformations within the whole limb.

    PubMed

    Pamuk, Uluç; Yucesoy, Can A

    2015-12-16

    Kinesio taping (KT) is widely used in the treatment of sports injuries and various neuro-musculoskeletal disorders. However, it is considered as selectively effective on targeted tissues and its mechanical effects have not been quantified objectively. Ascribed to continuity of muscular and connective tissues, mechanical loading imposed can have widespread heterogeneous effects. The aim was to characterize the mechanical effects of KT objectively and to test the hypotheses that KT causes acutely, local deformations not necessarily (I) in agreement with tape adhering direction and (II) limited to the directly targeted tissues. High-resolution 3D magnetic resonance image sets were acquired in healthy human subjects (n=5) prior to and acutely after KT application over the skin along m. tibialis anterior (TA). Hip, knee and ankle angles were kept constant. Demons image registration algorithm was used to calculate local tissue deformations within the lower leg, in vivo. Mean peak tissue strains were significantly higher than strain artifacts. Only KT-to-TA region in part shows local deformations in agreement with tape adhering direction whereas, superficial skin, the rest of KT-to-TA and TA regions show deformations (up to 51.5% length change) in other directions. Non-targeted tissues also show sizable heterogeneous deformations, but in smaller amplitudes. Inter-subject variability is notable. Magnetic resonance imaging analyses allow for a detailed assessment of local tissue deformation occurring acutely after KT application. The findings confirm our hypotheses and characterize how KT affects the underlying tissues, both immediately targeted and distant. This allows revealing mechanisms that can affect clinical outcomes of KT objectively.

  9. Synchronization of Early Afterdepolarizations and Arrhythmogenesis in Heterogeneous Cardiac Tissue Models

    PubMed Central

    de Lange, Enno; Xie, Yuanfang; Qu, Zhilin

    2012-01-01

    Early afterdepolarizations (EADs) are linked to both triggered arrhythmias and reentrant arrhythmias by causing premature ventricular complexes (PVCs), focal excitations, or heterogeneous tissue substrates for reentry formation. However, a critical number of cells that synchronously exhibit EADs are needed to result in arrhythmia triggers and substrates in tissue. In this study, we use mathematical modeling and computer simulations to investigate EAD synchronization and arrhythmia induction in tissue models with random cell-to-cell variations. Our major observations are as follows. Random cell-to-cell variations in action potential duration without EAD presence do not cause large dispersion of refractoriness in well-coupled tissue. In the presence of phase-2 EADs, the cells may synchronously exhibit the same number of EADs or no EADs with a very small dispersion of refractoriness, or synchronize regionally to result in large dispersion of refractoriness. In the presence of phase-3 EADs, regional synchronization leads to propagating EADs, forming PVCs in tissue. Interestingly, even though the uncoupled cells exhibit either no EAD or only a single EAD, when these cells are coupled to form a tissue, more than one PVC can occur. When the PVCs occur at different locations and time, multifocal arrhythmias are triggered, with the foci shifting in space and time in an irregular manner. The focal arrhythmias either spontaneously terminate or degenerate into reentrant arrhythmias due to heterogeneities and spatiotemporal chaotic dynamics of the foci. PMID:22853915

  10. Optimization and real-time control for laser treatment of heterogeneous soft tissues

    PubMed Central

    Feng, Yusheng; Fuentes, David; Hawkins, Andrea; Bass, Jon M.; Rylander, Marissa Nichole

    2010-01-01

    Predicting the outcome of thermotherapies in cancer treatment requires an accurate characterization of the bioheat transfer processes in soft tissues. Due to the biological and structural complexity of tumor (soft tissue) composition and vasculature, it is often very difficult to obtain reliable tissue properties that is one of the key factors for the accurate treatment outcome prediction. Efficient algorithms employing in vivo thermal measurements to determine heterogeneous thermal tissues properties in conjunction with a detailed sensitivity analysis can produce essential information for model development and optimal control. The goals of this paper are to present a general formulation of the bioheat transfer equation for heterogeneous soft tissues, review models and algorithms developed for cell damage, heat shock proteins, and soft tissues with nanoparticle inclusion, and demonstrate an overall computational strategy for developing a laser treatment framework with the ability to perform real-time robust calibrations and optimal control. This computational strategy can be applied to other thermotherapies using the heat source such as radio frequency or high intensity focused ultrasound. PMID:20485457

  11. Synchronization of early afterdepolarizations and arrhythmogenesis in heterogeneous cardiac tissue models.

    PubMed

    de Lange, Enno; Xie, Yuanfang; Qu, Zhilin

    2012-07-18

    Early afterdepolarizations (EADs) are linked to both triggered arrhythmias and reentrant arrhythmias by causing premature ventricular complexes (PVCs), focal excitations, or heterogeneous tissue substrates for reentry formation. However, a critical number of cells that synchronously exhibit EADs are needed to result in arrhythmia triggers and substrates in tissue. In this study, we use mathematical modeling and computer simulations to investigate EAD synchronization and arrhythmia induction in tissue models with random cell-to-cell variations. Our major observations are as follows. Random cell-to-cell variations in action potential duration without EAD presence do not cause large dispersion of refractoriness in well-coupled tissue. In the presence of phase-2 EADs, the cells may synchronously exhibit the same number of EADs or no EADs with a very small dispersion of refractoriness, or synchronize regionally to result in large dispersion of refractoriness. In the presence of phase-3 EADs, regional synchronization leads to propagating EADs, forming PVCs in tissue. Interestingly, even though the uncoupled cells exhibit either no EAD or only a single EAD, when these cells are coupled to form a tissue, more than one PVC can occur. When the PVCs occur at different locations and time, multifocal arrhythmias are triggered, with the foci shifting in space and time in an irregular manner. The focal arrhythmias either spontaneously terminate or degenerate into reentrant arrhythmias due to heterogeneities and spatiotemporal chaotic dynamics of the foci.

  12. Metabolomics Reveals the Heterogeneous Secretome of Two Entomopathogenic Fungi to Ex Vivo Cultured Insect Tissues

    PubMed Central

    de Bekker, Charissa; Smith, Philip B.; Patterson, Andrew D.; Hughes, David P.

    2013-01-01

    Fungal entomopathogens rely on cellular heterogeneity during the different stages of insect host infection. Their pathogenicity is exhibited through the secretion of secondary metabolites, which implies that the infection life history of this group of environmentally important fungi can be revealed using metabolomics. Here metabolomic analysis in combination with ex vivo insect tissue culturing shows that two generalist isolates of the genus Metarhizium and Beauveria, commonly used as biological pesticides, employ significantly different arrays of secondary metabolites during infectious and saprophytic growth. It also reveals that both fungi exhibit tissue specific strategies by a distinguishable metabolite secretion on the insect tissues tested in this study. In addition to showing the important heterogeneous nature of these two entomopathogens, this study also resulted in the discovery of several novel destruxins and beauverolides that have not been described before, most likely because previous surveys did not use insect tissues as a culturing system. While Beauveria secreted these cyclic depsipeptides when encountering live insect tissues, Metarhizium employed them primarily on dead tissue. This implies that, while these fungi employ comparable strategies when it comes to entomopathogenesis, there are most certainly significant differences at the molecular level that deserve to be studied. PMID:23940603

  13. Tissue-mimicking oil-in-gelatin dispersions for use in heterogeneous elastography phantoms.

    PubMed

    Madsen, E L; Frank, G R; Krouskop, T A; Varghese, T; Kallel, F; Ophir, J

    2003-01-01

    A ten-month study is presented of materials for use in heterogeneous elastography phantoms. The materials consist of gelatin with or without a suspension of microscopic safflower oil droplets. The highest volume percent of oil in the materials is 50%. Thimerosal acts as a preservative. The greater the safflower oil concentration, the lower the Young's modulus. Elastographic data for heterogeneous phantoms, in which the only variable is safflower oil concentration, demonstrate stability of inclusion geometry and elastic strain contrast. Young's modulus ratios (elastic contrasts) producible in a heterogeneous phantom are as high as 2.7. The phantoms are particularly useful for ultrasound elastography. They can also be employed in MR elastography, although the highest achievable ratio of longitudinal to transverse relaxation times is considerably less than is the case for soft tissues.

  14. Skin, subcutaneous tissue, and allograft infection with Mycobacterium fortuitum in a renal transplant recipient.

    PubMed

    Mushtaq, Raees F; Bappa, Adamu; Ahmad, Mustafa; AlShaebi, Fuad

    2014-11-01

    Different types of skin disorders are prevalent among kidney transplant recipients. The development of nodular skin lesions in these patients would usually raise a suspicion of Kaposi's sarcoma. We report a patient, who presented with nodular skin lesions one year post transplant, but the biopsy revealed a rare diagnosis - Mycobacterium fortuitum (M. fortuitum) infection of the skin, subcutaneous, and renal allograft. He was treated successfully with an initial two-week course of intravenous cefoxitin, followed by a six-month course of ciprofloxacin, clarithromycin, and co-trimoxazole. There are a few reported cases of M. fortuitum infection in renal transplant recipients in the literature - notably urinary tract infection, allograft infection, and psoas abscess, but to the best of our knowledge this is the first case demonstrating extensive infection involving the skin, subcutaneous tissue, and renal allograft. Physicians vested with the care of renal transplant patients should be aware of this rare infection in these patients.

  15. Assessment of cryopreserved donor skin viability: the experience of the regional tissue bank of Siena.

    PubMed

    Pianigiani, E; Tognetti, L; Ierardi, F; Mariotti, G; Rubegni, P; Cevenini, G; Perotti, R; Fimiani, M

    2016-06-01

    Skin allografts from cadaver donors are an important resource for treating extensive burns, slow-healing wounds and chronic ulcers. A high level of cell viability of cryopreserved allografts is often required, especially in burn surgery, in Italy. Thus, we aimed to determine which conditions enable procurement of highly viable skin in our Regional Skin Bank of Siena. For this purpose, we assessed cell viability of cryopreserved skin allografts procured between 2011 and 2013 from 127 consecutive skin donors, before and after freezing (at day 15, 180, and 365). For each skin donor, we collected data concerning clinical history (age, sex, smoking, phototype, dyslipidemia, diabetes, cause of death), donation process (multi-tissue or multi-organ) and timing of skin procurement (assessment of intervals such as death-harvesting, harvesting-banking, death-banking). All these variables were analysed in the whole case study (127 donors) and in different groups (e.g. multi-organ donors, non refrigerated multi-tissue donors, refrigerated multi-tissue donors) for correlations with cell viability. Our results indicated that cryopreserved skin allografts with higher cell viability were obtained from female, non smoker, heartbeating donors died of cerebral haemorrhage, and were harvested within 2 h of aortic clamping and banked within 12 h of harvesting (13-14 h from clamping). Age, cause of death and dyslipidaemia or diabetes did not appear to influence cell viability. To maintain acceptable cell viability, our skin bank needs to reduce the time interval between harvesting and banking, especially for refrigerated donors.

  16. Stem Cell Therapy for Healing Wounded Skin and Soft Tissues

    DTIC Science & Technology

    2014-03-01

    8217), though the signal was weak. (A) n • ID I IC :.:;:; ...... , I (B) (Cj (D) Transdifferentiation of ASCs to endothelial cell was addressed using a...Methods Mol Biol 456 (2008) 155-171. 6. C.T. Gomillion, K.J. Burg , Stem cells and adipose tissue engineering, Biomaterials 27 (2006) 6052-6063. 7. E

  17. The use of ex vivo human skin tissue for genotoxicity testing

    SciTech Connect

    Reus, Astrid A.; Usta, Mustafa; Krul, Cyrille A.M.

    2012-06-01

    As a result of the chemical legislation concerning the registration, evaluation, authorization and restriction of chemicals (REACH), and the Seventh Amendment to the Cosmetics Directive, which prohibits animal testing in Europe for cosmetics, alternative methods for safety evaluation of chemicals are urgently needed. Current in vitro genotoxicity assays are not sufficiently predictive for the in vivo situation, resulting in an unacceptably high number of misleading positives. For many chemicals and ingredients of personal care products the skin is the first site of contact, but there are no in vitro genotoxicity assays available in the skin for additional evaluation of positive or equivocal responses observed in regulatory in vitro genotoxicity assays. In the present study ex vivo human skin tissue obtained from surgery was used for genotoxicity evaluation of chemicals by using the comet assay. Fresh ex vivo human skin tissue was cultured in an air–liquid interface and topically exposed to 20 chemicals, including true positive, misleading positive and true negative genotoxins. Based on the results obtained in the present study, the sensitivity, specificity and accuracy of the ex vivo skin comet assay to predict in vivo genotoxicity were 89%, 90% and 89%, respectively. Donor and experimental variability were mainly reflected in the magnitude of the response and not the difference between the presence and absence of a genotoxic response. The present study indicates that human skin obtained from surgery is a promising and robust model for safety evaluation of chemicals that are in direct contact with the skin. -- Highlights: ► We use human skin obtained from surgery for genotoxicity evaluation of chemicals. ► We use the comet assay as parameter for genotoxicity in ex vivo human skin. ► Sensitivity, specificity and accuracy to predict in vivo genotoxins are determined. ► Sensitivity, specificity and accuracy are 89%, 90% and 90%, respectively. ► The method

  18. Schisandrin B protects against solar irradiation-induced oxidative stress in rat skin tissue.

    PubMed

    Lam, Philip Y; Yan, Chung Wai; Chiu, Po Yee; Leung, Hoi Yan; Ko, Kam Ming

    2011-04-01

    Schisandrin B (Sch B) and schisandrin C (Sch C), but not schisandrin A and dimethyl diphenyl bicarboxylate, protected rat skin tissue against solar irradiation-induced oxidative injury, as evidenced by a reversal of solar irradiation-induced changes in cellular reduced glutathione and α-tocopherol levels, as well as antioxidant enzyme activities and malondialdehyde production. The cytochrome P-450-mediated metabolism of Sch B or Sch C caused ROS production in rat skin microsomes. Taken together, Sch B or Sch C, by virtue of its pro-oxidant action and the subsequent eliciting of a glutathione antioxidant response, may prevent photo-aging of skin.

  19. [Repair of perforating skin and soft tissue defects of the palms with dorsalis pedis parallel flaps].

    PubMed

    Feng, Shiming; Wang, Aiguo; Gao, Shunhong

    2015-04-01

    To explore the effect of dorsalis pedis parallel flaps in repairing perforating skin and soft tissue defects of the palms. Eighteen patients with perforating skin and soft tissue defects of the palms were hospitalized from July 2008 to November 2010. The area of skin defect ranged from 2.0 cm x 1.5 cm to 5.0 cm x 2.5 cm. The dorsalis pedis parallel flaps were used to repair these defects, with the area ranging from 2.0 cm x 2.0 cm to 5.5 cm x 3.0 cm. The donor sites were covered with autologous full-thickness skin from inner thigh. All the 18 flaps and skin grafts of donor sites survived completely. Seventeen patients were followed up for 6 to 23 months, with mean time of 10 months, and one patient was lost to follow-up. The texture, elasticity, and appearance of all the 17 flaps were satisfactory, with no obvious pigmentation or cicatricial contracture. At the last follow-up, the distance of two-point discrimination of flaps ranged from 6 to 9 mm, with mean distance of 7.4 mm, and the sensation of flaps reached S3 in 13 patients who had nerve anastomosis. The dorsalis pedis parallel flap, with reliable blood supply and flexible design, is a good choice for repairing perforating skin and soft tissue defects of the palms.

  20. In vitro 3D full thickness skin equivalent tissue model using silk and collagen biomaterials

    PubMed Central

    Bellas, Evangelia; Seiberg, Miri; Garlick, Jonathan; Kaplan, David L.

    2013-01-01

    Current approaches to develop skin equivalents often only include the epidermal and dermal components. Yet, full thickness skin includes the hypodermis, a layer below the dermis of adipose tissue containing vasculature, nerves and fibroblasts, necessary to support the epidermis and dermis. In the present study, we developed a full thickness skin equivalent including an epidermis, dermis and hypodermis that could serve as an in vitro model for studying skin development, disease or as a platform for consumer product testing as a means to avoid animal testing. The full thickness skin equivalent was easy to handle and was maintained in culture for greater than 14 days while expressing physiologically relevant morphologies of both the epidermis and dermis, as seen by keratin 10, collagen I and collagen IV expression. The skin equivalent produced glycerol and leptin, markers of adipose tissue metabolism. This work serves as a foundation for our understanding of some of the necessary factors needed to develop a stable, functional model of full-thickness skin. PMID:23161763

  1. Detection of follicular transport of lidocaine and metabolism in adipose tissue in pig ear skin by DESI mass spectrometry imaging.

    PubMed

    D'Alvise, Janina; Mortensen, Rasmus; Hansen, Steen H; Janfelt, Christian

    2014-06-01

    Desorption electrospray ionization (DESI) mass spectrometry imaging is demonstrated as a detection technique for penetration experiments of drugs in skin. Lidocaine ointment was used as the model compound in ex vivo experiments with whole pig ears as the skin model. Follicular transport of lidocaine into the deeper skin layers is demonstrated for the first time. Furthermore, metabolism of lidocaine to 3-OH-lidocaine was observed in subcutaneous tissue as well as in lobules of white adipose tissue surrounding the hair follicles. These results suggest that it is advantageous to use full thickness skin, including subcutaneous tissue, for skin metabolism studies.

  2. Synthesis of highly interconnected 3D scaffold from Arothron stellatus skin collagen for tissue engineering application.

    PubMed

    Ramanathan, Giriprasath; Singaravelu, Sivakumar; Raja, M D; Sivagnanam, Uma Tiruchirapalli

    2015-11-01

    The substrate which is avidly used for tissue engineering applications should have good mechanical and biocompatible properties, and all these parameters are often considered as essential for dermal reformation. Highly interconnected three dimensional (3D) wound dressing material with enhanced structural integrity was synthesized from Arothron stellatus fish skin (AsFS) collagen for tissue engineering applications. The synthesized 3D collagen sponge (COL-SPG) was further characterized by different physicochemical methods. The scanning electron microscopy analysis of the material demonstrated that well interconnected pores with homogeneous microstructure on the surface aids higher swelling index and that the material also possessed good mechanical properties with a Young's modulus of 0.89±0.2 MPa. Biocompatibility of the 3D COL-SPG showed 92% growth for both NIH 3T3 fibroblasts and keratinocytes. Overall, the study revealed that synthesized 3D COL-SPG from fish skin will act as a promising wound dressing in skin tissue engineering.

  3. Water content distribution imaging of skin tissue using near-infrared camera and measurement depth analysis

    NASA Astrophysics Data System (ADS)

    Arimoto, Hidenobu; Egawa, Mariko

    2013-02-01

    Wavelength-dependent light penetration depth in the measurement of water distribution of the skin tissue is analyzed. Near-infrared (NIR) imaging enables 2-D water content map on the skin tissue because water absorbs light strongly in the NIR region particularly around the wavelengths of 1450 and 1920 nm. However, the depth of the light penetration depends largely on wavelength as the absorption coefficient of water changes considerably in the NIR range. We investigate the measurement depth of the water content mapping with a NIR camera and bandpass filters at the wavelengths of 1300, 1450 and 1920 nm. Analysis is performed with Monte Carlo light scattering simulation adopting the optical parameters which is derived from the depth profile of the water contents measured by the confocal Raman spectroscopy. It is found that the NIR image in 1920 nm gives the highest sensitivity to the water content in the surface layer of the skin tissue.

  4. Point-of-care device for quantification of bilirubin in skin tissue.

    PubMed

    Alla, Suresh K; Huddle, Adam; Butler, Joshua D; Bowman, Peggy S; Clark, Joseph F; Beyette, Fred R

    2011-03-01

    Steady state diffuse reflectance spectroscopy is a nondestructive method for obtaining biochemical and physiological information from skin tissue. In medical conditions such as neonatal jaundice excess bilirubin in the blood stream diffuses into the surrounding tissue leading to a yellowing of the skin. Diffuse reflectance measurement of the skin tissue can provide real time assessment of the progression of a disease or a medical condition. Here we present a noninvasive point-of-care system that utilizes diffuse reflectance spectroscopy to quantifying bilirubin from skin reflectance spectra. The device consists of an optical system integrated with a signal processing algorithm. The device is then used as a platform to study two different spectral databases. The first spectral database is a jaundice animal model in which the jaundice reflectance spectra are synthesized from normal skin. The second spectral database is the spectral measurements collected on human volunteers to quantify the different chromophores and other physical properties of the tissue such as Hematocrit, Hemoglobin, etc. The initial trials from each of these spectral databases have laid the foundation to verify the performance of this bilirubin quantification device.

  5. Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA-Seq

    DTIC Science & Technology

    2016-09-01

    AWARD NUMBER: W81XWH-15-1-0251 TITLE: Evaluation of Human Adipose Tissue Stromal Heterogeneity in Metabolic Disease Using Single Cell RNA -Seq...Using Single Cell RNA -Seq 5 b. GRANT NUMBER W81XWH-15-1-0251 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Linus Tzu-Yen Tsai 5e...Adipocytes, Stromal Vascular Fraction, Single-cell RNA - seq, Transcriptional profiling, Drop-seq 6 ACCOMPLISHMENTS: What were the major

  6. Extensive envelope heterogeneity of simian immunodeficiency virus in tissues from infected macaques.

    PubMed Central

    Campbell, B J; Hirsch, V M

    1994-01-01

    The extent of virus genetic variation within tissues and peripheral blood mononuclear cells (PBMC) from two simian immunodeficiency virus (SIV)-infected macaques was analyzed. The products of PCR amplification of two regions, region 1 (SIV V1 region) and region 2 (region corresponding to the human immunodeficiency virus V3 cysteine loop and part of the C3 region immediately downstream), of the SIV envelope were examined for single-stranded conformation polymorphism followed by sequence analysis of selected clones. The V1 region of the SIV envelope of viruses present within lymphoid tissues displayed extensive heterogeneity, while viral populations within the PBMC and brain appeared to be less variable. Region 2 heterogeneity in both animals was generally confined to three residues in a tissue-specific manner. In addition, virus from the brains of both animals appeared to be distinct compared with viruses present in other tissues and PBMC of the same animal, both in the pattern of PCR-single-stranded conformation polymorphism SCP and in the sequence of region 2. These studies revealed that the tissues of SIV-infected macaques were a reservoir for viral variants distinct from those seen in PBMC. Images PMID:8151778

  7. Tissue heterogeneity as a mechanism for localized neural stimulation by applied electric fields

    NASA Astrophysics Data System (ADS)

    Miranda, P. C.; Correia, L.; Salvador, R.; Basser, P. J.

    2007-09-01

    We investigate the heterogeneity of electrical conductivity as a new mechanism to stimulate excitable tissues via applied electric fields. In particular, we show that stimulation of axons crossing internal boundaries can occur at boundaries where the electric conductivity of the volume conductor changes abruptly. The effectiveness of this and other stimulation mechanisms was compared by means of models and computer simulations in the context of transcranial magnetic stimulation. While, for a given stimulation intensity, the largest membrane depolarization occurred where an axon terminates or bends sharply in a high electric field region, a slightly smaller membrane depolarization, still sufficient to generate action potentials, also occurred at an internal boundary where the conductivity jumped from 0.143 S m-1 to 0.333 S m-1, simulating a white-matter-grey-matter interface. Tissue heterogeneity can also give rise to local electric field gradients that are considerably stronger and more focal than those impressed by the stimulation coil and that can affect the membrane potential, albeit to a lesser extent than the two mechanisms mentioned above. Tissue heterogeneity may play an important role in electric and magnetic 'far-field' stimulation.

  8. [Skin and soft tissue infections in children: consensus on diagnosis and treatment].

    PubMed

    Moyano, Mónica; Peuchot, Agustina; Giachetti, Ana Claudia; Moreno, Rina; Cancellara, Aldo; Falaschi, Andrea; Chiarelli, Gloria; Villasboas, Rosa Mabel; Corazza, Rosana; Magneres, Cecilia; Calvari, Miriam; Roldán, Daniela

    2014-04-01

    Skin and soft tissue infections are a common reason for consultation in primary health care centers. Data from the local epidemiology of these infections are rare, but Staphylococcus aureus and Streptococcus pyogenes are known to be the major etiologic agents. The appearance in recent years of community-originated strains of methicillin-resistant S. aureus and erythromycin-resistant pyogenes raises controversy in the choice of initial empirical treatment. This national consensus is for pediatricians, dermatologists, infectologists and other health professionals. It is about clinical management, especially the diagnosis and treatment of community-originated skin and soft tissue infections in immunocompetent patients under the age of 19.

  9. [Skin and soft tissue infections in children: consensus on diagnosis and treatment].

    PubMed

    2014-02-01

    Skin and soft tissue infections are a common reason for consultation in primary health care centers. Data from the local epidemiology of these infections are rare, but Staphylococcus aureus and Streptococcus pyogenes are known to be the major etiologic agents. The appearance in recent years of community-originated strains of methicillin-resistant S. aureus and erythromycin-resistant pyogenes raises controversy in the choice of initial empirical treatment. This national consensus is for pediatricians, dermatologists, infectiologists and other health professionals. It is about clinical management, especially the diagnosis and treatment of community-originated skin and soft tissue infections in immunocompetent patients under the age of 19.

  10. Tissue stem cells: definition, plasticity, heterogeneity, self-organization and models--a conceptual approach.

    PubMed

    Loeffler, Markus; Roeder, Ingo

    2002-01-01

    The classical definition of adult tissue stem cells (TSC) is fundamentally based on a functional perspective. A TSC is an undifferentiated cell, capable of proliferation, self-renewal, production of a large number of differentiated functional progeny, regenerating tissue after injury and a flexibility in the use of these options. Here, we discuss the necessity for amending this definition in the light of recent insight into stem cell biology regarding stem cell heterogeneity, lineage plasticity, clonal fluctuation and cell-environment interactions. We conclude that the definition needs amendments. A decade ago the flexibility criterion has attracted little attention but recent findings have indicated its importance. Flexibility and reversibility of tissue and lineage specification (tissue plasticity) and of properties within a tissue (within-tissue plasticity) have major implications with regard to concepts of stem cell function. We advocate to give up the view of TSC as being entities with a preprogrammed development and to replace it by a concept that makes the capabilities for flexible and regulated tissue self-organization based on cell-cell and cell-environment interactions the new paradigm. This concept would permit to incorporate the context-dependent lineage plasticity, within-lineage plasticity and generation of stem cell heterogeneity as a result of a dynamically regulated process. Such concepts need a rigorous examination by formal modeling including simulation studies. We provide some general ideas on how to proceed with such theories and illustrate this with worked models for tissue stem cells of the hematopoietic system and the intestinal epithelium. Copyright 2002 S. Karger AG, Basel

  11. Forearm skin tissue dielectric constant measured at 300 MHz: effect of changes in skin vascular volume and blood flow.

    PubMed

    Mayrovitz, Harvey N; Guo, Xiaoran; Salmon, Mark; Uhde, Matt

    2013-01-01

    Skin tissue dielectric constant (TDC) values measured via the open-ended coaxial probe method are useful non-invasive indices of local skin tissue water. However, the effect of skin blood flow (SBF) or skin blood volume (SBV) on TDC values is unknown. To determine the magnitude of such effects, we decreased forearm SBV via vertical arm raising for 5 min (test 1) and increased SBV by bicep cuff compression to 50 mmHg for 5 min (test 2) in 20 healthy supine subjects (10 men). TDC values were measured to a depth of 1·5 mm on anterior forearm, and SBF was measured with laser-Doppler system simultaneously on forearm and finger. Results indicate that decreasing vascular volume (test 1) was associated with a small but statistically significant reduction in TDC (3·0 ± 4·3%, P = 0·003) and increasing vascular volume (test 2) was associated with a slight but statistically significant increase in TDC (3·5 ± 3·0%, P<0·001). SBF changes depended on test and measurement site. For forearm, test 1 significantly increased SBF (102·6 ± 156·2%, P<0·001) and test 2 significantly decreased it (39·5 ± 13·1%, P<0·001). In finger, SBF was significantly reduced by both tests: in test 1 by 55·3 ± 32·1%, P<0·001 and in test 2 by 53·3 ± 27·6%, P<0·001. We conclude that the small percentage changes in TDC values (3·0-3·5%) over the wide range of induced SBV and SBF changes suggest a minor effect on clinically determined TDC values because of SBV or SBF changes or differences when comparing TDC longitudinally over time or among individuals of different groups in a research setting.

  12. Using swept source optical coherence tomography to monitor wound healing in tissue engineered skin

    NASA Astrophysics Data System (ADS)

    Smith, L. E.; Lu, Z.; Bonesi, M.; Smallwood, R.; Matcher, S. J.; MacNeil, S.

    2010-02-01

    There is an increasing need for a robust simple to use non-invasive imaging technology for monitoring tissue engineered constructs as they develop. We have applied optical coherence tomography (OCT), a relatively new optical technique, to image tissue engineered constructs. Our aim was to evaluate the use of swept-source optical coherence tomography (SSOCT) to non-invasively image reconstructed skin as it developed over several weeks. The epidermis of the reconstructed skin was readily distinguished from the neodermis when examined with standard histology - a destructive imaging technique - of samples. The development of reconstructed skin based on deepithelialised acellular dermis (DED) was accurately monitored with SS-OCT over three weeks and confirmed with conventional histology. It was also possible to image changes in the epidermis due to the presence of melanoma and the healing of these 3D models after wounding with a scalpel, with or without the addition of a fibrin clot. SS-OCT is proving to be a valuable tool in tissue engineering, showing great promise for the non-invasive imaging of optically turbid tissue engineered constructs, including tissue engineered skin.

  13. Management of Tissue Ischemia in Mastectomy Skin Flaps: Algorithm Integrating SPY Angiography and Topical Nitroglycerin.

    PubMed

    Sanniec, Kyle; Teotia, Sumeet; Amirlak, Bardia

    2016-10-01

    Tissue ischemia can be managed in several different ways based on the cause of the perfusion defect, including topical nitroglycerin or surgical intervention. However, there are times when tissue perfusion is questioned and clinical examination is unable to determine definitively the cause of ischemic tissue and whether it will survive. In this technique article, we describe our comprehensive algorithm for the management of tissue ischemia in mastectomy skin flaps, which can be applied to other plastic surgery procedures by integrating SPY angiography and topical nitroglycerin.

  14. Management of Tissue Ischemia in Mastectomy Skin Flaps: Algorithm Integrating SPY Angiography and Topical Nitroglycerin

    PubMed Central

    Sanniec, Kyle; Teotia, Sumeet

    2016-01-01

    Summary: Tissue ischemia can be managed in several different ways based on the cause of the perfusion defect, including topical nitroglycerin or surgical intervention. However, there are times when tissue perfusion is questioned and clinical examination is unable to determine definitively the cause of ischemic tissue and whether it will survive. In this technique article, we describe our comprehensive algorithm for the management of tissue ischemia in mastectomy skin flaps, which can be applied to other plastic surgery procedures by integrating SPY angiography and topical nitroglycerin. PMID:27826472

  15. Multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties

    PubMed Central

    Chen, Alvin I.; Balter, Max L.; Chen, Melanie I.; Gross, Daniel; Alam, Sheikh K.; Maguire, Timothy J.; Yarmush, Martin L.

    2016-01-01

    Purpose: This paper describes the design, fabrication, and characterization of multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties. The phantoms comprise epidermis, dermis, and hypodermis skin layers, blood vessels, and blood mimicking fluid. Each tissue component may be individually tailored to a range of physiological and demographic conditions. Methods: The skin layers were constructed from varying concentrations of gelatin and agar. Synthetic melanin, India ink, absorbing dyes, and Intralipid were added to provide optical absorption and scattering in the skin layers. Bovine serum albumin was used to increase acoustic attenuation, and 40 μm diameter silica microspheres were used to induce acoustic backscatter. Phantom vessels consisting of thin-walled polydimethylsiloxane tubing were embedded at depths of 2–6 mm beneath the skin, and blood mimicking fluid was passed through the vessels. The phantoms were characterized through uniaxial compression and tension experiments, rheological frequency sweep studies, diffuse reflectance spectroscopy, and ultrasonic pulse-echo measurements. Results were then compared to in vivo and ex vivo literature data. Results: The elastic and dynamic shear behavior of the phantom skin layers and vessel wall closely approximated the behavior of porcine skin tissues and human vessels. Similarly, the optical properties of the phantom tissue components in the wavelength range of 400–1100 nm, as well as the acoustic properties in the frequency range of 2–9 MHz, were comparable to human tissue data. Normalized root mean square percent errors between the phantom results and the literature reference values ranged from 1.06% to 9.82%, which for many measurements were less than the sample variability. Finally, the mechanical and imaging characteristics of the phantoms were found to remain stable after 30 days of storage at 21 °C. Conclusions: The phantoms described in this

  16. Multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties.

    PubMed

    Chen, Alvin I; Balter, Max L; Chen, Melanie I; Gross, Daniel; Alam, Sheikh K; Maguire, Timothy J; Yarmush, Martin L

    2016-06-01

    This paper describes the design, fabrication, and characterization of multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties. The phantoms comprise epidermis, dermis, and hypodermis skin layers, blood vessels, and blood mimicking fluid. Each tissue component may be individually tailored to a range of physiological and demographic conditions. The skin layers were constructed from varying concentrations of gelatin and agar. Synthetic melanin, India ink, absorbing dyes, and Intralipid were added to provide optical absorption and scattering in the skin layers. Bovine serum albumin was used to increase acoustic attenuation, and 40 μm diameter silica microspheres were used to induce acoustic backscatter. Phantom vessels consisting of thin-walled polydimethylsiloxane tubing were embedded at depths of 2-6 mm beneath the skin, and blood mimicking fluid was passed through the vessels. The phantoms were characterized through uniaxial compression and tension experiments, rheological frequency sweep studies, diffuse reflectance spectroscopy, and ultrasonic pulse-echo measurements. Results were then compared to in vivo and ex vivo literature data. The elastic and dynamic shear behavior of the phantom skin layers and vessel wall closely approximated the behavior of porcine skin tissues and human vessels. Similarly, the optical properties of the phantom tissue components in the wavelength range of 400-1100 nm, as well as the acoustic properties in the frequency range of 2-9 MHz, were comparable to human tissue data. Normalized root mean square percent errors between the phantom results and the literature reference values ranged from 1.06% to 9.82%, which for many measurements were less than the sample variability. Finally, the mechanical and imaging characteristics of the phantoms were found to remain stable after 30 days of storage at 21 °C. The phantoms described in this work simulate the mechanical, optical, and

  17. Marine-derived biological macromolecule-based biomaterials for wound healing and skin tissue regeneration.

    PubMed

    Chandika, Pathum; Ko, Seok-Chun; Jung, Won-Kyo

    2015-01-01

    Wound healing is a complex biological process that depends on the wound condition, the patient's health, and the physicochemical support given through external materials. The development of bioactive molecules and engineered tissue substitutes to provide physiochemical support to enhance the wound healing process plays a key role in advancing wound-care management. Thus, identification of ideal molecules in wound treatment is still in progress. The discovery of natural products that contain ideal molecules for skin tissue regeneration has been greatly advanced by exploration of the marine bioenvironment. Consequently, tremendously diverse marine organisms have become a great source of numerous biological macromolecules that can be used to develop tissue-engineered substitutes with wound healing properties. This review summarizes the wound healing process, the properties of macromolecules from marine organisms, and the involvement of these molecules in skin tissue regeneration applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Joint hypermobility and skin elasticity: the hereditary disorders of connective tissue.

    PubMed

    Hakim, Alan J; Sahota, Anshoo

    2006-01-01

    The hereditary disorders of connective tissues (HDCTs) encompass a spectrum of conditions linked pathophysiologically by abnormalities of collagen, fibrillin, and matrix proteins. The clinical picture ranges from morbidity because of musculoskeletal, skin, ocular and visceral pathologies to mortality from acute vascular collapse. For many of the conditions, there is a considerable overlap in clinical features, although severity varies; appreciating the subtle differences in presentation is vital to the clinician in determining the diagnosis. Though conditions associated with severe vascular pathology are rare, other hereditary disorders of connective tissues such as the joint hypermobility syndrome and Stickler's disease are common and probably underrecognized. Abnormal skin elasticity and scaring, joint hypermobility, and chronic arthralgia are important clues that should trigger the clinician to search for underlying hereditary disorders of connective tissues. In this article, we discuss the spectrum of clinical findings, management, and genetic screening of the more common hereditary disorders of connective tissues, highlighting their diagnostic criteria and their differences.

  19. Nonlinear behaviour of conduction and block in cardiac tissue with heterogeneous expression of connexin 43.

    PubMed

    Prudat, Yann; Kucera, Jan P

    2014-11-01

    Altered gap junctional coupling potentiates slow conduction and arrhythmias. To better understand how heterogeneous connexin expression affects conduction at the cellular scale, we investigated conduction in tissue consisting of two cardiomyocyte populations expressing different connexin levels. Conduction was mapped using microelectrode arrays in cultured strands of foetal murine ventricular myocytes with predefined contents of connexin 43 knockout (Cx43KO) cells. Corresponding computer simulations were run in randomly generated two-dimensional tissues mimicking the cellular architecture of the strands. In the cultures, the relationship between conduction velocity (CV) and Cx43KO cell content was nonlinear. CV first decreased significantly when Cx43KO content was increased from 0 to 50%. When the Cx43KO content was ≥60%, CV became comparable to that in 100% Cx43KO strands. Co-culturing Cx43KO and wild-type cells also resulted in significantly more heterogeneous conduction patterns and in frequent conduction blocks. The simulations replicated this behaviour of conduction. For Cx43KO contents of 10-50%, conduction was slowed due to wavefront meandering between Cx43KO cells. For Cx43KO contents ≥60%, clusters of remaining wild-type cells acted as electrical loads that impaired conduction. For Cx43KO contents of 40-60%, conduction exhibited fractal characteristics, was prone to block, and was more sensitive to changes in ion currents compared to homogeneous tissue. In conclusion, conduction velocity and stability behave in a nonlinear manner when cardiomyocytes expressing different connexin amounts are combined. This behaviour results from heterogeneous current-to-load relationships at the cellular level. Such behaviour is likely to be arrhythmogenic in various clinical contexts in which gap junctional coupling is heterogeneous.

  20. Analytical Solution of Thermal Wave Models on Skin Tissue Under Arbitrary Periodic Boundary Conditions

    NASA Astrophysics Data System (ADS)

    Fazlali, R.; Ahmadikia, H.

    2013-01-01

    Modeling and understanding the heat transfer in biological tissues is important in medical thermal therapeutic applications. The biothermomechanics of skin involves interdisciplinary features, such as bioheat transfer, biomechanics, and burn damage. The hyperbolic thermal wave model of bioheat transfer and the parabolic Pennes bioheat transfer equations with blood perfusion and metabolic heat generation are applied for the skin tissue as a finite and semi-infinite domain when the skin surface temperature is suddenly exposed to a source of an arbitrary periodic temperature. These equations are solved analytically by Laplace transform methods. The thermal wave model results indicate that a non-Fourier model has predicted the thermal behavior correctly, compared to that of previous experiments. The results of the thermal wave model show that when the first thermal wave moves from the first boundary, the temperature profiles for finite and semi-infinite domains of skin become separated for these phenomena; the discrepancy between these profiles is negligible. The accuracy of the obtained results is validated through comparisons with existing numerical results. The results demonstrate that the non-Fourier model is significant in describing the thermal behavior of skin tissue.

  1. Full-thickness skin with mature hair follicles generated from tissue culture expanded human cells.

    PubMed

    Wu, Xunwei; Scott, Larry; Washenik, Ken; Stenn, Kurt

    2014-12-01

    The goal of regenerative medicine is to reconstruct fully functional organs from tissue culture expanded human cells. In this study, we report a method for human reconstructed skin (hRSK) when starting with human cells. We implanted tissue culture expanded human epidermal and dermal cells into an excision wound on the back of immunodeficient mice. Pigmented skin covered the wound 4 weeks after implantation. Hair shafts were visible at 12 weeks and prominent at 14 weeks. Histologically, the hRSK comprises an intact epidermis and dermis with mature hair follicles, sebaceous glands and most notably, and unique to this system, subcutis. Morphogenesis, differentiation, and maturation of the hRSK mirror the human fetal process. Human antigen markers demonstrate that the constituent cells are of human origin for at least 6 months. The degree of new skin formation is most complete when using tissue culture expanded cells from fetal skin, but it also occurs with expanded newborn and adult cells; however, no appendages formed when we grafted both adult dermal and epidermal cells. The hRSK system promises to be valuable as a laboratory model for studying biological, pathological, and pharmaceutical problems of human skin.

  2. Nanostructured anti-bacterial poly-lactic-co-glycolic acid films for skin tissue engineering applications.

    PubMed

    Karahaliloğlu, Zeynep; Ercan, Batur; Chung, Stanley; Taylor, Erik; Denkbaş, Emir B; Webster, Thomas J

    2014-12-01

    Major issues faced with the use of today's skin grafts are infection, scar tissue formation, insufficient keratinocyte (or skin producing cells) proliferation and high production costs. To overcome these limitations, we propose here for the first time, a nanofeatured poly(lactide-co-glycolide) (PLGA) membrane as a next generation antibacterial skin graft material. An alkaline surface treatment method was used to create random nanofeatures on PLGA membranes where sodium hydroxide (NaOH) concentration and exposure times were altered to control surface morphology. Most significantly, and without the use of antibiotics, results showed a decrease in Staphylococcus aureus (a dangerous pathogen infecting skin grafts) growth for up to ∼40% after 2 days of culture on nanofeatured PLGA membranes compared to untreated controls. Results also showed that while bacteria growth was stunted, mammalian cell growth was not. Specifically, cell culture results showed an increase in human epidermal keratinocyte density, while the density of scar tissue forming human dermal fibroblasts, did not change on nanofeatured PLGA surfaces compared to the untreated controls after 3 days of culture. These findings indicate that the alkaline treatment of PLGA membranes is a promising quick and effective manner to limit scar tissue formation and bacterial invasion while increasing skin cell proliferation for improving numerous wound-healing applications.

  3. Gene expression changes with age in skin, adipose tissue, blood and brain.

    PubMed

    Glass, Daniel; Viñuela, Ana; Davies, Matthew N; Ramasamy, Adaikalavan; Parts, Leopold; Knowles, David; Brown, Andrew A; Hedman, Asa K; Small, Kerrin S; Buil, Alfonso; Grundberg, Elin; Nica, Alexandra C; Di Meglio, Paola; Nestle, Frank O; Ryten, Mina; Durbin, Richard; McCarthy, Mark I; Deloukas, Panagiotis; Dermitzakis, Emmanouil T; Weale, Michael E; Bataille, Veronique; Spector, Tim D

    2013-07-26

    Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age. Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues. Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.

  4. Gene expression changes with age in skin, adipose tissue, blood and brain

    PubMed Central

    2013-01-01

    Background Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age. Results Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues. Conclusions Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases. PMID:23889843

  5. Non-O1, non-O139 Vibrio cholerae bacteremic skin and soft tissue infections.

    PubMed

    Maraki, Sofia; Christidou, Athanasia; Anastasaki, Maria; Scoulica, Efstathia

    2016-01-01

    Non-O1, non-O139 Vibrio cholerae can cause sporadic cases of gastroenteritis and extra-intestinal invasive infections, following exposure to contaminated seawater or freshwater or after consumption of raw seafood. Bacteremic infections with skin and soft tissue manifestations are uncommon and in most cases are associated with liver cirrhosis, haematologic malignancies, diabetes mellitus and other immunosuppressed conditions. The medical literature was reviewed and we found 47 published cases of non-O1, non-O139 Vibrio cholerae bacteremic skin and soft tissue infections. A fatal case of bacteremia with bullous cellulitis in a 43-year-old patient with liver cirrhosis is described, which is the first reported in Greece. From January 1974 to May 2015, a total of 48 patients with non-O1, non-O139 Vibrio cholerae bacteremia with skin and soft tissue infections were reported. Males predominated. Liver cirrhosis, chronic liver disease and alcohol abuse were common comorbidities. The soft tissue lesions most commonly described were localised cellulitis, with or without bullous and haemorrhagic lesions (66.7%), while necrotising fasciitis was more rare (29.2%). Of the 48 patients with non-O1, non-O139 V. cholerae bacteremic skin and soft tissue infections, 20 (41.7%) died despite treatment. Although rarely encountered, non-O1, non-O139 Vibrio cholerae should be included in the differential diagnosis of bacteremic skin and soft tissue infections in patients with underlying illnesses and epidemiologic risk factors. Timely and appropriate antibiotic and surgical treatments are important in the management of the infection.

  6. In vivo monitoring of external pressure induced hemodynamics in skin tissue using optical coherence tomography angiography

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Wang, Hequn; Wang, Ruikang K.

    2015-03-01

    Characterization of the relationship between external pressure and blood flow is important in the examination of pressure-induced disturbance in tissue microcirculation. Optical coherence tomography (OCT) angiography is a promising imaging technique, capable of providing the noninvasive extraction of functional vessels within the skin tissue with capillary-scale resolution. Here, we present a feasibility study of OCT angiography to monitor effect of external pressures on blood perfusion in human skin tissue in vivo. Graded external pressure is loaded normal to the surface of the nailfold tissue of a healthy human. The incremental loading is applied step by step and then followed by an immediate release. Concurrent OCT imaging of the nailfold is performed during the pre/post loading. Blood perfusion images including baseline (at pre-loading) and corresponding tissue strain maps are calculated from 3D OCT dataset obtained at the different applied pressures, allowing visualization of capillary perfusion events at stressed nailfold tissue. The results indicate that the perfusion progressively decreases with the constant increase of tissue strain. Reactive hyperemia is occurred right after the removal of the pressure corresponding to quick drop of the increased strain. The perfusion is returned to the baseline level after a few minutes. These findings suggest that OCT microangiography may have great potential for quantitatively assessing tissue microcirculation in the locally pressed tissue in vivo.

  7. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source.

    PubMed

    Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

    2010-09-21

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V(100) reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

  8. Nanocapsules for drug delivery through the skin barrier by tissue-tolerable plasma

    NASA Astrophysics Data System (ADS)

    Lademann, J.; Patzelt, A.; Richter, H.; Lademann, O.; Baier, G.; Breucker, L.; Landfester, K.

    2013-08-01

    For many years, several attempts have been made to enhance skin penetration by chemical, physical or mechanical manipulation to reduce the barrier function of the skin. The present study demonstrates the possibility of penetration enhancement for 400 nm sized nanocapsules loaded with a model drug consisting of a fluorescent dye by the application of tissue-tolerable plasma (TTP). Therefore, the stability of the nanocapsules and their penetration through the skin barrier prior to and in combination with TTP application was evaluated. The results revealed that the penetration of the nanocapsules could be effectively enhanced when applied in combination with TTP, hence delivering the model drug unaffected by plasma into deeper skin layers. The stability testing showed no significant structural changes of the nanocapsules after contact with TTP. Thus, the present study introduces a new strategy for the penetration enhancement of substances by the combined utilization of nanocapsules and TTP.

  9. Mueller matrix polarimetry for characterizing microstructural variation of nude mouse skin during tissue optical clearing.

    PubMed

    Chen, Dongsheng; Zeng, Nan; Xie, Qiaolin; He, Honghui; Tuchin, Valery V; Ma, Hui

    2017-08-01

    We investigate the polarization features corresponding to changes in the microstructure of nude mouse skin during immersion in a glycerol solution. By comparing the Mueller matrix imaging experiments and Monte Carlo simulations, we examine in detail how the Mueller matrix elements vary with the immersion time. The results indicate that the polarization features represented by Mueller matrix elements m22&m33&m44 and the absolute values of m34&m43 are sensitive to the immersion time. To gain a deeper insight on how the microstructures of the skin vary during the tissue optical clearing (TOC), we set up a sphere-cylinder birefringence model (SCBM) of the skin and carry on simulations corresponding to different TOC mechanisms. The good agreement between the experimental and simulated results confirm that Mueller matrix imaging combined with Monte Carlo simulation is potentially a powerful tool for revealing microscopic features of biological tissues.

  10. Multimode near-field microwave monitoring of free water content of skin and imaging of tissue.

    PubMed

    Lofland, S E; Mazzatenta, J D; Croman, J; Tyagi, S D

    2007-03-07

    We have used the near-field scanning microwave microscopy (NSMM) technique in the 1-10 GHz range to monitor the free water content of skin. The water content is interpreted from the measured dielectric properties of the epidermis. The finger skin was first hydrated by soaking in water at 37 degrees C for 30 min followed by monitoring of water content as the free water evaporated under ambient conditions. The same technique has also been employed to image a 1 cm x 1 cm sample of chicken skin. It has been shown that variations exist in the resonant frequencies and quality factors of tissue under varying physical parameters. The samples analysed were as-received and thermally dehydrated or damaged chicken tissue samples. We contrast between the dielectric properties with the optical images. We also discuss possible application of our imaging technique in clinical monitoring of the wound healing process.

  11. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves

    NASA Astrophysics Data System (ADS)

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J.; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-07-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW's are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

  12. Modelling far field pacing for terminating spiral waves pinned to ischaemic heterogeneities in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Boccia, E.; Luther, S.; Parlitz, U.

    2017-05-01

    In cardiac tissue, electrical spiral waves pinned to a heterogeneity can be unpinned (and eventually terminated) using electric far field pulses and recruiting the heterogeneity as a virtual electrode. While for isotropic media the process of unpinning is much better understood, the case of an anisotropic substrate with different conductivities in different directions still needs intensive investigation. To study the impact of anisotropy on the unpinning process, we present numerical simulations based on the bidomain formulation of the phase I of the Luo and Rudy action potential model modified due to the occurrence of acute myocardial ischaemia. Simulating a rotating spiral wave pinned to an ischaemic heterogeneity, we compare the success of sequences of far field pulses in the isotropic and the anisotropic case for spirals still in transient or in steady rotation states. Our results clearly indicate that the range of pacing parameters resulting in successful termination of pinned spiral waves is larger in anisotropic tissue than in an isotropic medium. This article is part of the themed issue `Mathematical methods in medicine: neuroscience, cardiology and pathology'.

  13. Modelling far field pacing for terminating spiral waves pinned to ischaemic heterogeneities in cardiac tissue.

    PubMed

    Boccia, E; Luther, S; Parlitz, U

    2017-06-28

    In cardiac tissue, electrical spiral waves pinned to a heterogeneity can be unpinned (and eventually terminated) using electric far field pulses and recruiting the heterogeneity as a virtual electrode. While for isotropic media the process of unpinning is much better understood, the case of an anisotropic substrate with different conductivities in different directions still needs intensive investigation. To study the impact of anisotropy on the unpinning process, we present numerical simulations based on the bidomain formulation of the phase I of the Luo and Rudy action potential model modified due to the occurrence of acute myocardial ischaemia. Simulating a rotating spiral wave pinned to an ischaemic heterogeneity, we compare the success of sequences of far field pulses in the isotropic and the anisotropic case for spirals still in transient or in steady rotation states. Our results clearly indicate that the range of pacing parameters resulting in successful termination of pinned spiral waves is larger in anisotropic tissue than in an isotropic medium.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'. © 2017 The Authors.

  14. Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling.

    PubMed

    Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru

    2016-07-19

    Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity.

  15. Quantitative segmentation of fluorescence microscopy images of heterogeneous tissue: Approach for tuning algorithm parameters

    NASA Astrophysics Data System (ADS)

    Mueller, Jenna L.; Harmany, Zachary T.; Mito, Jeffrey K.; Kennedy, Stephanie A.; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G.; Willett, Rebecca M.; Brown, J. Quincy; Ramanujam, Nimmi

    2013-02-01

    The combination of fluorescent contrast agents with microscopy is a powerful technique to obtain real time images of tissue histology without the need for fixing, sectioning, and staining. The potential of this technology lies in the identification of robust methods for image segmentation and quantitation, particularly in heterogeneous tissues. Our solution is to apply sparse decomposition (SD) to monochrome images of fluorescently-stained microanatomy to segment and quantify distinct tissue types. The clinical utility of our approach is demonstrated by imaging excised margins in a cohort of mice after surgical resection of a sarcoma. Representative images of excised margins were used to optimize the formulation of SD and tune parameters associated with the algorithm. Our results demonstrate that SD is a robust solution that can advance vital fluorescence microscopy as a clinically significant technology.

  16. Distinct tissue formation by heterogeneous printing of osteo- and endothelial progenitor cells.

    PubMed

    Fedorovich, Natalja E; Wijnberg, Hans M; Dhert, Wouter J A; Alblas, Jacqueline

    2011-08-01

    The organ- or tissue-printing approach, based on layered deposition of cell-laden hydrogels, is a new technique in regenerative medicine suitable to investigate whether mimicking the anatomical organization of cells, matrix, and bioactive molecules is necessary for obtaining or improving functional engineered tissues. Currently, data on performance of multicellular printed constructs in vivo are limited. In this study we illustrate the ability of the system to print intricate porous constructs containing two different cell types--endothelial progenitors and multipotent stromal cells--and show that these grafts retain heterogeneous cell organization after subcutaneous implantation in immunodeficient mice. We demonstrate that cell differentiation leading to the expected tissue formation occurs at the site of the deposited progenitor cell type. While perfused blood vessels are formed in the endothelial progenitor cell-laden part of the constructs, bone formation is taking place in the multipotent stromal cell-laden part of the printed grafts.

  17. Intense picosecond THz pulses alter gene expression in human skin tissue in vivo

    NASA Astrophysics Data System (ADS)

    Titova, Lyubov V.; Ayesheshim, Ayesheshim K.; Golubov, Andrey; Rodriguez-Juarez, Rocio; Kovalchuk, Anna; Hegmann, Frank A.; Kovalchuk, Olga

    2013-02-01

    Pulsed terahertz (THz) imaging has been suggested as a novel high resolution, noninvasive medical diagnostic tool. However, little is known about the influence of pulsed THz radiation on human tissue, i.e., its genotoxicity and effects on cell activity and cell integrity. We have carried out a comprehensive investigation of the biological effects of THz radiation on human skin tissue using a high power THz pulse source and an in vivo full-thickness human skin tissue model. We have observed that exposure to intense THz pulses causes DNA damage and changes in the global gene expression profile in the exposed skin tissue. Several of the affected genes are known to play major roles in human cancer. While the changes in the expression levels of some of them suggest possible oncogenic effects of pulsed THz radiation, changes in the expression of the other cancer-related genes might have a protective influence. This study may serve as a roadmap for future investigations aimed at elucidating the exact roles that all the affected genes play in skin carcinogenesis and in response to pulsed THz radiation.

  18. Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells.

    PubMed

    Klar, Agnieszka S; Güven, Sinan; Biedermann, Thomas; Luginbühl, Joachim; Böttcher-Haberzeth, Sophie; Meuli-Simmen, Claudia; Meuli, Martin; Martin, Ivan; Scherberich, Arnaud; Reichmann, Ernst

    2014-06-01

    The major problem in skin grafting is that tissue-engineered skin grafts after their transplantation are initially entirely dependent on diffusion. Since this process is slow and inefficient, nutrients, growth factors, and oxygen will insufficiently be supplied and the regenerating graft will undergo a physiological crisis, resulting in scar-like dermal structures and shrinkage. The tissue-engineering of a vascular network in human dermo-epidermal skin substitutes (DESS) is a promising approach to overcome this limitation. Here we report, for the first time, on the use of the adipose stromal vascular fraction (SVF)-derived endothelial cell population to tissue-engineer DESS containing a highly efficient capillary plexus. To develop vascular networks in vitro, we employed optimized 3D fibrin or collagen type I hydrogel systems. Upon transplantation onto immune-deficient rats, these pre-formed vascular networks anastomosed to the recipient's vasculature within only four days. As a consequence, the neo-epidermis efficiently established tissue homeostasis, the dermis underwent almost no contraction, and showed sustained epidermal coverage in vivo. Overall, the here described rapid and efficient perfusion of SVF-based skin grafts opens new perspectives for the treatment of hitherto unmet clinical needs in burn/plastic surgery and dermatology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Using human umbilical cord cells for tissue engineering: a comparison with skin cells.

    PubMed

    Hayward, Cindy J; Fradette, Julie; Morissette Martin, Pascal; Guignard, Rina; Germain, Lucie; Auger, François A

    2014-01-01

    The epithelial cells and Wharton׳s jelly cells (WJC) from the human umbilical cord have yet to be extensively studied in respect to their capacity to generate tissue-engineered substitutes for clinical applications. Our reconstruction strategy, based on the self-assembly approach of tissue engineering, allows the production of various types of living human tissues such as skin and cornea from a wide range of cell types originating from post-natal tissue sources. Here we placed epithelial cells and WJC from the umbilical cord in the context of a reconstructed skin substitute in combination with skin keratinocytes and fibroblasts. We compared the ability of the epithelial cells from both sources to generate a stratified, differentiated skin-like epithelium upon exposure to air when cultured on the two stromal cell types. Conversely, the ability of the WJC to behave as dermal fibroblasts, producing extracellular matrix and supporting the formation of a differentiated epithelium for both types of epithelial cells, was also investigated. Of the four types of constructs produced, the combination of WJC and keratinocytes was the most similar to skin engineered from dermal fibroblasts and keratinocytes. When cultured on dermal fibroblasts, the cord epithelial cells were able to differentiate in vitro into a stratified multilayered epithelium expressing molecules characteristic of keratinocyte differentiation after exposure to air, and maintaining the expression of keratins K18 and K19, typical of the umbilical cord epithelium. WJC were able to support the growth and differentiation of keratinocytes, especially at the early stages of air-liquid culture. In contrast, cord epithelial cells cultured on WJC did not form a differentiated epidermis when exposed to air. These results support the premise that the tissue from which cells originate can largely affect the properties and homoeostasis of reconstructed substitutes featuring both epithelial and stromal compartments

  20. High-throughput simultaneous analysis of RNA, protein, and lipid biomarkers in heterogeneous tissue samples.

    PubMed

    Reiser, Vladimír; Smith, Ryan C; Xue, Jiyan; Kurtz, Marc M; Liu, Rong; Legrand, Cheryl; He, Xuanmin; Yu, Xiang; Wong, Peggy; Hinchcliffe, John S; Tanen, Michael R; Lazar, Gloria; Zieba, Renata; Ichetovkin, Marina; Chen, Zhu; O'Neill, Edward A; Tanaka, Wesley K; Marton, Matthew J; Liao, Jason; Morris, Mark; Hailman, Eric; Tokiwa, George Y; Plump, Andrew S

    2011-11-01

    With expanding biomarker discovery efforts and increasing costs of drug development, it is critical to maximize the value of mass-limited clinical samples. The main limitation of available methods is the inability to isolate and analyze, from a single sample, molecules requiring incompatible extraction methods. Thus, we developed a novel semiautomated method for tissue processing and tissue milling and division (TMAD). We used a SilverHawk atherectomy catheter to collect atherosclerotic plaques from patients requiring peripheral atherectomy. Tissue preservation by flash freezing was compared with immersion in RNAlater®, and tissue grinding by traditional mortar and pestle was compared with TMAD. Comparators were protein, RNA, and lipid yield and quality. Reproducibility of analyte yield from aliquots of the same tissue sample processed by TMAD was also measured. The quantity and quality of biomarkers extracted from tissue prepared by TMAD was at least as good as that extracted from tissue stored and prepared by traditional means. TMAD enabled parallel analysis of gene expression (quantitative reverse-transcription PCR, microarray), protein composition (ELISA), and lipid content (biochemical assay) from as little as 20 mg of tissue. The mean correlation was r = 0.97 in molecular composition (RNA, protein, or lipid) between aliquots of individual samples generated by TMAD. We also demonstrated that it is feasible to use TMAD in a large-scale clinical study setting. The TMAD methodology described here enables semiautomated, high-throughput sampling of small amounts of heterogeneous tissue specimens by multiple analytical techniques with generally improved quality of recovered biomolecules.

  1. Study on the effect of blood content on diffuse reflectance spectra of basal cell carcinoma skin tissue.

    PubMed

    Nan, Miaoqing; He, Qingli

    2013-01-01

    Diffuse reflectance spectrum as a noninvasive method has been widely used to study the optical properties of cutaneous skin tissue. In this work, we optimized an eight-layered optical model of basal cell carcinoma skin tissue to study its optical properties. Based on the model, the diffuse reflectance spectra were reconstructed in visible wavelength range by Monte Carlo methods. After different blood contents were added to the optical model, the contribution of blood to diffuese reflectance spectra was investigated theoretically. The ratios of basal cell carcinoma skin and normal skin tissue were also calculated for both experimental result and rebuilt results to testify the theoretical reasonability of the model and methods.

  2. Raman spectroscopic analysis of human skin tissue sections ex-vivo: evaluation of the effects of tissue processing and dewaxing

    NASA Astrophysics Data System (ADS)

    Ali, Syed M.; Bonnier, Franck; Tfayli, Ali; Lambkin, Helen; Flynn, Kathleen; McDonagh, Vincent; Healy, Claragh; Clive Lee, T.; Lyng, Fiona M.; Byrne, Hugh J.

    2013-06-01

    Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections and the effects of tissue processing. Both hand and thigh sections of human cadavers were analyzed in their unprocessed and formalin-fixed, paraffin-processed (FFPP), and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum (SC), intermediate underlying epithelium, and dermal layers for sections from both anatomical sites. The SC is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that of the dermis is dominated by the characteristics of collagen. For a given anatomical site, little difference in layer structure and biochemistry is observed between samples from different cadavers. However, the hand and thigh sections are consistently differentiated for all cadavers, largely based on lipidic profiles. In dewaxed FFPP samples, while the SC, intermediate, and dermal layers are clearly differentiated by KMCA of Raman maps of tissue sections, the lipidic contributions to the spectra are significantly reduced, with the result that respective skin layers from different anatomical sites become indistinguishable. While efficient at removing the fixing wax, the tissue processing also efficiently removes the structurally similar lipidic components of the skin layers. In studies of dermatological processes in which lipids play an important role, such as wound healing, dewaxed samples are therefore not appropriate. Removal of the lipids does however accentuate the spectral features of the cellular and protein components, which may be more appropriate for retrospective analysis of disease progression and biochemical analysis using tissue banks.

  3. Tissue-engineered skin preserving the potential of epithelial cells to differentiate into hair after grafting.

    PubMed

    Larouche, Danielle; Cuffley, Kristine; Paquet, Claudie; Germain, Lucie

    2011-03-01

    The aim of this study was to evaluate whether tissue-engineered skin produced in vitro was able to sustain growth of hair follicles in vitro and after grafting. Different tissues were designed. Dissociated newborn mouse keratinocytes or newborn mouse hair buds (HBs) were added onto dermal constructs consisting of a tissue-engineered cell-derived matrix elaborated from either newborn mouse or adult human fibroblasts cultured with ascorbic acid. After 7-21 days of maturation at the air-liquid interface, no hair was noticed in vitro. Epidermal differentiation was observed in all tissue-engineered skin. However, human fibroblast-derived tissue-engineered dermis (hD) promoted a thicker epidermis than mouse fibroblast-derived tissue-engineered dermis (mD). In association with mD, HBs developed epithelial cyst-like inclusions presenting outer root sheath-like attributes. In contrast, epidermoid cyst-like inclusions lined by a stratified squamous epithelium were present in tissues composed of HBs and hD. After grafting, pilo-sebaceous units formed and hair grew in skin elaborated from HBs cultured 10-26 days submerged in culture medium in association with mD. However, the number of normal hair follicles decreased with longer culture time. This hair-forming capacity after grafting was not observed in tissues composed of hD overlaid with HBs. These results demonstrate that epithelial stem cells can be kept in vitro in a permissive tissue-engineered dermal environment without losing their potential to induce hair growth after grafting.

  4. Tissue-aware RNA-Seq processing and normalization for heterogeneous and sparse data.

    PubMed

    Paulson, Joseph N; Chen, Cho-Yi; Lopes-Ramos, Camila M; Kuijjer, Marieke L; Platig, John; Sonawane, Abhijeet R; Fagny, Maud; Glass, Kimberly; Quackenbush, John

    2017-10-03

    Although ultrahigh-throughput RNA-Sequencing has become the dominant technology for genome-wide transcriptional profiling, the vast majority of RNA-Seq studies typically profile only tens of samples, and most analytical pipelines are optimized for these smaller studies. However, projects are generating ever-larger data sets comprising RNA-Seq data from hundreds or thousands of samples, often collected at multiple centers and from diverse tissues. These complex data sets present significant analytical challenges due to batch and tissue effects, but provide the opportunity to revisit the assumptions and methods that we use to preprocess, normalize, and filter RNA-Seq data - critical first steps for any subsequent analysis. We find that analysis of large RNA-Seq data sets requires both careful quality control and the need to account for sparsity due to the heterogeneity intrinsic in multi-group studies. We developed Yet Another RNA Normalization software pipeline (YARN), that includes quality control and preprocessing, gene filtering, and normalization steps designed to facilitate downstream analysis of large, heterogeneous RNA-Seq data sets and we demonstrate its use with data from the Genotype-Tissue Expression (GTEx) project. An R package instantiating YARN is available at http://bioconductor.org/packages/yarn .

  5. Low-level lasers affect uncoupling protein gene expression in skin and skeletal muscle tissues

    NASA Astrophysics Data System (ADS)

    Canuto, K. S.; Sergio, L. P. S.; Paoli, F.; Mencalha, A. L.; Fonseca, A. S.

    2016-03-01

    Wavelength, frequency, power, fluence, and emission mode determine the photophysical, photochemical, and photobiological responses of biological tissues to low-level lasers. Free radicals are involved in these responses acting as second messengers in intracellular signaling processes. Irradiated cells present defenses against these chemical species to avoid unwanted effects, such as uncoupling proteins (UCPs), which are part of protective mechanisms and minimize the effects of free radical generation in mitochondria. In this work UCP2 and UCP3 mRNA gene relative expression in the skin and skeletal muscle tissues of Wistar rats exposed to low-level red and infrared lasers was evaluated. Samples of the skin and skeletal muscle tissue of Wistar rats exposed to low-level red and infrared lasers were withdrawn for total RNA extraction, cDNA synthesis, and the evaluation of gene expression by quantitative polymerase chain reaction. UCP2 and UCP3 mRNA expression was differently altered in skin and skeletal muscle tissues exposed to lasers in a wavelength-dependent effect, with the UCP3 mRNA expression dose-dependent. Alteration on UCP gene expression could be part of the biostimulation effect and is necessary to make cells exposed to red and infrared low-level lasers more resistant or capable of adapting in damaged tissues or diseases.

  6. Autologous Skin Cell Spray for Massive Soft Tissue War Injuries: A Prospective, Case-Control, Multicenter Trial

    DTIC Science & Technology

    2015-01-01

    both WRNMMC (45) and UPITT (21), male or female, ages 18 years of age and older with wounds requiring skin grafts will be asked to participate...AD______________ AWARD NUMBER: W81XWH-13-2-0031 TITLE: Autologous Skin Cell Spray for Massive Soft Tissue War Injuries: A Prospective, Case...DATES COVERED 15Mar2013-31Oct2014 4. TITLE AND SUBTITLE Autologous Skin Cell Spray for Massive Soft Tissue War Injuries: A Prospective, Case-Control

  7. The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin.

    PubMed

    Mackay, Laura K; Rahimpour, Azad; Ma, Joel Z; Collins, Nicholas; Stock, Angus T; Hafon, Ming-Li; Vega-Ramos, Javier; Lauzurica, Pilar; Mueller, Scott N; Stefanovic, Tijana; Tscharke, David C; Heath, William R; Inouye, Michael; Carbone, Francis R; Gebhardt, Thomas

    2013-12-01

    Tissue-resident memory T cells (T(RM) cells) provide superior protection against infection in extralymphoid tissues. Here we found that CD103(+)CD8(+) T(RM) cells developed in the skin from epithelium-infiltrating precursor cells that lacked expression of the effector-cell marker KLRG1. A combination of entry into the epithelium plus local signaling by interleukin 15 (IL-15) and transforming growth factor-β (TGF-β) was required for the formation of these long-lived memory cells. Notably, differentiation into T(RM) cells resulted in the progressive acquisition of a unique transcriptional profile that differed from that of circulating memory cells and other types of T cells that permanently reside in skin epithelium. We provide a comprehensive molecular framework for the local differentiation of a distinct peripheral population of memory cells that forms a first-line immunological defense system in barrier tissues.

  8. Production of human tissue-engineered skin trilayer on a plasma-based hypodermis.

    PubMed

    Monfort, Asun; Soriano-Navarro, Mario; García-Verdugo, José Manuel; Izeta, Ander

    2013-06-01

    Full thickness wounds require a dermal component to achieve functional permanent skin restoration. Currently available tissue-engineered skin substitutes lack a subcutaneous fat layer that would functionally contribute some of the mechanical and thermoregulatory properties of normal skin. To generate a trilayer engineered skin equivalent, we included bone marrow mesenchymal (BM-MSC) or adipose tissue-derived (ASC) stromal cells in a human plasma hydrogel exposed to adipogenic clues for three weeks. Approximately half of the cells differentiated under these conditions into mature adipocytes that survived for two years in culture with minimal medium change. In vitro generation of bona fide fully differentiated adipocytes was assessed by leptin secretion and ultrastructurally demonstrated through semithin to ultrathin sectioning and lipid staining with osmium tetroxide. Furthermore, presence of BM-MSCs or ASCs within the subcutaneous layer contributed to the epidermal differentiation program, with more proliferating basal cells depositing basal membrane proteins and differentiating into mature keratinocytes that were able to generate a pluristratified epithelium. In conclusion, we engineered a fully differentiated human skin trilayer that could present multiple applications such as use for in vitro drug absorption tests and regenerative therapies. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Chemokine Receptor-Dependent Control of Skin Tissue-Resident Memory T Cell Formation.

    PubMed

    Zaid, Ali; Hor, Jyh Liang; Christo, Susan N; Groom, Joanna R; Heath, William R; Mackay, Laura K; Mueller, Scott N

    2017-10-01

    Infection or inflammation of the skin recruits effector CD8(+) T cells that enter the epidermis and form populations of long-lived tissue-resident memory T (TRM) cells. These skin TRM cells migrate within the constrained epidermal environment by extending multiple dynamic dendritic projections and squeezing between keratinocytes to survey the tissue for pathogens. In this study, we examined the signals required for this distinctive mode of T cell migration by inhibiting key cytoskeletal components and performing intravital two-photon microscopy to visualize TRM cell behavior. We found that TRM cell motility and dendrite formation required an intact actomyosin cytoskeleton and the Rho-associated coiled-coil containing kinases. We also identified an essential role for microtubules for maintaining skin TRM cell shape and cellular integrity. We reveal a role for pertussis toxin-sensitive signaling for TRM cell dendritic morphology and migration that is independent of CXCR3 or CXCR6, or the skin-selective chemokine receptors CCR10 and CCR8. However, we found that CXCR6 and CCR10 expression by CD8(+) T cells was required for the optimal formation of memory T cell populations, in particular TRM cell populations in the skin. Copyright © 2017 by The American Association of Immunologists, Inc.

  10. Optical spectroscopic studies of animal skin used in modeling of human cutaneous tissue

    NASA Astrophysics Data System (ADS)

    Drakaki, E.; Makropoulou, M.; Serafetinides, A. A.; Borisova, E.; Avramov, L.; Sianoudis, J. A.

    2007-03-01

    Optical spectroscopy and in particular laser-induced autofluorescence spectroscopy (LIAFS) and diffuse reflectance spectroscopy (DRS), provide excellent possibilities for real-time, noninvasive diagnosis of different skin tissue pathologies. However, the introduction of optical spectroscopy in routine medical practice demands a statistically important data collection, independent from the laser sources and detectors used. The scientists collect databases either from patients, in vivo, or they study different animal models to obtain objective information for the optical properties of various types of normal and diseased tissue. In the present work, the optical properties (fluorescence and reflectance) of two animal skin models are investigated. The aim of using animal models in optical spectroscopy investigations is to examine the statistics of the light induced effects firstly on animals, before any extrapolation effort to humans. A nitrogen laser (λ=337.1 nm) was used as an excitation source for the autofluorescence measurements, while a tungsten-halogen lamp was used for the reflectance measurements. Samples of chicken and pig skin were measured in vitro and were compared with results obtained from measurements of normal human skin in vivo. The specific features of the measured reflectance and fluorescence spectra are discussed, while the limits of data extrapolation for each skin type are also depicted.

  11. Determination of the axial and circumferential mechanical properties of the skin tissue using experimental testing and constitutive modeling.

    PubMed

    Karimi, Alireza; Navidbakhsh, Mahdi; Haghighatnama, Maedeh; Haghi, Afsaneh Motevalli

    2015-01-01

    The skin, being a multi-layered material, is responsible for protecting the human body from the mechanical, bacterial, and viral insults. The skin tissue may display different mechanical properties according to the anatomical locations of a body. However, these mechanical properties in different anatomical regions and at different loading directions (axial and circumferential) of the mice body to date have not been determined. In this study, the axial and circumferential loads were imposed on the mice skin samples. The elastic modulus and maximum stress of the skin tissues were measured before the failure occurred. The nonlinear mechanical behavior of the skin tissues was also computationally investigated through a suitable constitutive equation. Hyperelastic material model was calibrated using the experimental data. Regardless of the anatomic locations of the mice body, the results revealed significantly different mechanical properties in the axial and circumferential directions and, consequently, the mice skin tissue behaves like a pure anisotropic material. The highest elastic modulus was observed in the back skin under the circumferential direction (6.67 MPa), while the lowest one was seen in the abdomen skin under circumferential loading (0.80 MPa). The Ogden material model was narrowly captured the nonlinear mechanical response of the skin at different loading directions. The results help to understand the isotropic/anisotropic mechanical behavior of the skin tissue at different anatomical locations. They also have implications for a diversity of disciplines, i.e., dermatology, cosmetics industry, clinical decision making, and clinical intervention.

  12. Computer-aided multiple-head 3D printing system for printing of heterogeneous organ/tissue constructs

    PubMed Central

    Jung, Jin Woo; Lee, Jung-Seob; Cho, Dong-Woo

    2016-01-01

    Recently, much attention has focused on replacement or/and enhancement of biological tissues via the use of cell-laden hydrogel scaffolds with an architecture that mimics the tissue matrix, and with the desired three-dimensional (3D) external geometry. However, mimicking the heterogeneous tissues that most organs and tissues are formed of is challenging. Although multiple-head 3D printing systems have been proposed for fabricating heterogeneous cell-laden hydrogel scaffolds, to date only the simple exterior form has been realized. Here we describe a computer-aided design and manufacturing (CAD/CAM) system for this application. We aim to develop an algorithm to enable easy, intuitive design and fabrication of a heterogeneous cell-laden hydrogel scaffolds with a free-form 3D geometry. The printing paths of the scaffold are automatically generated from the 3D CAD model, and the scaffold is then printed by dispensing four materials; i.e., a frame, two kinds of cell-laden hydrogel and a support. We demonstrated printing of heterogeneous tissue models formed of hydrogel scaffolds using this approach, including the outer ear, kidney and tooth tissue. These results indicate that this approach is particularly promising for tissue engineering and 3D printing applications to regenerate heterogeneous organs and tissues with tailored geometries to treat specific defects or injuries. PMID:26899876

  13. Computer-aided multiple-head 3D printing system for printing of heterogeneous organ/tissue constructs.

    PubMed

    Jung, Jin Woo; Lee, Jung-Seob; Cho, Dong-Woo

    2016-02-22

    Recently, much attention has focused on replacement or/and enhancement of biological tissues via the use of cell-laden hydrogel scaffolds with an architecture that mimics the tissue matrix, and with the desired three-dimensional (3D) external geometry. However, mimicking the heterogeneous tissues that most organs and tissues are formed of is challenging. Although multiple-head 3D printing systems have been proposed for fabricating heterogeneous cell-laden hydrogel scaffolds, to date only the simple exterior form has been realized. Here we describe a computer-aided design and manufacturing (CAD/CAM) system for this application. We aim to develop an algorithm to enable easy, intuitive design and fabrication of a heterogeneous cell-laden hydrogel scaffolds with a free-form 3D geometry. The printing paths of the scaffold are automatically generated from the 3D CAD model, and the scaffold is then printed by dispensing four materials; i.e., a frame, two kinds of cell-laden hydrogel and a support. We demonstrated printing of heterogeneous tissue models formed of hydrogel scaffolds using this approach, including the outer ear, kidney and tooth tissue. These results indicate that this approach is particularly promising for tissue engineering and 3D printing applications to regenerate heterogeneous organs and tissues with tailored geometries to treat specific defects or injuries.

  14. Computer-aided multiple-head 3D printing system for printing of heterogeneous organ/tissue constructs

    NASA Astrophysics Data System (ADS)

    Jung, Jin Woo; Lee, Jung-Seob; Cho, Dong-Woo

    2016-02-01

    Recently, much attention has focused on replacement or/and enhancement of biological tissues via the use of cell-laden hydrogel scaffolds with an architecture that mimics the tissue matrix, and with the desired three-dimensional (3D) external geometry. However, mimicking the heterogeneous tissues that most organs and tissues are formed of is challenging. Although multiple-head 3D printing systems have been proposed for fabricating heterogeneous cell-laden hydrogel scaffolds, to date only the simple exterior form has been realized. Here we describe a computer-aided design and manufacturing (CAD/CAM) system for this application. We aim to develop an algorithm to enable easy, intuitive design and fabrication of a heterogeneous cell-laden hydrogel scaffolds with a free-form 3D geometry. The printing paths of the scaffold are automatically generated from the 3D CAD model, and the scaffold is then printed by dispensing four materials; i.e., a frame, two kinds of cell-laden hydrogel and a support. We demonstrated printing of heterogeneous tissue models formed of hydrogel scaffolds using this approach, including the outer ear, kidney and tooth tissue. These results indicate that this approach is particularly promising for tissue engineering and 3D printing applications to regenerate heterogeneous organs and tissues with tailored geometries to treat specific defects or injuries.

  15. Monte Carlo mathematical modeling of the interactions between light and skin tissue of newborns

    NASA Astrophysics Data System (ADS)

    Pushkareva, Alexandra; Kozyreva, Olga

    2017-02-01

    A model of interactions between light and skin tissue was reviewed. For the present study the skin of newborns was examined. The characteristics of newborns skin tissue were taken into account when modeling. In the developed model the skin was introduced in three layers: the epidermis, the basal layer and the dermis. The thickness of the skin layers corresponds with the structure of newborns skin. Absorbance of each layer in the visible and near infrared regions of the spectrum was determined by the absorption of three main skin chromophores: blood, melanin and water. The formula of the scattering and absorption coefficients of blood is given in this study. This paper presents the study of the blood oxygenation effect on the signal of diffusely scattered radiation for three distances between the source and the receiver of radiation: 0.3 mm, 0.6 mm and 1.5 mm. The calculation was obtained using the Monte Carlo mathematical modeling. A detailed description of the model is given. The adequacy of the suggested model has been tested by comparing calculated characteristic with the experimental results obtained by means of double integral sphere. The results show that the wavelength range which provides sufficiently accurate measurements depends on the distance between the source and the receiver of radiation and certain data is provided. For the distance of 0.3 mm this range is at 700-780 nm, 950-1000 nm; for 0.6 mm it is at 640-670 nm, 760-780 nm, and 850-870 nm; for 1.5 mm at 620-740 nm.

  16. Characterization of a new tissue-engineered human skin equivalent with hair.

    PubMed

    Michel, M; L'Heureux, N; Pouliot, R; Xu, W; Auger, F A; Germain, L

    1999-06-01

    We designed a new tissue-engineered skin equivalent in which complete pilosebaceous units were integrated. This model was produced exclusively from human fibroblasts and keratinocytes and did not contain any synthetic material. Fibroblasts were cultured for 35 d with ascorbic acid and formed a thick fibrous sheet in the culture dish. The dermal equivalent was composed of stacked fibroblast sheets and exhibited some ultrastructural organization found in normal connective tissues. Keratinocytes seeded on this tissue formed a stratified and cornified epidermis and expressed typical markers of differentiation (keratin 10, filaggrin, and transglutaminase). After 4 wk of culture, a continuous and ultrastructurally organized basement membrane was observed and associated with the expression of laminin and collagen IV and VII. Complete pilosebaceous units were obtained by thermolysin digestion and inserted in this skin equivalent in order to assess the role of the transfollicular route in percutaneous absorption. The presence of hair follicles abolished the lag-time observed during hydrocortisone diffusion and increased significantly its rate of penetration in comparison to the control (skin equivalent with sham hair insertion). Therefore, this new hairy human skin equivalent model allowed an experimental design in which the only variable was the presence of pilosebaceous units and provided new data confirming the importance of hair follicles in percutaneous absorption.

  17. Spray-assisted layer-by-layer assembly on hyaluronic acid scaffolds for skin tissue engineering.

    PubMed

    Monteiro, Isa P; Shukla, Anita; Marques, Alexandra P; Reis, Rui L; Hammond, Paula T

    2015-01-01

    Tissue engineering approaches for the development of a single epidermal-dermal scaffold to treat full-thickness skin defects have been limited by difficulties in the fabrication of a bilayer scaffold combining the specific properties of the epidermis and the dermis. Here we present an innovative approach to developing a scaffold that holds promise for skin tissue engineering. We utilize the spray-assisted layer-by-layer assembly technique to deposit a polyelectrolyte multilayer film composed of hyaluronic acid and poly-L-lysine (the epidermal component) on a porous hyaluronic acid scaffold (the dermal component), in a rapid and controlled manner. The multilayer film promotes cell adhesion, contributing to regeneration of the epidermal barrier functions of skin. While human keratinocytes attached and proliferated on the coated porous scaffolds, they did not invade the porous dermal component, thus leaving room for seeding of relevant fibroblast cell types in this scaffold. This scaffold therefore holds promise for co-culture of different cells, which may be useful for treatment of full-thickness skin defects as well as other tissue engineering applications. © 2014 Wiley Periodicals, Inc.

  18. Three-dimensional electrospun silk-fibroin nanofiber for skin tissue engineering.

    PubMed

    Park, Ye Ri; Ju, Hyung Woo; Lee, Jung Min; Kim, Dong-Kyu; Lee, Ok Joo; Moon, Bo Mi; Park, Hyun Jung; Jeong, Ju Yeon; Yeon, Yeung Kyu; Park, Chan Hum

    2016-12-01

    Tissue-engineered skin substitutes may offer an effective therapeutic option for the treatment of patients with skin damages. In this study, a novel three-dimensional (3D) scaffold composed of electrospun silk fibroin (SF) nanofiber was fabricated using electrospinning with the addition of NaCl crystals. It has well known that the electrospun SF nanofibers were excellent scaffold for tissue. However, it is generally difficult for cells to infiltrate the electrospun silk fibroin due to its small pore size. To resolve this problem, we dropped the NaCl crystals above the rotating collector, which become incorporated into the nanofibers. Three methods (freeze-drying, salt-leaching, and electrospinning with NaCl) for fabrication of SF scaffolds were compared to the difference of their characteristics using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), mechanical strength, porosity, swelling abilities, and cell proliferation. Additionally, using air-liquid culture system, keratinocytes were co-cultured with fibroblasts in each type of SF scaffolds to construct an artificial bilayer skin in vitro. In our experimental results, histologic findings in only electrospun SF scaffolds showed more proliferation of fibroblasts in deep layer and more differentiation of keratinocytes in superficial layer. The present study suggests that 3D electrospun SF scaffolds might be a suitable for skin tissue engineering.

  19. Light-induced autofluorescence of animal skin used in tissue optical modeling

    NASA Astrophysics Data System (ADS)

    Borisova, E.; Bliznakova, I.; Troyanova, P.; Avramov, L.

    2007-07-01

    Light-induced autofluorescence spectroscopy provides many possibilities for medical diagnostics needs for differentiation of tissue pathologies including cancer. For the needs of clinical practice scientists collect spectral data from patients in vivo or they study different tumor models to obtain objective information for fluorescent properties of every kind of normal and diseased tissue. Therefore it is very important to find the most appropriate and close to the human skin samples from the point of view of laser-induced fluorescence spectroscopy, which will give the possibility for easier transfer of data obtained in animal models to spectroscopic medical diagnostics in humans. In this study are presented some results for in vitro detection of the autofluorescence signals of the animal skin (pig and chicken) with using of LEDs as excitation sources (maximum emission at 365, 375, 385 and 400 nm). The autofluorescence signals from in vivo human skin were also detected for comparison with the models' results. Specific features of the spectra measured are discussed and there are proposed some of the origins of the fluorescence signals obtained. Fluorescence maxima detected are addressed to the typical fluorophores existing in the cutaneous tissues. Influence of main skin absorbers, namely melanin and hemoglobin, is also discussed.

  20. Establishment and function of tissue-resident innate lymphoid cells in the skin.

    PubMed

    Yang, Jie; Zhao, Luming; Xu, Ming; Xiong, Na

    2017-07-01

    Innate lymphoid cells (ILCs) are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.

  1. [Design and application of noninvasive tissue recognition imaging in tomography of human skin and crystal structure].

    PubMed

    Yang, Bor-wen; Yang, Pao-keng; Chang, Yuan-shuo; Chen, Xin-chang; Shih, Wen-tse

    2010-09-01

    Cosmetic industry grows fast in recent years. To reveal the image of dermal structure, it is necessary to apply three-dimensional medical imaging technology. To reduce the invasiveness of laser source on tissues, tissue recognition imaging is proposed to retrieve the intrinsic optical property, namely, the reflection spectrum of every scanned point for imaging. The reflection spectra of main kinds of skin tissue, such as melanin, collagen and hemoglobin, were established as reference database. Broad-band rays were then employed to derive the reflection spectrum of each scanned sample element; the tissue type of the scanned point was identified by cross-correlation of the derived spectrum and the database. In imaging program, all scanned points were filled in with their corresponding tissue color, e.g., black for melanin, white for collagen, or red for hemoglobin, and finally the colored skin tomography resulted. Tissue recognition imaging has merits of easy configuration, low cost, color imaging, high resolution and real non-invasiveness. Substituting LED modules for its spectrometer, tissue recognition imaging is promising to be miniaturized as personal and portable skincare devices, which have great potential in future cosmetic market.

  2. The effect of keratinocytes on the biomechanical characteristics and pore microstructure of tissue engineered skin using deep dermal fibroblasts.

    PubMed

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

    2014-12-01

    Fibrosis affects most organs, it results in replacement of normal parenchymal tissue with collagen-rich extracellular matrix, which compromises tissue architecture and ultimately causes loss of function of the affected organ. Biochemical pathways that contribute to fibrosis have been extensively studied, but the role of biomechanical signaling in fibrosis is not clearly understood. In this study, we assessed the effect keratinocytes have on the biomechanical characteristics and pore microstructure of tissue engineered skin made with superficial or deep dermal fibroblasts in order to determine any biomaterial-mediated anti-fibrotic influences on tissue engineered skin. Tissue engineered skin with deep dermal fibroblasts and keratinocytes were found to be less stiff and contracted and had reduced number of myofibroblasts and lower expression of matrix crosslinking factors compared to matrices with deep fibroblasts alone. However, there were no such differences between tissue engineered skin with superficial fibroblasts and keratinocytes and matrices with superficial fibroblasts alone. Also, tissue engineered skin with deep fibroblasts and keratinocytes had smaller pores compared to those with superficial fibroblasts and keratinocytes; pore size of tissue engineered skin with deep fibroblasts and keratinocytes were not different from those matrices with deep fibroblasts alone. A better understanding of biomechanical characteristics and pore microstructure of tissue engineered skin may prove beneficial in promoting normal wound healing over pathologic healing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Collagen-chitosan scaffold - Lauric acid plasticizer for skin tissue engineering on burn cases

    NASA Astrophysics Data System (ADS)

    Widiyanti, Prihartini; Setyadi, Ewing Dian; Rudyardjo, Djony Izak

    2017-02-01

    The prevalence of burns in the world is more than 800 cases per one million people each year and this is the second highest cause of death due to trauma after traffic accident. Many studies are turning to skin substitute methods of tissue engineering. The purpose of this study is to determine the composition of the collagen, chitosan, and lauric acid scaffold, as well as knowing the results of the characterization of the scaffold. The synthesis of chitosan collagen lauric acid scaffold as a skin tissue was engineered using freeze dried method. Results from making of collagen chitosan lauric acid scaffold was characterized physically, biologically and mechanically by SEM, cytotoxicity, biodegradation, and tensile strength. From the morphology test, the result obtained is that pore diameter size ranges from 94.11 to 140.1 µm for samples A,B,C,D, which are in the range of normal pore size 63-150 µm, while sample E has value below the standard which is about 37.87 to 47.36 µm. From cytotoxicity assay, the result obtained is the percentage value of living cells between 20.11 to 21.51%. This value is below 50% the standard value of living cells. Incompatibility is made possible because of human error mainly the replication of washing process over the standard. Degradation testing obtained values of 19.44% - 40% by weight which are degraded during the 7 days of observation. Tensile test results obtained a range of values of 0.192 - 3.53 MPa. Only sample A (3.53 MPa) and B (1.935 MPa) meet the standard values of skin tissue scaffold that is 1-24 MPa. Based on the results of the characteristics of this study, composite chitosan collagen scaffold with lauric acid plasticizer has a potential candidate for skin tissue engineering for skin burns cases.

  4. Stretching Reduces Skin Thickness and Improves Subcutaneous Tissue Mobility in a Murine Model of Systemic Sclerosis.

    PubMed

    Xiong, Ying; Berrueta, Lisbeth; Urso, Katia; Olenich, Sara; Muskaj, Igla; Badger, Gary J; Aliprantis, Antonios; Lafyatis, Robert; Langevin, Helene M

    2017-01-01

    Although physical therapy can help preserve mobility in patients with systemic sclerosis (SSc), stretching has not been used systematically as a treatment to prevent or reverse the disease process. We previously showed in rodent models that stretching promotes the resolution of connective tissue inflammation and reduces new collagen formation after injury. Here, we tested the hypothesis that stretching would impact scleroderma development using a mouse sclerodermatous graft-versus-host disease (sclGvHD) model. The model consists in the adoptive transfer (allogeneic) of splenocytes from B10.D2 mice (graft) into Rag2(-/-) BALB/c hosts (sclGvHD), resulting in skin inflammation followed by fibrosis over 4 weeks. SclGvHD mice and controls were randomized to stretching in vivo for 10 min daily versus no stretching. Weekly ultrasound measurements of skin thickness and subcutaneous tissue mobility in the back (relative tissue displacement during passive trunk motion) successfully captured the different phases of the sclGvHD model. Stretching reduced skin thickness and increased subcutaneous tissue mobility compared to no stretching at week 3. Stretching also reduced the expression of CCL2 and ADAM8 in the skin at week 4, which are two genes known to be upregulated in both murine sclGvHD and the inflammatory subset of human SSc. However, there was no evidence that stretching attenuated inflammation at week 2. Daily stretching for 10 min can improve skin thickness and mobility in the absence of any other treatment in the sclGvHD murine model. These pre-clinical results suggest that a systematic investigation of stretching as a therapeutic modality is warranted in patients with SSc.

  5. Construction of tissue engineered skin with human amniotic mesenchymal stem cells and human amniotic epithelial cells.

    PubMed

    Yu, S-C; Xu, Y-Y; Li, Y; Xu, B; Sun, Q; Li, F; Zhang, X-G

    2015-12-01

    To establish a new model for construction of tissue engineered skin with human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial cells (hAECs). hAMSCs and hAECs were isolated from amniotic membrane. The morphology and phenotype of hAMSCs and hAECs were confirmed by microscope and flow cytometry, respectively. Then, we performed RT-PCR and immunofluorescence staining to assess the expression of stem cells and keratinocyte markers. Moreover, cell co-culture was performed to observe the growth and phenotype characteristics of hAMSCs and hAECs in vitro. In addition, tissue engineered skin with hAMSCs and hAECs was constructed and assessed with histological methods. hAMSCs and hAECs were successfully isolated, exhibiting fibroblast-like morphous and cobblestone-shape epithelial morphous, respectively. The surface biomarker analysis showed that hAMSCs and hAECs were both positive for CD73, CD90 and CD105, and negative for CD34 and HLA-DR. The RT-PCR showed that hAMSCs expressed stem cell marker Nanog and c-MYC, and keratinocyte marker K19, β1 integrin and K8, whereas hAECs expressed stem cell marker KLF4 and c-MYC, and keratinocyte marker K19, β1 integrin, K5 and K8. The expression of keratinocyte proliferation antigen K14 was also found on hAECs. Furthermore, we found co-culture has no impact on the phenotype of hAMSCs and hAECs, but increased the proliferation activity of hAECs and decreased the proliferation activity of hAMSCs. Finally, the histological analysis showed that the tissue engineered skin exhibited similar structure as normal skin. Tissue engineered skin with hAMSCs and hAECs was successfully constructed and shown a similar feature as a skin equivalent. The tissue engineered skin might have good application prospects in regenerative medicine.

  6. SU-E-T-481: Dosimetric Effects of Tissue Heterogeneity in Proton Therapy: Monte Carlo Simulation and Experimental Study Using Animal Tissue Phantoms.

    PubMed

    Liu, Y; Zheng, Y

    2012-06-01

    Accurate determination of proton dosimetric effect for tissue heterogeneity is critical in proton therapy. Proton beams have finite range and consequently tissue heterogeneity plays a more critical role in proton therapy. The purpose of this study is to investigate the tissue heterogeneity effect in proton dosimetry based on anatomical-based Monte Carlo simulation using animal tissues. Animal tissues including a pig head and beef bulk were used in this study. Both pig head and beef were scanned using a GE CT scanner with 1.25 mm slice thickness. A treatment plan was created, using the CMS XiO treatment planning system (TPS) with a single proton spread-out-Bragg-peak beam (SOBP). Radiochromic films were placed at the distal falloff region. Image guidance was used to align the phantom before proton beams were delivered according to the treatment plan. The same two CT sets were converted to Monte Carlo simulation model. The Monte Carlo simulated dose calculations with/without tissue omposition were compared to TPS calculations and measurements. Based on the preliminary comparison, at the center of SOBP plane, the Monte Carlo simulation dose without tissue composition agreed generally well with TPS calculation. In the distal falloff region, the dose difference was large, and about 2 mm isodose line shift was observed with the consideration of tissue composition. The detailed comparison of dose distributions between Monte Carlo simulation, TPS calculations and measurements is underway. Accurate proton dose calculations are challenging in proton treatment planning for heterogeneous tissues. Tissue heterogeneity and tissue composition may lead to isodose line shifts up to a few millimeters in the distal falloff region. By simulating detailed particle transport and energy deposition, Monte Carlo simulations provide a verification method in proton dose calculation where inhomogeneous tissues are present. © 2012 American Association of Physicists in Medicine.

  7. Algorithms for differentiating between images of heterogeneous tissue across fluorescence microscopes

    PubMed Central

    Chitalia, Rhea; Mueller, Jenna; Fu, Henry L.; Whitley, Melodi Javid; Kirsch, David G.; Brown, J. Quincy; Willett, Rebecca; Ramanujam, Nimmi

    2016-01-01

    Fluorescence microscopy can be used to acquire real-time images of tissue morphology and with appropriate algorithms can rapidly quantify features associated with disease. The objective of this study was to assess the ability of various segmentation algorithms to isolate fluorescent positive features (FPFs) in heterogeneous images and identify an approach that can be used across multiple fluorescence microscopes with minimal tuning between systems. Specifically, we show a variety of image segmentation algorithms applied to images of stained tumor and muscle tissue acquired with 3 different fluorescence microscopes. Results indicate that a technique called maximally stable extremal regions followed by thresholding (MSER + Binary) yielded the greatest contrast in FPF density between tumor and muscle images across multiple microscopy systems. PMID:27699108

  8. Effects of tissue heterogeneity on the optical estimate of breast density

    PubMed Central

    Taroni, Paola; Pifferi, Antonio; Quarto, Giovanna; Spinelli, Lorenzo; Torricelli, Alessandro; Abbate, Francesca; Balestreri, Nicola; Ganino, Serena; Menna, Simona; Cassano, Enrico; Cubeddu, Rinaldo

    2012-01-01

    Breast density is a recognized strong and independent risk factor for developing breast cancer. At present, breast density is assessed based on the radiological appearance of breast tissue, thus relying on the use of ionizing radiation. We have previously obtained encouraging preliminary results with our portable instrument for time domain optical mammography performed at 7 wavelengths (635–1060 nm). In that case, information was averaged over four images (cranio-caudal and oblique views of both breasts) available for each subject. In the present work, we tested the effectiveness of just one or few point measurements, to investigate if tissue heterogeneity significantly affects the correlation between optically derived parameters and mammographic density. Data show that parameters estimated through a single optical measurement correlate strongly with mammographic density estimated by using BIRADS categories. A central position is optimal for the measurement, but its exact location is not critical. PMID:23082283

  9. Algorithms for differentiating between images of heterogeneous tissue across fluorescence microscopes.

    PubMed

    Chitalia, Rhea; Mueller, Jenna; Fu, Henry L; Whitley, Melodi Javid; Kirsch, David G; Brown, J Quincy; Willett, Rebecca; Ramanujam, Nimmi

    2016-09-01

    Fluorescence microscopy can be used to acquire real-time images of tissue morphology and with appropriate algorithms can rapidly quantify features associated with disease. The objective of this study was to assess the ability of various segmentation algorithms to isolate fluorescent positive features (FPFs) in heterogeneous images and identify an approach that can be used across multiple fluorescence microscopes with minimal tuning between systems. Specifically, we show a variety of image segmentation algorithms applied to images of stained tumor and muscle tissue acquired with 3 different fluorescence microscopes. Results indicate that a technique called maximally stable extremal regions followed by thresholding (MSER + Binary) yielded the greatest contrast in FPF density between tumor and muscle images across multiple microscopy systems.

  10. Impact of Soft Tissue Heterogeneity on Augmented Reality for Liver Surgery.

    PubMed

    Haouchine, Nazim; Cotin, Stephane; Peterlik, Igor; Dequidt, Jeremie; Lopez, Mario Sanz; Kerrien, Erwan; Berger, Marie-Odile

    2015-05-01

    This paper presents a method for real-time augmented reality of internal liver structures during minimally invasive hepatic surgery. Vessels and tumors computed from pre-operative CT scans can be overlaid onto the laparoscopic view for surgery guidance. Compared to current methods, our method is able to locate the in-depth positions of the tumors based on partial three-dimensional liver tissue motion using a real-time biomechanical model. This model permits to properly handle the motion of internal structures even in the case of anisotropic or heterogeneous tissues, as it is the case for the liver and many anatomical structures. Experimentations conducted on phantom liver permits to measure the accuracy of the augmentation while real-time augmentation on in vivo human liver during real surgery shows the benefits of such an approach for minimally invasive surgery.

  11. Identification of viscoelastic parameters of skin with a scar in vivo, influence of soft tissue technique on changes of skin parameters.

    PubMed

    Vránová, Hana; Zeman, Josef; Cech, Zdenek; Otáhal, Stanislav

    2009-10-01

    The goal of the experiment was to develop an identification method capable of objective detection of changes of viscoelastic properties of skin with a scar remaining after a modified radical mastectomy. We compared the intact skin and the skin with a scar, a scar before and after physiotherapy. We used two methods. The first one is based on measurements of the local dynamic deformation response of the skin and the second one is the matrix identification of static deformation that identifies properties of the whole tested region of the explored tissues. We identified the skin stretchability, shiftability against deeper layers and deeply analysed both the methods. In some patients, we found statistically proven difference. In all these cases the measurement methods have detected changes of the observed tissue condition. We found both methods to be potentially applicable after further improvements as a diagnostic tool, which can contribute to the improvement of postoperative care of patients.

  12. A heterogeneous human tissue mimicking phantom for RF heating and MRI thermal monitoring verification

    NASA Astrophysics Data System (ADS)

    Yuan, Yu; Wyatt, Cory; Maccarini, Paolo; Stauffer, Paul; Craciunescu, Oana; MacFall, James; Dewhirst, Mark; Das, Shiva K.

    2012-04-01

    This paper describes a heterogeneous phantom that mimics a human thigh with a deep-seated tumor, for the purpose of studying the performance of radiofrequency (RF) heating equipment and non-invasive temperature monitoring with magnetic resonance imaging (MRI). The heterogeneous cylindrical phantom was constructed with an outer fat layer surrounding an inner core of phantom material mimicking muscle, tumor and marrow-filled bone. The component materials were formulated to have dielectric and thermal properties similar to human tissues. The dielectric properties of the tissue mimicking phantom materials were measured with a microwave vector network analyzer and impedance probe over the frequency range of 80-500 MHz and at temperatures of 24, 37 and 45 °C. The specific heat values of the component materials were measured using a differential scanning calorimeter over the temperature range of 15-55 °C. The thermal conductivity value was obtained from fitting the curves obtained from one-dimensional heat transfer measurement. The phantom was used to verify the operation of a cylindrical four-antenna annular phased array extremity applicator (140 MHz) by examining the proton resonance frequency shift (PRFS) thermal imaging patterns for various magnitude/phase settings (including settings to focus heating in tumors). For muscle and tumor materials, MRI was also used to measure T1/T2* values (1.5 T) and to obtain the slope of the PRFS phase change versus temperature change curve. The dielectric and thermal properties of the phantom materials were in close agreement to well-accepted published results for human tissues. The phantom was able to successfully demonstrate satisfactory operation of the tested heating equipment. The MRI-measured thermal distributions matched the expected patterns for various magnitude/phase settings of the applicator, allowing the phantom to be used as a quality assurance tool. Importantly, the material formulations for the various tissue types

  13. A heterogeneous human tissue mimicking phantom for RF heating and MRI thermal monitoring verification.

    PubMed

    Yuan, Yu; Wyatt, Cory; Maccarini, Paolo; Stauffer, Paul; Craciunescu, Oana; Macfall, James; Dewhirst, Mark; Das, Shiva K

    2012-04-07

    This paper describes a heterogeneous phantom that mimics a human thigh with a deep-seated tumor, for the purpose of studying the performance of radiofrequency (RF) heating equipment and non-invasive temperature monitoring with magnetic resonance imaging (MRI). The heterogeneous cylindrical phantom was constructed with an outer fat layer surrounding an inner core of phantom material mimicking muscle, tumor and marrow-filled bone. The component materials were formulated to have dielectric and thermal properties similar to human tissues. The dielectric properties of the tissue mimicking phantom materials were measured with a microwave vector network analyzer and impedance probe over the frequency range of 80-500 MHz and at temperatures of 24, 37 and 45 °C. The specific heat values of the component materials were measured using a differential scanning calorimeter over the temperature range of 15-55 °C. The thermal conductivity value was obtained from fitting the curves obtained from one-dimensional heat transfer measurement. The phantom was used to verify the operation of a cylindrical four-antenna annular phased array extremity applicator (140 MHz) by examining the proton resonance frequency shift (PRFS) thermal imaging patterns for various magnitude/phase settings (including settings to focus heating in tumors). For muscle and tumor materials, MRI was also used to measure T1/T2* values (1.5 T) and to obtain the slope of the PRFS phase change versus temperature change curve. The dielectric and thermal properties of the phantom materials were in close agreement to well-accepted published results for human tissues. The phantom was able to successfully demonstrate satisfactory operation of the tested heating equipment. The MRI-measured thermal distributions matched the expected patterns for various magnitude/phase settings of the applicator, allowing the phantom to be used as a quality assurance tool. Importantly, the material formulations for the various tissue types

  14. Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A2A Receptor Involvement.

    PubMed

    Veronesi, Francesca; Dallari, Dante; Sabbioni, Giacomo; Carubbi, Chiara; Martini, Lucia; Fini, Milena

    2017-09-01

    Polydeoxyribonucleotides (PDRNs) are low molecular weight DNA molecules of natural origin that stimulate cell migration and growth, extracellular matrix (ECM) protein production, and reduce inflammation. Most preclinical and clinical studies on tissue regeneration with PDRNs focused on skin, and only few are about musculoskeletal tissues. Starting from an overview on skin regeneration studies, through the analysis of in vitro, in vivo, and clinical studies (1990-2016), the present review aimed at defining the effects of PDRN and their mechanisms of action in the regeneration of musculoskeletal tissues. This would also help future researches in this area. A total of 29 studies were found by PubMed and www.webofknowledge.com searches: 20 were on skin (six in vitro, six in vivo, one vitro/vivo, seven clinical studies), while the other nine regarded bone (one in vitro, two in vivo, one clinical studies), cartilage (one in vitro, one vitro/vivo, two clinical studies), or tendon (one clinical study) tissues regeneration. PDRNs improved cell growth, tissue repair, ECM proteins, physical activity, and reduced pain and inflammation, through the activation of adenosine A2A receptor. PDRNs are currently used for bone, cartilage, and tendon diseases, with a great variability regarding the PDRN dosage to be used in clinical practice, while the dosage for skin regeneration is well established. PDRNs are usually administered from a minimum of three to a maximum of five times and they act trough the activation of A2A receptor. Further studies are advisable to confirm the effectiveness of PDRNs and to standardize the PDRN dose. J. Cell. Physiol. 232: 2299-2307, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Histopathology of Incontinence-Associated Skin Lesions: Inner Tissue Damage Due to Invasion of Proteolytic Enzymes and Bacteria in Macerated Rat Skin

    PubMed Central

    Mugita, Yuko; Minematsu, Takeo; Huang, Lijuan; Nakagami, Gojiro; Kishi, Chihiro; Ichikawa, Yoshie; Nagase, Takashi; Oe, Makoto; Noguchi, Hiroshi; Mori, Taketoshi; Abe, Masatoshi; Sugama, Junko; Sanada, Hiromi

    2015-01-01

    A common complication in patients with incontinence is perineal skin lesions, which are recognized as a form of dermatitis. In these patients, perineal skin is exposed to digestive enzymes and intestinal bacterial flora, as well as excessive water. The relative contributions of digestive enzymes and intestinal bacterial flora to skin lesion formation have not been fully shown. This study was conducted to reveal the process of histopathological changes caused by proteases and bacterial inoculation in skin maceration. For skin maceration, agarose gel containing proteases was applied to the dorsal skin of male Sprague-Dawley rats for 4 h, followed by Pseudomonas aeruginosa inoculation for 30 min. Macroscopic changes, histological changes, bacterial distribution, inflammatory response, and keratinocyte proliferation and differentiation were examined. Proteases induced digestion in the prickle cell layer of the epidermis, and slight bleeding in the papillary dermis and around hair follicles in the macerated skin without macroscopic evidence of erosion. Bacterial inoculation of the skin macerated by proteolytic solution resulted in the formation of bacteria-rich clusters comprising numerous microorganisms and inflammatory cells within the papillary dermis, with remarkable tissue damage around the clusters. Tissue damage expanded by day 2. On day 3, the proliferative keratinocyte layer was elongated from the bulge region of the hair follicles. Application of proteases and P. aeruginosa induced skin lesion formation internally without macroscopic erosion of the overhydrated area, suggesting that the histopathology might be different from regular dermatitis. The healing process of this lesion is similar to transepidermal elimination. PMID:26407180

  16. Influence of skin surface roughness degree on energy characteristics of light scattered by a biological tissue

    NASA Astrophysics Data System (ADS)

    Barun, V. V.; Ivanov, A. P.

    2017-05-01

    We present the results of modelling of photometric characteristics of light in soft tissues illuminated by a parallel beam along the normal to the surface, obtained with allowance for the skin roughness parameters and the angular structure of radiation approaching the surface from within the tissue. The depth structure of the fluence rate and the spectra of the diffuse reflection of light by the tissue in the interval of wavelengths 300 - 1000 nm are considered. We discuss the influence of the tilt angle variance of rough surface microelements and light refraction on the studied characteristics. It is shown that these factors lead to the reduction of the radiation flux only in the near-surface tissue layer and practically do not affect the depth of light penetration into the tissue. On the other hand, the degree of the surface roughness and the conditions of its illumination from within the tissue essentially affect the coefficient of diffuse reflection of light and lead to its considerable growth compared to the cases of a smooth interface and completely diffuse illumination, often considered to simplify the theoretical problem solution. The role of the roughness of skin surface is assessed in application to the solution of different direct and inverse problems of biomedical optics.

  17. The neuroimmune connection interferes with tissue regeneration and chronic inflammatory disease in the skin.

    PubMed

    Peters, Eva M J; Liezmann, Christiane; Klapp, Burghard F; Kruse, Johannes

    2012-07-01

    Research over the past decades has revealed close interactions between the nervous and immune systems that regulate peripheral inflammation and link psychosocial stress with chronic somatic disease. Besides activation of the sympathetic and the hypothalamus-pituitary-adrenal axis, stress leads to increased neurotrophin and neuropeptide production in organs at the self-environment interface. The scope of this short review is to discuss key functions of these stress mediators in the skin, an exemplary stress-targeted and stress-sensitive organ. We will focus on the skin's response to acute and chronic stress in tissue regeneration and pathogenesis of allergic inflammation, psoriasis, and skin cancer to illustrate the impact of local stress-induced neuroimmune interaction on chronic inflammation.

  18. Nanoparticle-enhanced spectral photoacoustic tomography: effect of oxygen saturation and tissue heterogeneity

    NASA Astrophysics Data System (ADS)

    Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Pfefer, T. Joshua

    2016-03-01

    Molecular imaging for breast cancer detection, infectious disease diagnostics and preclinical animal research may be achievable through combined use of targeted exogenous agents - such as nanoparticles - and spectral Photoacoustic Tomography (PAT). However, tissue heterogeneity can alter fluence distributions and acoustic propagation, corrupting measured PAT absorption spectra and complicating in vivo nanoparticle detection and quantitation. Highly absorptive vascular structures represent a common confounding factor, and variations in vessel hemoglobin saturation (SO2) may alter spectral content of signals from adjacent/deeper regions. To evaluate the impact of this effect on PAT nanoparticle detectability, we constructed heterogeneous phantoms with well-characterized channel-inclusion geometries and biologically relevant optical and acoustic properties. Phantoms contained an array of tubes at several depths filled with hemoglobin solutions doped with varying concentrations of gold nanorods with an absorption peak at 780 nm. Both overlying and target network SO2 was tuned using sodium dithionite. Phantoms were imaged from 700 to 900 nm using a custom PAT system comprised of a tunable pulsed laser and a research-grade ultrasound system. Recovered nanoparticle spectra were analyzed and compared with results from both spectrophotometry and PAT data from waterimmersed tubes containing blood and nanoparticle solutions. Results suggested that nanoparticle selection for a given PAT application should take into account expected oxygenation states of both target blood vessel and background tissue oxygenation to achieve optimal performance.

  19. Objective color measurements: clinimetric performance of three devices on normal skin and scar tissue.

    PubMed

    van der Wal, Martijn; Bloemen, Monica; Verhaegen, Pauline; Tuinebreijer, Wim; de Vet, Henrica; van Zuijlen, Paul; Middelkoop, Esther

    2013-01-01

    Color measurements are an essential part of scar evaluation. Thus, vascularization (erythema) and pigmentation (melanin) are common outcome parameters in scar research. The aim of this study was to investigate the clinimetric properties and clinical feasibility of the Mexameter, Colorimeter, and the DSM II ColorMeter for objective measurements on skin and scars. Fifty scars with a mean age of 6 years (2 months to 53 years) were included. Reliability was tested using the single-measure interobserver intraclass correlation coefficient. Validity was determined by measuring the Pearson correlation with the Fitzpatrick skin type classification (for skin) and the Patient and Observer Scar Assessment Scale (for scar tissue). All three instruments provided reliable readings (intraclass correlation coefficient ≥ 0.83; confidence interval: 0.71-0.90) on normal skin and scar tissue. Parameters with the highest correlations with the Fitzpatrick classification were melanin (Mexameter), 0.72; ITA (Colorimeter), -0.74; and melanin (DSM II), 0.70. On scars, the highest correlations with the Patient and Observer Scar Assessment Scale vascularization scores were the following: erythema (Mexameter), 0.59; LAB2 (Colorimeter), 0.69; and erythema (DSM II), 0.66. For hyperpigmentation, the highest correlations were melanin (Mexameter), 0.75; ITA (Colorimeter), -0.80; and melanin (DSM II), 0.83. This study shows that all three instruments can provide reliable color data on skin and scars with a single measurement. The authors also demonstrated that they can assist in objective skin type classification. For scar assessment, the most valid parameters in each instrument were identified.

  20. Tissue interface pressure and skin integrity in critically ill, mechanically ventilated patients.

    PubMed

    Grap, Mary Jo; Munro, Cindy L; Wetzel, Paul A; Schubert, Christine M; Pepperl, Anathea; Burk, Ruth S; Lucas, Valentina

    2017-02-01

    To describe tissue interface pressure, time spent above critical pressure levels and the effect on skin integrity at seven anatomical locations. Descriptive, longitudinal study in critically ill mechanically ventilated adults, from Surgical Trauma ICU-STICU; Medical Respiratory ICU-MRICU; Neuroscience ICU-NSICU in a Mid-Atlantic urban university medical centre. Subjects were enroled in the study within 24hours of intubation. Tissue interface pressure was measured continuously using the XSENSOR pressure mapping system (XSENSOR Technology Corporation, Calgary, Canada). Skin integrity was observed at all sites, twice daily, using the National Pressure Ulcer Advisory Panel staging system, for the first seven ICU days and at day 10 and 14. Of the 132 subjects, 90.9% had no observed changes in skin integrity. Maximum interface pressure was above 32mmHg virtually 100% of the time for the sacrum, left and right trochanter. At the 45mmHg level, the left and right trochanter had the greatest amount of time above this level (greater than 95% of the time), followed by the sacrum, left and right scapula, and the left and right heels. Similarly, at levels above 60mmHg, the same site order applied. For those six subjects with sacral skin integrity changes, maximum pressures were greater than 32mmHg 100% of the time. Four of the six sacral changes were associated with greater amounts of time above both 45mmHg and 60mmHg than the entire sample. Maximum tissue interface pressure was above critical levels for the majority of the documented periods, especially in the sacrum, although few changes in skin integrity were documented. Time spent above critical levels for mean pressures were considerably less compared to maximum pressures. Maximum pressures may have reflected pressure spikes, but the large amount of time above the critical pressure levels remains substantial. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Electromechanical method coupling non-invasive skin impedance probing and in vivo subcutaneous liquid microinjection: controlling the diffusion pattern of nanoparticles within living soft tissues.

    PubMed

    Sung, Baeckkyoung; Kim, Se Hoon; Lee, Jin-Kyu; Lee, Byung-Cheon; Soh, Kwang-Sup

    2014-08-01

    Transdermal drug delivery is the way to transport drug carriers, such as nanoparticles, across the skin barrier to the dermal and/or subcutaneous layer. In order to control the transdermal drug delivery process, based on the heterogeneous and nonlinear structures of the skin tissues, we developed a novel electromechanical method combining in vivo local skin impedance probing, subcutaneous micro-injection of colloidal nanoparticles, and transcutaneous electrical stimulation. Experiments on the nude mice using in vivo fluorescence imaging exhibited significantly different apparent diffusion patterns of the nanoparticles depending on the skin impedance: Anisotropic and isotropic patterns were observed upon injection into low and high impedance points, respectively. This result implies that the physical complexity in living tissues may cause anisotropic diffusion of drug carriers, and can be used as a parameter for controlling drug delivery process. This method also can be combined with microneedle-based drug release systems, micro-fabricated needle-electrodes, and/or advanced in vivo targeting/imaging technologies using nanoparticles.

  2. Influence of skin tissue properties on the radial reference point for glucose measurement

    NASA Astrophysics Data System (ADS)

    Yang, Yue; Xu, Kexin; Ding, Lijun; Shi, Zhenzhi; Chen, Wenliang

    2009-02-01

    A reference position where the diffuse reflectance light intensity is insensitive to the variation of glucose concentration exists in the radial detection space for glucose measurement in the scattering medium such as skin. The signal measured in this position could be used as an inside reference to evaluate the influence on spectrum caused by other interferential factors. The relationship between the position of radial reference point and the skin tissue property is studied in this paper. Three-layer skin models with different optical parameters are designed to get sample sets at 1200~1700nm. In these sets, μa, μs and g of dermis varies respectively, so does the depth of epidermis or dermis. The distribution rule of dispersion of diffuse reflectance light intensity in the radial space is confirmed with the glucose concentration changes. And the distribution property of the radial reference position in every sample set is obtained through Monte Carlo simulation. The result shows that the distance of radial reference position from light source is insensitive to the variation of absorption coefficient or the depth of dermis, but an increased scattering coefficient will shorten the distance; an increased anisotropy coefficient or depth of epidermis will lengthen it. On the basis of that, the optical probes with different structures are designed according to the skin tissue properties. So they could be used for the measurement of corresponding patients, which enhances the practicability of floating reference method greatly.

  3. Staphylococcus aureus–associated Skin and Soft Tissue Infections in Ambulatory Care

    PubMed Central

    McDonald, L. Clifford; Mandal, Sanjay; Jernigan, Daniel B.

    2006-01-01

    To describe the number and treatment of skin and soft tissue infections likely caused by Staphylococcus aureus in the United States, we analyzed data from the 1992–1994 and 2001–2003 National Ambulatory Medical Care Surveys and National Hospital Ambulatory Medical Care Surveys. Each year, data were reported by an average of 1,400 physicians, 230 outpatient departments, and 390 emergency departments for 30,000, 33,000, and 34,000 visits, respectively. During 2001–2003, the number of annual ambulatory care visits for skin and soft tissue infections was 11.6 million; the visit rate was 410.7 per 10,000 persons. During the study period, rates of overall and physician office visits did not differ; however, rates of visits to outpatient and emergency departments increased by 59% and 31%, respectively. This increase may reflect the emergence of community-acquired methicillin-resistant S. aureus infections. PMID:17283622

  4. Infrared mapping resolves soft tissue preservation in 50 million year-old reptile skin.

    PubMed

    Edwards, N P; Barden, H E; van Dongen, B E; Manning, P L; Larson, P L; Bergmann, U; Sellers, W I; Wogelius, R A

    2011-11-07

    Non-destructive Fourier Transform InfraRed (FTIR) mapping of Eocene aged fossil reptile skin shows that biological control on the distribution of endogenous organic components within fossilized soft tissue can be resolved. Mapped organic functional units within this approximately 50 Myr old specimen from the Green River Formation (USA) include amide and sulphur compounds. These compounds are most probably derived from the original beta keratin present in the skin because fossil leaf- and other non-skin-derived organic matter from the same geological formation do not show intense amide or thiol absorption bands. Maps and spectra from the fossil are directly comparable to extant reptile skin. Furthermore, infrared results are corroborated by several additional quantitative methods including Synchrotron Rapid Scanning X-Ray Fluorescence (SRS-XRF) and Pyrolysis-Gas Chromatography/Mass Spectrometry (Py-GC/MS). All results combine to clearly show that the organic compound inventory of the fossil skin is different from the embedding sedimentary matrix and fossil plant material. A new taphonomic model involving ternary complexation between keratin-derived organic molecules, divalent trace metals and silicate surfaces is presented to explain the survival of the observed compounds. X-ray diffraction shows that suitable minerals for complex formation are present. Previously, this study would only have been possible with major destructive sampling. Non-destructive FTIR imaging methods are thus shown to be a valuable tool for understanding the taphonomy of high-fidelity preservation, and furthermore, may provide insight into the biochemistry of extinct organisms.

  5. Concise review: tissue-engineered skin and nerve regeneration in burn treatment.

    PubMed

    Blais, Mathieu; Parenteau-Bareil, Rémi; Cadau, Sébastien; Berthod, François

    2013-07-01

    Burns not only destroy the barrier function of the skin but also alter the perceptions of pain, temperature, and touch. Different strategies have been developed over the years to cover deep and extensive burns with the ultimate goal of regenerating the barrier function of the epidermis while recovering an acceptable aesthetic aspect. However, patients often complain about a loss of skin sensation and even cutaneous chronic pain. Cutaneous nerve regeneration can occur from the nerve endings of the wound bed, but it is often compromised by scar formation or anarchic wound healing. Restoration of pain, temperature, and touch perceptions should now be a major challenge to solve in order to improve patients' quality of life. In addition, the cutaneous nerve network has been recently highlighted to play an important role in epidermal homeostasis and may be essential at least in the early phase of wound healing through the induction of neurogenic inflammation. Although the nerve regeneration process was studied largely in the context of nerve transections, very few studies have been aimed at developing strategies to improve it in the context of cutaneous wound healing. In this concise review, we provide a description of the characteristics of and current treatments for extensive burns, including tissue-engineered skin approaches to improve cutaneous nerve regeneration, and describe prospective uses for autologous skin-derived adult stem cells to enhance recovery of the skin's sense of touch.

  6. Levamisole-induced necrosis of skin, soft tissue, and bone: case report and review of literature.

    PubMed

    Ching, Jessica A; Smith, David J

    2012-01-01

    This represents the largest case of skin necrosis related to levamisole, a common cocaine contaminant, requiring closure with skin grafts, and is the only case resulting in nasal amputation, central upper lip excision, extremity bone necrosis, and above knee amputation. The case report is followed by a review of the literature. Unique considerations for the full-thickness necrosis induced by levamisole vasculitis are highlighted, including antibody level monitoring, need for multiple excisions, timing of skin grafting, and potential for soft tissue and bone necrosis as well. A 54-year-old man presented to an outside facility with fever, generalized weakness, and agranulocytosis, with a history of cocaine use 3 weeks before. After admission, he developed generalized violaceous lesions and an elevated p-antineutrophilic cytoplasmic antibody and was diagnosed with disseminated vasculitis and agranulocytosis secondary to levamisole-contaminated cocaine exposure. On transfer to the authors' facility, 52% TBSA was involved with violaceous, nonblanching lesions, which progressed to full-thickness necrosis. Local wound care continued until necrotic areas fully demarcated and progressive necrosis stabilized, and skin grafting for closure was not performed until antibody levels normalized. Current treatment of levamisole-induced skin rash or necrosis focuses on discontinuation of levamisole. As demonstrated by this case, extensive necrosis secondary to levamisole-induced vasculitis can be successfully treated with multiple excisions until necrosis stabilizes, and then, split-thickness autografts may be applied. In areas with poor vascular supply or areas with poor functional prognosis, amputation may ultimately be required.

  7. Integra artificial skin in the management of severe tissue defects, including bone exposure, in injured children.

    PubMed

    Violas, Philippe; Abid, Abdelazis; Darodes, Philippe; Galinier, Philippe; de Gauzy, Jérome Sales; Cahuzac, Jean-Philippe

    2005-09-01

    A dermal substitute, Integra (Integra Neurosciences Implants SA, Sophia Antipolis, France) artificial skin, was used for wound management on three children with lower limb injuries in our institutions. In one case this biosynthetic material was applied directly to a bony surface (patella). This technique allows an early wound coverage and provides a satisfactory preparation for autograft. It can be a useful adjunct in the treatment of severe tissue defects in child limb injuries.

  8. Bipolar cellular morphology of malignant melanoma in unstained human melanoma skin tissue

    NASA Astrophysics Data System (ADS)

    Zhang, Kai; Zhang, Wenkai; Yang, Chia-Yi; Yang, Haw

    2009-03-01

    Microstructures of unstained human melanoma skin tissues have been examined by multimodal nonlinear optical microscopy. The polarized shape of the individual melanoma cell can be readily recognized-a phenotype that has been identified in laboratory cultures as characteristic of proliferating melanocytes but has not been demonstrated in clinical instances. The results thus provide snapshots of invading melanoma cells in their native environment and suggest a practical means of connecting in vitro laboratory studies to in vivo processes.

  9. Posttraumatic Skin and Soft-Tissue Infection due to Pseudomonas fulva.

    PubMed

    Cobo, Fernando; Jiménez, Gemma; Rodríguez-Granger, Javier; Sampedro, Antonio

    2016-01-01

    We report a case of posttraumatic skin and soft-tissue infection in a patient with a left thigh wound after a traffic accident. Pseudomonas fulva was isolated from a wound aspirate and was identified to the species level by Maldi-tof. The patient responded to drainage, debridement of wound, and two weeks of intravenous antibiotic therapy. Follow-up after 3 weeks was satisfactory with healthy cover of the injured area.

  10. Posttraumatic Skin and Soft-Tissue Infection due to Pseudomonas fulva

    PubMed Central

    Jiménez, Gemma; Rodríguez-Granger, Javier; Sampedro, Antonio

    2016-01-01

    We report a case of posttraumatic skin and soft-tissue infection in a patient with a left thigh wound after a traffic accident. Pseudomonas fulva was isolated from a wound aspirate and was identified to the species level by Maldi-tof. The patient responded to drainage, debridement of wound, and two weeks of intravenous antibiotic therapy. Follow-up after 3 weeks was satisfactory with healthy cover of the injured area. PMID:27752373

  11. Evaluation of brachytherapy lung implant dose distributions from photon-emitting sources due to tissue heterogeneities.

    PubMed

    Yang, Yun; Rivard, Mark J

    2011-11-01

    Photon-emitting brachytherapy sources are used for permanent implantation to treat lung cancer. However, the current brachytherapy dose calculation formalism assumes a homogeneous water medium without considering the influence of radiation scatter or tissue heterogeneities. The purpose of this study was to determine the dosimetric effects of tissue heterogeneities for permanent lung brachytherapy. The MCNP5 v1.40 radiation transport code was used for Monte Carlo (MC) simulations. Point sources with energies of 0.02, 0.03, 0.05, 0.1, 0.2, and 0.4 MeV were simulated to cover the range of pertinent brachytherapy energies and to glean dosimetric trends independent of specific radionuclide emissions. Source positions from postimplant CT scans of five patient implants were used for source coordinates, with dose normalized to 200 Gy at the center of each implant. With the presence of fibrosis (around the implant), cortical bone, lung, and healthy tissues, dose distributions and (PTV)DVH were calculated using the MCNP ∗FMESH4 tally and the NIST mass-energy absorption coefficients. This process was repeated upon replacing all tissues with water. For all photon energies, 10(9) histories were simulated to achieve statistical errors (k = 1) typically of 1%. The mean PTV doses calculated using tissue heterogeneities for all five patients changed (compared to dose to water) by only a few percent over the examined photon energy range, as did PTV dose at the implant center. The (PTV)V(100) values were 81.2%, 90.0% (as normalized), 94.3%, 93.9%, 92.7%, and 92.2% for 0.02, 0.03, 0.05, 0.1, 0.2, and 0.4 MeV source photons, respectively. Relative to water, the maximum bone doses were higher by factors of 3.7, 5.1, 5.2, 2.4, 1.2, and 1.0 The maximum lung doses were about 0.98, 0.94, 0.91, 0.94, 0.97, and 0.99. Relative to water, the maximum healthy tissue doses at the mediastinal position were higher by factors of 9.8, 2.2, 1.3, 1.1, 1.1, and 1.1. However, the maximum doses to

  12. Evaluation of brachytherapy lung implant dose distributions from photon-emitting sources due to tissue heterogeneities

    SciTech Connect

    Yang Yun; Rivard, Mark J.

    2011-11-15

    Purpose: Photon-emitting brachytherapy sources are used for permanent implantation to treat lung cancer. However, the current brachytherapy dose calculation formalism assumes a homogeneous water medium without considering the influence of radiation scatter or tissue heterogeneities. The purpose of this study was to determine the dosimetric effects of tissue heterogeneities for permanent lung brachytherapy. Methods: The MCNP5 v1.40 radiation transport code was used for Monte Carlo (MC) simulations. Point sources with energies of 0.02, 0.03, 0.05, 0.1, 0.2, and 0.4 MeV were simulated to cover the range of pertinent brachytherapy energies and to glean dosimetric trends independent of specific radionuclide emissions. Source positions from postimplant CT scans of five patient implants were used for source coordinates, with dose normalized to 200 Gy at the center of each implant. With the presence of fibrosis (around the implant), cortical bone, lung, and healthy tissues, dose distributions and {sub PTV}DVH were calculated using the MCNP *FMESH4 tally and the NIST mass-energy absorption coefficients. This process was repeated upon replacing all tissues with water. For all photon energies, 10{sup 9} histories were simulated to achieve statistical errors (k = 1) typically of 1%. Results: The mean PTV doses calculated using tissue heterogeneities for all five patients changed (compared to dose to water) by only a few percent over the examined photon energy range, as did PTV dose at the implant center. The {sub PTV}V{sub 100} values were 81.2%, 90.0% (as normalized), 94.3%, 93.9%, 92.7%, and 92.2% for 0.02, 0.03, 0.05, 0.1, 0.2, and 0.4 MeV source photons, respectively. Relative to water, the maximum bone doses were higher by factors of 3.7, 5.1, 5.2, 2.4, 1.2, and 1.0 The maximum lung doses were about 0.98, 0.94, 0.91, 0.94, 0.97, and 0.99. Relative to water, the maximum healthy tissue doses at the mediastinal position were higher by factors of 9.8, 2.2, 1.3, 1.1, 1.1, and

  13. Effect of tissue heterogeneity on an in vivo range verification technique for proton therapy

    NASA Astrophysics Data System (ADS)

    Hassane Bentefour, El; Shikui, Tang; Prieels, Damien; Lu, Hsiao-Ming

    2012-09-01

    It was proposed recently that time-resolved dose measurements during proton therapy treatment by passively scattered beams may be used for in vivo range verification. The method was shown to work accurately in a water tank. In this paper, we further evaluated the potential of the method for more clinically relevant situations where proton beams must pass through regions with significant tissue heterogeneities. Specifically, we considered prostate treatment where the use of anterior or anterior- oblique fields was recently proposed in order to reduce rectal dose by taking advantage of the sharp distal fall-off of the Bragg peak. These beam portals pass through various parts of pubic bone and potential air cavities in the bladder and bowels. Using blocks of materials with densities equivalent to bone, air, etc, arranged in the water tank in relevant configurations, we tested the robustness of the method against range shifting and range mixing. In the former, the beam range is changed uniformly by changes in tissue density in the beam path, while in the latter, variations in tissue heterogeneities across the beam cross section causes the mixing of beam energies downstream, as often occurs when the beam travels along the interface of materials with significantly different densities. We demonstrated that in the region of interest, the method can measure water-equivalent path length with accuracy better than ±0.5 mm for pure range shifting and still reasonable accuracy for range mixing between close beam energies. In situations with range mixing between significantly different beam energies, the dose rate profiles may be simulated for verifying the beam range. We also found that the above performances can be obtained with very small amount of dose (<0.5 cGy), if silicon diodes are used as detectors. This makes the method suitable for in vivo range verification prior to each treatment delivery.

  14. Mixed connective tissue disease characterized by speckled epidermal nuclear IgG deposition in normal skin.

    PubMed

    Bentley-Phillips, C B; Geake, T M

    1980-05-01

    Four African female patients are described, who presented with the features of systemic sclerosis. Overlapping features of lupus erythematosus or dermatomyositis were present in three cases but were not prominent. Direct immunofluorescence of uninvolved skin revealed a particulate (or speckled) epidermal nuclear staining, with specificity for IgG. In view of the reported association between this finding and mixed connective tissue disease, these patients were treated with corticosteroids and marked improvment occurred in all cases. The usefulness of this investigation in making the distinction between systemic sclerosis and mixed connective tissue disease and in indicating a potentially effective form of therapy is discussed.

  15. Equine neutrophil elastase in plasma, laminar tissue, and skin of horses administered black walnut heartwood extract.

    PubMed

    de la Rebière de Pouyade, Geoffroy; Riggs, Laura M; Moore, James N; Franck, Thierry; Deby-Dupont, Ginette; Hurley, David J; Serteyn, Didier

    2010-06-15

    Laminitis is a local manifestation of a systemic inflammatory response that is characterized by neutrophil activation and movement of neutrophils into the laminar tissues. Given the evidence for the involvement of neutrophils in the development of laminitis, we measured concentrations of neutrophil elastase, a serine protease released from the azurophilic granules of neutrophils, in plasma, skin and laminar tissues obtained from control horses and horses given black walnut heartwood extract (BWHE) to induce laminitis. Healthy horses (5-15 years old) were randomly assigned to 4 groups: 3 experimental groups given BWHE via nasogastric tube, and a control group given an equal volume of water. The experimental groups consisted of horses euthanized 1.5h (n=5), 3h (n=6) or 12h (n=10) after BWHE administration. Control horses (n=7) were euthanized 12h after intragastric administration of water. Plasma samples were collected in all horses of the control and 12h BWHE groups at 0, 1, 2, 3, 4, 6, 8, 10, and 12h after treatment, and laminar tissue and skin from the middle region of the neck were harvested at the time of euthanasia in all 1.5 and 3h BWHE horses, in 6 of the 12h BWHE horses and in 5 of the control horses. Plasma and tissue concentrations of neutrophil elastase were determined using an equine specific ELISA, and statistical significance was set at p<0.05. Plasma concentrations of neutrophil elastase in the BWHE group were significantly higher at 6 and 8h compared to the control group and at 8 and 10h compared to time 0. Concentrations of neutrophil elastase in skin and laminar tissue were significantly higher in the 3 and 12h BWHE groups compared to the control group. Concentrations of neutrophil elastase were significantly higher in the skin than in the lamina in the 12h BWHE horses. The administration of BWHE thus results in significant increases in the concentration of neutrophil elastase in the circulation, skin and laminar tissue. These results confirm a

  16. Noninvasive fluorescence and Raman spectroscopic analysis of laser welded aorta and skin tissue

    NASA Astrophysics Data System (ADS)

    Katz, Alvin; Gayen, Tapan K.; Minko, Glenn; Alimova, Alexandra; Savage, Howard E.; McCormick, Steven A.; Alfano, Robert R.

    2002-05-01

    Laser tissue welding involves the denaturing and partial renaturing of collagen and elastin. Tissues welded with NIR lasers tuned to the 1455 nm water absorption band have demonstrated high tensile strength with minimal collateral damage. To better understand the welding process, welded tissue samples were investigated using fluorescence imaging and Raman spectroscopy. As part of this study, human aorta, and porcine aorta and skin, specimens were investigated. Emission and excitation/emission wavelengths corresponding to tryptophan and collagen emission and slightly weaker emission for wavelengths corresponding to elastin emission. The inner surface an cross-section images of the aortic specimens exhibited a very high degree of uniformity with no indication of the presence of a weld. The Raman spectra from the aortic specimens at the weld site and a few mm away form the weld were very similar. This work indicates the emission and Raman properties of the collagen helix after welding are very similar to native collagen tissue.

  17. Quantitative Estimations of Thermal Damage in Skin Tissue Using Monte Carlo Simulation of Polarized Light

    NASA Astrophysics Data System (ADS)

    Lee, G. W.; Kim, T. H.; Youn, J. I.

    2016-03-01

    Thermal treatment has been used for collagen tightening and tissue contour enhancement. It is important to monitor the condition of collagenous tissue during and immediately after thermal treatment. Collagen denaturation changes the optical properties such as scattering coefficient and anisotropy. In this study, Monte Carlo simulation of polarized light was used to calculate the degree of linear polarization (DOLP) of backscattered light from thermally damaged porcine skin, and the Mueller matrix was calculated to verify the result of DOLP. We observed a decrease in the DOLP and a significant change in the radial distribution of the Mueller matrix elements at temperatures ranging from 55 to 65°C. This could be attributed to the increase in scattering coefficient and decrease in anisotropy caused by thermal denaturation in the tissue. The DOLP method has a potential implementation as a real-time closed-loop feedback system for use in various thermal treatment methods through measuring changes in optical properties of target tissues.

  18. Near-infrared laser welding of aortic and skin tissues and microscopic investigation of welding efficacy

    NASA Astrophysics Data System (ADS)

    Gayen, Tapan K.; Katz, Alvin; Savage, Howard E.; Lee, John; Paul, M.; Halder, Rabindra K.; McCormick, Steven A.; Alfano, Robert R.

    2003-06-01

    Ex vivo specimens of human and porcine aorta and skin were welded using either Cr4+:YAG or Erbium fiber lasers tuned to the water absorption band at 1440-1460 nm. Welding was performed without the use of protein solders or glues. Welding efficacy was monitored by measuring the tensile strength of the welded tissue and the extent of collateral tissue damage. Full thickness tissue bonding with no collateral damage was observed with porcine aorta samples. The optimum tensile strength for porcine and human aorta was 1.33 +/- 0.15 kg/cm2 and 1.13 +/- 0.27 kg/cm2 respectively for welding at 1460 nm, while that for porcine and human skin was 0.94 +/- 0.15 kg/cm2 and 1.05 +/- 0.19 kg/cm2 respectively achieved with welding at 1455 nm. The weld strength as a function of laser wavelength demonstrated a correlation with the absorption spectrum of native water suggests that absorption of light by water in the tissue plays a significant role in laser tissue welding.

  19. Improvement of nerve regeneration in tissue-engineered skin enriched with schwann cells.

    PubMed

    Blais, Mathieu; Grenier, Myriam; Berthod, François

    2009-12-01

    The incorporation of Schwann cells in reconstructed skin (RS) could have a major role in achieving functional recovery of cutaneous sensory perception. We showed with a unique in vitro model of a tissue-engineered innervated reconstructed dermis that Schwann cells promoted a twofold increase in the number of sensory neurites migrating in the three-dimensional tissue as compared with the control. In addition, Schwann cells spontaneously colocalized along neurites and achieved the formation of myelin sheaths in vitro as assessed by transmission electron microscopy. We prepared RS samples enriched or not with Schwann cells and transplanted them on nude mice for 60-90 days. We demonstrated that Schwann cells induced a 1.8- and 1.7-fold increase in the number of nerve fibers migrating in the graft 60 and 90 days after transplantation, respectively. In addition, the RS sample enriched with Schwann cells had a current perception threshold similar to that of normal skin for the large and myelinated Abeta-sensory fibers, in contrast with the control. Thus, we showed that the addition of Schwann cells to tissue-engineered skin not only enhanced nerve migration but also promoted myelin sheath formation in vitro and nerve function recovery in vivo.

  20. Present status and applications of bacterial cellulose-based materials for skin tissue repair.

    PubMed

    Fu, Lina; Zhang, Jin; Yang, Guang

    2013-02-15

    Bacterial cellulose (BC, also known as microbial cellulose, MC) is a promising natural polymer which is biosynthesized by certain bacteria. This review focused on BC-based materials which can be utilized for skin tissue repair. Firstly, it is illustrated that BC has unique structural and mechanical properties as compared with higher plant cellulose, and is thus expected to become a commodity material. Secondly, we summarized the basic properties and different types of BC, including self-assembled, oriented BC, and multiform BC. Thirdly, composites prepared by using BC in conjunction with other polymers are explored, and the research on BC for application in skin tissue engineering is addressed. Finally, experimental results and clinical treatments assessing the performance of wound healing materials based on BC were examined. With its superior mechanical properties, as well as its excellent biocompatibility, BC was shown to have great potential for biomedical application and very high clinical value for skin tissue repair. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. [Treatment of skin and soft tissue defect in the hallex with flaps ].

    PubMed

    Junming, Li; Yanhua, Li; Lei, Wan; Hejun, Huang; Gaofeng, Peng; Daoxuan, Li; Xiaoguang, Zhang; Pengwei, Dai; Peng, Li

    2014-09-01

    To summarize the therapeutic effect of 5 kinds of flaps for the treatment of skin and soft tissue defect in the hallex. From Jan. 2008 to Jun. 2013, 24 cases with skin and soft tissue defects in the hallex were treated with 5 kinds of reversed flaps, including medial foot dorsal neurocutaneous flaps, medial foot neurocutaneous flaps, lateral tarsal flaps, anterior malleous flaps, medial cross leg and saphenous nerve flaps. The defects size ranged from 3 cm x 2 cm to 5 cm x 3 cm, with the flap size from 3. 5 cm x 2. 5 cm to 5. 5 cm x 4. 0 cm. Partial superficial necroisis happened at the distal end of one foot dorsal medial neurocutaneous flap. One third flap necrosis occurred in 1 foot medial neurocutaneous flap due to too tight suture at flap pedicle and resulted thrombosis. All the other 23 flaps survived completely. 15 cases were followed up for 3-36 months with normal walking function and satisfactory appearance. Among the 8 cases with nerve anastomosis, 4 cases were followed up with 2-point discrimination distance of 8-11 mm. the flaps without nerve anastomosis also had protective sense due to nerve ingrowth. Skin and soft tissue defects in the hallex can be treated with different appropriate flaps. The hallex length can be reserved with satisfactory function and appearance.

  2. Absorption and tissue distribution of dietary quercetin and quercetin glycosides of apple skin in broiler chickens.

    PubMed

    Rupasinghe, H P Vasantha; Ronalds, Clinton M; Rathgeber, Bruce; Robinson, Robin A

    2010-05-01

    Apple skins are a rich source of flavonols, in particular quercetin (Q) glycosides. The objective of the present study was to investigate the presence of Q metabolites in plasma, various tissues, and excreta when the commercial broiler chicken's diet was supplemented with Q (0, 50, 150, 300, or 600 mg kg(-1) body weight per day), an apple skin extract (ASE; 50, 150 mg total phenolics kg(-1) body weight per day), or a dried apple skin powder (ASP; 50 mg total phenolics kg(-1) body weight per day). When Q was supplemented for 3 days, Q sulfate, Q glucuronide, Q glucoside glucuronide, Q glucoside sulfate, and isorhamnetin glucoside were detected by liquid chromatography-tandem mass spectrometry in the liver and duodenum. Deconjugated Q was also detected in the breast and thigh tissues of ASE- and ASP-supplemented broilers. Regardless of the source or concentration of Q, the antioxidant capacity measured by ferric reducing ability of plasma (FRAP) assay in the plasma and tissues of the broilers did not change significantly. As far as is known, this is the first report to demonstrate that Q and its glycosides can be absorbed and metabolized by broiler chickens.

  3. Interactions of the Immune System with Skin and Bone Tissue in Psoriatic Arthritis: A Comprehensive Review.

    PubMed

    Sukhov, Andrea; Adamopoulos, Iannis E; Maverakis, Emanual

    2016-08-01

    Cutaneous psoriasis (e.g., psoriasis vulgaris (PsV)) and psoriatic arthritis (PsA) are complex heterogeneous diseases thought to have similar pathophysiology. The soluble and cellular mediators of these closely related diseases are being elucidated through genetic approaches such as genome-wide association studies (GWAS), as well as animal and molecular models. Novel therapeutics targeting these mediators (IL-12, IL-23, IL-17, IL-17 receptor, TNF) are effective in treating both the skin and joint manifestations of psoriasis, reaffirming the shared pathophysiology of PsV and PsA. However, the molecular and cellular interactions between skin and joint disease have not been well characterized. Clearly, PsV and PsA are highly variable in terms of their clinical manifestations, and this heterogeneity can partially be explained by differences in HLA-associations (HLA-Cw*0602 versus HLA-B*27, for example). In addition, there are numerous other genetic susceptibility loci (LCE3, CARD14, NOS2, NFKBIA, PSMA6, ERAP1, TRAF3IP2, IL12RB2, IL23R, IL12B, TNIP1, TNFAIP3, TYK2) and geoepidemiologic factors that contribute to the wide variability seen in psoriasis. Herein, we review the complex interplay between the genetic, cellular, ethnic, and geographic mediators of psoriasis, focusing on the shared mechanisms of PsV and PsA.

  4. Non-destructive detection of defects in artificial skin tissue by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Schmitt, R.; Marx, U.; Heymer, A.; Kaufmann, M.

    2009-07-01

    The application of optical coherence tomography OCT in tissue engineering facilities offers great potential for the automated detection of defects or inhomogeneities in tissue products. This non-invasive and non-destructive measurement technique enables the high speed generation of two dimensional cross sections of tissue with micron resolution. The integration of an OCT device into a tissue production facility allows the monitoring and quality control of tissue engineering products. By the selective exclusion of tissue products with insufficient quality features a high degree in production standard is guaranteed. In a first study, OCT tomograms of artificial skin equivalents were acquired and compared with microscopic images of associated histologies. As a result, a well-defined analogy of the obtained images is presented. The most common defect in terms of hole structures that occurs due to a procedural steps could be detected. Further characteristics like the topography, homogeneity and layer structure was analysed. Hence, OCT provides a powerful measurement technique to monitor the quality of tissue products in automated tissue engineering facilities.

  5. Fat tissue histological study at indocyanine green-mediated photothermal/photodynamic treatment of the skin in vivo

    NASA Astrophysics Data System (ADS)

    Yanina, Irina Yu.; Tuchin, Valery V.; Navolokin, Nikita A.; Matveeva, Olga V.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Altshuler, Gregory B.

    2012-05-01

    Histological slices of skin samples with the subcutaneous adipose tissue after photothermal/photodynamic treatment are analyzed. In the case of subcutaneous indocyanine green injection and 808-nm diode laser exposure of the rat skin site in vivo, the greatest changes in tissue condition were observed. Processes were characterized by dystrophy, necrosis, and desquamation of the epithelial cells, swelling and necrosis of the connective tissue, and widespread necrosis of the subcutaneous adipose tissue. The obtained data are useful for safe layer-by-layer dosimetry of laser illumination of ICG-stained adipose tissue for treatment of obesity and cellulite.

  6. Ultraviolet emission and excitation fluorescence spectroscopic characterization of DMBA-treated Swiss Albino mice skin carcinogenesis for measuring tissue transformation

    NASA Astrophysics Data System (ADS)

    Aruna, Prakasa R.; Hemamalini, Srinivasan; Ebenezar, Jeyasingh; Ganesan, Singaravelu

    2002-05-01

    The ultraviolet fluorescence emission spectra of skin tissues under different pathological conditions were measured at 280nm excitation. At this excitation wavelength, the normal skin showed a primary peak emission at 352nm and this primary peak emission from neoplastic skin shows a blue shift with respect to normal tissue. This blue shift increases as the stage of abnormality increases and it is maximum (19nm) for well-differentiated squamous cell carcinoma. This alteration is further confirmed from fluorescence excitation spectra of the tissues for 340nm emission. The study concludes that the change in the emission of tryptophan around 340nm may be due to partial unfolding of protein.

  7. Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue.

    PubMed

    Alazami, Anas M; Al-Qattan, Sarah M; Faqeih, Eissa; Alhashem, Amal; Alshammari, Muneera; Alzahrani, Fatema; Al-Dosari, Mohammed S; Patel, Nisha; Alsagheir, Afaf; Binabbas, Bassam; Alzaidan, Hamad; Alsiddiky, Abdulmonem; Alharbi, Nasser; Alfadhel, Majid; Kentab, Amal; Daza, Riza M; Kircher, Martin; Shendure, Jay; Hashem, Mais; Alshahrani, Saif; Rahbeeni, Zuhair; Khalifa, Ola; Shaheen, Ranad; Alkuraya, Fowzan S

    2016-05-01

    Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome.

  8. Biocomposite nanofibrous strategies for the controlled release of biomolecules for skin tissue regeneration.

    PubMed

    Gandhimathi, Chinnasamy; Venugopal, Jayarama Reddy; Bhaarathy, Velmurugan; Ramakrishna, Seeram; Kumar, Srinivasan Dinesh

    2014-01-01

    Nanotechnology and tissue engineering have enabled engineering of nanostructured strategies to meet the current challenges in skin tissue regeneration. Electrospinning technology creates porous nanofibrous scaffolds to mimic extracellular matrix of the native tissues. The present study was performed to gain some insights into the applications of poly(l-lactic acid)-co-poly-(ε-caprolactone) (PLACL)/silk fibroin (SF)/vitamin E (VE)/curcumin (Cur) nanofibrous scaffolds and to assess their potential for being used as substrates for the culture of human dermal fibroblasts for skin tissue engineering. PLACL/SF/VE/Cur nanofibrous scaffolds were fabricated by electrospinning and characterized by fiber morphology, membrane porosity, wettability, mechanical strength, and chemical properties by Fourier transform infrared (FTIR) analysis. Human dermal fibroblasts were cultured on these scaffolds, and the cell scaffold interactions were analyzed by cell proliferation, cell morphology, secretion of collagen, expression of F-actin, and 5-chloromethylfluorescein diacetate (CMFDA) dye. The electrospun nanofiber diameter was obtained between 198±4 nm and 332±13 nm for PLACL, PLACL/SF, PLACL/SF/VE, and PLACL/SF/VE/Cur nanofibrous scaffolds. FTIR analysis showed the presence of the amide groups I, II, and III, and a porosity of up to 92% obtained on these nanofibrous scaffolds. The results showed that the fibroblast proliferation, cell morphology, F-actin, CMFDA dye expression, and secretion of collagen were significantly increased in PLACL/SF/VE/Cur when compared to PLACL nanofibrous scaffolds. The accessibility of human dermal fibroblasts cultured on PLACL/SF/VE/Cur nanofibrous scaffolds proved to be a potential scaffold for skin tissue regeneration.

  9. Biocomposite nanofibrous strategies for the controlled release of biomolecules for skin tissue regeneration

    PubMed Central

    Gandhimathi, Chinnasamy; Venugopal, Jayarama Reddy; Bhaarathy, Velmurugan; Ramakrishna, Seeram; Kumar, Srinivasan Dinesh

    2014-01-01

    Nanotechnology and tissue engineering have enabled engineering of nanostructured strategies to meet the current challenges in skin tissue regeneration. Electrospinning technology creates porous nanofibrous scaffolds to mimic extracellular matrix of the native tissues. The present study was performed to gain some insights into the applications of poly(l-lactic acid)-co-poly-(ε-caprolactone) (PLACL)/silk fibroin (SF)/vitamin E (VE)/curcumin (Cur) nanofibrous scaffolds and to assess their potential for being used as substrates for the culture of human dermal fibroblasts for skin tissue engineering. PLACL/SF/VE/Cur nanofibrous scaffolds were fabricated by electrospinning and characterized by fiber morphology, membrane porosity, wettability, mechanical strength, and chemical properties by Fourier transform infrared (FTIR) analysis. Human dermal fibroblasts were cultured on these scaffolds, and the cell scaffold interactions were analyzed by cell proliferation, cell morphology, secretion of collagen, expression of F-actin, and 5-chloromethylfluorescein diacetate (CMFDA) dye. The electrospun nanofiber diameter was obtained between 198±4 nm and 332±13 nm for PLACL, PLACL/SF, PLACL/SF/VE, and PLACL/SF/VE/Cur nanofibrous scaffolds. FTIR analysis showed the presence of the amide groups I, II, and III, and a porosity of up to 92% obtained on these nanofibrous scaffolds. The results showed that the fibroblast proliferation, cell morphology, F-actin, CMFDA dye expression, and secretion of collagen were significantly increased in PLACL/SF/VE/Cur when compared to PLACL nanofibrous scaffolds. The accessibility of human dermal fibroblasts cultured on PLACL/SF/VE/Cur nanofibrous scaffolds proved to be a potential scaffold for skin tissue regeneration. PMID:25336949

  10. Transplantation of adipose tissue-derived stromal cells promotes the survival of venous-congested skin flaps in rabbit ear.

    PubMed

    Xu, Nan; Guo, Shu; Wang, Yuxin; Sun, Qiang; Wang, Chenchao

    2015-03-01

    Venous congestion after skin flap transplantation usually slows blood flow velocity and induces skin flap necrosis and surgical failure. Adipose tissue-derived stromal cells (ADSCs) can promote neovascularization and have been extensively applied in cell transplantation therapy and tissue regeneration. However, their function has not been reported in venous-congested skin flaps. In this study, rabbit ADSCs were isolated and identified. We established a rabbit ear venous-congested skin flap model and injected ADSCs into points along the midlines of skin flaps. The survival conditions of venous-congested skin flaps on postoperative day 7 showed that there was obvious swelling, hemorrhage, or necrosis in skin flaps of the control group, while the skin flap survival rate in the ADSC treatment group significantly increased. Hematoxylin and eosin (HE) staining results indicated that compared with the control group, thrombosis was significantly relieved and neovascularization was observed in the ADSC treatment group. Immunofluorescence revealed that the CD34 expression level and the number of capillaries significantly increased in the ADSC treatment group. In summary, ADSC transplantation promotes neovascularization in venous-congested skin flaps and skin flap survival. Therefore, ADSC transplantation may be an effective measure for promoting the survival of venous-congested skin flaps.

  11. Large Scale Tissue Morphogenesis Simulation on Heterogenous Systems Based on a Flexible Biomechanical Cell Model.

    PubMed

    Jeannin-Girardon, Anne; Ballet, Pascal; Rodin, Vincent

    2015-01-01

    The complexity of biological tissue morphogenesis makes in silico simulations of such system very interesting in order to gain a better understanding of the underlying mechanisms ruling the development of multicellular tissues. This complexity is mainly due to two elements: firstly, biological tissues comprise a large amount of cells; secondly, these cells exhibit complex interactions and behaviors. To address these two issues, we propose two tools: the first one is a virtual cell model that comprise two main elements: firstly, a mechanical structure (membrane, cytoskeleton, and cortex) and secondly, the main behaviors exhibited by biological cells, i.e., mitosis, growth, differentiation, molecule consumption, and production as well as the consideration of the physical constraints issued from the environment. An artificial chemistry is also included in the model. This virtual cell model is coupled to an agent-based formalism. The second tool is a simulator that relies on the OpenCL framework. It allows efficient parallel simulations on heterogenous devices such as micro-processors or graphics processors. We present two case studies validating the implementation of our model in our simulator: cellular proliferation controlled by cell signalling and limb growth in a virtual organism.

  12. Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling

    PubMed Central

    Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru

    2016-01-01

    Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity. DOI: http://dx.doi.org/10.7554/eLife.15034.001 PMID:27431614

  13. Metabolic heterogeneity of activated beige/brite adipocytes in inguinal adipose tissue

    PubMed Central

    Lee, Yun-Hee; Kim, Sang-Nam; Kwon, Hyun-Jung; Granneman, James G.

    2017-01-01

    Sustained β3 adrenergic receptor (ADRB3) activation simultaneously upregulates fatty acid synthesis and oxidation in mouse brown, beige, and white adipose tissues; however, the cellular basis of this dual regulation is not known. Treatment of mice with the ADRB3 agonist CL316,243 (CL) increased expression of fatty acid synthase (FASN) and medium chain acyl-CoA dehydrogenase (MCAD) protein within the same cells in classic brown and white adipose tissues. Surprisingly, in inguinal adipose tissue, CL-upregulated FASN and MCAD in distinct cell populations: high MCAD expression occurred in multilocular adipocytes that co-expressed UCP1+, whereas high FASN expression occurred in paucilocular adipocytes lacking detectable UCP1. Genetic tracing with UCP1-cre, however, indicated nearly half of adipocytes with a history of UCP1 expression expressed high levels of FASN without current expression of UCP1. Global transcriptomic analysis of FACS-isolated adipocytes confirmed the presence of distinct anabolic and catabolic phenotypes, and identified differential expression of transcriptional pathways known to regulate lipid synthesis and oxidation. Surprisingly, paternally-expressed genes of the non-classical gene imprinted network were strikingly enriched in anabolic phenotypes, suggesting possible involvement in maintaining the balance of metabolic phenotypes. The results indicate that metabolic heterogeneity is a distinct property of activated beige/brite adipocytes that might be under epigenetic control. PMID:28045125

  14. Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue.

    PubMed

    Drakaki, E; Kaselouris, E; Makropoulou, M; Serafetinides, A A; Tsenga, A; Stratigos, A J; Katsambas, A D; Antoniou, C

    2009-01-01

    The object of this study was to investigate whether laser-induced skin autofluorescence (LIF) and/or light reflectance spectra could provide a useful contrast between basal cell carcinoma (BCC) tissues and the surrounding healthy skin. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a nitrogen laser (lambda = 337 nm) for excitation of autofluorescence and a tungsten halogen lamp for the reflectance measurements. The ex vivo spectroscopic results were correlated with the histopathology images to distinguish the areas of BCC from those of the surrounding health skin. A simple spectral analysis technique was also applied for better skin diagnosis. In conclusion, it seems that LIF and reflectance spectra could be used to differentiate neoplastic from normal skin tissue using an appropriate classification model analysis. Copyright 2009 S. Karger AG, Basel.

  15. Toad skin extract cinobufatini inhibits migration of human breast carcinoma MDA-MB-231 cells into a model stromal tissue.

    PubMed

    Nakata, Munehiro; Mori, Shuya; Kamoshida, Yo; Kawaguchi, Shota; Fujita-Yamaguchi, Yoko; Gao, Bo; Tang, Wei

    2015-08-01

    Toad skin extract cinobufatini study has been focused on anticancer activity, especially apoptosis-inducing activity by bufosteroids. The present study examined effect of the toad skin extract on cancer cell migration into model stromal tissues. Human breast carcinoma cell line MDA-MB-231 was incubated in the presence or absence of toad skin extract on a surface of reconstituted type I collagen gel as a model stromal tissue allowing the cells to migrate into the gel. Frozen sections were microscopically observed after azan staining. Data showed a decrease of cell number in a microscopic field and shortening of cell migration into the model stromal tissue in a dose dependent manner. This suggests that toad skin extract may possess migration-preventing activity in addition to cell toxicity such as apoptosis-inducing activity. The multifaceted effects including apoptosis-inducing and cancer cell migration-preventing activities would improve usefulness of toad skin extract cinobufatini as an anticancer medicine.

  16. Design of a tissue oxygenation monitor and verification on human skin

    NASA Astrophysics Data System (ADS)

    Liu, Hongyuan; Kohl-Bareis, Matthias; Huang, Xiabing

    2011-07-01

    We report the design of a tissue oxygen and temperature monitor. The non-invasive, fibre based device monitors tissue haemoglobin (Hb) and oxygen saturation (SO2) and is based on white-light reflectance spectroscopy.Visible light with wavelengths in the 500 - 650nm range is utilized. The spectroscopic algorithm takes into account the tissue scattering and melanin absorption for the calculation of tissue haemoglobin concentration and oxygen saturation. The monitor can probe superficial layers of tissue with a high spatial resolution (mm3) and a high temporal resolution (40 Hz). It provides an accurate measurement with the accuracy of SO2 at 2 % and high reliability with less than 2 % variation of continuous SO2 measurement over 12 hours. It can also form a modular system when used in conjunction with a laser Doppler monitor, enabling simultaneous measurements of Hb, SO2 and blood flow. We found experimentally that the influence of the source-detector separation on the haemoglobin parameters is small. This finding is discussed by Monte Carlo simulations for the depth sensitivity profile. The influence of probe pressure and the skin pigmentation on the measurement parameters are assessed before in vivo experimental data is presented. The combination with laser Doppler flowmetry demonstrates the importance of a measurement of both the haemoglobin and the blood flow parameters for a full description of blood tissue perfusion. This is discussed in experimental data on human skin during cuff occlusion and after hyperemisation by a pharmacological cream. Strong correlation is observed between tissue oxygen (Hb and SO2) and blood flow measurements.

  17. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; hide

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  18. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; Rao, J. S.; Rayford, A. R.; Reddy, B. R.; Sears, J.; Thielke, R.; Ulm, M.; Vanderby, R.

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  19. Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissue

    PubMed Central

    Nakamura, Kazuhiro; Morrison, Shaun F.

    2008-01-01

    Control of thermoregulatory effectors by the autonomic nervous system is a critical component of rapid cold-defense responses, which are triggered by thermal information from the skin. However, the central autonomic mechanism driving thermoregulatory effector responses to skin thermal signals remains to be determined. Here, we examined the involvement of several autonomic brain regions in sympathetic thermogenic responses in brown adipose tissue (BAT) to skin cooling in urethane-chloralose-anesthetized rats by monitoring thermogenic (BAT sympathetic nerve activity (SNA) and BAT temperature), metabolic (expired CO2), and cardiovascular (arterial pressure and heart rate) parameters. Acute skin cooling, which did not reduce either rectal (core) or brain temperature, evoked increases in BAT SNA, BAT temperature, expired CO2, and heart rate. Skin cooling-evoked thermogenic, metabolic, and heart rate responses were inhibited by bilateral microinjections of bicuculline (GABAA receptor antagonist) into the preoptic area (POA), by bilateral microinjections of muscimol (GABAA receptor agonist) into the dorsomedial hypothalamic nucleus (DMH), or by microinjection of muscimol, glycine, 8-OH-DPAT (5-HT1A receptor agonist), or kynurenate (non-selective antagonist for ionotropic excitatory amino acid receptors) into the rostral raphe pallidus nucleus (rRPa), but not by bilateral muscimol injections into the lateral/dorsolateral part or ventrolateral part of the caudal periaqueductal gray. These results implicate the POA, DMH, and rRPa in the central efferent pathways for thermogenic, metabolic, and cardiac responses to skin cooling, and suggest that these pathways can be modulated by serotonergic inputs to the medullary raphe. PMID:16931649

  20. The role of subcutaneous tissue stiffness on microneedle performance in a representative in vitro model of skin.

    PubMed

    Moronkeji, K; Todd, S; Dawidowska, I; Barrett, S D; Akhtar, R

    2016-11-10

    There has been growing interest in the mechanical behaviour of skin due to the rapid development of microneedle devices for drug delivery applications into skin. However, most in vitro experimentation studies that are used to evaluate microneedle performance do not consider the biomechanical properties of skin or that of the subcutaneous layers. In this study, a representative experimental model of skin was developed which was comprised of subcutaneous and muscle mimics. Neonatal porcine skin from the abdominal and back regions was used, with gelatine gels of differing water content (67, 80, 88 and 96%) to represent the subcutaneous tissue, and a type of ballistic gelatine, Perma-Gel®, as a muscle mimic. Dynamic nanoindentation was used to characterize the mechanical properties of each of these layers. A custom-developed impact test rig was used to apply dense polymethylmethacrylate (PMMA) microneedles to the skin models in a controlled and repeatable way with quantification of the insertion force and velocity. Image analysis methods were used to measure penetration depth and area of the breach caused by microneedle penetration following staining and optical imaging. The nanoindentation tests demonstrated that the tissue mimics matched expected values for subcutaneous and muscle tissue, and that the compliance of the subcutaneous mimics increased linearly with water content. The abdominal skin was thinner and less stiff as compared to back skin. The maximum force decreased with gel water content in the abdominal skin but not in the back skin. Overall, larger and deeper perforations were found in the skin models with increasing water content. These data demonstrate the importance of subcutaneous tissue on microneedle performance and the need for representative skin models in microneedle technology development.

  1. Development of thin skin mimicking bilayer solid tissue phantoms for optical spectroscopic studies

    PubMed Central

    Nivetha, K. Bala; Sujatha, N.

    2017-01-01

    In vivo spectroscopic measurements have the proven potential to provide important insight about the changes in tissue during the development of malignancies and thus help to diagnose tissue pathologies. Extraction of intrinsic data in the presence of varying amounts of scatterers and absorbers offers great challenges in the development of such techniques to the clinical level. Fabrication of optical phantoms, tailored to the biochemical as well as morphological features of the target tissue, can help to generate a spectral database for a given optical spectral measurement system. Such databases, along with appropriate pattern matching algorithms, could be integrated with in vivo measurements for any desired quantitative analysis of the target tissue. This paper addresses the fabrication of such soft, photo stable, thin bilayer phantoms, mimicking skin tissue in layer dimensions and optical properties. The performance evaluation of the fabricated set of phantoms is carried out using a portable fluorescence spectral measurement system. The alterations in flavin adenine dinucleotide (FAD)–a tissue fluorophore that provides important information about dysplastic progressions in tissues associated with cancer development based on changes in emission spectra–fluorescence with varied concentrations of absorbers and scatterers present in the phantom are analyzed and the results are presented. Alterations in the emission intensity, shift in emission wavelength and broadening of the emission spectrum were found to be potential markers in the assessment of biochemical changes that occur during the progression of dysplasia. PMID:28717562

  2. Biomarker discovery in heterogeneous tissue samples -taking the in-silico deconfounding approach

    PubMed Central

    2010-01-01

    Background For heterogeneous tissues, such as blood, measurements of gene expression are confounded by relative proportions of cell types involved. Conclusions have to rely on estimation of gene expression signals for homogeneous cell populations, e.g. by applying micro-dissection, fluorescence activated cell sorting, or in-silico deconfounding. We studied feasibility and validity of a non-negative matrix decomposition algorithm using experimental gene expression data for blood and sorted cells from the same donor samples. Our objective was to optimize the algorithm regarding detection of differentially expressed genes and to enable its use for classification in the difficult scenario of reversely regulated genes. This would be of importance for the identification of candidate biomarkers in heterogeneous tissues. Results Experimental data and simulation studies involving noise parameters estimated from these data revealed that for valid detection of differential gene expression, quantile normalization and use of non-log data are optimal. We demonstrate the feasibility of predicting proportions of constituting cell types from gene expression data of single samples, as a prerequisite for a deconfounding-based classification approach. Classification cross-validation errors with and without using deconfounding results are reported as well as sample-size dependencies. Implementation of the algorithm, simulation and analysis scripts are available. Conclusions The deconfounding algorithm without decorrelation using quantile normalization on non-log data is proposed for biomarkers that are difficult to detect, and for cases where confounding by varying proportions of cell types is the suspected reason. In this case, a deconfounding ranking approach can be used as a powerful alternative to, or complement of, other statistical learning approaches to define candidate biomarkers for molecular diagnosis and prediction in biomedicine, in realistically noisy conditions and with

  3. Modular design of artificial tissue homeostasis: robust control through synthetic cellular heterogeneity.

    PubMed

    Miller, Miles; Hafner, Marc; Sontag, Eduardo; Davidsohn, Noah; Subramanian, Sairam; Purnick, Priscilla E M; Lauffenburger, Douglas; Weiss, Ron

    2012-01-01

    Synthetic biology efforts have largely focused on small engineered gene networks, yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge. Here we present the design, system integration, and analysis of several large scale synthetic gene circuits for artificial tissue homeostasis. Diabetes therapy represents a possible application for engineered homeostasis, where genetically programmed stem cells maintain a steady population of β-cells despite continuous turnover. We develop a new iterative process that incorporates modular design principles with hierarchical performance optimization targeted for environments with uncertainty and incomplete information. We employ theoretical analysis and computational simulations of multicellular reaction/diffusion models to design and understand system behavior, and find that certain features often associated with robustness (e.g., multicellular synchronization and noise attenuation) are actually detrimental for tissue homeostasis. We overcome these problems by engineering a new class of genetic modules for 'synthetic cellular heterogeneity' that function to generate beneficial population diversity. We design two such modules (an asynchronous genetic oscillator and a signaling throttle mechanism), demonstrate their capacity for enhancing robust control, and provide guidance for experimental implementation with various computational techniques. We found that designing modules for synthetic heterogeneity can be complex, and in general requires a framework for non-linear and multifactorial analysis. Consequently, we adapt a 'phenotypic sensitivity analysis' method to determine how functional module behaviors combine to achieve optimal system performance. We ultimately combine this analysis with Bayesian network inference to extract critical, causal relationships between a module's biochemical rate-constants, its high level functional behavior in isolation, and

  4. A heterogeneous human tissue mimicking phantom for RF heating and MRI thermal monitoring verification

    PubMed Central

    Yuan, Yu; Wyatt, Cory; Maccarini, Paolo; Stauffer, Paul; Craciunescu, Oana; MacFall, James; Dewhirst, Mark; Das, Shiva K.

    2013-01-01

    This paper describes a heterogeneous phantom that mimics a human thigh with a deep seated tumor, for the purpose of studying the performance of radiofrequency (RF) heating equipment and non-invasive temperature monitoring with magnetic resonance imaging (MRI). The heterogeneous cylindrical phantom was constructed with an outer fat layer surrounding an inner core of phantom material mimicking muscle, tumor and marrow-filled bone. The component materials were formulated to have dielectric and thermal properties similar to human tissues. The dielectric properties of the tissue-mimicking phantom materials were measured with a microwave vector network analyzer and impedance probe over the frequency range of 80 – 500 MHz and at temperatures of 24°C, 37°C, and 45°C. The specific heat values of the component materials were measured using a differential scanning calorimeter over the temperature range of 15 – 55°C. The thermal conductivity value was obtained from fitting the curves obtained from one-dimensional heat transfer measurement. The phantom was used to verify the operation of a cylindrical 4-antenna annular phased array extremity applicator (140 MHz), by examining the proton resonance frequency shift (PRFS) thermal imaging patterns for various magnitude/phase settings (including settings to focus heating in tumor). For muscle and tumor materials, MR imaging was also used to measure T1/T2* values (1.5 Tesla) and to obtain the slope of the PRFS phase change vs. temperature change curve. The dielectric and thermal properties of the phantom materials were in close agreement to well-accepted published results for human tissues. The phantom was able to successfully demonstrate satisfactory operation of the tested heating equipment. The MRI-measured thermal distributions matched the expected patterns for various magnitude/phase settings of the applicator, allowing the phantom to be used as a quality assurance tool. Importantly, the material formulations for the

  5. Pitfalls in the measurement of skin autofluorescence to determine tissue advanced glycosylation content in haemodialysis patients.

    PubMed

    Chaudhri, Saurabh; Fan, Stanley; Davenport, Andrew

    2013-10-01

    Skin autofluoresence has been advocated as a quick non-invasive method of measuring tissue advanced glycosylation end products (AGE), which have been reported to correlate with cardiovascular risk in the dialysis patient. Most studies have been performed in patients from a single racial group, and we wanted to look at the reliability of skin autofluoresence measurements in a multiracial dialysis population and whether results were affected by haemodialysis. We measured skin autofluoresence three times in both forearms of 139 haemodialysis patients pre-dialysis and 36 post-dialysis. One hundred and thirty-nine patients, 62.2% male, 35.3% diabetic, 59% Caucasoid, mean age 65.5 ± 15.2 years were studied. Reproducibility of measurements between the 1st and 2nd measurements was very good (r(2 ) = 0.94, P < 0.001, Bland Altman bias 0.05, confidence limits -0.02 to 0.04). However, skin autoflourescence measurements were not possible in one forearm in 8.5% Caucasoids, 25% Far Asian, 28% South Asians and 75% African or Afro Caribbean (P < 0.001). Mean skin autofluorescence in the right forearm was 3.3 ± 0.74 arbitrary units (AU) and left forearm 3.18 ± 0.82 AU pre-dialysis, and post-dialysis there was a fall in those patients dialysing with a left sided arteriovenous fistula (left forearm pre 3.85 ± 0.72 vs post 3.36 ± 0.55 AU, P = 0.012). Although skin autofluorescence is a relatively quick non-invasive method of measuring tissue AGE and measurements were reproducible, it was often not possible to obtain measurements in patients with highly pigmented skin. To exclude potential effects of arteriovenous fistulae we would suggest that measurements are made in the non-fistula forearm pre-dialysis. © 2013 The Authors. Nephrology © 2013 Asian Pacific Society of Nephrology.

  6. Malondialdehyde-Derived Epitopes In Human Skin Result From Acute Exposure To Solar UV And Occur In Nonmelanoma Skin Cancer Tissue

    PubMed Central

    Williams, Joshua D.; Bermudez, Yira; Park, Sophia L.; Stratton, Steven P.; Uchida, Koji; Hurst, Craig A.; Wondrak, Georg T.

    2014-01-01

    Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than three-fold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored. PMID:24584085

  7. A Molecular Clock Infers Heterogeneous Tissue Age Among Patients with Barrett’s Esophagus

    PubMed Central

    Wong, Chao-Jen; Hazelton, William D.; Kaz, Andrew M.; Willis, Joseph E.; Grady, William M.; Luebeck, E. Georg

    2016-01-01

    Biomarkers that drift differentially with age between normal and premalignant tissues, such as Barrett’s esophagus (BE), have the potential to improve the assessment of a patient’s cancer risk by providing quantitative information about how long a patient has lived with the precursor (i.e., dwell time). In the case of BE, which is a metaplastic precursor to esophageal adenocarcinoma (EAC), such biomarkers would be particularly useful because EAC risk may change with BE dwell time and it is generally not known how long a patient has lived with BE when a patient is first diagnosed with this condition. In this study we first describe a statistical analysis of DNA methylation data (both cross-sectional and longitudinal) derived from tissue samples from 50 BE patients to identify and validate a set of 67 CpG dinucleotides in 51 CpG islands that undergo age-related methylomic drift. Next, we describe how this information can be used to estimate a patient’s BE dwell time. We introduce a Bayesian model that incorporates longitudinal methylomic drift rates, patient age, and methylation data from individually paired BE and normal squamous tissue samples to estimate patient-specific BE onset times. Our application of the model to 30 sporadic BE patients’ methylomic profiles first exposes a wide heterogeneity in patient-specific BE onset times. Furthermore, independent application of this method to a cohort of 22 familial BE (FBE) patients reveals significantly earlier mean BE onset times. Our analysis supports the conjecture that differential methylomic drift occurs in BE (relative to normal squamous tissue) and hence allows quantitative estimation of the time that a BE patient has lived with BE. PMID:27168458

  8. Skin and soft tissue infections, active component, U.S. Armed Forces, 2013-2016.

    PubMed

    Stahlman, Shauna; Williams, Valerie F; Oh, Gi-Taik; Millar, Eugene V; Bennett, Jason W

    2017-07-01

    During the 4-year surveillance period, there were 282,571 incident cases of skin and soft tissue infection (SSTI) among active component U.S. military members diagnosed in inpatient or outpatient settings, corresponding to an overall incidence of 558.2 per 10,000 person-years (p-yrs). An additional 10,904 cases occurred in theater of operations (460.0 per 10,000 p-yrs). Approximately half (49.4%) were classified as "other SSTI" (e.g., folliculitis, impetigo); 45.9% were cellulitis/abscess; 4.6% were carbuncles/furuncles; and 0.1% were erysipelas. Annual incidence rates declined by 46.6% over the surveillance period. In general, higher rates of SSTIs were associated with younger age, recruit trainee status, and junior enlisted rank. During the surveillance period, 238,924 service members were treated for SSTIs in outpatient or inpatient settings, which accounted for 395,361 medical encounters and 19,213 hospital bed days. The history of operational significance of skin infections in the military, the high healthcare costs associated with evaluating and treating skin infections, and the risk of infections by antibiotic-resistant organisms highlight the importance of prevention, early diagnosis, and definitive treatment of skin infections, particularly in high-risk settings such as new recruit/basic training populations.

  9. The potential applications of fibrin-coated electrospun polylactide nanofibers in skin tissue engineering

    PubMed Central

    Bacakova, Marketa; Musilkova, Jana; Riedel, Tomas; Stranska, Denisa; Brynda, Eduard; Zaloudkova, Margit; Bacakova, Lucie

    2016-01-01

    Fibrin plays an important role during wound healing and skin regeneration. It is often applied in clinical practice for treatment of skin injuries or as a component of skin substitutes. We prepared electrospun nanofibrous membranes made from poly(l-lactide) modified with a thin fibrin nanocoating. Fibrin surrounded the individual fibers in the membrane and also formed a thin fibrous mesh on several places on the membrane surface. The cell-free fibrin nanocoating remained stable in the cell culture medium for 14 days and did not change its morphology. On membranes populated with human dermal fibroblasts, the rate of fibrin degradation correlated with the degree of cell proliferation. The cell spreading, mitochondrial activity, and cell population density were significantly higher on membranes coated with fibrin than on nonmodified membranes, and this cell performance was further improved by the addition of ascorbic acid in the cell culture medium. Similarly, fibrin stimulated the expression and synthesis of collagen I in human dermal fibroblasts, and this effect was further enhanced by ascorbic acid. The expression of beta1-integrins was also improved by fibrin, and on pure polylactide membranes, it was slightly enhanced by ascorbic acid. In addition, ascorbic acid promoted deposition of collagen I in the form of a fibrous extracellular matrix. Thus, the combination of nanofibrous membranes with a fibrin nanocoating and ascorbic acid seems to be particularly advantageous for skin tissue engineering. PMID:26955273

  10. Reproducibility of transcutaneous oximetry and laser Doppler flowmetry in facial skin and gingival tissue.

    PubMed

    Svalestad, J; Hellem, S; Vaagbø, G; Irgens, A; Thorsen, E

    2010-01-01

    Laser Doppler flowmetry (LDF) and transcutaneous oximetry (TcPO(2)) are non-invasive techniques, widely used in the clinical setting, for assessing microvascular blood flow and tissue oxygen tension, e.g. recording vascular changes after radiotherapy and hyperbaric oxygen therapy. With standardized procedures and improved reproducibility, these methods might also be applicable in longitudinal studies. The aim of this study was to evaluate the reproducibility of facial skin and gingival LDF and facial skin TcPO(2). The subjects comprised ten healthy volunteers, 5 men, aged 31-68 years. Gingival perfusion was recorded with the LDF probe fixed to a custom made, tooth-supported acrylic splint. Skin perfusion was recorded on the cheek. TcPO(2) was recorded on the forehead and cheek and in the second intercostal space. The reproducibility of LDF measurements taken after vasodilation by heat provocation was greater than for basal flow in both facial skin and mandibular gingiva. Pronounced intraday variations were observed. Interweek reproducibility assessed by intraclass correlation coefficient ranged from 0.74 to 0.96 for LDF and from 0.44 to 0.75 for TcPO(2). The results confirm acceptable reproducibility of LDF and TcPO(2) in longitudinal studies in a vascular laboratory where subjects serve as their own controls. The use of thermoprobes is recommended. Repeat measurements should be taken at the same time of day.

  11. Chitosan as a Modifying Component of Artificial Scaffold for Human Skin Tissue Engineering.

    PubMed

    Romanova, O A; Grigor'ev, T E; Goncharov, M E; Rudyak, S G; Solov'yova, E V; Krasheninnikov, S T; Saprykin, V P; Sytina, E V; Chvalun, S N; Pal'tsev, M A; Panteleev, A A

    2015-08-01

    We compared the structure and mechanical properties of scaffolds based on pure collagen, pure chitosan, and a mixture of these polymers. The role of the composition and structure of scaffolds in the maintenance of cell functions (proliferation, differentiation, and migration) was demonstrated in two experimental models: homogeneous tissue analogues (scaffold populated by fibroblasts) and complex skin equivalents (fibroblasts and keratinocytes). In contrast to collagen scaffolds, pure chitosan inhibited the growth of fibroblasts that did not form contacts with chitosan fibers, but formed specific cellular conglomerates, spheroids, and lose their ability to synthesize natural extracellular matrix. However, the use of chitosan as an additive stimulated proliferative activity of fibroblasts on collagen, which can be associated with improvement of mechanical properties of the collagen scaffolds. The effectiveness of chitosan as an additional cross-linking agent also manifested in its ability to improve significantly the resistance of collagen scaffolds to fibroblast contraction in comparison with glutaraldehyde treatment. Polymer scaffolds (without cells) accelerated complete healing of skin wounds in vivo irrespective of their composition healing, pure chitosan sponge being most effective. We concluded that the use of chitosan as the scaffold for skin equivalents populated with skin cells is impractical, whereas it can be an effective modifier of polymer scaffolds.

  12. The potential applications of fibrin-coated electrospun polylactide nanofibers in skin tissue engineering.

    PubMed

    Bacakova, Marketa; Musilkova, Jana; Riedel, Tomas; Stranska, Denisa; Brynda, Eduard; Zaloudkova, Margit; Bacakova, Lucie

    2016-01-01

    Fibrin plays an important role during wound healing and skin regeneration. It is often applied in clinical practice for treatment of skin injuries or as a component of skin substitutes. We prepared electrospun nanofibrous membranes made from poly(l-lactide) modified with a thin fibrin nanocoating. Fibrin surrounded the individual fibers in the membrane and also formed a thin fibrous mesh on several places on the membrane surface. The cell-free fibrin nanocoating remained stable in the cell culture medium for 14 days and did not change its morphology. On membranes populated with human dermal fibroblasts, the rate of fibrin degradation correlated with the degree of cell proliferation. The cell spreading, mitochondrial activity, and cell population density were significantly higher on membranes coated with fibrin than on nonmodified membranes, and this cell performance was further improved by the addition of ascorbic acid in the cell culture medium. Similarly, fibrin stimulated the expression and synthesis of collagen I in human dermal fibroblasts, and this effect was further enhanced by ascorbic acid. The expression of beta1-integrins was also improved by fibrin, and on pure polylactide membranes, it was slightly enhanced by ascorbic acid. In addition, ascorbic acid promoted deposition of collagen I in the form of a fibrous extracellular matrix. Thus, the combination of nanofibrous membranes with a fibrin nanocoating and ascorbic acid seems to be particularly advantageous for skin tissue engineering.

  13. Scar appearance of different skin and subcutaneous tissue closure techniques in caesarean section: a randomized study.

    PubMed

    Gaertner, Isabell; Burkhardt, Tilo; Beinder, Ernst

    2008-05-01

    To determine the role of skin and subcutaneous space closure in caesarean section on the cosmetic appearance of the scar and the patients' satisfaction. 153 patients undergoing caesarean section without prior abdominal delivery were included and randomly assigned in a non-blinded study to four different combinations of skin and subcutaneous tissue closure. The scar was assessed after a period of at least 4 months by a self-developed protocol and the patient was asked to complete a survey regarding her satisfaction with the scar. One hundred patients were eligible for long-term evaluation of the scar. Skin closure by either staples or intracutaneous suture in combination with closure or non-closure of the subcutaneous space has a comparable outcome in view of cosmetic outcome and patient satisfaction. All four methods of skin closure seem to be a reasonable choice in caesarean section because they have comparable cosmetic outcome, do not differ with respect to the patients' satisfaction and bear comparable costs.

  14. Premalignant and Malignant Skin Lesions in Two Recipients of Vascularized Composite Tissue Allografts (Face, Hands)

    PubMed Central

    Kanitakis, Jean; Petruzzo, Palmina; Gazarian, Aram; Testelin, Sylvie; Devauchelle, Bernard; Badet, Lionel; Dubernard, Jean-Michel; Morelon, Emmanuel

    2015-01-01

    Recipients of solid organ transplants (RSOT) have a highly increased risk for developing cutaneous premalignant and malignant lesions, favored by the lifelong immunosuppression. Vascularized composite tissue allografts (VCA) have been introduced recently, and relevant data are sparse. Two patients with skin cancers (one with basal cell carcinoma and one with squamous cell carcinomas) have been so far reported in this patient group. Since 2000 we have been following 9 recipients of VCA (3 face, 6 bilateral hands) for the development of rejection and complications of the immunosuppressive treatment. Among the 9 patients, one face-grafted recipient was diagnosed with nodular-pigmented basal cell carcinoma of her own facial skin 6 years after graft, and one patient with double hand allografts developed disseminated superficial actinic porokeratosis, a potentially premalignant dermatosis, on her skin of the arm and legs. Similar to RSOT, recipients of VCA are prone to develop cutaneous premalignant and malignant lesions. Prevention should be applied through sun-protective measures, regular skin examination, and early treatment of premalignant lesions. PMID:26550517

  15. Skin and Subcutaneous Tissue Ultrasonography Features in Breast Cancer-Related Lymphedema

    PubMed Central

    Morikage, Noriyasu; Yamashita, Osamu; Harada, Takasuke; Samura, Makoto; Takeuchi, Yuriko; Mizoguchi, Takahiro; Nakamura, Kaori; Hamano, Kimikazu

    2016-01-01

    Objective: To investigate skin, subepidermal low echogenic band (SELEB), and subcutaneous tissue (SCT) thickness as well as the degree of increase in subcutaneous echogenicity (SEG) and subcutaneous echo-free space (SEFS) in arms with lymphedema (LE). Materials and Methods: The skin and SCT of both arms of 30 patients with unilateral stage II breast cancer-related LE were scanned at five points (medial/lateral upper arm/forearm and dorsum of the hand). SEG and SEFS grades were determined according to severity (range: 0–2). Results: All measured parameters, except the SEFS in the medial upper arm, were significantly higher on the LE side than on the normal (N) side. The parameters differed most remarkably in the medial forearm (MFA; skin: LE 1.7 ± 0.8 mm vs. N 0.8 ± 0.2 mm; SELEB: LE 1.0 ± 0.6 mm vs. N 0.3 ± 0.1 mm; SCT: LE 8.7 ± 3.4 mm vs. N 3.8 ± 2.0 mm; SEG: LE 0.9 ± 0.5 vs. N 0.1 ± 0.3; and SEFS: LE 0.5 ± 0.7 vs. N 0). Conclusion: The differences in the thickness of the skin, SELEB, and SCT and the SEG and SEFS grades between the LE and N arms seemed most evident in the MFA. PMID:28018504

  16. Potential of a PLA-PEO-PLA-based scaffold for skin tissue engineering: in vitro evaluation.

    PubMed

    Garric, Xavier; Guillaume, Olivier; Dabboue, Hinda; Vert, Michel; Molès, Jean-Pierre

    2012-01-01

    This study aimed to investigate the in vitro behaviour of porous degradable scaffolds of the PLA-PEO-PLA-type designed prior to in vivo evaluation for skin tissue engineering. Two tri-block co-polymers were synthesized from PEO and DL-lactide and their degradation was studied under conditions that mimic a cutaneous wound environment. 3-D porous scaffolds with interconnected pores were fabricated using the salt leaching method and characterized by ESEM and Hg porosimetry. The degrading action of gamma sterilization was studied on the co-polymers. The less degraded one was selected to make porous scaffolds on which human dermal fibroblasts and human epidermal keratinocytes were cultured. The capacity of such scaffolds to act as a dermal equivalent was also considered. Colonization by human dermal fibroblasts was shown after hematoxylin staining and the production of major proteins normally found in the extracellular matrix was assessed by Western blotting of protein extracts. Finally, a skin substitute was generated by seeding human keratinocytes on the dermal equivalent and a new epidermis was characterized by using immuno-histological staining. Results show that gamma sterilization and that degradation under conditions that mimic skin wound healing were acceptable. The fact that fibroblasts produce extracellular matrix and that keratinocytes generated an epidermal barrier argues in favour of the interest of this type of porous scaffold for skin reconstruction.

  17. Non Diphtheritic Corynebacteria: An Emerging Nosocomial Pathogen in Skin and Soft Tissue Infection

    PubMed Central

    Ravi, GS; Alex, Ann Mary; Mamatha, KR; Sunitha, L; Ramya, K Thangam

    2015-01-01

    Introduction Non-diphtheritic corynebacteria are normal inhabitants of skin and mucous membrane. When isolated from clinical specimens they are often considered as contaminants. Recent reports suggest their role as emerging nosocomial pathogens. Aim To speciate non-diphtheritic corynebacteria isolated from wound specimens, to correlate their clinical significance and to determine their invitro antimicrobial susceptibilities to 9 antimicrobial agents. Materials and Methods Twenty five non-diphtheritic corynebacteria from skin and soft tissue infections were selected for study. Isolates were identified by battery of tests and minimum inhibitory concentration (MIC) was detected by Clinical & Laboratory Standards Institute (CLSI) described broth microdilution method. MIC was interpreted according CLSI and British Society for Antimicrobial Chemotherapy (BSAC) guidelines. Results C. amycolatum was the predominant species (20%) followed by C. striatum (16%). Penicillin was least effective invitro followed by clindamycin and ciprofloxacin. Excellent activities were shown by vancomycin, linezolid and imipenem. Multidrug resistance was found in all the species. Conclusion Non-diphtheritic corynebacteria are potential nosocomial pathogens among acute/chronic complicated skin and soft tissue infection. Vancomycin or linezolid can be used empirically to treat such infections until the invitro susceptibility results are available. PMID:26816891

  18. Heterogeneous nuclear transfer embryos reconstructed by bovine oocytes and camel (Camelus bactrianus) skin fibroblasts and their subsequent development.

    PubMed

    Zhou, Huanmin; Guo, Zhenhua

    2006-01-01

    This study reconstructed heterogeneous embryos using camel skin fibroblast cells as donor karyoplasts and the bovine oocytes as recipient cytoplasts to investigate the reprogramming of camel somatic cell nuclei in bovine oocyte cytoplasm and the developmental potential of the reconstructed embryos. Serum-starved skin fibroblast cells, obtained from adult camel, were electrically fused into enucleated bovine metaphase II (MII) oocytes that were matured in vitro. The fused eggs were activated by Inomycin with 2 mM/ml 6-dimethylaminopurine. The activated reconstructed embryos were cocultured with bovine cumulus cells in synthetic oviduct fluid supplemented with amino acid (SOFaa) and 10% fetal calf serum for 168 h. Results showed that 53% of the injected oocytes were successfully fused, 34% of the fused eggs underwent the first egg cleavage, and 100% of them developed to four- or 16-cell embryo stages. The first completed cleavage of xenonuclear transfer camel embryos occurred between 22 and 48 h following activation. This study demonstrated that the reconstructed embryos underwent the first embryonic division and that the reprogramming of camel fibroblast nuclei can be initiated in enucleated bovine MII oocytes.

  19. Noninvasive assessment of skin iron content in hemodialysis patients. An index of parenchymal tissue iron content

    SciTech Connect

    Friedlaender, M.M.; Kaufman, B.; Rubinger, D.; Moreb, J.; Popovtzer, M.M.; Goredetsky, R.

    1988-07-01

    Iron overload has been described in patients undergoing chronic hemodialysis. The present study was undertaken to evaluate a rapid, noninvasive method for determination of skin iron by the technique of diagnostic x-ray spectrometry (DXS). Thirty-five patients receiving chronic hemodialysis treatment entered the study and were compared with 25 normal controls. Since pathological skin iron deposition occurs mainly at the dermal-epidermal junction in the basal cells of the epidermis, measurements were made in the thenar eminence representing mainly epidermal tissue (FeE), and in the forearm representative mainly of dermis (FeD). The mean +/- SD FeE iron concentrations were equivalent to 14.5 +/- 8.8 and 18.2 +/- 10.2 parts per million wet weight tissue (ppm) and both were significantly higher than in normal controls in which they averaged 9.2 +/- 2.5 ppm (P less than 0.005) and 10.2 +/- 3.2 ppm (P less than 0.001), respectively. There was significant positive correlation between individual skin iron determinations with the total number of blood transfusions received, the rate of blood transfusion, and with serum ferritin levels. Bone marrow hemosiderin was examined in six patients and showed a similar trend. Despite correlation only with indirect indices of tissue iron, our findings suggest that DXS may serve as a reliable quick method for noninvasive estimation of nonreticuloendothelial tissue iron deposition in hemodialysis patients suspected of having transfusional iron overload. The method may be valuable in monitoring the effects of chelation therapy.

  20. Heterogeneous dental follicle cells and the regeneration of complex periodontal tissues.

    PubMed

    Guo, Weihua; Chen, Lei; Gong, Kun; Ding, Bofu; Duan, Yinzhong; Jin, Yan

    2012-03-01

    Dental follicle cells (DFCs) are a heterogeneous population that exhibit a variety of phenotypes. However, it remains unclear whether DFCs can maintain stem cell characteristics, or mediate tissue-regeneration to form single or complex tissues in the periodontium, after long-term culturing. Therefore, DFCs were isolated from human impacted molars (HIM-DFCs), passaged >30 times, and then evaluated for their heterogeneity and multipotential differentiation. Morphology, proliferation, epitope profile, and mineralization characteristics of clones derived from single HIM-DFCs in vitro were also assayed. HIM-DFCs (passage #30) were found to be positive for the heterogeneous markers, Notch-1, stro-1, alkaline phosphomonoesterase (ALP), type I collagen (COL-I), type III collagen (COL-III), and osteocalcine. Moreover, passage #30 of the HDF1, 2, and 3 subclone classes identified in this study were found to express high levels of the mesenchymal stem cells markers, CD146 and Stro1. HDF3 subclones were also associated with the strongest ALP staining detected, and strongly expressed osteoblast and cementoblast markers, including COL-I, COL-III, bone sialoprotein (BSP), and Runx2. In contrast, HDF1 subclone analyzed strongly expressed COL-I and COL-III, yet weakly expressed BSP and Runx2. The HDF2 subclone was associated with the strongest proliferative capacity. To evaluate differentiation characteristics in vivo, these various cell populations were combined with ceramic bovine bone and implanted into subcutaneous pockets of nude mice. The 30th passage of subclone HDF1 and 3 were observed to contribute to fiber collagens and the mineralized matrix present, respectively, whereas HDF2 subclones were found to have a minimal role in these formations. The formation of a cementum-periodontal ligament (PDL) complex was observed 6 weeks after HIM-DFCs (passage #30) were implanted in vivo, thus suggesting that these cells maintain stem cell characteristics. Therefore, subclone HDF1

  1. [Tissue-engineered graft constructed by bone marrow mononuclear cells and heterogeneous acellularized tissue matrix: an animal experiment].

    PubMed

    Huang, Hui-min; Ma, Liang-long; Ren, Hong; Wu, Shao-feng; Jiang, Zu-ming

    2007-12-25

    To construct a tissue-engineered graft by using bone marrow cells as seeding cells and heterogeneous acellularized matrix as scaffold. Mononuclear cells were isolated from the bone marrow from piglets and cultured in different mediums including either vessel endothelial growth factor (VEGF) or platelet derived growth factor BB (PDGF-BB) to observe the differentiation of cells. Immunoassay was used to detect the expression of specific markers of endothelial cells or specific markers of smooth muscle cells. Adult dogs were killed and their thoracic or abdominal aortas were taken out and processed by multi-step decellularizing technique to remove the original cells while the elastic and collagen fibers were preserved. The undifferentiated bone marrow mononuclear cells were seeded onto the acellularized matrix and incubated in vitro. The cell-seeded grafts were then transplanted to the bone marrow donating piglets to substitute part of the native pulmonary artery. Three weeks later right ventriculography was performed. 100 days later the piglets were sacrificed. The transplanted vessels and the nearby tissues of native pulmonary vessels were excised for inspection. The mononuclear cells cultured in the medium including VEGF showed the morphological features of endothelial cells and were positive of the specific markers of endothelial cells: platelet-endothelial cell adhesion molecule-l, vascular endothelial growth factor receptor Flk-1, VE-cadherin, and plasma factor VIII. The cells cultured in the medium including PDGF-BB showed morphological feature of smooth muscle cells and were positive of he specific marks of smooth muscle cells: alpha-SMA and calponin. One hundred days after transplantation, the inner surfaces of the grafts were smooth without thrombosis, calcification, and aneurysm. The maximal load was 2.76 N and the maximal elongation was 20.31 mm. Under the microscopy a great number of growing endothelial cells and smooth muscle cells could be seen and

  2. Heterogeneity of Skin Surface Oxygen Level of Wrist in Relation to Acupuncture Point

    PubMed Central

    Hong, Minyoung; Park, Sarah S.; Ha, Yejin; Lee, Jaegeun; Yoo, Kwangsik; Jhon, Gil-Ja; Suh, Minah; Lee, Youngmi

    2012-01-01

    The distribution of partial oxygen pressure (pO2) is analyzed for the anterior aspect of the left wrist with an amperometric oxygen microsensor composed of a small planar Pt disk-sensing area (diameter = 25 μm). The pO2 levels vary depending on the measurement location over the wrist skin, and they are systematically monitored in the analysis for both one-dimensional single line (along the wrist transverse crease) and two-dimensional square area of the wrist region. Relatively higher pO2 values are observed at certain area in close proximity to the position of acupuncture points with statistical significance, indicating strong relationship between oxygen and acupuncture point. The used oxygen microsensor is sensitive enough to detect the pO2 variation depending on the location. This study may provide information helpful to understand possible physiological roles of the acupuncture points. PMID:22666285

  3. Tissue repair genes: the TiRe database and its implication for skin wound healing

    PubMed Central

    Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E.

    2016-01-01

    Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that were shown to directly affect skin wound healing. To date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of skin wound healing-associated genes showed that skin wound healing genes are (i) over-conserved among vertebrates, but are under-conserved in invertebrates; (ii) enriched in extracellular and immuno-inflammatory genes; and display (iii) high interconnectivity and connectivity to other proteins. The latter may provide potential therapeutic targets. In addition, a slower or faster skin wound healing is indicative of an aging or longevity phenotype only when assessed in advanced ages, but not in the young. In the long run, we aim for TiRe to be a one-station resource that provides researchers and clinicians with the essential data needed for a better understanding of the mechanisms of wound healing, designing new experiments, and the development of new therapeutic strategies. TiRe is freely available online at http://www.tiredb.org. PMID:27049721

  4. Infrared mapping resolves soft tissue preservation in 50 million year-old reptile skin

    PubMed Central

    Edwards, N. P.; Barden, H. E.; van Dongen, B. E.; Manning, P. L.; Larson, P. L.; Bergmann, U.; Sellers, W. I.; Wogelius, R. A.

    2011-01-01

    Non-destructive Fourier Transform InfraRed (FTIR) mapping of Eocene aged fossil reptile skin shows that biological control on the distribution of endogenous organic components within fossilized soft tissue can be resolved. Mapped organic functional units within this approximately 50 Myr old specimen from the Green River Formation (USA) include amide and sulphur compounds. These compounds are most probably derived from the original beta keratin present in the skin because fossil leaf- and other non-skin-derived organic matter from the same geological formation do not show intense amide or thiol absorption bands. Maps and spectra from the fossil are directly comparable to extant reptile skin. Furthermore, infrared results are corroborated by several additional quantitative methods including Synchrotron Rapid Scanning X-Ray Fluorescence (SRS-XRF) and Pyrolysis-Gas Chromatography/Mass Spectrometry (Py-GC/MS). All results combine to clearly show that the organic compound inventory of the fossil skin is different from the embedding sedimentary matrix and fossil plant material. A new taphonomic model involving ternary complexation between keratin-derived organic molecules, divalent trace metals and silicate surfaces is presented to explain the survival of the observed compounds. X-ray diffraction shows that suitable minerals for complex formation are present. Previously, this study would only have been possible with major destructive sampling. Non-destructive FTIR imaging methods are thus shown to be a valuable tool for understanding the taphonomy of high-fidelity preservation, and furthermore, may provide insight into the biochemistry of extinct organisms. PMID:21429928

  5. [First results with Integra artificial skin in the management of severe tissue defects in children].

    PubMed

    Vázquez Rueda, F; Ayala Montoro, J; Blanco López, F; Ocaña Losa, J M

    2001-07-01

    In extreme cases of tissue defects, wound coverage after excision may be problematic because of the limited existence of donor sites. An option for temporary wound coverage used in the management after early scar release is a dermal substitute: Integral artificial skin. The biosinthetic material consists of un upper silicone film and a lower layer of porous cross-linked bovine collagen and chondroitin-6-sulfate as a template for dermal regeneration after staged tangencial necrectomy. In the third and fourth weeks following application the silicone layer was easily removed and the newly formed neodermis covered with widely unmeshed thin split thickness autograft. We report 6 patients with tissue defects with open fractures in three cases, one hemorrhagic necrosis of the skin by meningococcemia who requiring amputations of all four extremities and two traumatic necrosis. Other patient has a retractil scar. All were treated with Integral and epidermical autograft. The good results with Integral regarding recovery may affect initial treatment and reconstruction planning after extensive wound injuries with tissue defects to obtain immediate wound closure.

  6. Cellulose acetate based 3-dimensional electrospun scaffolds for skin tissue engineering applications.

    PubMed

    Atila, Deniz; Keskin, Dilek; Tezcaner, Ayşen

    2015-11-20

    Skin defects that are not able to regenerate by themselves are among the major problems faced. Tissue engineering approach holds promise for treating such defects. Development of tissue-mimicking-scaffolds that can promote healing process receives an increasing interest in recent years. In this study, 3-dimensional electrospun cellulose acetate (CA) pullulan (PULL) scaffolds were developed for the first time. PULL was intentionally used to obtain 3D structures with adjustable height. It was removed from the electrospun mesh to increase the porosity and biostability. Different ratios of the polymers were electrospun and analyzed with respect to degradation, porosity, and mechanical properties. It has been observed that fiber diameter, thickness and porosity of scaffolds increased with increased PULL content, on the other hand this resulted with higher degradation of scaffolds. Mechanical strength of scaffolds was improved after PULL removal suggesting their suitability as cell carriers. Cell culture studies were performed with the selected scaffold group (CA/PULL: 50/50) using mouse fibroblastic cell line (L929). In vitro cell culture tests showed that cells adhered, proliferated and populated CA/PULL (50/50) scaffolds showing that they are cytocompatible. Results suggest that uncrosslinked CA/PULL (50/50) electrospun scaffolds hold potential for skin tissue engineering applications.

  7. [Regenerative medicine: stem cells, cellular and matricial interactions in the reconstruction of skin and cornea by tissue engineering].

    PubMed

    Larouche, D; Lavoie, A; Proulx, S; Paquet, C; Carrier, P; Beauparlant, A; Auger, F A; Germain, L

    2009-06-01

    Considering that there is a shortage of organ donor, the aim of tissue engineering is to develop substitutes for the replacement of wounded or diseased tissues. Autologous tissue is evidently a preferable transplant material for long-term graft persistence because of the unavoidable rejection reaction occuring against allogeneic transplant. For the production of such substitutes, it is essential to control the culture conditions for post-natal human stem cells. Furthermore, histological organization and functionality of reconstructed tissues must approach those of native organs. For self-renewing tissues such as skin and cornea, tissue engineering strategies must include the preservation of stem cells during the in vitro process as well as after grafting to ensure the long-term regeneration of the transplants. We described a tissue engineering method named the self-assembly approach allowing the production of autologous living organs from human cells without any exogenous biomaterial. This approach is based on the capacity of mesenchymal cells to create in vitro their own extracellular matrix and then reform a tissue. Thereafter, various techniques allow the reorganization of such tissues in more complex organ such as valve leaflets, blood vessels, skin or cornea. These tissues offer the hope of new alternatives for organ transplantation in the future. In this review, the importance of preserving stem cells during in vitro expansion and controlling cell differentiation as well as tissue organization to ensure quality and functionality of tissue-engineered organs will be discussed, while focusing on skin and cornea.

  8. Segmentation of epidermal tissue with histopathological damage in images of haematoxylin and eosin stained human skin.

    PubMed

    Haggerty, Juliana M; Wang, Xiao N; Dickinson, Anne; O'Malley, Chris J; Martin, Elaine B

    2014-02-12

    Digital image analysis has the potential to address issues surrounding traditional histological techniques including a lack of objectivity and high variability, through the application of quantitative analysis. A key initial step in image analysis is the identification of regions of interest. A widely applied methodology is that of segmentation. This paper proposes the application of image analysis techniques to segment skin tissue with varying degrees of histopathological damage. The segmentation of human tissue is challenging as a consequence of the complexity of the tissue structures and inconsistencies in tissue preparation, hence there is a need for a new robust method with the capability to handle the additional challenges materialising from histopathological damage. A new algorithm has been developed which combines enhanced colour information, created following a transformation to the L*a*b* colourspace, with general image intensity information. A colour normalisation step is included to enhance the algorithm's robustness to variations in the lighting and staining of the input images. The resulting optimised image is subjected to thresholding and the segmentation is fine-tuned using a combination of morphological processing and object classification rules. The segmentation algorithm was tested on 40 digital images of haematoxylin & eosin (H&E) stained skin biopsies. Accuracy, sensitivity and specificity of the algorithmic procedure were assessed through the comparison of the proposed methodology against manual methods. Experimental results show the proposed fully automated methodology segments the epidermis with a mean specificity of 97.7%, a mean sensitivity of 89.4% and a mean accuracy of 96.5%. When a simple user interaction step is included, the specificity increases to 98.0%, the sensitivity to 91.0% and the accuracy to 96.8%. The algorithm segments effectively for different severities of tissue damage. Epidermal segmentation is a crucial first step in

  9. Segmentation of epidermal tissue with histopathological damage in images of haematoxylin and eosin stained human skin

    PubMed Central

    2014-01-01

    Background Digital image analysis has the potential to address issues surrounding traditional histological techniques including a lack of objectivity and high variability, through the application of quantitative analysis. A key initial step in image analysis is the identification of regions of interest. A widely applied methodology is that of segmentation. This paper proposes the application of image analysis techniques to segment skin tissue with varying degrees of histopathological damage. The segmentation of human tissue is challenging as a consequence of the complexity of the tissue structures and inconsistencies in tissue preparation, hence there is a need for a new robust method with the capability to handle the additional challenges materialising from histopathological damage. Methods A new algorithm has been developed which combines enhanced colour information, created following a transformation to the L*a*b* colourspace, with general image intensity information. A colour normalisation step is included to enhance the algorithm’s robustness to variations in the lighting and staining of the input images. The resulting optimised image is subjected to thresholding and the segmentation is fine-tuned using a combination of morphological processing and object classification rules. The segmentation algorithm was tested on 40 digital images of haematoxylin & eosin (H&E) stained skin biopsies. Accuracy, sensitivity and specificity of the algorithmic procedure were assessed through the comparison of the proposed methodology against manual methods. Results Experimental results show the proposed fully automated methodology segments the epidermis with a mean specificity of 97.7%, a mean sensitivity of 89.4% and a mean accuracy of 96.5%. When a simple user interaction step is included, the specificity increases to 98.0%, the sensitivity to 91.0% and the accuracy to 96.8%. The algorithm segments effectively for different severities of tissue damage. Conclusions Epidermal

  10. Assessment of Breast, Brain and Skin Pathological Tissue Using Full Field OCM

    NASA Astrophysics Data System (ADS)

    Dalimier, Eugénie; Assayag, Osnath; Harms, Fabrice; Boccara, A. Claude

    The aim of this chapter is to assess whether the images of the breast, brain, and skin tissue obtained by FFOCM contain sufficient detail to allow pathologists to make a diagnosis of cancer and other pathologies comparable to what was obtained by conventional histological techniques. More precisely, it is necessary to verify on FFOCM images if it is possible to differentiate a healthy area from a pathological area. The reader interested in other organs or in animal studies may find a large number of 2D or 3D images in the atlas [2].

  11. Bone tissue heterogeneity is associated with fracture toughness: a polarization Raman spectroscopy study

    NASA Astrophysics Data System (ADS)

    Makowski, Alexander J.; Granke, Mathilde; Uppuganti, Sasidhar; Mahadevan-Jansen, Anita; Nyman, Jeffry S.

    2015-02-01

    Polarization Raman Spectroscopy has been used to demonstrate microstructural features and collagen fiber orientation in human and mouse bone, concurrently measuring both organization and composition; however, it is unclear as to what extent these measurements explain the mechanical quality of bone. In a cohort of age and gender matched cadaveric cortical bone samples (23-101 yr.), we show homogeneity of both composition and structure are associated with the age related decrease in fracture toughness. 64 samples were machined into uniform specimens and notched for mechanical fracture toughness testing and polished for Raman Spectroscopy. Fingerprint region spectra were acquired on wet bone prior to mechanical testing by sampling nine different microstructural features spaced in a 750x750 μm grid in the region of intended crack propagation. After ASTM E1820 single edge notched beam fracture toughness tests, the sample was dried in ethanol and the osteonal-interstitial border of one osteon was samples in a 32x32 grid of 2μm2 pixels for two orthogonal orientations relative to the long bone axis. Standard peak ratios from the 9 separate microstructures show heterogeneity between structures but do not sufficiently explain fracture toughness; however, peak ratios from mapping highlight both lamellar contrast (ν1Phos/Amide I) and osteon-interstitial contrast (ν1Phos/Proline). Combining registered orthogonal maps allowed for multivariate analysis of underlying biochemical signatures. Image entropy and homogeneity metrics of single principal components significantly explain resistance to crack initiation and propagation. Ultimately, a combination of polarization content and multivariate Raman signatures allowed for the association of microstructural tissue heterogeneity with fracture resistance.

  12. Identification of organ tissue types and skin from forensic samples by microRNA expression analysis.

    PubMed

    Sauer, Eva; Extra, Antje; Cachée, Philipp; Courts, Cornelius

    2017-05-01

    The identification of organ tissues in traces recovered from scenes and objects with regard to violent crimes involving serious injuries can be of considerable relevance in forensic investigations. Molecular genetic approaches are provably superior to histological and immunological assays in characterizing organ tissues, and micro-RNAs (miRNAs), due to their cell type specific expression patterns and stability against degradation, emerged as a promising molecular species for forensic analyses, with a range of tried and tested indicative markers. Thus, herein we present the first miRNA based approach for the forensic identification of organ tissues. Using quantitative PCR employing an empirically derived strategy for data normalization and unbiased statistical decision making, we assessed the differential expression of 15 preselected miRNAs in tissues of brain, kidney, lung, liver, heart muscle, skeletal muscle and skin. We show that not only can miRNA expression profiling be used to reliably differentiate between organ tissues but also that this method, which is compatible with and complementary to forensic DNA analysis, is applicable to realistic forensic samples e.g. mixtures, aged and degraded material as well as traces generated by mock stabbings and experimental shootings at ballistic models. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Study on the Effect of Blood Content on Diffuse Reflectance Spectra of Basal Cell Carcinoma Skin Tissue

    PubMed Central

    He, Qingli

    2013-01-01

    Diffuse reflectance spectrum as a noninvasive method has been widely used to study the optical properties of cutaneous skin tissue. In this work, we optimized an eight-layered optical model of basal cell carcinoma skin tissue to study its optical properties. Based on the model, the diffuse reflectance spectra were reconstructed in visible wavelength range by Monte Carlo methods. After different blood contents were added to the optical model, the contribution of blood to diffuese reflectance spectra was investigated theoretically. The ratios of basal cell carcinoma skin and normal skin tissue were also calculated for both experimental result and rebuilt results to testify the theoretical reasonability of the model and methods. PMID:24023527

  14. Skin and hair on-a-chip: in vitro skin models versus ex vivo tissue maintenance with dynamic perfusion.

    PubMed

    Ataç, Beren; Wagner, Ilka; Horland, Reyk; Lauster, Roland; Marx, Uwe; Tonevitsky, Alexander G; Azar, Reza P; Lindner, Gerd

    2013-09-21

    Substantial progress has been achieved over the last few decades in the development of skin equivalents to model the skin as an organ. However, their static culture still limits the emulation of essential physiological properties crucial for toxicity testing and compound screening. Here, we describe a dynamically perfused chip-based bioreactor platform capable of applying variable mechanical shear stress and extending culture periods. This leads to improvements of culture conditions for integrated in vitro skin models, ex vivo skin organ cultures and biopsies of single hair follicular units.

  15. Effect of microwaves at X-band on guinea-pig skin in tissue culture: 3. Effect of pulsed microwaves on skin respiration and biochemistry

    PubMed Central

    Carney, S. A.; Lawrence, J. C.; Ricketts, C. R.

    1970-01-01

    Carney, S. A., Lawrence, J. C., and Ricketts, C. R. (1970).Brit. J. industr. Med.,27, 72-76. Effect of microwaves at X-band on guinea-pig skin in tissue culture. 3. Effect of pulsed microwaves on skin respiration and biochemistry. Small pieces of guinea-pig skin were exposed to known power densities of pulsed microwaves at X-band (9·6 GHz). The pulse duration was 0·25 microsecond and the pulse repetition frequency 4 KHz. The peak power was thus 1,000 times the mean power. Otherwise conditions were closely comparable with those of previous experiments using continuous microwaves. After exposure the skin was maintained on a nutrient medium in vitro. The respiration of the skin and the uptake of 35S-sulphate, 32P-phosphate, and 14C-L-proline into skin constituents were reduced by exposure. The reduction was very similar to that observed after exposure to the same mean power density of continuous microwaves. The effects are believed to be attributable to heating of the skin. PMID:5418922

  16. Heterogeneity of Borrelia burgdorferi Sensu Stricto Population and Its Involvement in Borrelia Pathogenicity: Study on Murine Model with Specific Emphasis on the Skin Interface.

    PubMed

    Kern, Aurélie; Schnell, Gilles; Bernard, Quentin; Bœuf, Amandine; Jaulhac, Benoît; Collin, Elody; Barthel, Cathy; Ehret-Sabatier, Laurence; Boulanger, Nathalie

    2015-01-01

    Lyme disease is a multisystemic disorder caused by B. burgdorferi sl. The molecular basis for specific organ involvement is poorly understood. The skin plays a central role in the development of Lyme disease as the entry site of B. burgdorferi in which specific clones are selected before dissemination. We compared the skin inflammatory response (antimicrobial peptides, cytokines and chemokines) elicited by spirochete populations recovered from patients presenting different clinical manifestations. Remarkably, these spirochete populations induced different inflammatory profiles in the skin of C3H/HeN mice. As spirochete population transmitted into the host skin is heterogeneous, we isolated one bacterial clone from a population recovered from a patient with neuroborreliosis and compared its virulence to the parental population. This clone elicited a strong cutaneous inflammatory response characterized by MCP-1, IL-6 and antimicrobial peptides induction. Mass spectrometry of this clone revealed 110 overexpressed proteins when compared with the parental population. We further focused on the expression of nine bacterial surface proteins. bb0347 coding for a protein that interacts with host fibronectin, allowing bacterial adhesion to vascular endothelium and extracellular matrix, was found to be induced in host skin with another gene bb0213 coding for a hypothetical protein. These findings demonstrate the heterogeneity of the B. burgdorferi ss population and the complexity of the interaction involved early in the skin.

  17. Tissue characterization of skin ulcer for bacterial infection by multiple statistical analysis of echo amplitude envelope

    NASA Astrophysics Data System (ADS)

    Omura, Masaaki; Yoshida, Kenji; Kohta, Masushi; Kubo, Takabumi; Ishiguro, Toshimichi; Kobayashi, Kazuto; Hozumi, Naohiro; Yamaguchi, Tadashi

    2016-07-01

    To characterize skin ulcers for bacterial infection, quantitative ultrasound (QUS) parameters were estimated by the multiple statistical analysis of the echo amplitude envelope based on both Weibull and generalized gamma distributions and the ratio of mean to standard deviation of the echo amplitude envelope. Measurement objects were three rat models (noninfection, critical colonization, and infection models). Ultrasound data were acquired using a modified ultrasonic diagnosis system with a center frequency of 11 MHz. In parallel, histopathological images and two-dimensional map of speed of sound (SoS) were observed. It was possible to detect typical tissue characteristics such as infection by focusing on the relationship of QUS parameters and to indicate the characteristic differences that were consistent with the scatterer structure. Additionally, the histopathological characteristics and SoS of noninfected and infected tissues were matched to the characteristics of QUS parameters in each rat model.

  18. Handheld spatial frequency domain spectrographic imager for depth-sensitive, quantitative spectroscopy of skin tissue

    NASA Astrophysics Data System (ADS)

    Saager, Rolf B.; Dang, An N.; Huang, Samantha S.; Kelly, Kristen M.; Durkin, Anthony J.

    2017-02-01

    Here we present a handheld, implementation of Spatial Frequency Domain Spectroscopy (SFDS) that employs line imaging. The new instrument can measure 1088 spatial locations that span a 3 cm line as opposed to our benchtop system that only collects a single 1 mm diameter spot. This imager, however, retains the spectral resolution ( 1 nm) and range (450 to 1000 nm) of our benchtop system. The device also has tremendously improved mobility and portability, allowing for greater ease of use in clinical setting. A smaller size also enables access to different tissue locations, which increases the flexibility of the device. The design of this portable system not only enables SFDS to be used in clinical settings, but also enables visualization of properties of layered tissues such as skin.

  19. Radioresistance of granulation tissue-derived cells from skin wounds combined with total body irradiation.

    PubMed

    Dai, Tingyu; Chen, Zelin; Tan, Li; Shi, Chunmeng

    2016-04-01

    Combined radiation and wound injury (CRWI) occurs following nuclear explosions and accidents, radiological or nuclear terrorism, and radiation therapy combined with surgery. CRWI is complicated and more difficult to heal than single injuries. Stem cell‑based therapy is a promising treatment strategy for CRWI, however, sourcing stem cells remains a challenge. In the present study, the granulation tissue-derived cells (GTCs) from the skin wounds (SWs) of CRWI mice (C‑GTCs) demonstrated a higher radioresistance to the damage caused by combined injury, and were easier to isolate and harvest when compared with bone marrow‑derived mesenchymal stromal cells (BMSCs). Furthermore, the C-GTCs exhibited similar stem cell-associated properties, such as self-renewal and multilineage differentiation capacity, when compared with neonatal dermal stromal cells (DSCs) and GTCs from unirradiated SWs. Granulation tissue, which is easy to access, may present as an optimal autologous source of stem/progenitor cells for therapeutic applications in CRWI.

  20. Experimental testing and constitutive modeling of the mechanical properties of the swine skin tissue.

    PubMed

    Łagan, Sylwia D; Liber-Kneć, Aneta

    2017-01-01

    The aim of the study was an estimation of the possibility of using hyperelastic material models to fit experimental data obtained in the tensile test for the swine skin tissue. The uniaxial tensile tests of samples taken from the abdomen and back of a pig was carried out. The mechanical properties of the skin such as the mean Young's modulus, the mean maximum stress and the mean maximum elongation were calculated. The experimental data have been used to identify the parameters in specific strain-energy functions given in seven constitutive models of hyperelastic materials: neo-Hookean, Mooney-Rivlin, Ogden, Yeoh, Martins, Humphrey and Veronda-Westmann. An analysis of errors in fitting of theoretical and experimental data was done. Comparison of load -displacement curves for the back and abdomen regions of skin taken showed a different scope of both the mean maximum loading forces and the mean maximum elongation. Samples which have been prepared from the abdominal area had lower values of the mean maximum load compared to samples from the spine area. The reverse trend was observed during the analysis of the values of elongation. An analysis of the accuracy of model fitting to the experimental data showed that, the least accurate were the model of neo- -Hookean, model of Mooney-Rivlin for the abdominal region and model of Veronda-Westmann for the spine region. An analysis of seven hyperelastic material models showed good correlations between the experimental and the theoretical data for five models.

  1. Methicillin-Susceptible Staphylococcus aureus in Skin and Soft Tissue Infections, Northern Italy

    PubMed Central

    Tinelli, Marco; Monaco, Monica; Vimercati, Maurizio; Ceraminiello, Antonio

    2009-01-01

    During February 2004–September 2006, familial clusters and sporadic cases of Staphylococcus aureus skin and soft tissue infections were observed in a suburban area near Milan in northern Italy. Molecular typing of the isolates showed an epidemic methicillin-susceptible S. aureus (MSSA) strain, spa type 005 and sequence type 22 that harbored Panton-Valentine leukocidin (PVL) genes. The first case-patients were neonates or mothers who had recently delivered in the local hospital. Examination of the medical records showed a cluster of postpartum mastitis and neonatal skin infections antedating the emergence of infections in the community. Nasal swabs of neonates, mothers, and hospital staff were positive for the epidemic MSSA. Hospital circulation of the strain was interrupted by implementation of infection control measures, although infections continued to occur in the community. The PVL-positive MSSA strain resembles typical community-acquired methicillin-resistant S. aureus in its ability to cause prolonged community and hospital outbreaks of skin infections. PMID:19193269

  2. Novel keratin modified bacterial cellulose nanocomposite production and characterization for skin tissue engineering.

    PubMed

    Keskin, Zalike; Sendemir Urkmez, Aylin; Hames, E Esin

    2017-06-01

    As it is known that bacterial cellulose (BC) is a biocompatible and natural biopolymer due to which it has a large set of biomedical applications. But still it lacks some desired properties, which limits its uses in many other applications. Therefore, the properties of BC need to be boosted up to an acceptable level. Here in this study for the first time, a new natural nanocomposite was produced by the incorporating keratin (isolated from human hair) to the BC (produced by Acetobacter xylinum) to enhance dermal fibroblast cells' attachment. Two different approaches were used in BC based nanocomposite production: in situ and post modifications. BC/keratin nanocomposites were characterized using SEM, FTIR, EDX, XRD, DSC and XPS analyses. Both production methods have yielded successful results for production of BC based nanocomposite-containing keratin. In vitro cell culture experiments performed with human skin keratinocytes and human skin fibroblast cells indicate the potential of the novel BC/keratin nanocomposites for use in skin tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Composite cell support membranes based on collagen and polycaprolactone for tissue engineering of skin.

    PubMed

    Dai, N-T; Williamson, M R; Khammo, N; Adams, E F; Coombes, A G A

    2004-08-01

    The preparation and characterisation of collagen:PCL composites for manufacture of tissue engineered skin substitutes and models are reported. Films having collagen:PCL (w/w) ratios of 1:4, 1:8 and 1:20 were prepared by impregnation of lyophilised collagen mats by PCL solutions followed by solvent evaporation. In vitro assays of collagen release and residual collagen content revealed an expected inverse relationship between the collagen release rate and the content of synthetic polymer in the composite that may be exploited for controlled presentation and release of biopharmaceuticals such as growth factors. DSC analysis revealed the characteristic melting point of PCL at around 60 degrees C and a tendency for the collagen component, at high loading, to impede crystallinity development within the PCL phase. The preparation of fibroblast/composite constructs was investigated using cell culture as a first stage in mimicking the dermal/epidermal structure of skin. Fibroblasts were found to attach and proliferate on all the composites investigated reaching a maximum of 2 x 10(5)/cm(2) on 1:20 collagen:PCL materials at day 8 with cell numbers declining thereafter. Keratinocyte growth rates were similar on all types of collagen:PCL materials investigated reaching a maximum of 6.6 x 10(4)/cm(2) at day 6. The results revealed that composite films of collagen and PCL are favourable substrates for growth of fibroblasts and keratinocytes and may find utility for skin repair.

  4. Modeling of the Light Speckle Field Structure Inside a Multilayer Human Skin Tissue

    NASA Astrophysics Data System (ADS)

    Barun, V. V.; Dik, S. K.; Ivanov, A. P.; Abramovich, N. D.

    2013-11-01

    We present an analytic method and the results of investigating the characteristics of the interference pattern formed by multiply scattered light in a multilayer biological tissue of the type of human skin at the wavelengths of the visible and neat IR spectral regions under laser irradiation. Calculations were performed with the use of the known solutions of the equations of radiation transfer in the biotissue and the relation between the theory of propagation of light in a scattering medium and the coherence theory. The radial structure of the light field in the depth of the human skin formed by coherent and incoherent radiation depending on its biophysical parameters has been investigated. The characteristic sizes of speckles in each layer of the skin have been estimated. The biophysical factors connected with the volume concentration of blood in the dermis and the degree of its oxygenation influencing the contrast of the speckle pattern in the dermis have been discussed. The possibility of formulating and solving inverse problems of biomedical optics on the restoration of blood parameters from measurements of speckle characteristics has been shown.

  5. Analysis of blood and lymph vascularization patterns in tissue-engineered human dermo-epidermal skin analogs of different pigmentation.

    PubMed

    Klar, Agnieszka S; Böttcher-Haberzeth, Sophie; Biedermann, Thomas; Schiestl, Clemens; Reichmann, Ernst; Meuli, Martin

    2014-02-01

    Bioengineered dermo-epidermal skin analogs containing melanocytes represent a promising approach to cover large skin defects including restoration of the patient's own skin color. So far, little is known about the development of blood and lymphatic vessels in pigmented skin analogs after transplantation. In this experimental study, we analyzed the advancement and differences of host blood and lymphatic vessel ingrowth into light- and dark-pigmented human tissue-engineered skin analogs in a rat model. Keratinocytes, melanocytes, and fibroblasts from light- and dark-pigmented skin biopsies were isolated, cultured, and expanded. For each donor, melanocytes and keratinocytes were seeded in ratios of 1:1, 1:5, and 1:10 onto fibroblast-containing collagen gels. The skin analogs were subsequently transplanted onto full-thickness wounds of immuno-incompetent rats and quantitatively analyzed for vascular and lymphatic vessel density after 8 and 15 weeks. The skin analogs revealed a significant difference in vascularization patterns between light- and dark-pigmented constructs after 8 weeks, with a higher amount of blood vessels in light compared to dark skin. In contrast, no obvious difference could be detected within the light- and dark-pigmented group when varying melanocyte/keratinocyte ratios were used. However, after 15 weeks, the aforementioned difference in blood vessel density between light and dark constructs could no longer be detected. Regarding lymphatic vessels, light and dark analogs showed similar vessel density after 8 and 15 weeks, while there were generally less lymphatic than blood vessels. These data suggest that, at least during early skin maturation, keratinocytes, melanocytes, and fibroblasts from different skin color types used to construct pigmented dermo-epidermal skin analogs have distinct influences on the host tissue after transplantation. We speculate that different VEGF expression patterns might be involved in this disparate revascularization

  6. Analysis of laser surgery in non-melanoma skin cancer for optimal tissue removal

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, Félix; Salas-García, Irene; Arce-Diego, José Luis

    2015-02-01

    Laser surgery is a commonly used technique for tissue ablation or the resection of malignant tumors. It presents advantages over conventional non-optical ablation techniques, like a scalpel or electrosurgery, such as the increased precision of the resected volume, minimization of scars and shorter recovery periods. Laser surgery is employed in medical branches such as ophthalmology or dermatology. The application of laser surgery requires the optimal adjustment of laser beam parameters, taking into account the particular patient and lesion. In this work we present a predictive tool for tissue resection in biological tissue after laser surgery, which allows an a priori knowledge of the tissue ablation volume, area and depth. The model employs a Monte Carlo 3D approach for optical propagation and a rate equation for plasma-induced ablation. The tool takes into account characteristics of the specific lesion to be ablated, mainly the geometric, optical and ablation properties. It also considers the parameters of the laser beam, such as the radius, spatial profile, pulse width, total delivered energy or wavelength. The predictive tool is applied to dermatology tumor resection, particularly to different types of non-melanoma skin cancer tumors: basocellular carcinoma, squamous cell carcinoma and infiltrative carcinoma. The ablation volume, area and depth are calculated for healthy skin and for each type of tumor as a function of the laser beam parameters. The tool could be used for laser surgery planning before the clinical application. The laser parameters could be adjusted for optimal resection volume, by personalizing the process to the particular patient and lesion.

  7. Reversibility of D-penicillamine induced collagen alterations in rat skin and granulation tissue.

    PubMed

    Junker, P; Lorenzen, I

    1983-06-01

    Granulation tissue was produced in rats by subcutaneous implantation of Visella sponges. D-penicillamine (D-pen) 100 or 500 mg/kg was administered daily for 42 days by gastric tubing. Pairfed, placebo treated animals were included as controls. Half of the groups were kept for additionally 28 days without medication. The inhibitory effect of D-pen on cross-link formation in newly synthesized collagen was readily reversible. By contrast, cross-link deficiency lasting beyond the observation period was observed in the higher polymeric collagen variants released by dilute acid, heat exposure or limited pepsin proteolysis as estimated by solubility, alpha/beta chain ratio and/or aldehyde content. By SDS-polyacrylamide gel electrophoresis on gels containing 3.6 M urea it was shown that purified dermal acid soluble collagen from treated animals consisted of a mixture of type I and III collagen, whereas only type I collagen was detected in controls. The band pattern was identical in reduced and unreduced collagen samples. Four weeks after D-pen discontinuance type III collagen had disappeared from the acid extract. Moreover, the ratio of type III to type I collagen in the pepsin digest from both granulation tissue and skin showed a persistent rise with D-pen. These observations indicate that D-pen destabilized type III collagen in particular by interference with its disulfide linkages. The amount of granulation tissue remained unaffected throughout the experiment, whereas the skin collagen content decreased at the higher dose level. The regeneration was not completed by the end of the observation period. Modulation of the molecular stability of granuloma collagens may be of relevance for the antirheumatoid effect of D-pen, but the sustained effect on normal tissues may imply a long standing impairment of their supportive capacity.

  8. Modular Design of Artificial Tissue Homeostasis: Robust Control through Synthetic Cellular Heterogeneity

    PubMed Central

    Sontag, Eduardo; Davidsohn, Noah; Subramanian, Sairam; Purnick, Priscilla E. M.; Lauffenburger, Douglas; Weiss, Ron

    2012-01-01

    Synthetic biology efforts have largely focused on small engineered gene networks, yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge. Here we present the design, system integration, and analysis of several large scale synthetic gene circuits for artificial tissue homeostasis. Diabetes therapy represents a possible application for engineered homeostasis, where genetically programmed stem cells maintain a steady population of β-cells despite continuous turnover. We develop a new iterative process that incorporates modular design principles with hierarchical performance optimization targeted for environments with uncertainty and incomplete information. We employ theoretical analysis and computational simulations of multicellular reaction/diffusion models to design and understand system behavior, and find that certain features often associated with robustness (e.g., multicellular synchronization and noise attenuation) are actually detrimental for tissue homeostasis. We overcome these problems by engineering a new class of genetic modules for ‘synthetic cellular heterogeneity’ that function to generate beneficial population diversity. We design two such modules (an asynchronous genetic oscillator and a signaling throttle mechanism), demonstrate their capacity for enhancing robust control, and provide guidance for experimental implementation with various computational techniques. We found that designing modules for synthetic heterogeneity can be complex, and in general requires a framework for non-linear and multifactorial analysis. Consequently, we adapt a ‘phenotypic sensitivity analysis’ method to determine how functional module behaviors combine to achieve optimal system performance. We ultimately combine this analysis with Bayesian network inference to extract critical, causal relationships between a module's biochemical rate-constants, its high level functional behavior in isolation

  9. Skin and Soft Tissue Infection due to Rapidly Growing Mycobacteria: Case Series and Literature Review

    PubMed Central

    Yu, Jung Re; Lee, Keun Hwa; Kim, Jinseok; Sung, Jae Kyung; Kim, Young Ree; Kim, Jae Wang

    2013-01-01

    Background Nontuberculous mycobacteria (NTM) are ubiquitous in soil and water. Most NTM cause disease in humans only rarely unless some aspect of host defense is impaired. Recently, rapidly growing mycobacteria (RGM) is not uncommon, and the prevalence of RGM infection has been increasing. RGM causes a wide spectrum of pulmonary and extrapulmonary diseases and has been shown as an important source for opportunistic infection. Materials and Methods We report 5 patients of skin and soft tissue infection due to RGM in tertiary medical center in Jeju Island and analyzed 21 patients of skin and soft tissue infection due to RGM in Republic of Korea. Clinical, microbiological and epidemiological data were collected from each patient. NTM isolates were identified using conventional and molecular methods including 16S rDNA gene sequencing. Results The mean age of the RGM patients (n=26) was 54.9 ± 15.9 years and 73% were women. Mycobacterium fortuitum complex was the most common (12/26). Antimicrobial resistance for clarithromycin and quinolone were 12% and 60%, respectively. Clarithromycin based therapy was done in 46%. The mean duration of treatment was 21.2 ± 8.7 weeks. Conclusions Many cases can be cured after therapy for 4-7 month with at least 2 or 3 antibiotics according to in vitro susceptibility. Recent increasing of NTM cases suggests that species and subspecies identification is epidemiologically important, especially related to medical procedure, and surgery. PMID:24265954

  10. Gelatin-GAG electrospun nanofibrous scaffold for skin tissue engineering: fabrication and modeling of process parameters.

    PubMed

    Pezeshki-Modaress, Mohamad; Mirzadeh, Hamid; Zandi, Mojgan

    2015-03-01

    Electrospinning is a very useful technique for producing polymeric nanofibers by applying electrostatic forces. In this study, fabrication of novel gelatin/GAG nanofibrous mats and also the optimization of electrospinning process using response surface methodology were reported. At optimization section, gelatin/GAG blend ratio, applied voltage and feeding rate, their individual and interaction effects on the mean fiber diameter (MFD) and standard deviation of fiber diameter (SDF) were investigated. The obtained model for MFD has a quadratic relationship with gelatin/GAG blend ratio, applied voltage and feeding rate. The interactions of blend ratio and applied voltage and also applied voltage and flow rate were found significant but the interactions of blend ratio and flow rate were ignored. The optimum condition for gelatin/GAG electrospinning was also introduced using the model obtained in this study. The potential use of optimized electrospun mat in skin tissue engineering was evaluated using culturing of human dermal fibroblast cells (HDF). The SEM micrographs of HDF cells on the nanofibrous structure show that fibroblast cells can highly attach, grow and populate on the fabricated scaffold surface. The electrospun gelatin/GAG nanofibrous mats have a potential for using as scaffold for skin, cartilage and cornea tissue engineering.

  11. Thermal interaction of short-pulsed laser focused beams with skin tissues

    NASA Astrophysics Data System (ADS)

    Jiao, Jian; Guo, Zhixiong

    2009-07-01

    Time-dependent thermal interaction is developed in a skin tissue cylinder subjected to the irradiation of a train of short laser pulses. The skin embedded with a small tumor is stratified as three layers: epidermis, dermis and subcutaneous fat with different optical, thermal and physiological properties. The laser beam is focused to the tumor site by an objective lens for thermal therapy. The ultrafast radiation heat transfer of the focused beam is simulated by the transient discrete ordinates method. The transient Pennes bio-heat equation is solved numerically by the finite volume method with alternating direction implicit scheme. Emphasis is placed on the characterization of the focused beam propagation and absorption and the temperature rise in the focal spot. The effects of the focal spot size and location, the laser power, and the bio-heat equation are investigated. Comparisons with collimated irradiation are conducted. The focused beam can penetrate a greater depth and produce higher temperature rise at the target area, and thus reduce the possibility of thermal damage to the surrounding healthy tissue. It is ideal for killing cancerous cells and small tumors.

  12. Vibrational microscopy and imaging of skin: from single cells to intact tissue

    PubMed Central

    Zhang, Guojin; Moore, David J.; Mendelsohn, Richard

    2006-01-01

    Vibrational microscopy and imaging offer several advantages for a variety of dermatological applications, ranging from studies of isolated single cells (corneocytes) to characterization of endogenous components in intact tissue. Two applications are described to illustrate the power of these techniques for skin research. First, the feasibility of tracking structural alterations in the components of individual corneocytes is demonstrated. Two solvents, DMSO and chloroform/methanol, commonly used in dermatological research, are shown to induce large reversible alterations (α-helix to β-sheet) in the secondary structure of keratin in isolated corneocytes. Second, factor analysis of image planes acquired with confocal Raman microscopy to a depth of 70 μm in intact pigskin, demonstrates the delineation of specific skin regions. Two particular components that are difficult to identify by other means were observed in the epidermis. One small region was formed from a conformationally ordered lipid phase containing cholesterol. In addition, the presence of nucleated cells in the tissue (most likely keratinocytes) was revealed by the spectral signatures of the phosphodiester and cytosine moieties of cellular DNA. PMID:17160382

  13. Skin and Soft Tissue Infections due to Shewanella algae – An Emerging Pathogen

    PubMed Central

    Pillai, Meera; Vinod, Vivek; Dinesh, R. Kavitha

    2015-01-01

    Introduction: Shewanella spp. are emerging human pathogens, the predominant species being Shewanella algae. Shewanella skin and soft tissue infections are more commonly seen in immunocompromised patients with a pre-existing cutaneous ulcer and most often associated with exposure to marine environments. Aim: The study was conducted to investigate the epidemiological and clinical characteristics of Shewanella skin and soft tissue infections (SSTIs) for a period of five years. Materials and Methods: All Gram-negative non-fermenting motile isolates which produced pigmented colonies and positive for oxidase and H2S were further identified with Vitek 2 system. Results: A total of 16 patients with SSTIs due to Shewanella species were identified during the period from 2010 to 2014. Majority of patients were urban, elderly and fisher men. Shewanella algae (n=12, 75%) was the predominant isolate. Skin or mucosal portal of entry was found in all patients and seawater contact was recorded in 56.25% of the patients. 81% of infections were polymicrobial, common concomitant pathogens being gut and marine flora. Peripheral vascular diseases were the predominant risk factors with comorbidities like diabetes, hypertension and hepatobiliary diseases. Third generation cephalosporins, meropenem and gentamicin were the most effective antibiotics while two of the isolates were multidrug resistant. 75% of the infected patients recovered completely and three patients died of complications. Conclusion: Shewanella algae should be considered as an emerging pathogen of SSTIs mainly in patients with chronic ulcers and at times be multidrug resistant. These infections have a good clinical outcome if prompt medical, surgical and supportive treatment is offered. PMID:25859455

  14. Expression heterogeneity research of ITGB3 and BCL-2 in lung adenocarcinoma tissue and adenocarcinoma cell line.

    PubMed

    Xia, Zong-Jiang; Hu, Wei; Wang, Yue-Bin; Zhou, Kun; Sun, Guo-Ju

    2014-06-01

    To analyze expression heterogeneity of Integrin beta 3 (ITGB3) and B-cell lymphoma 2 (BCL-2) in lung adenocarcinoma tissue and adenocarcinoma cell line and further provide theoretical direction for molecular biological research of lung adenocarcinoma. Tissue microarray was used to observe relation among expression, heterogeneitpy and clinical characteristics of ITGB3 and BCL-2 in lung cancer. ITGB3 and BCL-2 increased significantly in A549 cells in CAFs group withβ-actin as control; the expression level of BCL-2 also increased in ITGB3 transfected cells with GFP plasmid transfected A549 cells as control; immunohistochemistry staining showed that positive rates of ITGB3, ITGB1 and BCL-2 in normal lung tissues were 0, the positive rates in lung adenocarcinoma were 7.04%, 84.51% and 4.23%, respectively; in the results of immunohistochemistry staining, the expression of Girdin protein in lung adenocarcinoma was homogeneous, however protein expression of ITGB3, ITGB1 and BCL-2 showed different patterns in the same location with significant heterogeneity; majority of ITGB3, ITGB1 or BCL-2 positive tissue showed heterogeneity that expression in trailing edge was higher than that of trailing edge in lung adenocarcinoma tissue, the patients with BCL-2 heterogeneity showed higher lymph node metastasis ratio and lower clinical stage (P<0.05); and the expression of ITGB3 and the clinical characteristics of patients were not significant related (P>0.05). Expression of ITGB3 and BCL-2 in lung adenocarcinoma and adenocarcinoma cell line showed heterogeneity that expression in trailing edge was higher than that of trailing edge, which may play an important role in promoting tumor lymph node metastasis and vascular invasion, and provides a new research direction for exploration of lung adenocarcinoma metastasis mechanism. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  15. Discrimination of non-melanoma skin lesions from non-tumor human skin tissues in vivo using Raman spectroscopy and multivariate statistics.

    PubMed

    Silveira, Fabricio L; Pacheco, Marcos T T; Bodanese, Benito; Pasqualucci, Carlos A; Zângaro, Renato A; Silveira, Landulfo

    2015-01-01

    Raman spectroscopy was used to discriminate human non-melanoma skin lesions from non-tumor tissues in vivo. This work proposed the discrimination between non-melanoma (basal cell carcinoma, BCC; squamous cell carcinoma, SCC) and pre-cancerous lesions (actinic keratosis, AK) from benign lesions and normal (non-tumor group, NT) tissues, using near-infrared Raman spectroscopy with a Raman probe. Prior to surgery, the spectra of suspicious lesions were obtained in situ. The spectra of adjacent, clinically normal skin were also obtained. Lesions were resectioned and submitted for histopathology. The Raman spectra were measured using a Raman spectrometer (830 nm). Two types of discrimination models were developed to distinguish the different histopathological groups. The principal components analysis discriminant analysis (PCA/DA) and the partial least squares discriminant analysis (PLS/DA) were based on Euclidean, quadratic and Mahalanobis distances. PCA and PLS spectral vectors showed spectral features of skin constituents, such as lipids (between 1,250 cm(-1) and 1,300 cm(-1) and at 1,450 cm(-1)) and proteins (between 870 cm(-1) and 940 cm(-1), 1,240 cm(-1) and 1,271 cm(-1), and at 1,000 cm(-1) and 1,450 cm(-1)). Despite the small spectral differences between malignant lesions and benign tissues, the algorithms discriminated the spectra of non-melanoma skin and pre-cancerous lesions from benign and normal tissues, with an overall accuracy of 82.8% and 91.9%, respectively. PCA and PLS could discriminate Raman spectra of skin tissues, opening the way for an in vivo optical diagnosis. © 2015 Wiley Periodicals, Inc.

  16. Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity

    PubMed Central

    Krönig, Malte; Walter, Max; Drendel, Vanessa; Werner, Martin; Jilg, Cordula A.; Richter, Andreas S.; Backofen, Rolf; McGarry, David; Follo, Marie; Schultze-Seemann, Wolfgang; Schüle, Roland

    2015-01-01

    A lack of cell surface markers for the specific identification, isolation and subsequent analysis of living prostate tumor cells hampers progress in the field. Specific characterization of tumor cells and their microenvironment in a multi-parameter molecular assay could significantly improve prognostic accuracy for the heterogeneous prostate tumor tissue. Novel functionalized gold-nano particles allow fluorescence-based detection of absolute mRNA expression levels in living cells by fluorescent activated flow cytometry (FACS). We use of this technique to separate prostate tumor and benign cells in human prostate needle biopsies based on the expression levels of the tumor marker alpha-methylacyl-CoA racemase (AMACR). We combined RNA and protein detection of living cells by FACS to gate for epithelial cell adhesion molecule (EPCAM) positive tumor and benign cells, EPCAM/CD45 double negative mesenchymal cells and CD45 positive infiltrating lymphocytes. EPCAM positive epithelial cells were further sub-gated into AMACR high and low expressing cells. Two hundred cells from each population and several biopsies from the same patient were analyzed using a multiplexed gene expression profile to generate a cell type resolved profile of the specimen. This technique provides the basis for the clinical evaluation of cell type resolved gene expression profiles as pre-therapeutic prognostic markers for prostate cancer. PMID:25514598

  17. The influence of stromal cells on the pigmentation of tissue-engineered dermo-epidermal skin grafts.

    PubMed

    Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Klar, Agnieszka S; Widmer, Daniel S; Pontiggia, Luca; Weber, Andreas D; Weber, Daniel M; Schiestl, Clemens; Meuli, Martin; Reichmann, Ernst

    2015-03-01

    It has been shown in vitro that melanocyte proliferation and function in palmoplantar skin is regulated by mesenchymal factors derived from fibroblasts. In this study, we investigated in vivo the influence of mesenchymal-epithelial interactions in human tissue-engineered skin substitutes reconstructed from palmar- and nonpalmoplantar-derived fibroblasts. Tissue-engineered dermo-epidermal analogs based on collagen type I hydrogels were populated with either human palmar or nonpalmoplantar fibroblasts and seeded with human nonpalmoplantar-derived melanocytes and keratinocytes. These skin substitutes were transplanted onto full-thickness skin wounds of immunoincompetent rats. Four weeks after transplantation the development of skin color was measured and grafts were excised and analyzed with regard to epidermal characteristics, in particular melanocyte number and function. Skin substitutes containing palmar-derived fibroblasts in comparison to nonpalmoplantar-derived fibroblasts showed (a) a significantly lighter pigmentation; (b) a reduced amount of epidermal melanin granules; and (c) a distinct melanosome expression. However, the number of melanocytes in the basal layer remained similar in both transplantation groups. These findings demonstrate that human palmar fibroblasts regulate the function of melanocytes in human pigmented dermo-epidermal skin substitutes after transplantation, whereas the number of melanocytes remains constant. This underscores the influence of site-specific stromal cells and their importance when constructing skin substitutes for clinical application.

  18. The Influence of Stromal Cells on the Pigmentation of Tissue-Engineered Dermo-Epidermal Skin Grafts

    PubMed Central

    Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Klar, Agnieszka S.; Widmer, Daniel S.; Pontiggia, Luca; Weber, Andreas D.; Weber, Daniel M.; Schiestl, Clemens; Meuli, Martin

    2015-01-01

    It has been shown in vitro that melanocyte proliferation and function in palmoplantar skin is regulated by mesenchymal factors derived from fibroblasts. In this study, we investigated in vivo the influence of mesenchymal–epithelial interactions in human tissue-engineered skin substitutes reconstructed from palmar- and nonpalmoplantar-derived fibroblasts. Tissue-engineered dermo-epidermal analogs based on collagen type I hydrogels were populated with either human palmar or nonpalmoplantar fibroblasts and seeded with human nonpalmoplantar-derived melanocytes and keratinocytes. These skin substitutes were transplanted onto full-thickness skin wounds of immunoincompetent rats. Four weeks after transplantation the development of skin color was measured and grafts were excised and analyzed with regard to epidermal characteristics, in particular melanocyte number and function. Skin substitutes containing palmar-derived fibroblasts in comparison to nonpalmoplantar-derived fibroblasts showed (a) a significantly lighter pigmentation; (b) a reduced amount of epidermal melanin granules; and (c) a distinct melanosome expression. However, the number of melanocytes in the basal layer remained similar in both transplantation groups. These findings demonstrate that human palmar fibroblasts regulate the function of melanocytes in human pigmented dermo-epidermal skin substitutes after transplantation, whereas the number of melanocytes remains constant. This underscores the influence of site-specific stromal cells and their importance when constructing skin substitutes for clinical application. PMID:25300246

  19. [Use of vacuum sealing drainage and mesh grafting in treating defects of skin and soft tissue in foot].

    PubMed

    Ye, Zhou; Zhan, Bei-Lei; Zhan, Yun-Zhong

    2010-03-01

    To explore the therapeutic effectiveness of vacuum sealing drainage (VSD) technique and mesh grafting in treating defects of skin and soft tissues in foot. A retrospective analysis was done on 17 cases (11 male and 6 female) suffering from defects of skin and soft tissues in foot, which were treated by vacuum sealing drainage and mesh grafting. The age of patients was from 18 to 67 years with an average of 43 years. The wound surface was filled with polyvinyl alcohol gelatin sponge after debridement and continuous negative pressure drainage was taken for 24 h. After 7 days, granulation tissue growing mesh grafting was performed and to observe the skin colour, survival rate and feet function. All the infection of wounds was controlled with VSD for 1 to 3 times. Skin survival rate of 14 cases more than 98%, 2 cases more than 95%; skin edge of 1 case had little necrosis, but foot function obtained rehabilitation after dress-changing. Vacuum sealing drainage (VSD) technique and mesh grafting is effective methods for the treatment of defects of skin and soft tissues in foot and is worthy generalization and application.

  20. The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

    SciTech Connect

    Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.; Lien, Katie A.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Sacksteder, Colette A.

    2012-12-01

    Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-γ, IL-2, MIP-1α, were significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-γ, MIP-1α, TNF α, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1α, IL-8, MIP-1α, MIP-1β, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.

  1. Psoriasis Skin Inflammation-Induced microRNA-26b Targets NCEH1 in Underlying Subcutaneous Adipose Tissue.

    PubMed

    Cheung, Louisa; Fisher, Rachel M; Kuzmina, Natalia; Li, Dongqing; Li, Xi; Werngren, Olivera; Blomqvist, Lennart; Ståhle, Mona; Landén, Ning Xu

    2016-03-01

    Psoriasis is an immune-mediated inflammatory disease, which is associated with a high risk of developing systemic comorbidities, such as obesity, cardiovascular disease, and diabetes mellitus. However, the mechanistic links between psoriatic skin inflammation and systemic comorbidities remain largely unknown. MicroRNAs (miRNAs) are recently discovered gene regulators that play important roles in psoriasis skin inflammation. In this study we aimed to explore whether the skin inflammation in psoriasis affects miRNA expression of the underlying subcutaneous adipose tissue and whether this may be a link between psoriasis and comorbidities. To this end, we compared the miRNA expression profile of subcutaneous adipose tissue underneath lesional and nonlesional psoriatic skin. We further validated the differential expression of several miRNAs and characterized their expression patterns in different cell types present in subcutaneous adipose tissue. We focused on miR-26b-5p, which was highly up-regulated in subcutaneous adipose tissue underneath lesional psoriasis skin. We showed that it targets and down-regulates neutral cholesterol ester hydrolase 1, an enzyme essential for cholesterol efflux, in monocytes/macrophages, adipocytes, vascular endothelial cells, and fibroblasts. We conclude that this miRNA may serve as a mechanistic link between psoriatic skin inflammation and its systemic comorbidities.

  2. Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections

    PubMed Central

    Weigelt, John; Itani, Kamal; Stevens, Dennis; Lau, William; Dryden, Matthew; Knirsch, Charles

    2005-01-01

    Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P = 0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P < 0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA. PMID:15917519

  3. Quality control of cultured tissues requires tools for quantitative analyses of heterogeneous features developed in manufacturing process.

    PubMed

    Kino-Oka, Masahiro; Takezawa, Yasunori; Taya, Masahito

    2009-02-01

    Tissue engineering and related technology have attracted a great deal of medical attention as promising fields for curing defective tissues in vivo. Nowadays, many companies have been established for supplying the reconstructed grafts of cultured tissues for transplantation. The manufacturing processes generally deals with the handlings of starter cells offered by patients (or donors) as raw materials to cultured tissues as products, requiring the construction of novel ex vivo methodologies based on principles different from conventional processes for chemical and pharmaceutical productions. In addition, the raw materials have heterogeneity depending on the state of patients and location of cell harvests, and the products possess spatial cell distribution in the three dimensional structure. These features request a unique strategy in manufacturing process accompanied with the quality control for raw materials and products. This review article describes the contribution of tissue bankers and biochemical engineers to the quality control of cultured tissues during manufacturing, introducing the advances in methodologies to evaluate spatial heterogeneity of cells (or aggregates) and matrices in cultured tissues.

  4. In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

    PubMed

    Walters, Russel M; Gandolfi, Lisa; Mack, M Catherine; Fevola, Michael; Martin, Katharine; Hamilton, Mathew T; Hilberer, Allison; Barnes, Nicole; Wilt, Nathan; Nash, Jennifer R; Raabe, Hans A; Costin, Gertrude-Emilia

    2016-12-01

    The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing. 2016 FRAME.

  5. How mitochondria record the effects of UV exposure and oxidative stress using human skin as a model tissue.

    PubMed

    Birch-Machin, Mark A; Swalwell, Helen

    2010-03-01

    The accumulation of mitochondrial DNA (mtDNA) mutations has been proposed as an underlying cause of the ageing process and mutations have been associated with cancer in many tissues, including human skin. This involvement is linked to the key roles of mitochondrial function and mtDNA in oxidative stress production and as a mediator of apoptosis. We and others have pioneered the use of mtDNA damage as a highly sensitive biomarker of ultraviolet exposure in human skin and have also shown that the accumulation of an ageing-dependent mtDNA mutation is accelerated by exposure to sunlight, which is known to induce oxidative stress in skin. This is important as ultraviolet radiation (UVR)-induced gene mutations play a key role in the development of skin cancer and ageing in human skin. Novel applications of mtDNA as a biomarker of UVR-induced oxidative stress will also be highlighted in this review.

  6. [Effect of topical application of aminoguanidine cream on skin tissue of rats with diabetes].

    PubMed

    Tian, Ming; Qing, Chun; Cao, Xiao-Zan; Niu, Yi-Wen; Lu, Shu-Liang

    2011-02-01

    To investigate the effects of aminoguanidine cream on the proliferation of keratinocytes (KC), content of advanced glycosylation end products (AGE) and oxidative stress in skin tissue of rats with diabetes. Stearic acid, liquid paraffin, vaseline, lanolin, isopropyl myristate fat, glycerol, 50 g/L alcohol paraben, aminoguanidine hydrochloride etc. were mixed in certain proportion to make aminoguanidine cream, and cream without aminoguanidine was used as matrix. The dorsal skin of normal rats were harvested and treated by aminoguanidine cream with dose of 5, 10 g/L, or 5 g/L together with 10 g/L azone. The transdermal effect was respectively measured at post treatment hour 2, 4, 7, 10, 12, 24. Thirty SD rats were divided into normal control (NC, n = 6), diabetes (D, n = 8), aminoguanidine cream-interfered (AI, n = 8), matrix cream-interfered groups (MI, n = 8) according to the random number table. Diabetes was reproduced by intraperitoneal injection of STZ (65 mg/kg) in rats of D, AI, and MI groups, and rats in NC group were injected with 0.05 mmol/L citrate buffer as control. One week later, dorsal skin of rats in AI and MI groups were respectively treated with 10 g/L aminoguanidine cream and matrix cream by external use for 4 weeks. AGE content was determined with fluorescence detection from skin collagen extract. KC cell cycle was detected by flow cytometry. Skin tissue specimens were obtained for determination of levels of superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO), and total antioxidant capacity. Data were processed with t test. Transdermal effect of aminoguanidine cream with dose of 10 g/L was better than that with 5 g/L or 5 g/L + 10 g/L azone cream. One rat was not induced successfully in MI group. Four weeks after model reproduction, 4 rats died in D group and 1 rat died in AI group. The AGE content in D group was obviously higher than that in NC group [(36.8 +/- 2.6), (24.6 +/- 2.7) U per milligram hydroxyproline, respectively

  7. Ultrahigh Detective Heterogeneous Photosensor Arrays with In-Pixel Signal Boosting Capability for Large-Area and Skin-Compatible Electronics.

    PubMed

    Kim, Jaehyun; Kim, Jaekyun; Jo, Sangho; Kang, Jingu; Jo, Jeong-Wan; Lee, Myungwon; Moon, Juhyuk; Yang, Lin; Kim, Myung-Gil; Kim, Yong-Hoon; Park, Sung Kyu

    2016-04-01

    An ultra-thin and large-area skin-compatible heterogeneous organic/metal-oxide photosensor array is demonstrated which is capable of sensing and boosting signals with high detectivity and signal-to-noise ratio. For the realization of ultra-flexible and high-sensitive heterogeneous photosensor arrays on a polyimide substrate having organic sensor arrays and metal-oxide boosting circuitry, solution-processing and room-temperature alternating photochemical conversion routes are applied. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Practical concept of pharmacokinetics/pharmacodynamics in the management of skin and soft tissue infections.

    PubMed

    Pea, Federico

    2016-04-01

    This article gives an overview of the practical concept of pharmacokinetic/pharmacodynamic principles useful for clinicians in the management of skin and soft tissue infections (SSTIs). Recent studies suggest that distinguishing between bacteriostatic or bactericidal activity when choosing an antimicrobial for the treatment of severe infections could probably be clinically irrelevant. Conversely, what could help clinicians in maximizing the therapeutic efficacy of the various drugs in routine practice is taking care of some pharmacokinetic/pharmacodynamic principles. Concentration-dependent agents may exhibit more rapid bacterial killing than observed with time-dependent agents. Serum concentrations may not always adequately predict tissue exposure in patients with SSTIs, and measuring concentrations at the infection site is preferable. Hydrophilic antimicrobials showed generally lower penetration rates than the lipophilic ones and might require alternative dosing approaches in the presence of severe sepsis or septic shock. Conversely, tissue penetration of lipophilic antimicrobials is often unaffected by the pathophysiological status. Real-time therapeutic drug monitoring may be a very helpful tool for optimizing therapy of severe infections. Taking care of pharmacokinetic/pharmacodynamic principles deriving from the most recent findings may help clinicians in maximizing treatment of SSTIs with antimicrobials in every situation.

  9. Characterizing the beam steering and distortion of Gaussian and Bessel beams focused in tissues with microscopic heterogeneities

    PubMed Central

    Chen, Ye; Liu, Jonathan T.C.

    2015-01-01

    Bessel beams have recently been investigated as a means of improving deep-tissue microscopy in highly scattering and heterogeneous media. It has been suggested that the long depth-of-field and self-reconstructing property of a Bessel beam enables an increased penetration depth of the focused beam in tissues compared to a conventional Gaussian beam. However, a study is needed to better quantify the magnitude of the beam steering as well as the distortion of focused Gaussian and Bessel beams in tissues with microscopic heterogeneities. Here, we have developed an imaging method and quantitative metrics to evaluate the motion and distortion of low-numerical-aperture (NA) Gaussian and Bessel beams focused in water, heterogeneous phantoms, and fresh mouse esophagus tissues. Our results indicate that low-NA Bessel beams exhibit reduced beam-steering artifacts and distortions compared to Gaussian beams, and are therefore potentially useful for microscopy applications in which pointing accuracy and beam quality are critical, such as dual-axis confocal (DAC) microscopy. PMID:25909015

  10. Characterizing the beam steering and distortion of Gaussian and Bessel beams focused in tissues with microscopic heterogeneities.

    PubMed

    Chen, Ye; Liu, Jonathan T C

    2015-04-01

    Bessel beams have recently been investigated as a means of improving deep-tissue microscopy in highly scattering and heterogeneous media. It has been suggested that the long depth-of-field and self-reconstructing property of a Bessel beam enables an increased penetration depth of the focused beam in tissues compared to a conventional Gaussian beam. However, a study is needed to better quantify the magnitude of the beam steering as well as the distortion of focused Gaussian and Bessel beams in tissues with microscopic heterogeneities. Here, we have developed an imaging method and quantitative metrics to evaluate the motion and distortion of low-numerical-aperture (NA) Gaussian and Bessel beams focused in water, heterogeneous phantoms, and fresh mouse esophagus tissues. Our results indicate that low-NA Bessel beams exhibit reduced beam-steering artifacts and distortions compared to Gaussian beams, and are therefore potentially useful for microscopy applications in which pointing accuracy and beam quality are critical, such as dual-axis confocal (DAC) microscopy.

  11. Grape skin extract mitigates tissue degeneration, genotoxicity, and oxidative status in multiple organs of rats exposed to cadmium.

    PubMed

    Boiago Gollucke, Andrea P; Claudio, Samuel R; Yamamura, Hirochi; Morais, Damila R; Bataglion, Giovana A; Eberlin, Marcos N; Aguiar, Odair; Ribeiro, Daniel A

    2016-07-28

    The aim of this study was to investigate whether grape skin extract can mitigate the noxious activities induced by cadmium exposure in multiple organs of rats. For this purpose, histopathological analysis for the liver, genotoxicity, and oxidative status in the blood and liver were investigated in this setting. A total of 20 Wistar rats weighing 250 g, on average, and 8 weeks of age were distributed into four groups (n=5) as follows: control group (nontreated group); cadmium group (Cd); and grape skin extract groups (Cd+GS) at 175 or 350 mg/l. Histopathological analysis in liver showed that animals treated with grape skin extract showed improved tissue degeneration induced by cadmium intoxication. Genetic damage was reduced in blood and hepatocytes as indicated by comet and micronucleus assays in animals treated with grape skin extract. Copper-zinc superoxide dismutase and cytochrome c gene expression increased in groups treated with grape skin extract in liver cells. Grape skin extract also reduced the 8-hydroxy-2'-deoxyguanosine levels in liver cells compared with the cadmium group. Taken together, our results indicate that grape skin extract can mitigate tissue degeneration, genotoxicity, and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.

  12. A Nth-order linear algorithm for extracting diffuse correlation spectroscopy blood flow indices in heterogeneous tissues

    SciTech Connect

    Shang, Yu; Yu, Guoqiang

    2014-09-29

    Conventional semi-infinite analytical solutions of correlation diffusion equation may lead to errors when calculating blood flow index (BFI) from diffuse correlation spectroscopy (DCS) measurements in tissues with irregular geometries. Very recently, we created an algorithm integrating a Nth-order linear model of autocorrelation function with the Monte Carlo simulation of photon migrations in homogenous tissues with arbitrary geometries for extraction of BFI (i.e., αD{sub B}). The purpose of this study is to extend the capability of the Nth-order linear algorithm for extracting BFI in heterogeneous tissues with arbitrary geometries. The previous linear algorithm was modified to extract BFIs in different types of tissues simultaneously through utilizing DCS data at multiple source-detector separations. We compared the proposed linear algorithm with the semi-infinite homogenous solution in a computer model of adult head with heterogeneous tissue layers of scalp, skull, cerebrospinal fluid, and brain. To test the capability of the linear algorithm for extracting relative changes of cerebral blood flow (rCBF) in deep brain, we assigned ten levels of αD{sub B} in the brain layer with a step decrement of 10% while maintaining αD{sub B} values constant in other layers. Simulation results demonstrate the accuracy (errors < 3%) of high-order (N ≥ 5) linear algorithm in extracting BFIs in different tissue layers and rCBF in deep brain. By contrast, the semi-infinite homogenous solution resulted in substantial errors in rCBF (34.5% ≤ errors ≤ 60.2%) and BFIs in different layers. The Nth-order linear model simplifies data analysis, thus allowing for online data processing and displaying. Future study will test this linear algorithm in heterogeneous tissues with different levels of blood flow variations and noises.

  13. A Nth-order linear algorithm for extracting diffuse correlation spectroscopy blood flow indices in heterogeneous tissues.

    PubMed

    Shang, Yu; Yu, Guoqiang

    2014-09-29

    Conventional semi-infinite analytical solutions of correlation diffusion equation may lead to errors when calculating blood flow index (BFI) from diffuse correlation spectroscopy (DCS) measurements in tissues with irregular geometries. Very recently, we created an algorithm integrating a Nth-order linear model of autocorrelation function with the Monte Carlo simulation of photon migrations in homogenous tissues with arbitrary geometries for extraction of BFI (i.e., αDB ). The purpose of this study is to extend the capability of the Nth-order linear algorithm for extracting BFI in heterogeneous tissues with arbitrary geometries. The previous linear algorithm was modified to extract BFIs in different types of tissues simultaneously through utilizing DCS data at multiple source-detector separations. We compared the proposed linear algorithm with the semi-infinite homogenous solution in a computer model of adult head with heterogeneous tissue layers of scalp, skull, cerebrospinal fluid, and brain. To test the capability of the linear algorithm for extracting relative changes of cerebral blood flow (rCBF) in deep brain, we assigned ten levels of αDB in the brain layer with a step decrement of 10% while maintaining αDB values constant in other layers. Simulation results demonstrate the accuracy (errors < 3%) of high-order (N ≥ 5) linear algorithm in extracting BFIs in different tissue layers and rCBF in deep brain. By contrast, the semi-infinite homogenous solution resulted in substantial errors in rCBF (34.5% ≤ errors ≤ 60.2%) and BFIs in different layers. The Nth-order linear model simplifies data analysis, thus allowing for online data processing and displaying. Future study will test this linear algorithm in heterogeneous tissues with different levels of blood flow variations and noises.

  14. Monte Carlo simulation of radiation transport in human skin with rigorous treatment of curved tissue boundaries.

    PubMed

    Majaron, Boris; Milanič, Matija; Premru, Jan

    2015-01-01

    In three-dimensional (3-D) modeling of light transport in heterogeneous biological structures using the Monte Carlo (MC) approach, space is commonly discretized into optically homogeneous voxels by a rectangular spatial grid. Any round or oblique boundaries between neighboring tissues thus become serrated, which raises legitimate concerns about the realism of modeling results with regard to reflection and refraction of light on such boundaries. We analyze the related effects by systematic comparison with an augmented 3-D MC code, in which analytically defined tissue boundaries are treated in a rigorous manner. At specific locations within our test geometries, energy deposition predicted by the two models can vary by 10%. Even highly relevant integral quantities, such as linear density of the energy absorbed by modeled blood vessels, differ by up to 30%. Most notably, the values predicted by the customary model vary strongly and quite erratically with the spatial discretization step and upon minor repositioning of the computational grid. Meanwhile, the augmented model shows no such unphysical behavior. Artifacts of the former approach do not converge toward zero with ever finer spatial discretization, confirming that it suffers from inherent deficiencies due to inaccurate treatment of reflection and refraction at round tissue boundaries.

  15. Evaluation of peripheral vasodilative indices in skin tissue of type 1 diabetic rats by use of RGB images

    NASA Astrophysics Data System (ADS)

    Tanaka, Noriyuki; Nishidate, Izumi; Nakano, Kazuya; Aizu, Yoshihisa; Niizeki, Kyuichi

    2016-04-01

    We investigated a method to evaluate the arterial inflow and the venous capacitance in the skin tissue of streptozotocin-induced type 1 diabetic rats from RGB digital color images. The arterial inflow and the venous capacitance in the dorsal reversed McFarlane skin flap are calculated based on the responses of change in the total blood concentration to occlusion of blood flow to and from the flap tissues at a pressure of 50 mmHg. The arterial inflow and the venous capacitance in the skin flap tissue were significantly reduced in type 1 diabetic rat group compared with the non-diabetic rat group. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular dysfunctions in diabetes mellitus.

  16. Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss.

    PubMed

    Swift, Joshua M; Swift, Sibyl N; Smith, Joan T; Kiang, Juliann G; Allen, Matthew R

    2015-12-01

    The present study investigated the detrimental effects of non-lethal, high-dose (whole body) γ-irradiation on bone, and the impact that radiation combined with skin trauma (i.e. combined injury) has on long-term skeletal tissue health. Recovery of bone after an acute dose of radiation (RI; 8 Gy), skin wounding (15-20% of total body skin surface), or combined injury (RI+Wound; CI) was determined 3, 7, 30, and 120 days post-irradiation in female B6D2F1 mice and compared to non-irradiated mice (SHAM) at each time-point. CI mice demonstrated long-term (day 120) elevations in serum TRAP 5b (osteoclast number) and sclerostin (bone formation inhibitor), and suppression of osteocalcin levels through 30 days as compared to SHAM (p<0.05). Radiation-induced reductions in distal femur trabecular bone volume fraction and trabecular number through 120 days post-exposure were significantly greater than non-irradiated mice (p<0.05) and were exacerbated in CI mice by day 30 (p<0.05). Negative alterations in trabecular bone microarchitecture were coupled with extended reductions in cancellous bone formation rate in both RI and CI mice as compared to Sham (p<0.05). Increased osteoclast surface in CI animals was observed for 3 days after irradiation and remained elevated through 120 days (p<0.01). These results demonstrate a long-term, exacerbated response of bone to radiation when coupled with non-lethal wound trauma. Changes in cancellous bone after combined trauma were derived from extended reductions in osteoblast-driven bone formation and increases in osteoclast activity.

  17. Staphylococcus lugdunensis, a Common Cause of Skin and Soft Tissue Infections in the Community▿

    PubMed Central

    Böcher, Sidsel; Tønning, Birgitte; Skov, Robert L.; Prag, Jørgen

    2009-01-01

    Staphylococcus lugdunensis, a rare cause of severe infections such as native valve endocarditis, often causes superficial skin infections similar to Staphylococcus aureus infections. We initiated a study to optimize the identification methods in the routine laboratory, followed by a population-based epidemiologic analysis of patients infected with S. lugdunensis in Viborg County, Denmark. Recognition of a characteristic Eikenella corrodens-like odor on Columbia sheep blood agar combined with colony pleomorphism and prominent β-hemolysis after 2 days of incubation, confirmed by API-ID-32 Staph, led to an 11-fold increase in the detection of S. lugdunensis. By these methods we found 491 S. lugdunensis infections in 4 years, corresponding to an incidence of 53 per 100,000 per year, an increase from 5 infections per 100,000 inhabitants in the preceding years. Seventy-five percent of the cases were found in general practice; these were dominated by skin abscesses (36%), wound infections (25%), and paronychias (13%). Fifty-six percent of the infections occurred below the waist, and toes were the most frequently infected site (21%). Only 3% of the patients suffered from severe invasive infections. The median age was 52 years, and the male/female ratio was 0.69. Our study shows that S. lugdunensis is a common cause of skin and soft-tissue infections (SSTI) and is probably underrated by many laboratories. S. lugdunensis should be accepted as a significant pathogen in SSTI and should be looked for in all routine bacteriological examinations, and clinicians should be acquainted with the name and the pathology of the bacterium. PMID:19244465

  18. Optical coherence tomography microangiography for monitoring the response of vascular perfusion to external pressure on human skin tissue

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Wang, Hequn; Wang, Ruikang K.

    2014-05-01

    Characterization of the relationship between external pressure and blood flow is important in the examination of pressure-induced disturbance in tissue microcirculation. Optical coherence tomography (OCT)-based microangiography is a promising imaging technique, capable of providing the noninvasive extraction of functional vessels within the skin tissue with capillary-scale resolution. Here, we present a feasibility study of OCT microangiography (OMAG) to evaluate changes in blood perfusion in response to externally applied pressure on human skin tissue in vivo. External force is loaded normal to the tissue surface at the nailfold region of a healthy human volunteer. An incremental force is applied step by step and then followed by an immediate release. Skin perfusion events including baseline are continuously imaged by OMAG, allowing for visualization and quantification of the capillary perfusion in the nailfold tissue. The tissue strain maps are simultaneously evaluated through the available OCT structural images to assess the relationship of the microcirculation response to the applied pressure. The results indicate that the perfusion progressively decreases with the constant increase of pressure. Reactive hyperemia occurs right after the removal of the pressure. The perfusion returns to the baseline level after a few minutes. These findings suggest that OMAG may have great potential for quantitatively assessing tissue microcirculation in the locally pressed tissue in vivo.

  19. TISSUE-SPECIFIC VENOUS EXPRESSION OF THE EPH FAMILY RECEPTOR EPHB1 IN THE SKIN VASCULATURE

    PubMed Central

    Li, Wenling; Mukouyama, Yoh-suke

    2013-01-01

    Background The major arteries and veins are formed early during development. The molecular tools to identify arterial and venous endothelial cells improve our understanding of arterial-venous differentiation and branching morphogenesis. Compared to arterial differentiation, relatively little is known about what controls venous development, due to a lack of definitive molecular markers for venous endothelial cells. Results Here we report that the antibody against EphB1, an EphB class receptor, makes it possible to establish a reliable whole-mount immunohistochemical analysis of venous identity with greater resolution than previously possible in embryonic and adult skin vasculature models. EphB1 expression is restricted to the entire venous vasculature throughout embryonic development to adulthood, whereas the previously established venous marker EphB4 is also detectable in lymphatic vasculature. This venous-restricted expression of EphB1 is established after the vascular remodeling of the primary capillary plexus has occurred. Compared to its venous-specific expression in the skin, however, EphB1 is not restricted to the venous vasculature in yolk sac, trunk and lung. Conclusions These studies introduce EphB1 as a new venous-restricted marker in a tissue-specific and time-dependent manner. PMID:23649798

  20. Biocompatibility of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers for skin tissue engineering.

    PubMed

    Sundaramurthi, Dhakshinamoorthy; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2013-08-01

    Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) a biodegradable polymer, was electrospun to obtain defect-free nanofibers. The structural similarity of PHBV nanofibers and the extracellular matrix in skin may present well for fibroblast cell adhesion and proliferation. The average fiber diameter of the electrospun fibers was 583 +/- 90 nm. The potential of PHBV scaffolds for human keratinocytes (HaCaT) adhesion, proliferation and gene expression were evaluated. Our results demonstrated that PHBV nanofibers favor HaCaT adhesion and proliferation. After 14 days of culture, loricrin and keratin-1 gene expression were significantly higher when compared to 3 and 7 days (p < 0.05). The expression of genes associated with T lymphocyte activation (HLA-DRB, thymosin beta 10 (h-Tim)) and IL-2 mediated lymphocyte activation genes (h-Tim, Tumour Rejection Antigen (TRA 1), nRap 2) were investigated in human lymphocyte cultured on PHBV nanofibers. T Lymphocyte activation and IL-2 mediated lymphocyte activation genes were down-regulated after 48 and 72 hours of culture. After 24, 48 and 72 hours of culture there was no inflammatory cytokines production by the cultured lymphocytes. Thus, our results confirm the biocompatibility of PHBV nanofibers and suggest that consideration can be given to the use of PHBV nanofibers for skin tissue engineering applications.

  1. New nanotechnology for the guided tissue regeneration of skin--potential of lyotropic liquid crystals.

    PubMed

    Yamaguchi, Y; Nagasawa, T; Kitagawa, A; Nakamura, N; Matsumoto, K; Uchiwa, H; Hirata, K; Igarashi, R

    2006-02-01

    Tissue in body must quickly recognize injury to response to the rapid pace of epidermal growth. In skin, the epidermal cells must also react to danger signals from the surrounding extracellular lipid of the stratum corneum spaces and immediately participate by initiating the wound repair process. The topical administration of the lyotropic liquid crystal nanocube to stratum corneum rapidly broke down the lipid lamella structure which would be recognized as a wound without organ-change. This can activate a variety of biological processes. This study set out to determine whether the phase transition of the lipid to a neighbouring different physicochemical structure can stimulate keratinocyte cells and what mechanism is responsible for this response. Using small angle x-ray scattering (SAXS) analysis, a response to the transient structural change of lipid was detected which might result from the diffusion of oil and/or water from nanocube liquid crystal towards the lipid lamella phase. Simultaneously, a significant increase in growth factors and inflammatory cytokines was detected after administration of nanocube. Not only the excess expression of cytokines but also the extent of TEWL as a barrier marker of skin increased. These observations suggest that a structural change in lipid can stimulate and trigger recognition of a slight injury in the wound defence and a repair response as homeostasis. This method actually succeeded in improving photo-induced hyperpigmentation on a human face.

  2. Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients

    PubMed Central

    Stratton, Richard; Shiwen, Xu; Martini, Giorgia; Holmes, Alan; Leask, Andrew; Haberberger, Thomas; Martin, George R.; Black, Carol M.; Abraham, David

    2001-01-01

    Patients with scleroderma receiving Iloprost as a treatment for severe Raynaud’s phenomenon report a reduction in skin tightness, suggesting that this drug inhibits skin fibrosis. Connective tissue growth factor (CTGF), a recently described profibrotic cytokine, acts downstream and in concert with TGF-β to stimulate the fibrotic process and is involved in the fibrosis seen in scleroderma. Here we show that Iloprost, acting by elevation of cAMP, blocks the induction of CTGF and the increase in collagen synthesis in fibroblasts exposed to TGF-β. The potency of Iloprost with respect to suppression of CTGF far exceeds that of other prostanoid receptor agonists, suggesting that its effect is mediated by the prostacyclin receptor IP. By sampling dermal interstitial fluid using a suction blister device, we show that CTGF levels are greatly elevated in the dermis of scleroderma patients compared with healthy controls and that Iloprost infusion causes a marked decrease in dermal CTGF levels. These studies suggest that Iloprost could be reducing the level of a key profibrotic cytokine in scleroderma patients and that endogenous production of eicosanoids may limit the fibrotic response to TGF-β. PMID:11457877

  3. Investigation of the effect of hydration on dermal collagen in ex vivo human skin tissue using second harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Samatham, Ravikant; Wang, Nicholas K.; Jacques, Steven L.

    2016-02-01

    Effect of hydration on the dermal collagen structure in human skin was investigated using second harmonic generation microscopy. Dog ears from the Mohs micrographic surgery department were procured for the study. Skin samples with subject aged between 58-90 years old were used in the study. Three dimensional Multiphoton (Two-photon and backward SHG) control data was acquired from the skin samples. After the control measurement, the skin tissue was either soaked in deionized water for 2 hours (Hydration) or kept at room temperature for 2 hours (Desiccation), and SHG data was acquired. The data was normalized for changes in laser power and detector gain. The collagen signal per unit volume from the dermis was calculated. The desiccated skin tissue gave higher backward SHG compared to respective control tissue, while hydration sample gave a lower backward SHG. The collagen signal decreased with increase in hydration of the dermal collagen. Hydration affected the packing of the collagen fibrils causing a change in the backward SHG signal. In this study, the use of multiphoton microscopy to study the effect of hydration on dermal structure was demonstrated in ex vivo tissue.

  4. Mapping tissue shear modulus on Thiel soft-embalmed mouse skin with shear wave optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Song, Shaozhen; Joy, Joyce; Wang, Ruikang K.; Huang, Zhihong

    2015-03-01

    A quantitative measurement of the mechanical properties of biological tissue is a useful assessment of its physiologic conditions, which may aid medical diagnosis and treatment of, e.g., scleroderma and skin cancer. Traditional elastography techniques such as magnetic resonance elastography and ultrasound elastography have limited scope of application on skin due to insufficient spatial resolution. Recently, dynamic / transient elastography are attracting more applications with the advantage of non-destructive measurements, and revealing the absolute moduli values of tissue mechanical properties. Shear wave optical coherence elastography (SW-OCE) is a novel transient elastography method, which lays emphasis on the propagation of dynamic mechanical waves. In this study, high speed shear wave imaging technique was applied to a range of soft-embalmed mouse skin, where 3 kHz shear waves were launched with a piezoelectric actuator as an external excitation. The shear wave velocity was estimated from the shear wave images, and used to recover a shear modulus map in the same OCT imaging range. Results revealed significant difference in shear modulus and structure in compliance with gender, and images on fresh mouse skin are also compared. Thiel embalming technique is also proven to present the ability to furthest preserve the mechanical property of biological tissue. The experiment results suggest that SW-OCE is an effective technique for quantitative estimation of skin tissue biomechanical status.

  5. Novel wearable-type biometric devices based on skin tissue optics with multispectral LED–photodiode matrix

    NASA Astrophysics Data System (ADS)

    Jo, Young Chang; Kim, Hae Na; Kang, Jae Hwan; Hong, Hyuck Ki; Choi, Yeon Shik; Jung, Suk Won; Kim, Sung Phil

    2017-04-01

    In this study, we examined the possibility of using a multispectral skin photomatrix (MSP) module as a novel biometric device. The MSP device measures optical patterns of the wrist skin tissue. Optical patterns consist of 2 × 8 photocurrent intensities of photodiode arrays, which are generated by optical transmission and diffuse reflection of photons from LED light sources with variable wavelengths into the wrist skin tissue. Optical patterns detected by the MSP device provide information on both the surface and subsurface characteristics of the human skin tissue. We found that in the 21 subjects we studied, they showed their unique characteristics, as determined using several wavelengths of light. The experimental results show that the best personal identification accuracy can be acquired using a combination of infrared light and yellow light. This novel biometric device, the MSP module, exhibited an excellent false acceptance rate (FAR) of 0.3% and a false rejection rate (FRR) of 0.0%, which are better than those of commercialized biometric devices such as a fingerprint biometric system. From these experimental results, we found that people exhibit unique optical patterns of their inner-wrist skin tissue and this uniqueness could be used for developing novel high-accuracy personal identification devices.

  6. Management of Skin and Soft Tissue Infections in a County Correctional Center: A Quality Improvement Project.

    PubMed

    Mullen, Lisa A; O'Keefe, Catherine

    2015-10-01

    The number of antibiotic-resistant infections continues to increase. In 2005, there were nearly 11,406 deaths from methicillin-resistant Staphylococcus aureus (MRSA) infection in the United States. Since 1980, the United States has seen a 300% increase in the rate of incarceration. This is noteworthy because individuals who enter correctional facilities have an increased risk for MRSA skin and soft tissue infections (SSTIs) and the risk of colonization proportional to the length of stay. Correctional institutions have a vested interest in improving the screening and treatment of MRSA SSTIs, as it is a costly and potentially preventable problem. This article describes the process of implementing an MRSA screening and treatment policy in a county correctional center.

  7. Alcaligenes faecalis: an unusual cause of skin and soft tissue infection.

    PubMed

    Tena, Daniel; Fernández, Cristina; Lago, María R

    2015-01-01

    Skin and soft tissue infection (SSTI) due to Alcaligenes faecalis is very rare and has never been studied. The aim of the present study was to investigate the clinical and microbiological characteristics of this infection. We conducted a retrospective review of 5 cases that occurred at our institution over a period of 6 years. All patients had underlying diseases, and infection was secondary to vascular disease or recent surgery in 4 of them. The most common clinical presentations were vascular ulcer infection and surgical site infection. The clinical outcome was uniformly good after treatment, except in 1 patient. In conclusion, A. faecalis should be considered a potential pathogen of SSTI, particularly in patients with vascular diseases or after surgery. The history of contact with water or aqueous solutions should be investigated in all cases. The clinical outcome is usually good, but treatment can be difficult in some cases due to the high level of resistance to commonly used antibiotics.

  8. Crosslinked hydrogels based on biological macromolecules with potential use in skin tissue engineering.

    PubMed

    Vulpe, Raluca; Popa, Marcel; Picton, Luc; Balan, Vera; Dulong, Virginie; Butnaru, Maria; Verestiuc, Liliana

    2016-03-01

    Zero-length crosslinked hydrogels have been synthesized by covalent linking of three natural polymers (collagen, hyaluronic acid and sericin), in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The hydrogels have been investigated by FT-IR spectroscopy, microcalorimetry, in vitro swelling, enzymatic degradation, and in vitro cell viability studies. The obtained crosslinked hydrogels showed a macroporous structure, high swelling degree and in vitro enzymatic resistance compared to uncrosslinked collagen. The in vitro cell viability studies performed on normal human dermal fibroblasts assessed the sericin proliferation properties indicating a potential use of the hydrogels based on collagen, hyaluronic acid and sericin in skin tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Evaluation of nanofibrous scaffolds obtained from blends of chitosan, gelatin and polycaprolactone for skin tissue engineering.

    PubMed

    Gomes, Susana; Rodrigues, Gabriela; Martins, Gabriel; Henriques, Célia; Silva, Jorge Carvalho

    2017-09-01

    Polymer blending is a strategy commonly used to obtain hybrid materials possessing properties better than those of the individual constituents regarding their use in scaffolds for Tissue Engineering. In the present work, the scaffolds produced by electrospinning solutions of polymeric blends obtained using a polyester (polycaprolactone, PCL), a polysaccharide (chitosan, CS) and a protein (gelatin extracted from cold water fish skin, GEL), were investigated. Solutions conductivity, shear viscosity and surface tension were determined. GEL-containing scaffolds were crosslinked with vapour phase glutaraldehyde (GTA). The scaffolds were characterized physico-chemically regarding fibre morphology, porosity, water contact angle, mechanical properties, chemical bonds and fibre and dimensional stability upon immersion in water and cell culture medium. The scaffolds were further tested in vitro for cell adhesion, growth and morphology of human foetal fibroblasts (cell line HFFF2). Results show that the nanofibrous scaffolds are hydrophilic and display the typical porosity of non-woven fibre mats. The CS/PCL and CS/PCL/GEL scaffolds have the highest elastic modulus (48MPa). Dimensional stability is best for the CS/PCL/GEL scaffolds. FTIR spectra confirm the occurrence of cross-linking reactions of GTA with both GEL and CS. Cell adhesion ratio ranked from excellent (close to 100%) to satisfactory (around 50%) in the order PCL/GEL>CS/GEL>CS/PCL/GEL>CS/PCL. Cell populations show an extended lag phase in comparison with the controls but cell proliferation occurs on all scaffolds until confluence is reached. In conclusion, all scaffolds studied possess characteristics that enable them to be used in skin tissue engineering but the CS/PCL/GEL scaffolds have better physical properties whereas the PCL/GEL scaffolds support a higher cell adhesion. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Tedizolid: A New Oxazolidinone Antibiotic for Skin and Soft Tissue Infections.

    PubMed

    Chahine, Elias B; Sucher, Allana J; Knutsen, Shannon D

    2015-07-01

    To review the chemistry, pharmacology, microbiology, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug interactions, dosing, and administration of tedizolid phosphate (TDZ). A search of PubMed using the terms "tedizolid," "torezolid," "TR-701," "TR-700," "DA-7157," and "DA-7218" was performed. The manufacturer's Web site was also reviewed to further identify relevant information. All English-language articles from 2006 to November 2014 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not uncovered in the searches. TDZ is the second oxazolidinone antibiotic with a spectrum of activity targeted against gram-positive organisms including methicillin-resistant Staphylococcus aureus . It is administered via intravenous infusion or orally without regard to food. The primary route of elimination is fecal excretion. Advanced age, hepatic dysfunction, or renal impairment does not alter its disposition. Phase III clinical trials have demonstrated that TDZ 200 mg daily for 6 days is noninferior to linezolid 600 mg twice daily for 10 days in the treatment of adults with skin and soft tissue infections caused or suspected to be caused by gram-positive organisms. TDZ has a side effect profile similar to that of linezolid and a lower potential for drug interactions. TDZ has been shown to be safe and effective for the treatment of adults with skin and soft tissue infections. Further research is needed to refine its role, particularly for the treatment of patients requiring a longer duration of therapy and in those receiving concomitant serotonergic agents.

  11. Patagonfibrase modifies protein expression of tissue factor and protein disulfide isomerase in rat skin.

    PubMed

    Peichoto, María Elisa; Santoro, Marcelo Larami

    2016-09-01

    Patagonfibrase is a hemorrhagic metalloproteinase isolated from the venom of the South American rear-fanged snake Philodryas patagoniensis, and is an important contributor to local lesions inflicted by this species. The tissue factor (TF)-factor VIIa complex, besides triggering the coagulation cascade, has been demonstrated to be involved in inflammatory events. Our aim was to determine whether patagonfibrase affects the expression of TF and protein disulfide isomerase (PDI), an enzyme that controls TF biological activity, at the site of patagonfibrase injection, and thus if they may play a role in hemostatic and inflammatory events induced by snake venoms. Patagonfibrase (60 μg/kg) was administered s.c. to rats, and after 3 h blood was collected to evaluate hemostasis parameters, and skin fragments close to the site of injection were taken to assess TF and PDI expression. Patagonfibrase did not alter blood cell counts, plasma fibrinogen levels, or levels of TF activity in plasma. However, by semiquantitative Western blotting, patagonfibrase increased TF expression by 2-fold, and decreased PDI expression by 3-fold in skin samples. In agreement, by immunohistochemical analyses, prominent TF expression was observed in the subcutaneous tissue. Thus, patagonfibrase affects the local expression of TF and PDI without inducing any systemic hemostatic disturbance, although that they may be involved in the local inflammatory events induced by hemorrhagic metalloproteinases. Once antivenom therapy is not totally effective to treat the local injury induced by snake venoms, modulation of the activity and expression of TF and/or PDI might become a strategy for treating snake envenomation.

  12. An Optimized Method for Extracting Bacterial RNA from Mouse Skin Tissue Colonized by Mycobacterium ulcerans.

    PubMed

    Robbe-Saule, Marie; Babonneau, Jérémie; Sismeiro, Odile; Marsollier, Laurent; Marion, Estelle

    2017-01-01

    Bacterial transcriptome analyses during host colonization are essential to decipher the complexity of the relationship between the bacterium and its host. RNA sequencing (RNA-seq) is a promising approach providing valuable information about bacterial adaptation, the host response and, in some cases, mutual tolerance underlying crosstalk, as recently observed in the context of Mycobacterium ulcerans infection. Buruli ulcer is caused by M. ulcerans. This neglected disease is the third most common mycobacterial disease worldwide. Without treatment, M. ulcerans provokes massive skin ulcers. A healing process may be observed in 5% of Buruli ulcer patients several months after the initiation of disease. This spontaneous healing process suggests that some hosts can counteract the development of the lesions caused by M. ulcerans. Deciphering the mechanisms involved in this process should open up new treatment possibilities. To this end, we recently developed the first mouse model for studies of the spontaneous healing process. We have shown that the healing process is based on mutual tolerance between the bacterium and its host. In this context, RNA-seq seems to be the most appropriate method for deciphering bacterial adaptation. However, due to the low bacterial load in host tissues, the isolation of mycobacterial RNA from skin tissue for RNA-seq analysis remains challenging. We developed a method for extracting and purifying mycobacterial RNA whilst minimizing the amount of host RNA in the sample. This approach was based on the extraction of bacterial RNA by a differential lysis method. The challenge in the development of this method was the choice of a lysis system favoring the removal of host RNA without damage to the bacterial cells. We made use of the thick, resistant cell wall of M. ulcerans to achieve this end.

  13. An Optimized Method for Extracting Bacterial RNA from Mouse Skin Tissue Colonized by Mycobacterium ulcerans

    PubMed Central

    Robbe-Saule, Marie; Babonneau, Jérémie; Sismeiro, Odile; Marsollier, Laurent; Marion, Estelle

    2017-01-01

    Bacterial transcriptome analyses during host colonization are essential to decipher the complexity of the relationship between the bacterium and its host. RNA sequencing (RNA-seq) is a promising approach providing valuable information about bacterial adaptation, the host response and, in some cases, mutual tolerance underlying crosstalk, as recently observed in the context of Mycobacterium ulcerans infection. Buruli ulcer is caused by M. ulcerans. This neglected disease is the third most common mycobacterial disease worldwide. Without treatment, M. ulcerans provokes massive skin ulcers. A healing process may be observed in 5% of Buruli ulcer patients several months after the initiation of disease. This spontaneous healing process suggests that some hosts can counteract the development of the lesions caused by M. ulcerans. Deciphering the mechanisms involved in this process should open up new treatment possibilities. To this end, we recently developed the first mouse model for studies of the spontaneous healing process. We have shown that the healing process is based on mutual tolerance between the bacterium and its host. In this context, RNA-seq seems to be the most appropriate method for deciphering bacterial adaptation. However, due to the low bacterial load in host tissues, the isolation of mycobacterial RNA from skin tissue for RNA-seq analysis remains challenging. We developed a method for extracting and purifying mycobacterial RNA whilst minimizing the amount of host RNA in the sample. This approach was based on the extraction of bacterial RNA by a differential lysis method. The challenge in the development of this method was the choice of a lysis system favoring the removal of host RNA without damage to the bacterial cells. We made use of the thick, resistant cell wall of M. ulcerans to achieve this end. PMID:28392785

  14. Frequent bacterial skin and soft tissue infections: diagnostic signs and treatment.

    PubMed

    Sunderkötter, Cord; Becker, Karsten

    2015-06-01

    Skin and soft tissue infections rank among the most frequent infections worldwide. Classic erysipelas is defined as a non-purulent infection by beta-hemolytic streptococci. The typical signs are tender, warm, bright erythema with tongue-like extensions and early systemic symptoms such as fever or at least chills. Erysipelas always and best responds to penicillin. Limited soft tissue infection or limited cellulitis are the terms we have introduced for infections frequently caused by S. aureus and often originating from chronic wounds or acute trauma. Clinically, they are marked by tender, erythematous swelling which, unlike erysipelas, exhibit a darker red hue and is not always accompanied by fever or chills at onset. Severe cellulitis is a purulent, partially necrotic infection extending to the fascia, with general symptoms of infection, requiring surgical management in addition to antibiotics. It often fulfils criteria of so-called complicated soft tissue infections according to the definition of the FDA, due to their frequent association with e.g. severe diabetes mellitus, peripheral arterial occlusive disease or severe immunosuppression. In contrast, the rare necrotizing skin and soft tissue infections represent a distinct entity, characterized by rapid progression to ischemic necroses and shock due to special bacterial toxins. Limited cellulitis should be treated with cephalosporins group 1 or 2, or, when S.aureus is the isolated or highly likely causative agent, isoxazolyl-penicillins (exploiting their minimal selection pressure on other bacteria). For severe cellulitis, initial antibiotic treatment (mostly iv) includes - depending on the location - agents also active against gram-negative and/or anaerobic bacteria. (e.g. clindamycine, aminopeniclilline with inhibitors of betalaktamase, fluochinolons, cephalosporines group 4). For cutaneous abscesses, drainage presents the therapy of choice. Only under certain conditions additional antibiotic therapy is

  15. Experimental study on tissue phantoms to understand the effect of injury and suturing on human skin mechanical properties.

    PubMed

    Chanda, Arnab; Unnikrishnan, Vinu; Flynn, Zachary; Lackey, Kim

    2017-01-01

    Skin injuries are the most common type of injuries occurring in day-to-day life. A skin injury usually manifests itself in the form of a wound or a cut. While a shallow wound may heal by itself within a short time, deep wounds require surgical interventions such as suturing for timely healing. To date, suturing practices are based on a surgeon's experience and may vary widely from one situation to another. Understanding the mechanics of wound closure and suturing of the skin is crucial to improve clinical suturing practices and also to plan automated robotic surgeries. In the literature, phenomenological two-dimensional computational skin models have been developed to study the mechanics of wound closure. Additionally, the effect of skin pre-stress (due to the natural tension of the skin) on wound closure mechanics has been studied. However, in most of these analyses, idealistic two-dimensional skin geometries, materials and loads have been assumed, which are far from reality, and would clearly generate inaccurate quantitative results. In this work, for the first time, a biofidelic human skin tissue phantom was developed using a two-part silicone material. A wound was created on the phantom material and sutures were placed to close the wound. Uniaxial mechanical tests were carried out on the phantom specimens to study the effect of varying wound size, quantity, suture and pre-stress on the mechanical behavior of human skin. Also, the average mechanical behavior of the human skin surrogate was characterized using hyperelastic material models, in the presence of a wound and sutures. To date, such a robust experimental study on the effect of injury and sutures on human skin mechanics has not been attempted. The results of this novel investigation will provide important guidelines for surgical planning and validation of results from computational models in the future.

  16. Epidermal stem cells and skin tissue engineering in hair follicle regeneration

    PubMed Central

    Balañá, María Eugenia; Charreau, Hernán Eduardo; Leirós, Gustavo José

    2015-01-01

    The reconstitution of a fully organized and functional hair follicle from dissociated cells propagated under defined tissue culture conditions is a challenge still pending in tissue engineering. The loss of hair follicles caused by injuries or pathologies such as alopecia not only affects the patients’ psychological well-being, but also endangers certain inherent functions of the skin. It is then of great interest to find different strategies aiming to regenerate or neogenerate the hair follicle under conditions proper of an adult individual. Based upon current knowledge on the epithelial and dermal cells and their interactions during the embryonic hair generation and adult hair cycling, many researchers have tried to obtain mature hair follicles using different strategies and approaches depending on the causes of hair loss. This review summarizes current advances in the different experimental strategies to regenerate or neogenerate hair follicles, with emphasis on those involving neogenesis of hair follicles in adult individuals using isolated cells and tissue engineering. Most of these experiments were performed using rodent cells, particularly from embryonic or newborn origin. However, no successful strategy to generate human hair follicles from adult cells has yet been reported. This review identifies several issues that should be considered to achieve this objective. Perhaps the most important challenge is to provide three-dimensional culture conditions mimicking the structure of living tissue. Improving culture conditions that allow the expansion of specific cells while protecting their inductive properties, as well as methods for selecting populations of epithelial stem cells, should give us the necessary tools to overcome the difficulties that constrain human hair follicle neogenesis. An analysis of patent trends shows that the number of patent applications aimed at hair follicle regeneration and neogenesis has been increasing during the last decade. This

  17. SU-E-T-477: An Efficient Dose Correction Algorithm Accounting for Tissue Heterogeneities in LDR Brachytherapy

    SciTech Connect

    Mashouf, S; Lai, P; Karotki, A; Keller, B; Beachey, D; Pignol, J

    2014-06-01

    Purpose: Seed brachytherapy is currently used for adjuvant radiotherapy of early stage prostate and breast cancer patients. The current standard for calculation of dose surrounding the brachytherapy seeds is based on American Association of Physicist in Medicine Task Group No. 43 (TG-43 formalism) which generates the dose in homogeneous water medium. Recently, AAPM Task Group No. 186 emphasized the importance of accounting for tissue heterogeneities. This can be done using Monte Carlo (MC) methods, but it requires knowing the source structure and tissue atomic composition accurately. In this work we describe an efficient analytical dose inhomogeneity correction algorithm implemented using MIM Symphony treatment planning platform to calculate dose distributions in heterogeneous media. Methods: An Inhomogeneity Correction Factor (ICF) is introduced as the ratio of absorbed dose in tissue to that in water medium. ICF is a function of tissue properties and independent of source structure. The ICF is extracted using CT images and the absorbed dose in tissue can then be calculated by multiplying the dose as calculated by the TG-43 formalism times ICF. To evaluate the methodology, we compared our results with Monte Carlo simulations as well as experiments in phantoms with known density and atomic compositions. Results: The dose distributions obtained through applying ICF to TG-43 protocol agreed very well with those of Monte Carlo simulations as well as experiments in all phantoms. In all cases, the mean relative error was reduced by at least 50% when ICF correction factor was applied to the TG-43 protocol. Conclusion: We have developed a new analytical dose calculation method which enables personalized dose calculations in heterogeneous media. The advantages over stochastic methods are computational efficiency and the ease of integration into clinical setting as detailed source structure and tissue segmentation are not needed. University of Toronto, Natural Sciences and

  18. Use of Clotted Human Plasma and Aprotinin in Skin Tissue Engineering: A Novel Approach to Engineering Composite Skin on a Porous Scaffold.

    PubMed

    Paul, Michelle; Kaur, Pritinder; Herson, Marisa; Cheshire, Perdita; Cleland, Heather; Akbarzadeh, Shiva

    2015-10-01

    Tissue-engineered composite skin is a promising therapy for the treatment of chronic and acute wounds, including burns. Providing the wound bed with a dermal scaffold populated by autologous dermal and epidermal cellular components can further entice host cell infiltration and vascularization to achieve permanent wound closure in a single stage. However, the high porosity and the lack of a supportive basement membrane in most commercially available dermal scaffolds hinders organized keratinocyte proliferation and stratification in vitro and may delay re-epithelization in vivo. The objective of this study was to develop a method to enable the in vitro production of a human skin equivalent (HSE) that included a porous scaffold and dermal and epidermal cells expanded ex vivo, with the potential to be used for definitive treatment of skin defects in a single procedure. A collagen-glycosaminoglycan dermal scaffold (Integra(®)) was populated with adult fibroblasts. A near-normal skin architecture was achieved by the addition of coagulated human plasma to the fibroblast-populated scaffold before seeding cultured keratinocytes. This resulted in reducing scaffold pore size and improving contact surfaces. Skin architecture and basement membrane formation was further improved by the addition of aprotinin (a serine protease inhibitor) to the culture media to inhibit premature clot digestion. Histological assessment of the novel HSE revealed expression of keratin 14 and keratin 10 similar to native skin, with a multilayered neoepidermis morphologically comparable to human skin. Furthermore, deposition of collagen IV and laminin-511 were detected by immunofluorescence, indicating the formation of a continuous basement membrane at the dermal-epidermal junction. The proposed method was efficient in producing an in vitro near native HSE using the chosen off-the-shelf porous scaffold (Integra). The same principles and promising outcomes should be applicable to other biodegradable

  19. Near-infrared optical properties of ex-vivo human skin and subcutaneous tissues using reflectance and transmittance measurements

    NASA Astrophysics Data System (ADS)

    Simpson, Rebecca; Laufer, Jan G.; Kohl-Bareis, Matthias; Essenpreis, Matthias; Cope, Mark

    1997-08-01

    The vast majority of 'non-invasive' measurements of human tissues using near infrared spectroscopy rely on passing light through the dermis and subdermis of the skin. Accurate knowledge of the optical properties of these tissues is essential to put into models of light transport and predict the effects of skin perfusion on measurements of deep tissue. Additionally, the skin could be a useful accessible organ for non-invasively determining the constituents of blood flowing through it. Samples of abdominal human skin (including subdermal tissue) were obtained from either post mortem examinations or plastic surgery. The samples were separated into a dermal layer (epidermis and dermis, 1.5 to 2 mm tick), and a sub-cutaneous layer comprised largely of fat. They were enclosed between two glass coverslips and placed in an integrating sphere to measure their reflectance and transmittance over a range of wavelengths from 600 to 1000 nm. The reflectance and transmittance values were converted into average absorption and reduced scattering coefficients by comparison with a Monte Carlo model of light transport. Improvements to the Monte Carlo model and measurement technique removed some previous uncertainties. The results show excellent separation of reduced scattering and absorption coefficient, with clear absorption peaks of hemoglobin, water and lipid. The effect of tissue storage upon measured optical properties was investigated.

  20. The effects of different lying positions on interface pressure, skin temperature, and tissue blood flow in nursing home residents.

    PubMed

    Källman, Ulrika; Engström, Maria; Bergstrand, Sara; Ek, Anna-Christina; Fredrikson, Mats; Lindberg, Lars-Göran; Lindgren, Margareta

    2015-03-01

    Although repositioning is considered an important intervention to prevent pressure ulcers, tissue response during loading in different lying positions has not been adequately explored. To compare the effects of different lying positions on interface pressure, skin temperature, and tissue blood flow in nursing home residents. From May 2011 to August 2012, interface pressure, skin temperature, and blood flow at three tissue depths were measured for 1 hr over the sacrum in 30° supine tilt and 0° supine positions and over the trochanter major in 30° lateral and 90° lateral positions in 25 residents aged 65 years or older. Measurement of interface pressure was accomplished using a pneumatic pressure transmitter connected to a digital manometer, skin temperature using a temperature sensor, and blood flow using photoplethysmography and laser Doppler flowmetry. Interface pressure was significantly higher in the 0° supine and 90° lateral positions than in 30° supine tilt and 30° lateral positions. The mean skin temperature increased from baseline in all positions. Blood flow was significantly higher in the 30° supine tilt position compared to the other positions. A hyperemic response in the post pressure period was seen at almost all tissue depths and positions. The 30° supine tilt position generated less interface pressure and allowed greater tissue perfusion, suggesting that this position is the most beneficial. © The Author(s) 2014.

  1. UVB-induced inflammatory cytokine release, DNA damage and apoptosis of human oral compared with skin tissue equivalents.

    PubMed

    Breger, Joyce; Baeva, Larissa; Agrawal, Anant; Shindell, Eli; Godar, Dianne E

    2013-01-01

    People can get oral cancers from UV (290-400 nm) exposures. Besides high outdoor UV exposures, high indoor UV exposures to oral tissues can occur when consumers use UV-emitting tanning devices to either tan or whiten their teeth. We compared the carcinogenic risks of skin to oral tissue cells after UVB (290-320 nm) exposures using commercially available 3D-engineered models for human skin (EpiDerm™), gingival (EpiGing™) and oral (EpiOral™) tissues. To compare the relative carcinogenic risks, we investigated the release of cytokines, initial DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), repair of CPDs and apoptotic cell numbers. We measured cytokine release using cytometric beads with flow cytometry and previously developed a fluorescent immunohistochemical assay to quantify simultaneously CPD repair rates and apoptotic cell numbers. We found that interleukin-8 (IL-8) release and the initial CPDs are significantly higher, whereas the CPD repair rates and apoptotic cell numbers are significantly lower for oral compared with skin tissue cells. Thus, the increased release of the inflammatory cytokine IL-8 along with inefficient CPD repair and decreased death rates for oral compared with skin tissue cells suggests that mutations are accumulating in the surviving population of oral cells increasing people's risks for getting oral cancers.

  2. Combination effects of tissue heterogeneity and geometric targeting error in stereotactic body radiotherapy for lung cancer using CyberKnife.

    PubMed

    Kang, Ki Mun; Jeong, Bae Kwon; Choi, Hoon-Sik; Yoo, Seung Hoon; Hwang, Ui-Jung; Lim, Young Kyung; Jeong, Hojin

    2015-09-08

    We have investigated the combined effect of tissue heterogeneity and its variation associated with geometric error in stereotactic body radiotherapy (SBRT) for lung cancer. The treatment plans for eight lung cancer patients were calculated using effective path length (EPL) correction and Monte Carlo (MC) algorithms, with both having the same beam configuration for each patient. These two kinds of plans for individual patients were then subsequently recalculated with adding systematic and random geometric errors. In the ordinary treatment plans calculated with no geometric offset, the EPL calculations, compared with the MC calculations, largely overestimated the doses to PTV by ~ 21%, whereas the overestimation were markedly lower in GTV by ~ 12% due to relatively higher density of GTV than of PTV. When recalculating the plans for individual patients with assigning the systematic and random geometric errors, no significant changes in the relative dose distribution, except for overall shift, were observed in the EPL calculations, whereas largely altered in the MC calculations with a consistent increase in dose to GTV. Considering the better accuracy of MC than EPL algorithms, the present results demonstrated the strong coupling of tissue heterogeneity and geometric error, thereby emphasizing the essential need for simultaneous correction for tissue heterogeneity and geometric targeting error in SBRT of lung cancer.

  3. Quantitative Segmentation of Fluorescence Microscopy Images of Heterogeneous Tissue: Application to the Detection of Residual Disease in Tumor Margins

    PubMed Central

    Mueller, Jenna L.; Harmany, Zachary T.; Mito, Jeffrey K.; Kennedy, Stephanie A.; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G.; Willett, Rebecca M.; Brown, J. Quincy; Ramanujam, Nimmi

    2013-01-01

    Purpose To develop a robust tool for quantitative in situ pathology that allows visualization of heterogeneous tissue morphology and segmentation and quantification of image features. Materials and Methods Tissue excised from a genetically engineered mouse model of sarcoma was imaged using a subcellular resolution microendoscope after topical application of a fluorescent anatomical contrast agent: acriflavine. An algorithm based on sparse component analysis (SCA) and the circle transform (CT) was developed for image segmentation and quantification of distinct tissue types. The accuracy of our approach was quantified through simulations of tumor and muscle images. Specifically, tumor, muscle, and tumor+muscle tissue images were simulated because these tissue types were most commonly observed in sarcoma margins. Simulations were based on tissue characteristics observed in pathology slides. The potential clinical utility of our approach was evaluated by imaging excised margins and the tumor bed in a cohort of mice after surgical resection of sarcoma. Results Simulation experiments revealed that SCA+CT achieved the lowest errors for larger nuclear sizes and for higher contrast ratios (nuclei intensity/background intensity). For imaging of tumor margins, SCA+CT effectively isolated nuclei from tumor, muscle, adipose, and tumor+muscle tissue types. Differences in density were correctly identified with SCA+CT in a cohort of ex vivo and in vivo images, thus illustrating the diagnostic potential of our approach. Conclusion The combination of a subcellular-resolution microendoscope, acriflavine staining, and SCA+CT can be used to accurately isolate nuclei and quantify their density in anatomical images of heterogeneous tissue. PMID:23824589

  4. Boundary discretization in the numerical simulation of light propagation in skin tissue: problem and strategy.

    PubMed

    Jia, Hao; Chen, Bin; Li, Dong; Zhang, Yong

    2015-02-01

    To adapt the complex tissue structure, laser propagation in a two-layered skin model is simulated to compare voxel-based Monte Carlo (VMC) and tetrahedron-based MC (TMC) methods with a geometry-based MC (GMC) method. In GMC, the interface is mathematically defined without any discretization. GMC is the most accurate but is not applicable to complicated domains. The implementation of VMC is simple because of its structured voxels. However, unavoidable errors are expected because of the zigzag polygonal interface. Compared with GMC and VMC, TMC provides a balance between accuracy and flexibility by the tetrahedron cells. In the present TMC, the body-fitted tetrahedra are generated in different tissues. No interface tetrahedral cells exist, thereby avoiding the photon reflection error in the interface cells in VMC. By introducing a distance threshold, the error caused by confused optical parameters between neighboring cells when photons are incident along the cell boundary can be avoided. The results show that the energy deposition error by TMC in the interfacial region is one-tenth to one-fourth of that by VMC, yielding more accurate computations of photon reflection, refraction, and energy deposition. The results of multilayered and n-shaped vessels indicate that a laser with a 1064-nm wavelength should be introduced to clean deep-buried vessels. © 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)

  5. Boundary discretization in the numerical simulation of light propagation in skin tissue: problem and strategy

    NASA Astrophysics Data System (ADS)

    Jia, Hao; Chen, Bin; Li, Dong; Zhang, Yong

    2015-02-01

    To adapt the complex tissue structure, laser propagation in a two-layered skin model is simulated to compare voxel-based Monte Carlo (VMC) and tetrahedron-based MC (TMC) methods with a geometry-based MC (GMC) method. In GMC, the interface is mathematically defined without any discretization. GMC is the most accurate but is not applicable to complicated domains. The implementation of VMC is simple because of its structured voxels. However, unavoidable errors are expected because of the zigzag polygonal interface. Compared with GMC and VMC, TMC provides a balance between accuracy and flexibility by the tetrahedron cells. In the present TMC, the body-fitted tetrahedra are generated in different tissues. No interface tetrahedral cells exist, thereby avoiding the photon reflection error in the interface cells in VMC. By introducing a distance threshold, the error caused by confused optical parameters between neighboring cells when photons are incident along the cell boundary can be avoided. The results show that the energy deposition error by TMC in the interfacial region is one-tenth to one-fourth of that by VMC, yielding more accurate computations of photon reflection, refraction, and energy deposition. The results of multilayered and n-shaped vessels indicate that a laser with a 1064-nm wavelength should be introduced to clean deep-buried vessels.

  6. Electrospun fibrous mats with high porosity as potential scaffolds for skin tissue engineering.

    PubMed

    Zhu, Xinli; Cui, Wenguo; Li, Xiaohong; Jin, Yan

    2008-07-01

    Diffusional limitations of mass transport have adverse effects on engineering tissues that normally have high vascularity and cellularity. The current electrospinning method is not always successful to create micropores to encourage cell infiltration within the scaffold, especially when relatively large-sized pores are required. In this study, a slow rotating frame cylinder was developed as the collector to extend the pore size and increase the porosity of electrospun fibrous scaffolds. Fibrous mats with porosity as high as 92.4% and average pore size of 132.7 microm were obtained. Human dermal fibroblasts (HDFs) were seeded onto these mats, which were fixed on a cell-culture ring to prevent the shrinkage and contraction during the incubation. The viability test indicated that significantly more HDFs were generated on highly porous fibrous mats. Toluidine blue staining showed that the highly porous scaffold provided mechanical support for cells to maintain uniform distribution. The cross-section observations indicated that cells migrated and infiltrated more than 100 microm inside highly porous fibrous mats after 5 d incubation. The immunohistochemistry analysis demonstrated that cells began secreting collagen, which is the main constituent of extracellular matrix. It is supposed that highly porous electrospun fibrous scaffolds could be constructed by this elaboration and may be used for skin tissue engineering.

  7. Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering.

    PubMed

    Ma, Lie; Gao, Changyou; Mao, Zhengwei; Zhou, Jie; Shen, Jiacong; Hu, Xueqing; Han, Chunmao

    2003-11-01

    Porous scaffolds for skin tissue engineering were fabricated by freeze-drying the mixture of collagen and chitosan solutions. Glutaraldehyde (GA) was used to treat the scaffolds to improve their biostability. Confocal laser scanning microscopy observation confirmed the even distribution of these two constituent materials in the scaffold. The GA concentrations have a slight effect on the cross-section morphology and the swelling ratios of the cross-linked scaffolds. The collagenase digestion test proved that the presence of chitosan can obviously improve the biostability of the collagen/chitosan scaffold under the GA treatment, where chitosan might function as a cross-linking bridge. A detail investigation found that a steady increase of the biostability of the collagen/chitosan scaffold was achieved when GA concentration was lower than 0.1%, then was less influenced at a still higher GA concentration up to 0.25%. In vitro culture of human dermal fibroblasts proved that the GA-treated scaffold could retain the original good cytocompatibility of collagen to effectively accelerate cell infiltration and proliferation. In vivo animal tests further revealed that the scaffold could sufficiently support and accelerate the fibroblasts infiltration from the surrounding tissue. Immunohistochemistry analysis of the scaffold embedded for 28 days indicated that the biodegradation of the 0.25% GA-treated scaffold is a long-term process. All these results suggest that collagen/chitosan scaffold cross-linked by GA is a potential candidate for dermal equivalent with enhanced biostability and good biocompatibility.

  8. Studies in fat grafting: Part III. Fat grafting irradiated tissue--improved skin quality and decreased fat graft retention.

    PubMed

    Garza, Rebecca M; Paik, Kevin J; Chung, Michael T; Duscher, Dominik; Gurtner, Geoffrey C; Longaker, Michael T; Wan, Derrick C

    2014-08-01

    Following radiation therapy, skin becomes fibrotic and can present a difficult problem for reconstructive surgeons. There is an increasing belief that fat grafting under irradiated skin can reverse the damage caused by radiation. The present study evaluated the effect of fat grafting on irradiated skin, along with fat graft quality and retention rates in irradiated tissue. Nine adult Crl:NU-Foxn1 CD-1 mice underwent 30-Gy external beam irradiation of the scalp. Four weeks after irradiation, scalp skin from irradiated and nonirradiated mice was harvested and compared histologically for dermal thickness, collagen content, and vascular density. Human fat grafts were then injected in the subcutaneous plane of the scalp. Skin assessment was performed in the irradiated group at 2 and 8 weeks after grafting, and fat graft retention was measured at baseline and every 2 weeks up to 8 weeks after grafting using micro-computed tomography. Finally, fat graft samples were explanted at 8 weeks, and quality scoring was performed. Fat grafting resulted in decreased dermal thickness, decreased collagen content, and increased vascular density in irradiated skin. Computed tomographic analysis revealed significantly decreased fat graft survival in the irradiated group compared with the nonirradiated group. Histologic scoring of explanted fat grafts demonstrated no difference in quality between the irradiated and nonirradiated groups. Fat grafting attenuates dermal collagen deposition and vessel depletion characteristic of radiation fibrosis. Although fat graft retention rates are significantly lower in irradiated than in nonirradiated tissue, the quality of retained fat between the groups is similar.

  9. In vivo measurement of skin surface strain and sub-surface layer deformation induced by natural tissue stretching.

    PubMed

    Maiti, Raman; Gerhardt, Lutz-Christian; Lee, Zing S; Byers, Robert A; Woods, Daniel; Sanz-Herrera, José A; Franklin, Steve E; Lewis, Roger; Matcher, Stephen J; Carré, Matthew J

    2016-09-01

    Stratum corneum and epidermal layers change in terms of thickness and roughness with gender, age and anatomical site. Knowledge of the mechanical and tribological properties of skin associated with these structural changes are needed to aid in the design of exoskeletons, prostheses, orthotics, body mounted sensors used for kinematics measurements and in optimum use of wearable on-body devices. In this case study, optical coherence tomography (OCT) and digital image correlation (DIC) were combined to determine skin surface strain and sub-surface deformation behaviour of the volar forearm due to natural tissue stretching. The thickness of the epidermis together with geometry changes of the dermal-epidermal junction boundary were calculated during change in the arm angle, from flexion (90°) to full extension (180°). This posture change caused an increase in skin surface Lagrange strain, typically by 25% which induced considerable morphological changes in the upper skin layers evidenced by reduction of epidermal layer thickness (20%), flattening of the dermal-epidermal junction undulation (45-50% reduction of flatness being expressed as Ra and Rz roughness profile height change) and reduction of skin surface roughness Ra and Rz (40-50%). The newly developed method, DIC combined with OCT imaging, is a powerful, fast and non-invasive methodology to study structural skin changes in real time and the tissue response provoked by mechanical loading or stretching. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Reverse lateral supramalleolar adipofascial flap and skin grafting for one-stage soft tissue reconstruction of foot and ankle joint.

    PubMed

    Lee, Jae-Hoon; Chung, Duke-Whan

    2010-09-01

    The aim of this report is to present the clinical result and efficacy of reverse lateral supramalleolar adipofascial flap and skin grafting for one stage soft tissue reconstruction of the foot and ankle joints. Reconstruction using a reverse lateral supramalleolar adipofascial flap and skin grafting was performed in eight cases between January 2005 and March 2009. All the subjects were male with a mean age of 53 years. The mean follow-up period was 20 months. The reasons for soft tissue defects were diabetic foot, infected bursitis, open injuries of the foot, and chronic osteomyelitis. The mean size of the flaps was 3.5 (3-4) × 4.5 (4-6) cm. The flaps were elevated in the form of an adipofascial flap and split-thickness skin grafting was performed over the flaps and adjoining raw areas. Flaps survived in all cases. The implantation of the split-thickness skin graft over the flap was also successful in all cases. Neither partial necrosis in the adipofascial flap nor venous congestion was observed. At the last follow-up, there were no limited motions in the ankle and the toe. No cases complained of inconveniences in ambulation or had difficulties in selecting footwear. In cases that require a flap for the exposed bone or tendon of the foot with a small-sized defect, reverse lateral supramalleolar adipofascial flap and skin grafting is considered a useful method as it lowers the morbidity rate of the donor site and reconstructs soft tissues.

  11. Remote skin tissue diagnostics in vivo by fiber optic evanescent wave Fourier transform infrared (FEW-FTIR) spectroscopy

    NASA Astrophysics Data System (ADS)

    Afanasyeva, Natalia I.; Kolyakov, Sergei F.; Butvina, Leonid N.

    1998-04-01

    The new method of fiber-optical evanescent wave Fourier transform IR (FEW-FTIR) spectroscopy has been applied to the diagnostics of normal tissue, as well as precancerous and cancerous conditions. The FEW-FTIR technique is nondestructive and sensitive to changes of vibrational spectra in the IR region, without heating and damaging human and animal skin tissue. Therefore this method and technique is an ideal diagnostic tool for tumor and cancer characterization at an early stage of development on a molecular level. The application of fiber optic technology in the middle IR region is relatively inexpensive and can be adapted easily to any commercially available tabletop FTIR spectrometers. This method of diagnostics is fast, remote, and can be applied to many fields Noninvasive medical diagnostics of skin cancer and other skin diseases in vivo, ex vivo, and in vitro allow for the development convenient, remote clinical applications in dermatology and related fields. The spectral variations from normal to pathological skin tissue and environmental influence on skin have been measured and assigned in the regions of 850-4000 cm-1. The lipid structure changes are discussed. We are able to develop the spectral histopathology as a fast and informative tool of analysis.

  12. Novel concept of iSALT (inducible skin-associated lymphoid tissue) in the elicitation of allergic contact dermatitis

    PubMed Central

    HONDA, Tetsuya; KABASHIMA, Kenji

    2016-01-01

    Allergic contact dermatitis (ACD) is one of the most common inflammatory skin diseases, which is classified as a delayed-type hypersensitivity immune response. The development of ACD is divided into two phases: sensitization and elicitation. In the sensitization phase, antigen-specific effector T cells are induced in the draining lymph nodes by antigen-captured cutaneous dendritic cells (DCs) that migrate from the skin. In the elicitation phase, the effector T cells are activated in the skin by antigen-captured cutaneous DCs and produce various chemical mediators, which create antigen-specific inflammation. In this review, we discuss the recent advancements in the immunological mechanisms of ACD, focusing on the mechanisms in the elicitation phase. The observations of elicitation of CHS lead to the emerging novel concept of iSALT (inducible skin-associated lymphoid tissue). PMID:26755397

  13. Source investigation of two outbreaks of skin and soft tissue infection by Mycobacterium abscessus subsp. abscessus in Venezuela.

    PubMed

    Torres-Coy, J A; Rodríguez-Castillo, B A; Pérez-Alfonzo, R; DE Waard, J H

    2016-04-01

    Outbreaks of soft tissue or skin infection due to non-tuberculous mycobacteria are reported frequently in scientific journals but in general the infection source in these outbreaks remains unknown. In Venezuela, in two distinct outbreaks, one after breast augmentation surgery and another after hydrolipoclasy therapy, 16 patients contracted a soft tissue infection due to Mycobacterium abscessus subsp. abscessus. Searching for the possible environmental infection sources in these outbreaks, initially the tap water (in the hydrolipoclasy therapy outbreak) and a surgical skin marker (in the breast implant surgery outbreak), were identified as the infection sources. Molecular typing of the strains with a variable number tandem repeat typing assay confirmed the tap water as the infection source but the molecular typing technique excluded the skin marker. We discuss the results and make a call for the implementation of stringent hygiene and disinfection guidelines for cosmetic procedures in Venezuela.

  14. Wound Healing Effect of Conditioned Media Obtained From Adipose Tissue on Human Skin Cells: A Comparative in Vitro Study.

    PubMed

    Kober, Johanna; Gugerell, Alfred; Schmid, Melanie; Zeyda, Maximilian; Buchberger, Elisabeth; Nickl, Stefanie; Hacker, Stefan; Ankersmit, Hendrik Jan; Keck, Maike

    2016-08-01

    Split-thickness skin grafting is the gold standard to cover extensive acute and chronic wounds with a well-vascularized wound bed. Although some headway has been made in developing biological agents to speed up healing, there is still no treatment that sufficiently replaces skin grafts to date. The use of secretory factors of adipose tissue may be a feasible approach to developing topical wound applications for faster wound healing. In this study, the effect of conditioned media (CMs) of human adipose-derived stem cells (ASCs), adipocytes, or adipose tissue on human skin cells was evaluated for viability, proliferation, and migration in vitro. Differentiation potential of stem cells treated with CM was monitored by AdipoRed staining and qualitative real-time polymerase chain reaction. Angiogenic potential of human endothelial cells treated with CM was tested via sprouting assay. The CM of adipose tissue significantly enhanced ASC proliferation (P < 0.01). Treatment with CM showed no inductive effect on ASC differentiation into adipocytes but, at the same time, significantly induced cell sprouting of endothelial cells (P < 0.001). We show for the first time that CM of adipose tissue is a potent inducer of proliferation of ASCs and angiogenesis, with comparable effects with those of stem cell-enriched CM. We suggest the use of the secretome of adipose tissue to produce CM for topical application on wounds, rather than working with adipose tissue or including the difficult process of enriching the patients' stem cells in vitro.

  15. [Systemic therapy for defects of skin and soft tissue on the knees after severe trauma or burn].

    PubMed

    Tao, Ke; Hu, Da-hai; Zhu, Xiong-xiang; Han, Jun-tao; Zheng, Zhao; Xie, Song-tao; Ge, Jin-bo; Hu, Xiao-long

    2013-04-01

    To explore the methods of systemic treatment of defects of skin and soft tissue on the knees after severe trauma or burn. Twenty patients with defects of skin and soft tissue on the knees after severe trauma or burn hospitalized in our center from January 2009 to December 2011. The injury areas on the knees ranged from 5 cm×4 cm to 30 cm×20 cm. The wounds were treated with radical debridement, vacuum sealing drainage, and douche through dripping to control infection in early stage. Then they were covered with transplantation of skin grafts plus flap or only with flap. Totally 8 local flaps (including 6 local rotation or transposition flaps and 2 saphenous artery flaps) and 12 free flaps (including 8 anterolateral thigh flaps and 4 latissimus dorsi musculocutaneous flaps) were used. The flap size ranged from 6 cm×5 cm to 32 cm×22 cm. The rehabilitation training of the knee joints was carried out in the early stage after wound healing. All free skin grafts and flaps used in 15 patients survived. Thirteen of them were primarily healed, while some small parts of skin grafts of the other two patients were in poor condition because of infection, and they healed after another session of skin transplantation. Infection occurred under the free flap in one of the 5 patients transplanted with flaps only, which was healed after continuous douche through dripping and another surgical debridement following wet dressing. The knee joints were in good function during the follow-up period of 1 - 3 years. The systemic therapy of radical debridement, vacuum sealing drainage technique, douche through dripping, transplantation of large autologous grafts and flaps, and the early rehabilitation training are effective and reliable in repairing defects of skin and soft tissue at the knee region after severe injuries.

  16. Parasitism and inflammation in ear skin and in genital tissues of symptomatic and asymptomatic male dogs with visceral leishmaniasis.

    PubMed

    Carvalho Junior, C G; Teixeira Neto, R G; Lopes, V V; Belo, V S; Alves, N R; de Paula, T B; Ribeiro, R I M A; Silva, E S

    2017-03-01

    Canine visceral leishmaniasis (CVL) is transmitted through vector, although venereal transmission has been suggested. This study aimed to compare the parasitic loads and inflammatory processes in genital tissues with ear skin from seropositive male dogs. Forty-five seropositive dogs were separated into groups containing symptomatic (n = 23) and asymptomatic (n = 22) animals. The control group (n = 2) healthy animals with seronegative and negative results in direct parasitological test. Samples of ear tip skin, prepuce, glans penis, testis, epididymis, and prostate were collected for evaluation of parasitic load and inflammatory infiltrate. Although ear tip skin was the most intensely parasitized, prepuce and epididymis revealed no difference in parasitism when compared with ear tip skin (P > 0.05). Parasitic loads in testis and prostate were lower than other tissues (P < 0.05). Parasitism in glans penis was high, similar to prepuce and epididymis, but lower than ear tip skin. High parasitism was more frequent in symptomatic dogs than asymptomatic animals. Severe inflammatory processes were more frequent within the symptomatic animals compared with asymptomatic and more predominant in prepuce and epididymis. Ear tip skin and genital tissues presented signs of chronic inflammation. There were weak and moderate positive correlations between parasitic loads and inflammatory processes. Our results demonstrate that, likewise with the ear tip skin, the genital of seropositive dogs can carry a large number of Leishmania infantum amastigotes and this process are more intense in symptomatic animals. These data have important implications for understanding the possibility of venereal transmission of CVL.

  17. Evaluation of methicillin-resistant Staphylococcus aureus skin and soft-tissue infection prevention strategies at a military training center.

    PubMed

    Morrison, Stephanie M; Blaesing, Carl R; Millar, Eugene V; Chukwuma, Uzo; Schlett, Carey D; Wilkins, Kenneth J; Tribble, David R; Ellis, Michael W

    2013-08-01

    Military trainees are at high risk for skin and soft-tissue infections (SSTIs), especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). A multicomponent hygiene-based SSTI prevention strategy was implemented at a military training center. After implementation, we observed 30% and 64% reductions in overall and MRSA-associated SSTI rates, respectively.

  18. Autologous Skin Cell Spray for Massive Soft Tissue War Injuries: A Prospective, Case-Control, Multicenter Trial

    DTIC Science & Technology

    2014-04-01

    extrapolated to complex traumatic civilian injuries that likewise pose significant issues with available autologous skin coverage (e.g. necrotizing ... fasciitis , motor vehicle accidents or other trauma with associated soft tissue avulsion injuries, etc.). Important data on the mechanism of action

  19. Practices and Procedures to Prevent the Transmission of Skin and Soft Tissue Infections in High School Athletes

    ERIC Educational Resources Information Center

    Fritz, Stephanie A.; Long, Marcus; Gaebelein, Claude J.; Martin, Madeline S.; Hogan, Patrick G.; Yetter, John

    2012-01-01

    Skin and soft tissue infections (SSTIs) are frequent in student athletes and are often caused by community-associated methicillin-resistant "Staphylococcus aureus" (CA-MRSA). We evaluated the awareness of CA-MRSA among high school coaches and athletic directors in Missouri (n = 4,408) and evaluated hygiene practices affecting SSTI…

  20. Practices and Procedures to Prevent the Transmission of Skin and Soft Tissue Infections in High School Athletes

    ERIC Educational Resources Information Center

    Fritz, Stephanie A.; Long, Marcus; Gaebelein, Claude J.; Martin, Madeline S.; Hogan, Patrick G.; Yetter, John

    2012-01-01

    Skin and soft tissue infections (SSTIs) are frequent in student athletes and are often caused by community-associated methicillin-resistant "Staphylococcus aureus" (CA-MRSA). We evaluated the awareness of CA-MRSA among high school coaches and athletic directors in Missouri (n = 4,408) and evaluated hygiene practices affecting SSTI…

  1. Coagulation and ablation patterns of high-intensity focused ultrasound on a tissue-mimicking phantom and cadaveric skin.

    PubMed

    Kim, Hee-Jin; Kim, Han Gu; Zheng, Zhenlong; Park, Hyoun Jun; Yoon, Jeung Hyun; Oh, Wook; Lee, Cheol Woo; Cho, Sung Bin

    2015-12-01

    High-intensity focused ultrasound (HIFU) can be applied noninvasively to create focused zones of tissue coagulation on various skin layers. We performed a comparative study of HIFU, evaluating patterns of focused tissue coagulation and ablation upon application thereof. A tissue-mimicking (TM) phantom was prepared with bovine serum albumin and polyacrylamide hydrogel to evaluate the geometric patterns of HIFU-induced thermal injury zones (TIZs) for five different HIFU devices. Additionally, for each device, we investigated histologic patterns of HIFU-induced coagulation and ablation in serial sections of cadaveric skin of the face and neck. All HIFU devices generated remarkable TIZs in the TM phantom, with different geometric values of coagulation for each device. Most of the TIZs seemed to be separated into two or more tiny parts. In cadaveric skin, characteristic patterns of HIFU-induced ablation and coagulation were noted along the mid to lower dermis at the focal penetration depth of 3 mm and along subcutaneous fat to the superficial musculoaponeurotic system or the platysma muscle of the neck at 4.5 mm. Additionally, remarkable pre-focal areas of tissue coagulation were observed in the upper and mid dermis at the focal penetration depth of 3 mm and mid to lower dermis at 4.5 mm. For five HIFU devices, we outlined various patterns of HIFU-induced TIZ formation along pre-focal, focal, and post-focal areas of TM phantom and cadaveric skin of the face and neck.

  2. Avoidable Antibiotic Exposure for Uncomplicated Skin and Soft Tissue Infections in the Ambulatory Care Setting

    PubMed Central

    Hurley, Hermione J.; Knepper, Bryan C.; Price, Connie S.; Mehler, Philip S.; Burman, William J.; Jenkins, Timothy C.

    2014-01-01

    Background Uncomplicated skin and soft tissue infections are among the most frequent indications for outpatient antibiotics. A detailed understanding of current prescribing practices is necessary to optimize antibiotic use for these conditions. Methods This was a retrospective cohort study of children and adults treated in the ambulatory care setting for uncomplicated cellulitis, wound infection, or cutaneous abscess between March 1, 2010 and February 28, 2011. We assessed the frequency of avoidable antibiotic exposure, defined as: use of antibiotics with broad gram-negative activity, combination antibiotic therapy, or treatment for 10 or more days. Total antibiotic-days prescribed for the cohort were compared to antibiotic-days in four hypothetical short-course (5 – 7 days), single-antibiotic treatment models consistent with national guidelines. Results 364 cases were included for analysis (155 cellulitis, 41 wound infection, and 168 abscess). Antibiotics active against methicillin-resistant Staphylococcus aureus were prescribed in 61% of cases of cellulitis. Of 139 cases of abscess where drainage was performed, antibiotics were prescribed in 80% for a median of 10 (interquartile range 7 – 10) days. Of 292 total cases where complete prescribing data were available, avoidable antibiotic exposure occurred in 46%. This included use of antibiotics with broad gram-negative activity in 4%, combination therapy in 12%, and treatment for 10 or more days in 42%. Use of the short-course, single-antibiotic treatment strategies would have reduced prescribed antibiotic-days by 19 – 55%. Conclusions Nearly half of uncomplicated skin infections involved avoidable antibiotic exposure. Antibiotic use could be reduced through treatment approaches utilizing short courses of a single antibiotic. PMID:24262724

  3. "Spider bite" lesions are usually diagnosed as skin and soft-tissue infections.

    PubMed

    Suchard, Jeffrey Ross

    2011-11-01

    Many people seek medical attention for skin lesions and other conditions they attribute to spider bites. Prior experience suggests that many of these lesions have alternate causes, especially infections with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). This study determined the percentage of emergency department (ED) patients reporting a "spider bite" who received a clinical diagnosis of spider bite by their physician vs. other etiologies, and if the diagnoses correlated with demographic risk factors for developing CA-MRSA infections. ED patients who reported that their condition was caused by a "spider bite" were prospectively enrolled in an anonymous, voluntary survey regarding details of their illness and demographic information. Discharge diagnoses were also collected and categorized as: spider bite, bite from other animal (including unknown arthropod), infection, or other diagnosis. There were 182 patients enrolled over 23 months. Seven patients (3.8%) were diagnosed with actual spider bites, 9 patients (4.9%) with bites from other animals, 156 patients (85.7%) with infections, and 6 patients (3.3%) were given other diagnoses. Four patients were given concurrent diagnoses in two categories, and 8 (4.4%) did not have the diagnosis recorded on the data collection instrument. No statistically significant associations were found between the patients' diagnostic categories and the demographic risk factors for CA-MRSA assessed. ED patients reporting a "spider bite" were most frequently diagnosed with skin and soft-tissue infections. Clinically confirmed spider bites were rare, and were caused by black widow spiders when the species could be identified. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. DeconRNASeq: a statistical framework for deconvolution of heterogeneous tissue samples based on mRNA-Seq data.

    PubMed

    Gong, Ting; Szustakowski, Joseph D

    2013-04-15

    For heterogeneous tissues, measurements of gene expression through mRNA-Seq data are confounded by relative proportions of cell types involved. In this note, we introduce an efficient pipeline: DeconRNASeq, an R package for deconvolution of heterogeneous tissues based on mRNA-Seq data. It adopts a globally optimized non-negative decomposition algorithm through quadratic programming for estimating the mixing proportions of distinctive tissue types in next-generation sequencing data. We demonstrated the feasibility and validity of DeconRNASeq across a range of mixing levels and sources using mRNA-Seq data mixed in silico at known concentrations. We validated our computational approach for various benchmark data, with high correlation between our predicted cell proportions and the real fractions of tissues. Our study provides a rigorous, quantitative and high-resolution tool as a prerequisite to use mRNA-Seq data. The modularity of package design allows an easy deployment of custom analytical pipelines for data from other high-throughput platforms. DeconRNASeq is written in R, and is freely available at http://bioconductor.org/packages. Supplementary data are available at Bioinformatics online.

  5. Chromium Is Elevated in Fin Whale (Balaenoptera physalus) Skin Tissue and Is Genotoxic to Fin Whale Skin Cells

    PubMed Central

    Wise, Catherine F.; Wise, Sandra S.; Thompson, W. Douglas; Perkins, Christopher; Wise, John Pierce

    2015-01-01

    Hexavalent chromium (Cr(VI)) is present in the marine environment and is a known carcinogen and reproductive toxicant. Cr(VI) is the form of chromium that is well absorbed through the cell membrane. It is also the most prevalent form in seawater. We measured the total Cr levels in skin biopsies obtained from healthy free-ranging fin whales from the Gulf of Maine and found elevated levels relative to marine mammals in other parts of the world. The levels in fin whale biopsies ranged from 1.71 ug/g to 19.6 ug/g with an average level of 10.07 ug/g. We also measured the cytotoxicity and genotoxicity of Cr(VI) in fin whale skin cells. We found that particulate and soluble Cr(VI) are both cytotoxic and genotoxic to fin whale skin cells in a concentration-dependent manner. The concentration range used in our cell culture studies used environmentally relevant concentrations based on the biopsy measurements. These data suggest that Cr(VI) may be a concern for whales in the Gulf of Maine. PMID:25805270

  6. Opening a Window into Living Tissue: Histopathologic Features of Confocal Microscopic Findings in Skin Tumors.

    PubMed

    Tavoloni Braga, Juliana Casagrande; de Paula Ramos Castro, Raquel; Moraes Pinto Blumetti, Tatiana Cristina; Rocha Mendes, Fernanda Berti; Arêas de Souza Lima Beltrame Ferreira, Juliana; Rezze, Gisele Gargantini

    2016-10-01

    The knowledge of histopathology and in vivo reflectance confocal microscopy correlation has several potential applications. Reflectance confocal microscopy can be performed in all skin tumors, and in this article, the most common histopathologic features of confocal microscopic findings in melanocytic skin tumors and nonmelanocytic skin tumors are described. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Comparative Genomics of Escherichia coli Isolated from Skin and Soft Tissue and Other Extraintestinal Infections.

    PubMed

    Ranjan, Amit; Shaik, Sabiha; Nandanwar, Nishant; Hussain, Arif; Tiwari, Sumeet K; Semmler, Torsten; Jadhav, Savita; Wieler, Lothar H; Alam, Munirul; Colwell, Rita R; Ahmed, Niyaz

    2017-08-15

    Escherichia coli, an intestinal Gram-negative bacterium, has been shown to be associated with a variety of diseases in addition to intestinal infections, such as urinary tract infections (UTIs), meningitis in neonates, septicemia, skin and soft tissue infections (SSTIs), and colisepticemia. Thus, for nonintestinal infections, it is categorized as extraintestinal pathogenic E. coli (ExPEC). It is also an opportunistic pathogen, causing cross infections, notably as an agent of zoonotic diseases. However, comparative genomic data providing functional and genetic coordinates for ExPEC strains associated with these different types of infections have not proven conclusive. In the study reported here, ExPEC E. coli isolated from SSTIs was characterized, including virulence and drug resistance profiles, and compared with isolates from patients suffering either pyelonephritis or septicemia. Results revealed that the majority of the isolates belonged to two pathogenic phylogroups, B2 and D. Approximately 67% of the isolates were multidrug resistant (MDR), with 85% producing extended-spectrum beta-lactamase (ESBL) and 6% producing metallo-beta-lactamase (MBL). The blaCTX-M-15 genotype was observed in at least 70% of the E. coli isolates in each category, conferring resistance to an extended range of beta-lactam antibiotics. Whole-genome sequencing and comparative genomics of the ExPEC isolates revealed that two of the four isolates from SSTIs, NA633 and NA643, belong to pandemic sequence type ST131, whereas functional characteristics of three of the ExPEC pathotypes revealed that they had equal capabilities to form biofilm and were resistant to human serum. Overall, the isolates from a variety of ExPEC infections demonstrated similar resistomes and virulomes and did not display any disease-specific functional or genetic coordinates.IMPORTANCE Infections caused by extraintestinal pathogenic E. coli (ExPEC) are of global concern as they result in significant costs to health

  8. Approaching Solid Tumor Heterogeneity on a Cellular Basis by Tissue Proteomics Using Laser Capture Microdissection and Biological Mass Spectrometry

    PubMed Central

    Johann, Donald J.; Rodriguez-Canales, Jaime; Mukherjee, Sumana; Prieto, DaRue A.; Hanson, Jeffrey C.; Emmert-Buck, Michael; Blonder, Josip

    2010-01-01

    The purpose of this study was to examine solid tumor heterogeneity on a cellular basis using tissue proteomics that relies on a functional relationship between Laser Capture Microdissection (LCM) and biological mass spectrometry (MS). With the use of LCM, homogeneous regions of cells exhibiting uniform histology were isolated and captured from fresh frozen tissue specimens, which were obtained from a human lymph node containing breast carcinoma metastasis. Six specimens ∼50 000 cell each (three from tumor proper and three from tumor stroma) were collected by LCM. Specimens were processed directly on LCM caps, using sonication in buffered methanol to lyse captured cells, solubilize, and digest extracted proteins. Prepared samples were analyzed by LC/MS/MS resulting in more than 500 unique protein identifications. Decoy database searching revealed a false-positive rate between 5 and 10%. Subcellular localization analysis for stromal cells revealed plasma membrane 14%, cytoplasm 39%, nucleus 11%, extracellular space 27%, and unknown 9%; and tumor cell results were 5%, 58%, 26%, 4%, and 7%, respectively. Western blot analysis confirmed specific linkage of validated proteins to underlying pathology and their potential role in solid tumor heterogeneity. With continued research and optimization of this method including analysis of additional clinical specimens, this approach may lead to an improved understanding of tumor heterogeneity, and serve as a platform for solid tumor biomarker discovery. PMID:19284784

  9. MOSFET dosimeter depth-dose measurements in heterogeneous tissue-equivalent phantoms at diagnostic x-ray energies

    SciTech Connect

    Jones, A.K.; Pazik, F.D.; Hintenlang, D.E.; Bolch, W.E.

    2005-10-15

    The objective of the present study was to explore the use of the TN-1002RD metal-oxide-semiconductor field effect transistor (MOSFET) dosimeter for measuring tissue depth dose at diagnostic photon energies in both homogeneous and heterogeneous tissue-equivalent materials. Three cylindrical phantoms were constructed and utilized as a prelude to more complex measurements within tomographic physical phantoms of pediatric patients. Each cylindrical phantom was constructed as a stack of seven 5-cm-diameter and 1-cm-thick discs of materials radiographically representative of either soft tissue (S), bone (B), or lung tissue (L) at diagnostic photon energies. In addition to a homogeneous phantom of soft tissue (SSSSSSS), two heterogeneous phantoms were constructed: SSBBSSS and SBLLBSS. MOSFET dosimeters were then positioned at the interface of each disc, and the phantoms were then irradiated at 66 kVp and 200 mAs. Measured values of absorbed dose at depth were then compared to predicated values of point tissue dose as determined via Monte Carlo radiation transport modeling. At depths exceeding 2 cm, experimental results matched the computed values of dose with high accuracy regardless of the dosimeter orientation (epoxy bubble facing toward or away from the x-ray beam). Discrepancies were noted, however, between measured and calculated point doses near the surface of the phantom (surface to 2 cm depth) when the dosimeters were oriented with the epoxy bubble facing the x-ray beam. These discrepancies were largely eliminated when the dosimeters were placed with the flat side facing the x-ray beam. It is therefore recommended that the MOSFET dosimeters be oriented with their flat sides facing the beam when they are used at shallow depths or on the surface of either phantoms or patients.

  10. PLLA-collagen and PLLA-gelatin hybrid scaffolds with funnel-like porous structure for skin tissue engineering

    NASA Astrophysics Data System (ADS)

    Lu, Hongxu; Oh, Hwan Hee; Kawazoe, Naoki; Yamagishi, Kozo; Chen, Guoping

    2012-12-01

    In skin tissue engineering, a three-dimensional porous scaffold is necessary to support cell adhesion and proliferation and to guide cells moving into the repair area in the wound healing process. Structurally, the porous scaffold should have an open and interconnected porous architecture to facilitate homogenous cell distribution. Moreover, the scaffolds should be mechanically strong to protect deformation during the formation of new skin. In this study, the hybrid scaffolds were prepared by forming funnel-like collagen or gelatin sponge on a woven poly(l-lactic acid) (PLLA) mesh. The hybrid scaffolds combined the advantages of both collagen or gelatin (good cell-interactions) and PLLA mesh (high mechanical strength). The hybrid scaffolds were used to culture dermal fibroblasts for dermal tissue engineering. The funnel-like porous structure promoted homogeneous cell distribution and extracellular matrix production. The PLLA mesh reinforced the scaffold to avoid deformation. Subcutaneous implantation showed that the PLLA-collagen and PLLA-gelatin scaffolds promoted the regeneration of dermal tissue and epidermis and reduced contraction during the formation of new tissue. These results indicate that funnel-like hybrid scaffolds can be used for skin tissue regeneration.

  11. PLLA–collagen and PLLA–gelatin hybrid scaffolds with funnel-like porous structure for skin tissue engineering

    PubMed Central

    Lu, Hongxu; Oh, Hwan Hee; Kawazoe, Naoki; Yamagishi, Kozo; Chen, Guoping

    2012-01-01

    In skin tissue engineering, a three-dimensional porous scaffold is necessary to support cell adhesion and proliferation and to guide cells moving into the repair area in the wound healing process. Structurally, the porous scaffold should have an open and interconnected porous architecture to facilitate homogenous cell distribution. Moreover, the scaffolds should be mechanically strong to protect deformation during the formation of new skin. In this study, the hybrid scaffolds were prepared by forming funnel-like collagen or gelatin sponge on a woven poly(l-lactic acid) (PLLA) mesh. The hybrid scaffolds combined the advantages of both collagen or gelatin (good cell-interactions) and PLLA mesh (high mechanical strength). The hybrid scaffolds were used to culture dermal fibroblasts for dermal tissue engineering. The funnel-like porous structure promoted homogeneous cell distribution and extracellular matrix production. The PLLA mesh reinforced the scaffold to avoid deformation. Subcutaneous implantation showed that the PLLA–collagen and PLLA–gelatin scaffolds promoted the regeneration of dermal tissue and epidermis and reduced contraction during the formation of new tissue. These results indicate that funnel-like hybrid scaffolds can be used for skin tissue regeneration. PMID:27877537

  12. Dermal microvasculature and tissue selective thinning techniques (ultrasound and water-jet) of short-time expanded skin in dogs.

    PubMed

    Siegert, R; Danter, J; Jurk, V; Eggers, R; Krüger, S

    1998-01-01

    Certain reconstructive procedures, like auricular reconstructions, require thin and well-vascularized skin. The aims of this study were to analyze if the increased survival of expanded skin flaps was due to morphologic changes of the dermis, if thinning of short-time expanded skin was possible without harm to the microcirculation and if tissue selective cutting methods could be used to resect subcutaneous fat without damaging its vessels. Eighty-two 200-ml expanders were implanted into the trunk regions of 26 beagles and filled immediately with sterile saline. In the first series of experiments, the expansion was terminated after intervals of 0.5-5 weeks and dermal vessels were analyzed morphometrically. In the second series the expanded flaps were raised after 2 weeks and thinned solely surgically or with the additional use of an ultrasonic knife or with cutting by water jet. In contrast to sham flaps, the expanded skin showed only very few areas of necrosis and these were located superficially in most cases. The relative volume of the dermal vessels and their quantity showed a significant increase after the expansion. Additionally, the subcutaneous tissue could be thinned down to 0.4 mm with the water-jet-cutter. Findings demonstrated that the method used could create a well-vascularized skin flap of minimal thickness that could be very helpful for special reconstructive procedures.

  13. Successive Release of Tissue Inhibitors of Metalloproteinase-1 Through Graphene Oxide-Based Delivery System Can Promote Skin Regeneration.

    PubMed

    Zhong, Cheng; Shi, Dike; Zheng, Yixiong; Nelson, Peter J; Bao, Qi

    2017-09-15

    The purpose of this study was to testify the hypothesis that graphene oxide (GO) could act as an appropriate vehicle for the release of tissue inhibitors of metalloproteinase-1 (TIMP-1) protein in the context of skin repair. GO characteristics were observed by scanning electron microscopy, atomic force microscopy, and thermal gravimetric analysis. After TIMP-1 absorbing GO, the release profiles of various concentrations of TIMP-1 from GO were compared. GO biocompatibility with fibroblast viability was assessed by measuring cell cycle and apoptosis. In vivo wound healing assays were used to determine the effect of TIMP-1-GO on skin regeneration. The greatest intensity of GO was 1140 nm, and the most intensity volume was 10,674.1 nm (nanometer). TIMP-1 was shown to be continuously released for at least 40 days from GO. The proliferation and viability of rat fibroblasts cultured with TIMP-1-GO were not significantly different as compared with the cells grown in GO or TIMP-1 alone (p > 0.05). Skin defect of rats treated with TIMP-1 and TIMP-1-GO showed significant differences in histological and immunohistochemical scores (p < 0.05). GO can be controlled to release carrier materials. The combination of TIMP-1 and GO promoted the progression of skin tissue regeneration in skin defect.

  14. Skin-sparing mastectomy and immediate tissue expander breast reconstruction in patients with macromastia using the Passot breast reduction pattern.

    PubMed

    Rinker, Brian; Thornton, Brian P

    2014-01-01

    Skin-sparing mastectomy (SSM) with immediate tissue expander reconstruction poses a challenge in the patient with macromastia or excessive ptosis. Skin reduction via the Wise pattern has been described but is associated with high rates of skin necrosis. The study group consisted of 43 women with grade 2 or 3 ptosis who underwent SSM and immediate reconstruction with tissue expanders, using the Passot (horizontal) skin reduction pattern. Age ranged from 31 to 67 years (mean, 51 years). The endpoints measured were time to final expansion, mastectomy skin flap necrosis, infectious complications, and total complications. Thirty reconstructions were bilateral and 13 were unilateral (73 breasts total). Follow-up ranged from 6 to 55 months (mean, 20). Common comorbid conditions included hypertension (n = 16), obesity (n = 22), and smoking (n = 9). The mean body mass index was 30.6 (range, 19.4-58.6). Twenty-one patients underwent chemotherapy; 12 received radiation. The mean initial fill was 196 mL (range, 0-420 mL), and the mean time to final expansion was 84 days (range, 28-225 days). Five patients did not complete the reconstruction, 2 because of cancer recurrence and 3 because of infection. There were 3 cases of mastectomy flap necrosis occurring after tissue expander placement (7%). There were 7 infectious complications (16%). The use of a horizontal breast reduction pattern at the time of expander placement produces consistently good esthetic outcomes and a low rate of skin necrosis, and it should be considered as an option in patients with macromastia or ptosis undergoing SSM and immediate reconstruction.

  15. Discrimination between basal cell carcinoma and hair follicles in skin tissue sections by Raman micro-spectroscopy

    NASA Astrophysics Data System (ADS)

    Larraona-Puy, M.; Ghita, A.; Zoladek, A.; Perkins, W.; Varma, S.; Leach, I. H.; Koloydenko, A. A.; Williams, H.; Notingher, I.

    2011-05-01

    Skin cancer is the most common human malignancy and basal cell carcinoma (BCC) represents approximately 80% of the non-melanoma cases. Current methods of treatment require histopathological evaluation of the tissues by qualified personnel. However, this method is subjective and in some cases BCC can be confused with other structures in healthy skin, including hair follicles. In this preliminary study, we investigated the potential of Raman micro-spectroscopy (RMS) to discriminate between hair follicles and BCC in skin tissue sections excised during Mohs micrographic surgery (MMS). Imaging and diagnosis of skin sections was automatically generated using ' a priori'-built spectral model based on LDA. This model had 90 ± 9% sensitivity and 85 ± 9% specificity for discrimination of BCC from dermis and epidermis. The model used selected Raman bands corresponding to the largest spectral differences between the Raman spectra of BCC and the normal skin regions, associated mainly with nucleic acids and collagen type I. Raman spectra corresponding to the epidermis regions of the hair follicles were found to be closer to those of healthy epidermis rather than BCC. Comparison between Raman spectral images and the gold standard haematoxylin and eosin (H&E) histopathology diagnosis showed good agreement. Some hair follicle regions were misclassified as BCC; regions corresponded mainly to the outermost layer of hair follicle (basal cells) which are expected to have higher nucleic acid concentration. This preliminary study shows the ability of RMS to distinguish between BCC and other tissue structures associated to healthy skin which can be confused with BCC due to their similar morphology.

  16. Antibiotics for skin and soft tissues infections in type 2 diabetes mellitus.

    PubMed

    Butranova, O I; Razdrogina, T N

    2015-01-01

    Type 2 diabetes mellitus is a chronic pathology characterized by high prevalence, high morbidity and mortality. According to the data of the Ministry of Health of Volgograd region the number of patients with type 2 diabetes was 68,227 people on 01.01.2014. Medical and social significance of type 2 diabetes mellitus is determined by its complications. Skin and soft tissue infections (SSTIs) in patients with type 2 diabetes are among the main factors of hospitalization and mortality [1]. Diabetic foot syndrome is found in 30-80% of patients [2]. Pharmacoepidemiological analysis of the structure of skin and soft tissues infections in patients with type 2 diabetes, taking into account data on pathogens, parameters of their sensitivity, analysis of prescribed medicines and evaluation of their compliance with current clinical guidelines and standards. A retrospective descriptive cross-sectional pharmacoepidemiological study using randomization by random numbers. The sample consisted of 253 medical records of patients with SSTIs and type 2 diabetes. These were patients admitted to the surgical departments of hospitals of the city of Volgograd for the period from January 2011 to December 2014. Gender structure was the following: 51.4% - women, 48.6% - men. The average age of patients was 64.5 years. The average number of hospital days was 19,5 ± 14,9. Diabetic foot syndrome was found in 81.3% of cases (n-204). The most common forms of diabetic foot syndrome were the following: gangrene of the lower extremities - 28% (n-58), ulcers of the skin - 26% (n-53), mixed forms of SSTIs - 18% (n-37 ). Surgical manipulations were performed in 39.1% of cases (n-99), including amputations in 65.7% (n-65) of cases. The blood glucose level on admission was studied in 97.6% (n-247), at discharge - in 89% (n-225). Urine analysis on admission was performed in 66.4% of patients (n-168), at discharge - in 51% of patients (n-129). The glycemic profile was studied in 81.4% of patients (n-206

  17. Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections

    PubMed Central

    2013-01-01

    Background Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. Results A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). Conclusions This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin. PMID:23924370

  18. Staphylococcus aureus-Associated Skin and Soft Tissue Infections: Anatomical Localization, Epidemiology, Therapy and Potential Prophylaxis.

    PubMed

    Olaniyi, Reuben; Pozzi, Clarissa; Grimaldi, Luca; Bagnoli, Fabio

    2016-10-16

    Skin and soft tissue infections (SSTIs) are among the most common infections worldwide. They range in severity from minor, self-limiting, superficial infections to life-threatening diseases requiring all the resources of modern medicine. Community (CA) and healthcare (HA) acquired SSTIs are most commonly caused by Staphylococcus aureus . They have variable presentations ranging from impetigo and folliculitis to surgical site infections (SSIs). Superficial SSTIs may lead to even more invasive infections such as bacteraemia and osteomyelitis. Here we describe the anatomical localization of the different SSTI associated with S. aureus, the virulence factors known to play a role in these infections, and their current epidemiology. Current prevention and treatment strategies are also discussed. Global epidemiological data show increasing incidence and severity of SSTIs in association with methicillin-resistant S. aureus strains (MRSA). CA-SSTIs are usually less morbid compared to other invasive infections caused by S. aureus, but they have become the most prevalent, requiring a great number of medical interventions, extensive antibiotic use, and therefore a high cost burden. Recurrence of SSTIs is common after initial successful treatment, and decolonization strategies have not been effective in reducing recurrence. Furthermore, decolonization approaches may be contributing to the selection and maintenance of multi-drug resistant strains. Clinical studies from the early 1900s and novel autovaccination approaches suggest an alternative strategy with potential effectiveness: using vaccines to control S. aureus cutaneous infections.

  19. [Description of 3 cases of skin and soft tissue infections caused by Streptococcus pneumoniae].

    PubMed

    Martínez, Mónica Elisabeth; Grenón, Sandra Liliana; López, Oscar Herminio; Leguizamón, Lorena Beatriz; Mollerach, Marta Eugenia; von Specht, Martha Helena

    The role of Streptococcus pneumoniae as a causative agent of skin and soft tissue infections (SSTI) is unusual and its clinical interpretation is difficult. We describe here three cases of SSTI due to S. pneumoniae in patients admitted to the Provincial Pediatric Hospital of Misiones, Argentina that were detected during 10 years of invasive disease (ID) surveillance documented in 2010, 2011 and 2015. These cases involved two girls aged 8 and 7 months old, and a two-year-old male child with diagnoses of gluteal abscess, preseptal cellulites and pyoderma respectively. All the patients were eutrophic and in good general condition on admission; one of them was seropositive for HIV. Antimicrobial susceptibility and serotypes were framed within the local epidemiology of invasive pneumococcal disease. Despite its low frequency, S. pneumoniae as an etiological agent of SSTI must be considered. Our findings revalue the role of the diagnostic laboratory and contribute to document the behavior of this pathogen. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Acinetobacter baumannii-associated skin and soft tissue infections: recognizing a broadening spectrum of disease.

    PubMed

    Guerrero, Dubert M; Perez, Federico; Conger, Nicholas G; Solomkin, Joseph S; Adams, Mark D; Rather, Philip N; Bonomo, Robert A

    2010-02-01

    Acinetobacter baumannii is gaining importance as a cause of nosocomial infections, but its role in skin and soft tissue infection (SSTI) is not well defined. As a result of the outbreak of A. baumannii occurring in military personnel in Iraq and Afghanistan, reports of severe wound infections and SSTI caused by this pathogen are increasing in frequency. We describe four cases of monomicrobial and polymicrobial A. baumannii-associated necrotizing SSTI accompanied by A. baumannii bacteremia and offer a review of similar experiences published in the literature. Our comparative analysis reveals four unique features associated with necrotizing SSTI associated with A. baumannii: i) Occurs in hosts with underlying comorbidities (e.g., trauma, cirrhosis); ii) is often accompanied by bacteremia; iii) multiple drug resistance and the presence of co-pathogens frequently complicated treatment (64% of cases); iv) the cases reported here and in our review required surgical debridement (84% of cases) and led to substantial mortality (approximately 30%). As the prevalence of A. baumannii continues to increase in our health care system, SSTIs caused by this organism may become more common. Clinicians must be aware that the spectrum of disease caused by A. baumannii could include severe necrotizing SSTI and that vigilance for potential complications is necessary.