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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. 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

  3. 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.

  4. 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

  5. [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.

  6. 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.

  7. 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

  8. Molecular Heterogeneity in Primary and Metastatic Prostate Tumor Tissue

    DTIC Science & Technology

    2015-06-01

    AWARD NUMBER: W81XWH-12-1-0072 TITLE: Molecular Heterogeneity in Primary and Metastatic Prostate Tumor Tissue PRINCIPAL INVESTIGATOR: Dr. Julie...Molecular Heterogeneity in Primary and Metastatic Prostate Tumor Tissue 5a. CONTRACT NUMBER W81XWH-12-1-0072 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...heterogeneity in PTEN loss in tumor tissue and prostate cancer prognosis. Aim 2 aimed to compare gene expression profiles between primary and lymph

  9. 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.

  10. 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.

  11. 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)

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. [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).

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  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. 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)

  19. 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.

  20. 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.

  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. Angiotensin II regulates collagen metabolism through modulating tissue inhibitor of metalloproteinase-1 in diabetic skin tissues.

    PubMed

    Ren, Meng; Hao, Shaoyun; Yang, Chuan; Zhu, Ping; Chen, Lihong; Lin, Diaozhu; Li, Na; Yan, Li

    2013-09-01

    We investigated the effect of angiotensin II (Ang II) on matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) balance in regulating collagen metabolism of diabetic skin. Skin tissues from diabetic model were collected, and the primary cultured fibroblasts were treated with Ang II receptor inhibitors before Ang II treatment. The collagen type I (Coll I) and collagen type III (Coll III) were measured by histochemistry. The expressions of transforming growth factor-β (TGF-β), MMP-1, TIMP-1 and propeptides of types I and III procollagens in skin tissues and fibroblasts were quantified using polymerase chain reaction (PCR), Western blot or enzyme-linked immunosorbent assay (ELISA). Collagen dysfunction was documented by changed collagen I/III ratio in streptozotocin (STZ)-injected mice compared with controls. This was accompanied by increased expression of TGF-β, TIMP-1 and propeptides of types I and III procollagens in diabetic skin tissues. In primary cultured fibroblasts, Ang II prompted collagen synthesis accompanied by increases in the expressions of TGF-β, TIMP-1 and types I and III procollagens, and these increases were inhibited by losartan, an Ang II type 1 (AT1) receptor blocker, but not affected by PD123319, an Ang II type 2 (AT2) receptor antagonist. These findings present evidence that Ang-II-mediated changes in the productions of MMP-1 and TIMP-1 occur via AT1 receptors and a TGF-β-dependent mechanism.

  3. Regenerating the skin: a task for the heterogeneous stem cell pool and surrounding niche.

    PubMed

    Solanas, Guiomar; Benitah, Salvador Aznar

    2013-11-01

    In the past years, our view of the molecular and cellular mechanisms that ensure the self-renewal of the skin has dramatically changed. Several populations of stem cells have been identified that differ in their spatio-temporal contribution to their compartment in steady-state and damaged conditions, suggesting that epidermal stem cell heterogeneity is far greater than previously anticipated. There is also increasing evidence that these different stem cells require a tightly controlled spatial and temporal communication between other skin residents to carry out their function.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Molecular Heterogeneity in Primary and Metastatic Prostate Tumor Tissue

    DTIC Science & Technology

    2013-10-01

    PSMA ) and prostate cancer-specific mortality, Kasperzyk et al. found that PSMA was positively correlated with...expressed  in  prostate  tissue:  prostate  specific   membrane  antigen  ( PSMA ).  Utilizing  archival  prostate  tumor  tissue...from  two  US-­‐based  cohort   studies,  Kasperzyk  et  al.  found  that   PSMA  protein  expression  measured

  2. 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.

  3. 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.

  4. 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

    2017-03-31

    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.

  5. 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.

  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. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. [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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  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. 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

  14. 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.

  15. 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.

  16. Advances in the medical management of skin and soft tissue infections.

    PubMed

    McClain, Sarah L; Bohan, Jefferson G; Stevens, Dennis L

    2016-12-14

    Skin and soft tissue infections are some of the most common infectious disease diagnoses in both inpatient and outpatient settings. With bacterial resistance to antimicrobials growing, decision making on empiric antibiotics is becoming increasingly difficult. Additionally, the most recent guidance from a professional society on the treatment of skin and soft tissue infections was published in 2014 by the Infectious Diseases Society of America and is now two years old. New antimicrobial agents have been developed and approved for the treatment of skin and soft tissue infections since then, and more are in the pipeline. This review summarizes the evidence on treatments that are new or in development and the potential repurposing of old antimicrobials. The clinical utility of these treatments is also discussed.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. [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.

  2. [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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for topical approximation of skin. 878.4011 Section 878.4011 Food and Drugs FOOD AND DRUG... approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for the topical approximation of skin is a device indicated for topical application only to hold closed...

  2. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... for topical approximation of skin. 878.4011 Section 878.4011 Food and Drugs FOOD AND DRUG... approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for the topical approximation of skin is a device indicated for topical application only to hold closed...

  3. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... for topical approximation of skin. 878.4011 Section 878.4011 Food and Drugs FOOD AND DRUG... approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for the topical approximation of skin is a device indicated for topical application only to hold closed...

  4. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... for topical approximation of skin. 878.4011 Section 878.4011 Food and Drugs FOOD AND DRUG... approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for the topical approximation of skin is a device indicated for topical application only to hold closed...

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  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. 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.

  18. [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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  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. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. AN INQUIRY INTO THE STRUCTURAL CONDITIONS AFFECTING FLUID TRANSPORT IN THE INTERSTITIAL TISSUE OF THE SKIN

    PubMed Central

    McMaster, Philip D.

    1941-01-01

    With the aim of determining the structural conditions which affect fluid movement in the cutaneous connective tissue of mice, various test fluids were brought into contact with it under conditions such that neither blood vessels nor lymphatics were directly entered. Locke's solution, mouse serum, and a mixture of Locke's solution with a dye which causes edema were all employed. At atmospheric pressure, Locke's solution entered the tissues intermittently. When subjected to very low pressures it continued to enter the skin intermittently and at approximately the same rate. At pressures above 4.5 cm. of water, however, the flow became continuous but it did not increase in rate significantly until pressures of about 8.5 cm. were employed. There was no relationship between the rate of flow and the pressure employed. At a pressure of about 8.5 cm. the resistance of the tissues seemed to give way abruptly as if the formed elements had been separated. This has been termed the "breaking point." After it had been reached each further increase of pressure produced a proportionately greater inflow. Under the conditions of our experiments, the dye-Locke"s solution and also the homologous serum failed to enter the tissues at atmospheric pressure. It was necessary to subject these fluids to pressure to force them into the skin at the same rate at which the Locke's solution entered it spontaneously. Under these circumstances the dye-Locke's solution and the serum entered the skin continuously, not intermittently like the plain Locke's solution. As the pressure was gradually raised, no significant increase of flow into the tissues occurred until a point was reached, on the average 8.5 cm. of water, at which fluid suddenly began to enter very rapidly. This point, the "breaking point" already mentioned, was reached at the same pressure irrespective of the character of the fluid employed, showing that the phenomenon was produced by the fluid bulk. Once it had been attained, further

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. [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.

  7. 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.

  8. 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

  9. [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.

  10. 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.

  11. 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].

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  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. 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.

  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. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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…

  2. 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

  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. 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.

  5. 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.

  6. 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.

  7. 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.

  8. A novel approach for the cryodesiccated preservation of tissue-engineered skin substitutes with trehalose.

    PubMed

    Sun, Mei; Jiang, Man; Cui, Jihong; Liu, Wei; Yin, Lu; Xu, Chunli; Wei, Qi; Yan, Xingrong; Chen, Fulin

    2016-03-01

    Tissue-engineered skin (TES) holds great promise for wound healing in the clinic. However, optimized preservation methods remain an obstacle for its wide application. In this experimental work, we developed a novel approach to preserve TES in the desiccated state with trehalose. The uptake of trehalose by fibroblasts under various conditions, including the trehalose concentration, incubation temperature and time, was studied. The cell viability was investigated by the MTT assay and CFSE/PI staining after cryodesiccation and rehydration. TES was then prepared and incubated with trehalose, and the wound healing effect was investigated after desiccated preservation. The results showed that the optimized conditions for trehalose uptake by fibroblasts were incubation in 200 mM trehalose at 37 °C for 8 h. Cryodesiccated cells and TES maintained 37.55% and 28.31% viabilities of controls, respectively. Furthermore, cryodesiccated TES exhibited a similar wound healing effect to normal TES. This novel approach enabled the preservation and transportation of TES at ambient temperature with a prolonged shelf time, which provides great advantages for the application of TES.

  9. Molecular Basis for Erythromycin Resistance in Group A Streptococcus Isolated From Skin and Soft Tissue Infections

    PubMed Central

    Menon, Thangam

    2015-01-01

    Background In recent years there has been an increase in the use of erythromycin in the treatment of infections caused by bacteria other than Group A Streptococcus (GAS), which has resulted in increased resistance to this antibiotic. Erythromycin and other macrolides are alternative agents for treating GAS infections in patients, who are allergic to penicillin and its derivatives. Aim The main aim of this study was to identify frequency, pattern and genetic determinant of erythromycin resistance among the GAS isolated from skin and soft tissue infections. Materials and Methods A total 100 isolates of GAS were screened for erythromycin resistance by phenotypic and genotypic method. Results The results of the present study showed that 38% isolates were resistant to erythromycin. The iMLS (inducible macrolide-lincosamide-streptogramin) phenotype was predominant (55.26%) followed by M phenotype (26.32%) and cMLS (constitutive macrolide-lincosamide-streptogramin) (18.42%). Conclusion Phenotypic and genotypic analysis showed that the MLSB phenotype with ermB mediated mechanism of resistance was found the most common (76.31%) followed by mefA (20.51%). The ermTR genes was absent in all the isolates. PMID:26672671

  10. Vasculature based model for characterizing the oxygen transport in skin tissues - analogy to the Weinbaum-Jiji bioheat equation

    NASA Astrophysics Data System (ADS)

    Ji, Yan; Liu, Jing

    Based on the conceptual three-layer microvascular structure of skin tissues proposed by Weinbaum et al. [20-25] and in analogy to the well known Weinbaum-Jiji (W-J) bioheat equation, a new oxygen transport model was established in this paper, which collectively included the contributions of the vascular geometry and the blood flow condition. The new one-dimensional three-layer oxygen transport model was then applied to predict the average oxygen concentration distribution in skin tissues and numerical solutions for the boundary value problem coupling the three layers were obtained. A simple expression for the tensor diffusivity (Deff) of oxygen transport over the deep tissue layer was presented, which was orders of magnitude higher than the intrinsic diffusivity (Dt) in tissue without blood flow. Effects of blood flow velocity and vascular geometry to the oxygen transport were investigated. Calculations indicated that the vascular geometry had significant effects on oxygen transport. The oxygen exchange between the arteries and veins was relatively small for the deep tissue layer. Further, the average oxygen concentration gradient appears low in intermediate layer due to large capillary perfusion. The theoretical results were implemented to interpret some previous experimental results and a better understanding on the oxygen transport across the vascularized living tissues was obtained. The strategy proposed in this paper may provide a feasible way to comprehensively characterize the oxygen transport behaviors in living tissues with real and complex vasculature.

  11. Tissue Kallikrein Inhibitors Based on the Sunflower Trypsin Inhibitor Scaffold – A Potential Therapeutic Intervention for Skin Diseases

    PubMed Central

    Chen, Wenjie; Kinsler, Veronica A.

    2016-01-01

    Tissue kallikreins (KLKs), in particular KLK5, 7 and 14 are the major serine proteases in the skin responsible for skin shedding and activation of inflammatory cell signaling. In the normal skin, their activities are controlled by an endogenous protein protease inhibitor encoded by the SPINK5 gene. Loss-of-function mutations in SPINK5 leads to enhanced skin kallikrein activities and cause the skin disease Netherton Syndrome (NS). We have been developing inhibitors based on the Sunflower Trypsin Inhibitor 1 (SFTI-1) scaffold, a 14 amino acids head-to-tail bicyclic peptide with a disulfide bond. To optimize a previously reported SFTI-1 analogue (I10H), we made five analogues with additional substitutions, two of which showed improved inhibition. We then combined those substitutions and discovered a variant (Analogue 6) that displayed dual inhibition of KLK5 (tryptic) and KLK7 (chymotryptic). Analogue 6 attained a tenfold increase in KLK5 inhibition potency with an Isothermal Titration Calorimetry (ITC) Kd of 20nM. Furthermore, it selectively inhibits KLK5 and KLK14 over seven other serine proteases. Its biological function was ascertained by full suppression of KLK5-induced Protease-Activated Receptor 2 (PAR-2) dependent intracellular calcium mobilization and postponement of Interleukin-8 (IL-8) secretion in cell model. Moreover, Analogue 6 permeates through the cornified layer of in vitro organotypic skin equivalent culture and inhibits protease activities therein, providing a potential drug lead for the treatment of NS. PMID:27824929

  12. Spectral investigation of normal skin tissue in vivo via fiber-optical evanescent wave Fourier transform infrared (FEW-FTIR) spectroscopy

    NASA Astrophysics Data System (ADS)

    Kano, Angelique

    2001-11-01

    New applications for the Fiberoptic Evanescent Wave Fourier Transform (FEW-FTIR) method have been developed for the diagnostics of skin surfaces. Our technique allows for the detection of functional groups in the molecular structure of skin tissue noninvasively and in vivo. The FEW-FTIR spectroscopic method is direct, nondestructive, and fast. Our optical fibers for the middle infrared (MIR) range are nontoxic, nonhygroscopic, flexible, and characterized by extremely low losses. This combination of traditional FTIR spectroscopy and advanced fiber technology has enabled us to noninvasively investigate normal skin tissue in vivo in the range of 900 to 4000 cm-1. The second derivative spectra of the baseline-corrected and normalized data have been calculated to determine the peak positions. We have obtained for the first time a more detailed understanding of normal skin tissue fusing FTIR spectroscopy. Despite the complex nature of human skin tissue, the MIR spectra of normal human skin surface tissue has some basic characteristics seen in all cases. The results of our surface analysis of skin tissue are discussed in terms of spectral parameters, band assignments, and molecular structural similarities and differences. Our results have revealed that our spectral parameters can be separated into four distinct classes, providing us with a preliminary model of normal human skin tissue.

  13. 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

  14. In vitro study of ethosome penetration in human skin and hypertrophic scar tissue.

    PubMed

    Zhang, Zhen; Wo, Yan; Zhang, Yixin; Wang, Danru; He, Rong; Chen, Huijin; Cui, Daxiang

    2012-08-01

    The purpose of this study is to characterize a novel transdermal delivery carrier, ethosomes containing 5-fluorouracil. The delivery of drugs from ethosomes in human hypertrophic scar (HS) and the mechanisms of action of ethosomes in human HS were investigated. Percutaneous ethosome permeation was evaluated in vitro in human HS and skin using a Franz's cell. The amount of 5-fluorouracil that permeated HS and skin after 24 hours was most abundant in ethosomes via HS (E-Scar), followed by hydroethanolic solution via HS (H-Scar), ethosomes via skin (E-Skin), and hydroethanolic solution via skin (H-Skin). The penetration of ethosomes in HS and skin was analyzed by ethosomes fluorescently labeled with rhodamine 6GO using confocal laser scanning microscopy. The fluorescence intensity after application for 24 hours was highest in E-Scar, followed by E-Skin, H-Scar, and H-Skin, which indicates the penetration of ethosomes in HS was greatest. In conclusion, we consider that ethosomes are a highly efficient carrier in HS.

  15. Improving light propagation Monte Carlo simulations with accurate 3D modeling of skin tissue

    SciTech Connect

    Paquit, Vincent C; Price, Jeffery R; Meriaudeau, Fabrice; Tobin Jr, Kenneth William

    2008-01-01

    In this paper, we present a 3D light propagation model to simulate multispectral reflectance images of large skin surface areas. In particular, we aim to simulate more accurately the effects of various physiological properties of the skin in the case of subcutaneous vein imaging compared to existing models. Our method combines a Monte Carlo light propagation model, a realistic three-dimensional model of the skin using parametric surfaces and a vision system for data acquisition. We describe our model in detail, present results from the Monte Carlo modeling and compare our results with those obtained with a well established Monte Carlo model and with real skin reflectance images.

  16. Hyperbranched poly(NIPAM) polymers modified with antibiotics for the reduction of bacterial burden in infected human tissue engineered skin.

    PubMed

    Shepherd, Joanna; Sarker, Prodip; Rimmer, Stephen; Swanson, Linda; MacNeil, Sheila; Douglas, Ian

    2011-01-01

    The escalating global incidence of bacterial infection, particularly in chronic wounds, is a problem that requires significant improvements to existing therapies. We have developed hyperbranched poly(NIPAM) polymers functionalized with the antibiotics Vancomycin and Polymyxin-B that are sensitive to the presence of bacteria in solution. Binding of bacteria to the polymers causes a conformational change, resulting in collapse of the polymers and the formation of insoluble polymer/bacteria complexes. We have applied these novel polymers to our tissue engineered human skin model of a burn wound infected with Pseudomonas aeruginosa and Staphylococcus aureus. When the polymers were removed from the infected skin, either in a polymer gel solution or in the form of hydrogel membranes, they removed bound bacteria, thus reducing the bacterial load in the infected skin model. These bacteria-binding polymers have many potential uses, including coatings for wound dressings.

  17. Tissue deposition of the insect repellent DEET and the sunscreen oxybenzone from repeated topical skin applications in rats.

    PubMed

    Fediuk, Daryl J; Wang, Tao; Raizman, Joshua E; Parkinson, Fiona E; Gu, Xiaochen

    2010-12-01

    Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are capable of enhancing skin permeation of each other when applied simultaneously. We carried out a cellular study in rat astrocytes and neurons to assess cell toxicity of DEET and oxybenzone and a 30-day study in Sprague-Dawley rats to characterize skin permeation and tissue disposition of the compounds. Cellular toxicity occurred at 1 µg/mL for neurons and 7-day treatment for astrocytes and neurons. DEET and oxybenzone permeated across the skin to accumulate in blood, liver, and brain after repeated topical applications. DEET disappeared from the application site faster than oxybenzone. Combined application enhanced the disposition of DEET in liver. No overt sign of behavioral toxicity was observed from several behavioral testing protocols. It was concluded that despite measurable disposition of the study compounds in vivo, there was no evidence of neurotoxicological deficits from repeated topical applications of DEET, oxybenzone, or both.

  18. Antimicrobial susceptibility, virulence determinant carriage and molecular characteristics of Staphylococcus aureus isolates associated with skin and soft tissue infections.

    PubMed

    Yu, Fangyou; Liu, Yunling; Lv, Jinnan; Qi, Xiuqin; Lu, Chaohui; Ding, Yu; Li, Dan; Liu, Huanle; Wang, Liangxing

    2015-01-01

    A better understanding of the antimicrobial susceptibility, carriage of virulence determinants and molecular characteristics of Staphylococcus aureus isolates associated with skin and soft tissue infections (SSTIs) may provide further insights related to clinical outcomes with these infections. From January 2012 to September 2013, a total of 128 non-duplicate S. aureus isolates were recovered from patients with SSTIs. All 128 S. aureus SSTI isolates carried at least five virulence genes tested. Virulence genes detected among at least 70% of all tested isolates included hld (100%), hla (95.3%), icaA (96.9%), clf (99.2%), sdrC (79.7%), sdrD (70.3%), and sdrE (72.7%). The prevalence of MRSA isolates with 10 virulence genes tested (54.4%, 31/56) was significantly higher than that among MSSA isolates (35.2%, 25/71) (p<0.05). The positive rates of seb, sen, sem, sdrE and pvl among MRSA isolates were significantly higher than among MSSA isolates (p<0.05). ST7 and ST630 accounting for 10.9% were found to be the predominant STs. The most prevalent spa type was t091 (8.6%). MRSA-ST59-SCCmec IV was the most common clone (12.3%) among MRSA isolates whereas among MSSA isolates the dominant clone was MSSA-ST7 (15.5%). Six main clonal complexes (CCs) were found, including CC5 (52.3%), CC7 (11.7%), CC59 (8.6%), CC88 (6.3%), CC398 (4.7%), and CC121 (3.1%). A higher carriage of seb and sec was found among CC59 isolates. In comparison to CC5 and CC7 isolates, those with the highest carriage rates (>80.0%) of sdrC and sdrD, CC59 isolates had lower prevalence of these two virulence genes. All CC59 isolates were susceptible to gentamicin and trimethoprim/sulfamethoxazole, while CC5 and CC7 isolates had resistance rates to these two antimicrobials of 25.4% and 20.9%, and 40.0% and 40.0%, respectively. The resistance rates for tetracycline, clindamycin, and erythromycin among CC5 isolates were lower than among CC7 and CC59 isolates. In conclusion, the molecular typing of S. aureus SSTI

  19. Adaptation of the dermal collagen structure of human skin and scar tissue in response to stretch: an experimental study.

    PubMed

    Verhaegen, Pauline D; Schouten, Hennie J; Tigchelaar-Gutter, Wikky; van Marle, Jan; van Noorden, Cornelis J; Middelkoop, Esther; van Zuijlen, Paul P

    2012-01-01

    Surgeons are often faced with large defects that are difficult to close. Stretching adjacent skin can facilitate wound closure. In clinical practice, intraoperative stretching is performed in a cyclical or continuous fashion. However, exact mechanisms of tissue adaptation to stretch remain unclear. Therefore, we investigated collagen and elastin orientation and morphology of stretched and nonstretched healthy skin and scars. Tissue samples were stretched, fixed in stretched-out position, and processed for histology. Objective methods were used to quantify the collagen orientation index (COI), bundle thickness, and bundle spacing. Also sections were analyzed for elastin orientation and quantity. Significantly more parallel aligned collagen bundles were found after cyclical (COI = 0.57) and continuous stretch (COI = 0.57) compared with nonstretched skin (COI = 0.40). Similarly, more parallel aligned elastin was found after stretch. Also, significantly thicker collagen bundles and more bundle spacing were found after stretch. For stretched scars, significantly more parallel aligned collagen was found (COI = 0.61) compared with nonstretched scars (COI = 0.49). In conclusion, both elastin and collagen realign in a parallel fashion in response to stretch. For healthy skin, thicker bundles and more space between the bundles were found. Rapid changes in extension, alignment, and collagen morphology appear to be the underlying mechanisms of adaptation to stretching.

  20. Hybrid method for fast Monte Carlo simulation of diffuse reflectance from a multilayered tissue model with tumor-like heterogeneities.

    PubMed

    Zhu, Caigang; Liu, Quan

    2012-01-01

    We present a hybrid method that combines a multilayered scaling method and a perturbation method to speed up the Monte Carlo simulation of diffuse reflectance from a multilayered tissue model with finite-size tumor-like heterogeneities. The proposed method consists of two steps. In the first step, a set of photon trajectory information generated from a baseline Monte Carlo simulation is utilized to scale the exit weight and exit distance of survival photons for the multilayered tissue model. In the second step, another set of photon trajectory information, including the locations of all collision events from the baseline simulation and the scaling result obtained from the first step, is employed by the perturbation Monte Carlo method to estimate diffuse reflectance from the multilayered tissue model with tumor-like heterogeneities. Our method is demonstrated to shorten simulation time by several orders of magnitude. Moreover, this hybrid method works for a larger range of probe configurations and tumor models than the scaling method or the perturbation method alone.

  1. Ceftaroline in the management of complicated skin and soft tissue infections and community acquired pneumonia

    PubMed Central

    Mpenge, Mbiye A; MacGowan, Alasdair P

    2015-01-01

    Ceftaroline is a new parenteral cephalosporin approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of complicated skin and soft tissue infections (cSSTIs) including those due to methicillin-resistant Staphylococcus aureus (MRSA), and community-acquired pneumonia (CAP). Ceftaroline has broad-spectrum activity against gram-positive and gram-negative bacteria and exerts its bactericidal effects by binding to penicillin-binding proteins (PBPs), resulting in inhibition of bacterial cell wall synthesis. It binds to PBP 2a of MRSA with high affinity and also binds to all six PBPs in Streptococcus pneumoniae. In in vitro studies, ceftaroline demonstrated potent activity against Staphylococcus aureus (including MRSA and vancomycin-intermediate isolates), Streptococcus pneumoniae (including multidrug resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, and many common gram-negative pathogens, excluding extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and Pseudomonas aeruginosa. In Phase II and Phase III clinical trials, ceftaroline was noninferior to its comparator agents and demonstrated high clinical cure rates in the treatment of cSSTIs and CAP. It demonstrated favorable outcomes in patients treated for both regulatory-approved indications and unlicensed indications in a retrospective analysis. Ceftaroline is a safe and effective option for treatment in specific patient populations in which its efficacy and safety have been proven. This article reviews the challenges in the treatment of cSSTI and CAP, ceftaroline and its microbiology, pharmacology, efficacy, and safety data which support its use in treatment of cSSTIs and CAP. PMID:25897241

  2. Distribution of Fatal Vibrio Vulnificus Necrotizing Skin and Soft-Tissue Infections

    PubMed Central

    Huang, Kuo-Chin; Weng, Hsu-Huei; Yang, Tien-Yu; Chang, Te-Sheng; Huang, Tsan-Wen; Lee, Mel S.

    2016-01-01

    Abstract Vibrio vulnificus necrotizing skin and soft tissue infections (VNSSTIs), which have increased significantly over the past few decades, are still highly lethal and disabling diseases despite advancing antibiotic and infection control practices. We, therefore, examined the spatiotemporal distribution of worldwide reported episodes and associated mortality rates of VNSSTIs between 1966 and 2014. The PubMed and Cochrane Library databases were systematically searched for observational studies on patients with VNSSTIs. The primary outcome was all-cause mortality. We did random-effects meta-analysis to obtain estimates for primary outcomes; the estimates are presented as means plus a 95% confidence interval (CI). Data from the selected studies were also extracted and pooled for correlation analyses. Nineteen studies of 2227 total patients with VNSSTIs were analyzed. More than 95% of the episodes occurred in the subtropical western Pacific and Atlantic coastal regions of the northern hemisphere. While the number of cases and the number of deaths were not correlated with the study period (rs = 0.476 and 0.310, P = 0.233 and 0.456, respectively), the 5-year mortality rate was significantly negatively correlated with them (rs = −0.905, P = 0.002). Even so, the pooled estimate of total mortality rates from the random-effects meta-analysis was as high as 37.2% (95% CI: 0.265–0.479). These data suggest that VNSSTIs are always an important public health problem and will become more critical and urgent because of global warming. Knowing the current distribution of VNSSTIs will help focus education, policy measures, early clinical diagnosis, and appropriate medical and surgical treatment for them. PMID:26844475

  3. Use of Daptomycin in Critically Ill Children With Bloodstream Infections and Complicated Skin and Soft-tissue Infections.

    PubMed

    Tedeschi, Sara; Tumietto, Fabio; Conti, Matteo; Giannella, Maddalena; Viale, Pierluigi

    2016-02-01

    We report our clinical experience with the use of daptomycin, administered in the dosage of 8 mg/kg/d in 3 minutes, in treating 12 critically ill children younger than 12 years, with bloodstream infections (n = 9) and complicated skin and soft-tissue infections (n = 3). Mean treatment duration was 14 ± 5 days; microbiologic eradication was achieved in all patients, and no drug related adverse events occurred.

  4. Clinical and Molecular Characteristics of Invasive and Noninvasive Skin and Soft Tissue Infections Caused by Group A Streptococcus▿

    PubMed Central

    Lin, Jiun-Nong; Chang, Lin-Li; Lai, Chung-Hsu; Lin, Hsi-Hsun; Chen, Yen-Hsu

    2011-01-01

    The severity of skin and soft tissue infections caused by group A Streptococcus (GAS) is variable, and there are only a limited number of studies evaluating the characteristics of these infections in the literature. From May 2005 to November 2007, 73 patients with skin and soft tissue infections caused by group A Streptococcus were included in this study. Among these patients, 34 (46.6%) had invasive diseases. Diabetes mellitus, alcoholism, and hypertension were the most common underlying disorders. The overall mortality rate was 6.8%, and the elderly were predisposed to invasive infections (P < 0.001). Neutrophil percentages of ≥80, serum creatinine levels of ≥2 mg/dl, and high serum C-reactive protein levels were noted more frequently in patients with invasive infections than in patients with noninvasive infections, as were bacteremia and a high mortality rate. Of the 73 isolates, 93.2%, 97.3%, and 37% exhibited susceptibility to erythromycin, clindamycin, and tetracycline, respectively. The five most prevalent emm types were emm106 (24.7%), emm11 (12.3%), emm102 (9.6%), emm4 (8.2%), and emm12 (8.2%). Compared to other types, the emm106 type was significantly more likely to be associated with invasive diseases (P = 0.012). Dendrogram analysis showed a unique SmaI-digested pulsed-field gel electrophoresis pattern of the emm106 type that was particularly prone to cause invasive skin and soft tissue infections (P < 0.001). The results of this study suggest that isolates with the emm106 gene may be an emerging group A Streptococcus strain that causes invasive skin and soft tissue infections. Further surveillance study to understand the significance of this invasive strain is critical. PMID:21865425

  5. Disinfection of human skin allografts in tissue banking: a systematic review report.

    PubMed

    Johnston, C; Callum, J; Mohr, J; Duong, A; Garibaldi, A; Simunovic, N; Ayeni, O R

    2016-12-01

    The use of skin allografts to temporarily replace lost or damaged skin is practiced worldwide. Naturally occurring contamination can be present on skin or can be introduced at recovery or during processing. This contamination can pose a threat to allograft recipients. Bacterial culture and disinfection of allografts are mandated, but the specific practices and methodologies are not dictated by standards. A systematic review of literature from three databases found 12 research articles that evaluated bioburden reduction processes of skin grafts. The use of broad spectrum antibiotics and antifungal agents was the most frequently identified disinfection method reported demonstrating reductions in contamination rates. It was determined that the greatest reduction in the skin allograft contamination rates utilized 0.1 % peracetic acid or 25 kGy of gamma irradiation at lower temperatures.

  6. How do heterogeneities in single cell rigidity influence the mechanical behavior at the tissue level?

    NASA Astrophysics Data System (ADS)

    Bi, Dapeng; Wetzel, Franziska; Fritsch, Anatol; Marchetti, M. Cristina; Manning, M. Lisa; Kaes, Josef

    It has been long recognized that solid tumor tissues are mechanically more rigid than surrounding healthy tissues. However recent experiments have shown that in primary tumor samples from patients with mammary and cervix carcinomas, cells exhibit a broad distribution of rigidities, with a higher fraction of softer and more contractile cells compared to normal tissues. This gives rise to a paradox: does softness emerge from adaptation to mechanical and chemical cues in the external microenvironment, or are soft cells already present inside a primary solid tumor? Motivated by these observations, we study a model of dense tissues that incorporates the experimental data for cell stiffness variations to reveal that, surprisingly, tumors with a significant fraction of very soft cells can still remain rigid. Moreover, in tissues with the observed distributions of cell stiffnesses, softer cells spontaneously self-organize into lines or streams, possibly facilitating cancer metastasis.

  7. In-vivo characterization of endogenous porphyrin fluorescence from DMBA-treated Swiss Albino mice skin carcinogenesis for measuring tissue transformation

    NASA Astrophysics Data System (ADS)

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

    2002-05-01

    Steady state fluorescence spectroscopic characterization of endogenous porphyrin emission from DMBA treated skin carcinogenesis in Swiss albino mice was carried out. The emission of endogenous porphyrin from normal and abnormal skin tissues was studied both in the presence and absence of exogenous ALA to compare the resultant porphyrin emission characterictics. The mice skin is excited at 405nm and emission spectra are scanned from 430 to 700nm. The average fluorescence emission spectra of mice skin at normal and various tissues transformation conditions were found to be different. Two peaks around 460nm and 636nm were observed and they may be attributed to NADH, Elastin and collagen combination and endogenous porphyrin emission. The intensity at 636nm increases as the stage of the cancer increases. Although exogenous ALA enhances the PPIX level in tumor, the synthesis of PPIX was also found in normal surrounding skin, in fact, with higher concentration than that of tumor tissues.

  8. The role of skin conductivity in a low frequency exposure assessment for peripheral nerve tissue according to the ICNIRP 2010 guidelines.

    PubMed

    Schmid, Gernot; Cecil, Stefan; Überbacher, Richard

    2013-07-07

    Based on numerical computations using commercially available finite difference time domain code and a state-of-the art anatomical model of a 5-year old child, the influence of skin conductivity on the induced electric field strength inside the tissue for homogeneous front-to-back magnetic field exposure and homogeneous vertical electric field exposure was computed. Both ungrounded as well as grounded conditions of the body model were considered. For electric field strengths induced inside CNS tissue the impact of skin conductivity was found to be less than 15%. However, the results demonstrated that the use of skin conductivity values as obtainable from the most widely used data base of dielectric tissue properties and recommended by safety standards are not suitable for exposure assessment with respect to peripheral nerve tissue according to the ICNIRP 2010 guidelines in which the use of the induced electric field strengths inside the skin is suggested as a conservative surrogate for peripheral nerve exposure. This is due to the fact that the skin conductivity values derived from these data bases refer to the stratum corneum, the uppermost layer of the skin, which does not contain any nerve or receptor cells to be protected from stimulation effects. Using these skin conductivity values which are approximately a factor 250-500 lower than skin conductivity values used in studies on which the ICNIRP 2010 guidelines are based on, may lead to overestimations of the induced electric field strengths inside the skin by substantially more than a factor of 10. However, reliable conductivity data of deeper skin layers where nerve and preceptor cells are located is very limited. It is therefore recommended to include appropriate background information in the ICNIRP guidelines and the dielectric tissue property databases, and to put some emphasis on a detailed layer-specific characterization of skin conductivity in near future.

  9. Epidermal Stem Cells Cultured on Collagen-Modified Chitin Membrane Induce In Situ Tissue Regeneration of Full-Thickness Skin Defects in Mice

    PubMed Central

    Shen, Yan; Dai, Libing; Li, Xiaojian; Liang, Rong; Guan, Guangxiong; Zhang, Zhi; Cao, Wenjuan; Liu, Zhihe; Mei, Shirley; Liang, Weiguo; Qin, Shennan; Xu, Jiake; Chen, Honghui

    2014-01-01

    A Large scale of full-thickness skin defects is lack of auto-grafts and which requires the engineered skin substitutes for repair and regeneration. One major obstacle in skin tissue engineering is to expand epidermal stem cells (ESCs) and develop functional substitutes. The other one is the scaffold of the ESCs. Here, we applied type I collagen-modified chitin membrane to form collagen-chitin biomimetic membrane (C-CBM), which has been proved to have a great biocompatibility and degraded totally when it was subcutaneously transplanted into rat skin. ESCs were cultured, and the resulting biofilm was used to cover full-thickness skin defects in nude mice. The transplantation of ESCs- collagen- chitn biomimetic membrane (ESCs-C-CBM) has achieved in situ skin regeneration. In nude mice, compared to controls with collagen-chitin biomimetic membrane (C-CBM) only, the ESCs-C-CBM group had significantly more dermatoglyphs on the skin wound 10 w after surgery, and the new skin was relatively thick, red and elastic. In vivo experiments showed obvious hair follicle cell proliferation in the full-thickness skin defect. Stem cell markers examination showed active ESCs in repair and regeneration of skin. The results indicate that the collagen-modified chitin membrane carry with ESCs has successfully regenerated the whole skin with all the skin appendages and function. PMID:24516553

  10. Preparation, characteristics and assessment of a novel gelatin-chitosan sponge scaffold as skin tissue engineering material.

    PubMed

    Han, Fei; Dong, Yang; Su, Zhen; Yin, Ran; Song, Aihua; Li, Sanming

    2014-12-10

    In order to develop a skin tissue engineering material for wound dressing application, a novel gelatin-chitosan sponge scaffold was designed and studied. The effect of chitosan and gelatin ratio on the morphology, pore size, porosity, water uptake capacity, water retention capacity and the degradation behavior were evaluated. Biocompatibility was investigated by both MTT method and AO/EB staining method. Antibacterial assessment and in vivo pharmacodynamic was also studied to evaluate the potential for wound healing. Results showed the sponge scaffold have uniform porous structure with pore size range between 120 and 140 μm, high porosity (>90%), high water uptake capacity (>1500%), high water retention capacity (>400%), and degradation percent in 28 days between 38.3 and 53.9%. Biocompatibility results showed that the activity of cells could not be affected by the nature of the sponge and it was suitable for cell adhesion and proliferation for 21 days. In vivo evaluation indicated that the sponge scaffold could offer effective support and attachment to cells for skin wound healing. In conclusion, the developed sponge scaffold was a potential skin tissue engineering material with appropriate physical properties and good biocompatibility.

  11. [Gene delivery system based on low molecular weight polyethylenimine and its transfection activity in the skin tissue].

    PubMed

    Liu, Yong Jun; Li, Ya Ping; Li, Jun; Jia, Jing Fen; Liu, Lei

    2004-04-01

    Low molecular weight polyethylenimine (LMW-PEI) was linked to an expressing plasmid contains a green fluorescence protein (GFP) reporter gene and effective gene transfer was observed in CM7221 cell line tested. We examined the relationship among the molecular weight, structure of PEI and their transfection activity and cytotoxicity on CM7221 cell line. We also examined the position and continuance time of the GFP reporter gene expressed in the skin tissue of mouse. Results showed that LMW-PEI/DNA complexes led to high levels of expression in the CM7221 cell line (about 55%). However, with the increasing of PEI molecular weight, the transfection activity of PEI was decreasing. There was an increasing cytotoxicity with the larger PEI molecules. Further research showed that LMW-PEI induced a significant and long-lasting (7 days) expression of the GFP reporter gene in the hair vesicle, sweat, gland, sebaceous gland in the mouse skin tissues. The LMW-PEI described here is a new, highly efficient and non-cytotoxic vector. It would be a useful non-viral vector for gene delivery technology, particular useful as simple skin-specific vehicles of therapeutic genes.

  12. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen.

    PubMed

    Ariotti, Silvia; Beltman, Joost B; Chodaczek, Grzegorz; Hoekstra, Mirjam E; van Beek, Anna E; Gomez-Eerland, Raquel; Ritsma, Laila; van Rheenen, Jacco; Marée, Athanasius F M; Zal, Tomasz; de Boer, Rob J; Haanen, John B A G; Schumacher, Ton N

    2012-11-27

    Recent work has demonstrated that following the clearance of infection a stable population of memory T cells remains present in peripheral organs and contributes to the control of secondary infections. However, little is known about how tissue-resident memory T cells behave in situ and how they encounter newly infected target cells. Here we demonstrate that antigen-specific CD8(+) T cells that remain in skin following herpes simplex virus infection show a steady-state crawling behavior in between keratinocytes. Spatially explicit simulations of the migration of these tissue-resident memory T cells indicate that the migratory dendritic behavior of these cells allows the detection of antigen-expressing target cells in physiologically relevant time frames of minutes to hours. Furthermore, we provide direct evidence for the identification of rare antigen-expressing epithelial cells by skin-patrolling memory T cells in vivo. These data demonstrate the existence of skin patrol by memory T cells and reveal the value of this patrol in the rapid detection of renewed infections at a previously infected site.

  13. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen

    PubMed Central

    Ariotti, Silvia; Beltman, Joost B.; Chodaczek, Grzegorz; Hoekstra, Mirjam E.; van Beek, Anna E.; Gomez-Eerland, Raquel; Ritsma, Laila; van Rheenen, Jacco; Marée, Athanasius F. M.; Zal, Tomasz; de Boer, Rob J.; Haanen, John B. A. G.; Schumacher, Ton N.

    2012-01-01

    Recent work has demonstrated that following the clearance of infection a stable population of memory T cells remains present in peripheral organs and contributes to the control of secondary infections. However, little is known about how tissue-resident memory T cells behave in situ and how they encounter newly infected target cells. Here we demonstrate that antigen-specific CD8+ T cells that remain in skin following herpes simplex virus infection show a steady-state crawling behavior in between keratinocytes. Spatially explicit simulations of the migration of these tissue-resident memory T cells indicate that the migratory dendritic behavior of these cells allows the detection of antigen-expressing target cells in physiologically relevant time frames of minutes to hours. Furthermore, we provide direct evidence for the identification of rare antigen-expressing epithelial cells by skin-patrolling memory T cells in vivo. These data demonstrate the existence of skin patrol by memory T cells and reveal the value of this patrol in the rapid detection of renewed infections at a previously infected site. PMID:23150545

  14. The effect of topically applied tissue expanders on radial forearm skin pliability: a prospective self-controlled study

    PubMed Central

    2014-01-01

    Background The use of pre-operatively applied topical tissue expansion tapes have previously demonstrated increased rates of primary closure of radial forearm free flap donor sites. This is associated with a reduced cost of care as well as improved cosmetic appearance of the donor site. Unfortunately, little is known about the biomechanical changes these tapes cause in the forearm skin. This study tested the hypothesis that the use of topically applied tissue expansion tapes will result in an increase in forearm skin pliability in patients undergoing radial forearm free flap surgery. Methods Twenty-four patients scheduled for head and neck surgery requiring a radial forearm free flap were enrolled in this prospective self-controlled observational study. DynaClose tissue expansion tapes (registered Canica Design Inc, Almonte, Canada) were applied across the forearm one week pre-operatively. Immediately prior to surgery, the skin pliability of the dorsal and volar forearm sites were measured with the Cutometer MPA 580 (registered Courage-Khazaka Electronic GmbH, Cologne, Germany) on both the treatment and contralateral (control) arms. Paired t-tests were used to compare treatment to control at both sites, with p < 0.025 defined as statistically significant. Results There was a statistically significant increase in pliability by a mean of 0.05 mm (SD = 0.09 mm) between treatment and control arms on the dorsal site (95% CI [0.01, 0.08], p = 0.018). This corresponded to an 8% increase in pliability. In contrast, the volar site did not show a statistically significant difference between treatment and control (mean difference = 0.04 mm, SD = 0.20 mm, 95% CI [−0.04, 0.12], p = 0.30). Conclusions This result provides evidence that the pre-operative application of topical tissue expansion tapes produces measurable changes in skin biomechanical properties. The location of this change on the dorsal forearm is consistent with the method of tape

  15. Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure.

    PubMed

    Tewari-Singh, Neera; Agarwal, Rajesh

    2016-06-01

    Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, 2-chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent-induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents.

  16. A survey of knowledge, attitudes, and practices towards skin and soft tissue infections in rural Alaska

    PubMed Central

    Gaines, Joanna; Bulkow, Lisa R.; Kinzer, Michael H.; Hennessy, Thomas W.; Klejka, Joseph A.; Bruce, Michael G.

    2016-01-01

    Background Community-acquired methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus infections are common to south-western Alaska and have been associated with traditional steambaths. More than a decade ago, recommendations were made to affected communities that included preventive skin care, cleaning methods for steambath surfaces, and the use of protective barriers while in steambaths to reduce the risk of S. aureus infection. Objective A review of community medical data suggested that the number of skin infection clinical encounters has increased steadily over the last 3 years and we designed a public health investigation to seek root causes. Study design Using a mixed methods approach with in-person surveys, a convenience sample (n=492) from 3 rural communities assessed the range of knowledge, attitudes and practices concerning skin infections, skin infection education messaging, prevention activities and home self-care of skin infections. Results We described barriers to implementing previous recommendations and evaluated the acceptability of potential interventions. Prior public health messages appear to have been effective in reaching community members and appear to have been understood and accepted. We found no major misconceptions regarding what a boil was or how someone got one. Overall, respondents seemed concerned about boils as a health problem and reported that they were motivated to prevent boils. We identified current practices used to avoid skin infections, such as the disinfection of steambaths. We also identified barriers to engaging in protective behaviours, such as lack of access to laundry facilities. Conclusions These findings can be used to help guide public health strategic planning and identify appropriate evidence-based interventions tailored to the specific needs of the region. PMID:26928370

  17. Age-related changes in male forearm skin-to-fat tissue dielectric constant at 300 MHz.

    PubMed

    Mayrovitz, Harvey N; Grammenos, Alexandra; Corbitt, Kelly; Bartos, Simona

    2017-03-01

    Prior research suggests that tissue dielectric constant (TDC) values are useful to assess localized skin water in females for early diagnosing breast cancer treatment-related lymphoedema and TDC values in young adults have shown gender differences. However, no TDC data are available for older males nor have ageing effects been studied despite known shifts in water state and other skin age-related changes. Thus our goals were to (i) characterize TDC values at various skin depths in young and older males, (ii) determine the dependence of these values on body composition parameters and (iii) establish inter-arm TDC ratios for use as normal male reference values. TDC measurements were made to depths of 0·5, 1·5, 2·5 and 5·0 mm bilaterally on volar forearm skin in 60 males in three groups of 20 that had mean ages ± SD of 24·0 ± 0·9, 40·0 ± 12·9 and 71·0 ± 8·0 years. Total body fat and water percentages were determined via bioimpedance at 50 KHz. Results showed that (i) for all age groups TDC values decreased with increasing depth, (ii) TDC values were not statistically different among age groups except at a depth of 0·5 mm, (iii) TDC values were highly negatively correlated with total body fat and (iv) inter-arm ratios varied little among age groups and depths. It is concluded that (i) age-related larger TDC values at only the shallowest depth is consistent with skin water shifting state from bound to more mobile in the oldest group and (ii) inter-arm ratios at any depth provide a basis to test for unilateral oedema.

  18. Intense THz pulses cause H2AX phosphorylation and activate DNA damage response in human skin tissue

    PubMed Central

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

    2013-01-01

    Recent emergence and growing use of terahertz (THz) radiation for medical imaging and public security screening raise questions on reasonable levels of exposure and health consequences of this form of electromagnetic radiation. In particular, picosecond-duration THz pulses have shown promise for novel diagnostic imaging techniques. However, the effects of THz pulses on human cells and tissues thus far remain largely unknown. We report on the investigation of the biological effects of pulsed THz radiation on artificial human skin tissues. We observe that exposure to intense THz pulses for ten minutes leads to a significant induction of H2AX phosphorylation, indicating that THz pulse irradiation may cause DNA damage in exposed skin tissue. At the same time, we find a THz-pulse-induced increase in the levels of several proteins responsible for cell-cycle regulation and tumor suppression, suggesting that DNA damage repair mechanisms are quickly activated. Furthermore, we find that the cellular response to pulsed THz radiation is significantly different from that induced by exposure to UVA (400 nm). PMID:23577291

  19. Intracellular signalling and intercellular coupling coordinate heterogeneous contractile events to facilitate tissue folding

    NASA Astrophysics Data System (ADS)

    Xie, Shicong; Martin, Adam C.

    2015-05-01

    Cellular forces generated in the apical domain of epithelial cells reshape tissues. Recent studies highlighted an important role for dynamic actomyosin contractions, called pulses, that change cell and tissue shape. Net cell shape change depends on whether cell shape is stabilized, or ratcheted, between pulses. Whether there are different classes of contractile pulses in wild-type embryos and how pulses are spatiotemporally coordinated is unknown. Here we develop a computational framework to identify and classify pulses and determine how pulses are coordinated during invagination of the Drosophila ventral furrow. We demonstrate biased transitions in pulse behaviour, where weak or unratcheted pulses transition to ratcheted pulses. The transcription factor Twist directs this transition, with cells in Twist-depleted embryos exhibiting abnormal reversed transitions in pulse behaviour. We demonstrate that ratcheted pulses have higher probability of having neighbouring contractions, and that ratcheting of pulses prevents competition between neighbouring contractions, allowing collective behaviour.

  20. Primo vascular system of murine melanoma and heterogeneity of tissue oxygenation of the melanoma.

    PubMed

    Hong, Minyoung; Park, Sarah S; Do, Hyunkyung; Jhon, Gil-ja; Suh, Minah; Lee, Youngmi

    2011-09-01

    Murine melanoma requires the complex development of lymphatic, vascular, and non-vascular structures. A possible relationship between the primo vascular system (PVS) and the melanoma metastasis has been proposed. In particular, the PVS may be involved in oxygen transport. Vasculogenic-like networks, similar to the PVS, have been found within melanoma tumors, but their functional relationship with the PVS and meridian structures are unclear. Herein, we report on the use of an electrochemical O(2) sensor to study oxygenation levels of melanoma tumors in mice. We consistently found higher tissue oxygenation in specific sites of tumors (n=5). These sites were strongly associated with vascular structures or the PVS. Furthermore, the PVS on the tumor surface was associated with adipose tissue. Our findings suggest that the PVS is involved in the regulation of metastasis.

  1. Evaluation of the role of the cyclooxygenase signaling pathway during inflammation in skin and muscle tissues of ball pythons (Python regius).

    PubMed

    Sadler, Ryan A; Schumacher, Juergen P; Rathore, Kusum; Newkirk, Kim M; Cole, Grayson; Seibert, Rachel; Cekanova, Maria

    2016-05-01

    OBJECTIVE To determine degrees of production of cyclooxygenase (COX)-1 and -2 and other mediators of inflammation in noninflamed and inflamed skin and muscle tissues in ball pythons (Python regius). ANIMALS 6 healthy adult male ball pythons. PROCEDURES Biopsy specimens of noninflamed skin and muscle tissue were collected from anesthetized snakes on day 0. A 2-cm skin and muscle incision was then made 5 cm distal to the biopsy sites with a CO2 laser to induce inflammation. On day 7, biopsy specimens of skin and muscle tissues were collected from the incision sites. Inflamed and noninflamed tissue specimens were evaluated for production of COX-1, COX-2, phosphorylated protein kinase B (AKT), total AKT, nuclear factor κ-light-chain-enhancer of activated B cells, phosphorylated extracellular receptor kinases (ERKs) 1 and 2, and total ERK proteins by western blot analysis. Histologic evaluation was performed on H&E-stained tissue sections. RESULTS All biopsy specimens of inflamed skin and muscle tissues had higher histologic inflammation scores than did specimens of noninflamed tissue. Inflamed skin specimens had significantly greater production of COX-1 and phosphorylated ERK than did noninflamed skin specimens. Inflamed muscle specimens had significantly greater production of phosphorylated ERK and phosphorylated AKT, significantly lower production of COX-1, and no difference in production of COX-2, compared with production in noninflamed muscle specimens. CONCLUSIONS AND CLINICAL RELEVANCE Production of COX-1, but not COX-2, was significantly greater in inflamed versus noninflamed skin specimens from ball pythons. Additional research into the reptilian COX signaling pathway is warranted.

  2. Preparation and characterization of electrospun PLCL/Poloxamer nanofibers and dextran/gelatin hydrogels for skin tissue engineering.

    PubMed

    Pan, Jian-feng; Liu, Ning-hua; Sun, Hui; Xu, Feng

    2014-01-01

    In this study, two different biomaterials were fabricated and their potential use as a bilayer scaffold for skin tissue engineering applications was assessed. The upper layer biomaterial was a Poly(ε-caprolactone-co-lactide)/Poloxamer (PLCL/Poloxamer) nanofiber membrane fabricated using electrospinning technology. The PLCL/Poloxamer nanofibers (PLCL/Poloxamer, 9/1) exhibited strong mechanical properties (stress/strain values of 9.37 ± 0.38 MPa/187.43 ± 10.66%) and good biocompatibility to support adipose-derived stem cells proliferation. The lower layer biomaterial was a hydrogel composed of 10% dextran and 20% gelatin without the addition of a chemical crosslinking agent. The 5/5 dextran/gelatin hydrogel displayed high swelling property, good compressive strength, capacity to present more than 3 weeks and was able to support cells proliferation. A bilayer scaffold was fabricated using these two materials by underlaying the nanofibers and casting hydrogel to mimic the structure and biological function of native skin tissue. The upper layer membrane provided mechanical support in the scaffold and the lower layer hydrogel provided adequate space to allow cells to proliferate and generate extracellular matrix. The biocompatibility of bilayer scaffold was preliminarily investigated to assess the potential cytotoxicity. The results show that cell viability had not been affected when cocultured with bilayer scaffold. As a consequence, the bilayer scaffold composed of PLCL/Poloxamer nanofibers and dextran/gelatin hydrogels is biocompatible and possesses its potentially high application prospect in the field of skin tissue engineering.

  3. Validation of a new dielectric device to assess changes of tissue water in skin and subcutaneous fat.

    PubMed

    Nuutinen, J; Ikäheimo, R; Lahtinen, T

    2004-04-01

    Easily applicable and inexpensive water-specific techniques to evaluate local oedema, swollen tissue problems and fluid retention in humans are not available. In the present investigation a recently constructed non-invasive device for a local measurement of changes in tissue water in human skin and subcutaneous fat (SSF) was validated. The instrument transmits an ultra high-frequency electromagnetic (EM) wave of 300 MHz into a coaxial line and further into an open-ended coaxial probe which is in contact with the skin. Due to the dimensions of the applied probe the penetration of the EM field extends to subcutaneous fat. A major part of the EM energy is absorbed by tissue water while the rest is reflected back into a coaxial line. From the information of the reflected wave an electrical parameter, directly proportional to tissue water content, called a dielectric constant of SSF, was calculated. For system validation, the decrease of water content in SSF measured with the dielectric technique in the volar forearm of seven patients during haemodialysis treatment was compared with the decrease of the circumference of the forearm and the amount of fluid removed. Statistically highly significant correlations were obtained between the decreasing dielectric constant (i.e. water content) of the SSF and the fluid removed during haemodialysis treatment (r = -0.99, p < 0.01) and between the decreasing dielectric constant and the circumference of the arm (r = 0.97, p < 0.05). The sensitivity of the dielectric method was four-fold compared with the circumferential measurement. The repeatability 3.0% was not dependent on the phase of haemodialysis. The new device allows an easy and non-invasive measurement technique to assess changes of tissue water in SSF.

  4. Comparative Genomic, MicroRNA, and Tissue Analyses Reveal Subtle Differences between Non-Diabetic and Diabetic Foot Skin.

    PubMed

    Ramirez, Horacio A; Liang, Liang; Pastar, Irena; Rosa, Ashley M; Stojadinovic, Olivera; Zwick, Thomas G; Kirsner, Robert S; Maione, Anna G; Garlick, Jonathan A; Tomic-Canic, Marjana

    2015-01-01

    Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular

  5. Molecular characterization of Staphylococcus aureus isolates from skin and soft tissue infections samples and healthy carriers in the Central Slovenia region.

    PubMed

    Svent-Kucina, Natasa; Pirs, Mateja; Kofol, Romina; Blagus, Rok; Smrke, Dragica Maja; Bilban, Marjan; Seme, Katja

    2016-04-01

    Staphylococcus aureus is among the most important human pathogens. It is associated with different infections and is a major cause of skin and soft tissue infections (SSTIs). The aim of our study was to compare S. aureus isolates associated with SSTIs with isolates obtained from healthy carriers in the Central Slovenia region in terms of antimicrobial susceptibility, genetic diversity by clonal complex (CC)/sequence type, spa type, and by toxin gene profiling. In total, 274 S. aureus isolates were collected prospectively by culturing wound samples from 461 SSTI patients and nasal samples from 451 healthy carriers. We have demonstrated high heterogeneity in terms of CCs and spa type in both groups of isolates. The main clone among SSTI strains was Panton-Valentine leukocidin gene (pvl) positive CC121, whereas the main clone among carrier strains was CC45 carrying a large range of toxin genes. The main spa type in both groups was t091. Pvl was more frequently present in SSTI strains (31.2% SSTI vs 3.6% carrier strains) and staphylococcal enterotoxin C was more frequently present in carrier strains (1.6% SSTI vs 17.0% carrier strains). We have also demonstrated that methicillin-resistant S. aureus was a rare cause (2.8%) of SSTIs in our region.

  6. Changes in the electrical properties of the electrode-skin-underlying tissue composite during a week-long programme of neuromuscular electrical stimulation.

    PubMed

    Bîrlea, S I; Breen, P P; Corley, G J; Bîrlea, N M; Quondamatteo, F; ÓLaighin, G

    2014-02-01

    Particular neuromuscular electrical stimulation (NMES) applications require the use of the same electrodes over a long duration (>1 day) without having access to them. Under such circumstance the quality of the electrode-skin contact cannot be assessed. We used the NMES signal itself to assess the quality of the electrode-skin contact and the electrical properties of the underlying tissues over a week. A 14% decrease in the skin's stratum corneum resistance (from 20 to 17 kΩ) and a 15% decrease in the resistance of the electrodes and underlying tissues (from 550 to 460 Ω) were observed in the 14 healthy subjects investigated. A follow-on investigation of the effect of exercise-induced sweating on the electrical properties of the electrode-skin-underlying tissue composite during NMES indicated a correlation between the decrease in the resistance values observed over the course of the week and the accumulation of sweat at the electrode-skin interface. The value of the capacitance representing the dielectric properties of the skin's stratum corneum increased after exercise-induced sweating but did not change significantly over the course of the week. We conclude that valuable information about the electrode-skin-underlying tissue composite can be gathered using the NMES signal itself, and suggest that this is a practical, safe and relatively simple method for monitoring these electrical properties during long-term stimulation.

  7. The Infectious Diseases Clinical Research Program: addressing the challenge of infections related to war injuries and skin and soft tissues.

    PubMed

    Martin, Gregory J; Tribble, David R

    2010-07-01

    The Infectious Diseases Clinical Research Program (IDCRP) at the Uniformed Services University of the Health Sciences (USU) is a National Institute of Allergy and Infectious Diseases (NIAID)-funded network of military treatment and research facilities coordinated through USU and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF). IDCRP functions in collaboration with the NIAID, universities, and industry to address infectious diseases threats to the U.S. military and to the nation. Although IDCRP has projects in diseases from HIV to tuberculosis, a major focus has been on skin, soft-tissue, and war-related infections.

  8. Transcriptional Heterogeneity of IgM+ Cells in Rainbow Trout (Oncorhynchus mykiss) Tissues

    PubMed Central

    Abós, Beatriz; Castro, Rosario; Pignatelli, Jaime; Luque, Alfonso; González, Lucia; Tafalla, Carolina

    2013-01-01

    Two major classes of B lymphocytes have been described to date in rainbow trout: IgM+ and IgT+ cells. IgM+ cells are mainly localized in the spleen, peripheral blood and kidney but are also found in other tissues. However, differences among IgM+ cell populations attending to its location are poorly defined in fish. Thus, the aim of this work was to characterize the expression of different immune molecules such as chemokine receptors, Toll-like receptors (TLRs) and transcription factors on sorted IgM+ lymphocytes from different rainbow trout tissues. IgM+ populations from blood, spleen, kidney, gills, intestine and liver were isolated by cell sorting and the constitutive levels of transcription of these genes evaluated by real-time PCR. To further characterize B cells, we identified an MS4A sequence. In humans, the MS4A family includes several genes with immune functions, such as the B cell marker CD20 or FcRβ. Subsequently, we have also evaluated the mRNA levels of this MS4A gene in the different IgM+ populations. The relevant differences in transcriptional patterns observed for each of these IgM+ populations analyzed, point to the presence of functionally different tissue-specific B cell populations in rainbow trout. The data shown provides a pattern of genes transcribed in IgM+ B cells not previously revealed in teleost fish. Furthermore, the constitutive expression of all the TLR genes analyzed in IgM+ cells suggests an important role for these cells in innate immunity. PMID:24324826

  9. Antisepsis of the Skin by Treatment with Tissue-Tolerable Plasma (TTP): Risk Assessment and Perspectives

    NASA Astrophysics Data System (ADS)

    Lademann, Jürgen; Richter, Heike; Patzelt, Alexa; Meinke, Martina C.; Fluhr, Joachim W.; Kramer, Axel; Weltmann, Klaus-Dieter; Lademann, Olaf

    The application of tissue tolerable plasma (TTP) is well suited for ­disinfection of living tissue. In particular, when treating chronic wounds, it has ­several advantages in comparison to the classical application of antiseptics, which do not penetrate sufficiently into the tissue or inhibit wound regeneration. The mode of action of the plasma is mainly based on synergetic effects between temperature increase and the formation of free radicals, which destroy the bacteria and fungi.

  10. An anisotropically and heterogeneously aligned patterned electrospun scaffold with tailored mechanical property and improved bioactivity for vascular tissue engineering.

    PubMed

    Xu, He; Li, Haiyan; Ke, Qinfei; Chang, Jiang

    2015-04-29

    The development of vascular scaffolds with controlled mechanical properties and stimulatory effects on biological activities of endothelial cells still remains a significant challenge to vascular tissue engineering. In this work, we reported an innovative approach to prepare a new type of vascular scaffolds with anisotropically and heterogeneously aligned patterns using electrospinning technique with unique wire spring templates, and further investigated the structural effects of the patterned electrospun scaffolds on mechanical properties and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs). Results showed that anisotropically aligned patterned nanofibrous structure was obtained by depositing nanofibers on template in a structurally different manner, one part of nanofibers densely deposited on the embossments of wire spring and formed cylindrical-like structures in the transverse direction, while others loosely suspended and aligned along the longitudinal direction, forming a three-dimensional porous microstructure. We further found that such structures could efficiently control the mechanical properties of electrospun vascular scaffolds in both longitudinal and transverse directions by altering the interval distances between the embossments of patterned scaffolds. When HUVECs were cultured on scaffolds with different microstructures, the patterned scaffolds distinctively promoted adhesion of HUVECs at early stage and proliferation during the culture period. Most importantly, cells experienced a large shape change associated with cell cytoskeleton and nuclei remodeling, leading to a stimulatory effect on angiogenesis differentiation of HUVECs by the patterned microstructures of electrospun scaffolds, and the scaffolds with larger distances of intervals showed a higher stimulatory effect. These results suggest that electrospun scaffolds with the anisotropically and heterogeneously aligned patterns, which could efficiently control the

  11. Reexcitation mechanisms in epicardial tissue: role of I(to) density heterogeneities and I(Na) inactivation kinetics.

    PubMed

    Cantalapiedra, Inma R; Peñaranda, Angelina; Mont, Lluis; Brugada, Josep; Echebarria, Blas

    2009-08-21

    Dispersion of action potential repolarization is known to be an important arrhythmogenic factor in cardiopathies such as Brugada syndrome. In this work, we analyze the effect of a variation in sodium current (I(Na)) inactivation and a heterogeneous rise of transient outward current (I(to)) in the probability of reentry in epicardial tissue. We use the Luo-Rudy model of epicardial ventricular action potential to study wave propagation in a one-dimensional fiber. Spatial dispersion in repolarization is introduced by splitting the fiber into zones with different strength of I(to). We then analyze the pro-arrhythmic effect of a variation in the relaxation time and steady-state of the sodium channel fast inactivating gate h. We quantify the probability of reentry measuring the percentage of reexcitations that occurs in 200 beats. We find that, for high stimulation rates, this percentage is negligible, but increases notably for pacing periods above 700ms. Surprisingly, with decreasing I(Na) inactivation time, the percentage of reexcitations does not grow monotonically, but presents vulnerable windows, separated by values of the I(Na) inactivation speed-up where reexcitation does not occur. By increasing the strength of L-type calcium current I(CaL) above a certain threshold, reexcitation disappears. Finally, we show the formation of reentry in stimulated two-dimensional epicardial tissue with modified I(Na) kinetics and I(to) heterogeneity. Thus, we confirm that while I(to) dispersion is necessary for phase-2 reentry, altered sodium inactivation kinetics influences the probability of reexcitation in a highly nonlinear fashion.

  12. Cross-linking of the dermo-epidermal junction of skin regenerating from keratinocyte autografts. Anchoring fibrils are a target for tissue transglutaminase.

    PubMed

    Raghunath, M; Höpfner, B; Aeschlimann, D; Lüthi, U; Meuli, M; Altermatt, S; Gobet, R; Bruckner-Tuderman, L; Steinmann, B

    1996-09-01

    Since transglutaminases create covalent gamma-glutamyl-epsilon-lysine cross-links between extracellular matrix proteins they are prime candidates for stabilizing tissue during wound healing. Therefore, we studied the temporo-spatial expression of transglutaminase activity in skin regenerating from cultured epithelial autografts in severely burned children by the specific incorporation of monodansylcadaverine into cryostat sections from skin biopsies obtained between 5 d to 17 mo after grafting. The dansyl label was subsequently immunolocalized in the epidermis, dermal connective tissue, and along the basement membrane. Incubation of cryosections of normal and regenerating skin with purified tissue transglutaminase confirmed the dermo-epidermal junction and the papillary dermis as targets for this enzyme and revealed that in regenerating skin transamidation of the basement membrane zone was completed only 4-5 mo after grafting. Immunoelectron microscopy revealed that three distinct regions on the central portion of anchoring fibrils were positive for monodansylcadaverine in normal skin which were negative during the initial phase of de novo formation of anchoring fibrils in regenerating skin. Biochemically, we identified collagen VII as potential substrate for tissue transglutaminase. Thus, tissue transglutaminase appears to play an important role not only in cross-linking of the papillary dermis but also of the dermo-epidermal junction in particular.

  13. Adipose Tissue-Derived Mesenchymal Stem Cells Increase Skin Allograft Survival and Inhibit Th-17 Immune Response

    PubMed Central

    Larocca, Rafael Assumpção; Moraes-Vieira, Pedro Manoel; Bassi, Ênio José; Semedo, Patrícia; de Almeida, Danilo Candido; da Silva, Marina Burgos; Thornley, Thomas; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

    2013-01-01

    Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive capabilities both in vitro and in vivo. Their use for therapy in the transplant field is attractive as they could render the use of immunosuppressive drugs unnecessary. The aim of this study was to investigate the effect of ADSC therapy on prolonging skin allograft survival. Animals that were treated with a single injection of donor allogeneic ADSC one day after transplantation showed an increase in donor skin graft survival by approximately one week. This improvement was associated with preserved histological morphology, an expansion of CD4+ regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10 expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naïve CD4+ T cell proliferation and constrain Th-1 and Th-17 polarization. In summary, infusion of ADSC one day post-transplantation dramatically increases skin allograft survival by inhibiting the Th-17 pathogenic immune response and enhancing the protective Treg immune response. Finally, these data suggest that ADSC therapy will open new opportunities for promoting drug-free allograft survival in clinical transplantation. PMID:24124557

  14. Skin equivalent tissue-engineered construct: co-cultured fibroblasts/ keratinocytes on 3D matrices of sericin hope cocoons.

    PubMed

    Nayak, Sunita; Dey, Sancharika; Kundu, Subhas C

    2013-01-01

    The development of effective and alternative tissue-engineered skin replacements to autografts, allografts and xenografts has became a clinical requirement due to the problems related to source of donor tissue and the perceived risk of disease transmission. In the present study 3D tissue engineered construct of sericin is developed using co-culture of keratinocytes on the upper surface of the fabricated matrices and with fibroblasts on lower surface. Sericin is obtained from "Sericin Hope" silkworm of Bombyx mori mutant and is extracted from cocoons by autoclave. Porous sericin matrices are prepared by freeze dried method using genipin as crosslinker. The matrices are characterized biochemically and biophysically. The cell proliferation and viability of co-cultured fibroblasts and keratinocytes on matrices for at least 28 days are observed by live/dead assay, Alamar blue assay, and by dual fluorescent staining. The growth of the fibroblasts and keratinocytes in co-culture is correlated with the expression level of TGF-β, b-FGF and IL-8 in the cultured supernatants by enzyme-linked immunosorbent assay. The histological analysis further demonstrates a multi-layered stratified epidermal layer of uninhibited keratinocytes in co-cultured constructs. Presence of involucrin, collagen IV and the fibroblast surface protein in immuno-histochemical stained sections of co-cultured matrices indicates the significance of paracrine signaling between keratinocytes and fibroblasts in the expression of extracellular matrix protein for dermal repair. No significant amount of pro inflammatory cytokines (TNF-α, IL-1β and nitric oxide) production are evidenced when macrophages grown on the sericin matrices. The results all together depict the potentiality of sericin 3D matrices as skin equivalent tissue engineered construct in wound repair.

  15. On the characterization of the heterogeneous mechanical response of human brain tissue.

    PubMed

    Forte, Antonio E; Gentleman, Stephen M; Dini, Daniele

    2016-12-08

    The mechanical characterization of brain tissue is a complex task that scientists have tried to accomplish for over 50 years. The results in the literature often differ by orders of magnitude because of the lack of a standard testing protocol. Different testing conditions (including humidity, temperature, strain rate), the methodology adopted, and the variety of the species analysed are all potential sources of discrepancies in the measurements. In this work, we present a rigorous experimental investigation on the mechanical properties of human brain, covering both grey and white matter. The influence of testing conditions is also shown and thoroughly discussed. The material characterization performed is finally adopted to provide inputs to a mathematical formulation suitable for numerical simulations of brain deformation during surgical procedures.

  16. Effects of tissue heterogeneity on single-coil, scanning MIT imaging

    NASA Astrophysics Data System (ADS)

    Feldkamp, J. R.; Quirk, S.

    2016-03-01

    We recently reported on the use of a single induction coil to accomplish imaging of the electrical conductivity in human tissues via magnetic induction tomography (MIT). A key to the method was the development of a mapping equation that quantitatively relates an arbitrary electrical conductivity distribution to ohmic loss in a coil consisting of concentric circular loops in a plane. By making multiple coil loss measurements at a number of locations in the vicinity of the target (scan), this mapping equation can be used to build an algorithm for 3D image construction of electrical conductivity. Important assumptions behind the mathematical formula included uniform relative permittivity throughout all space and continuous variation in conductivity. In this paper, these two assumptions were tested in a series of experiments involving the use of human tissue phantoms created from agarose, doped with sufficient sodium chloride to yield physiological conductivities. Inclusions of doped agarose were scanned both while isolated and also while embedded in a matrix of agarose gel having lowered conductivity - to help evaluate the effects of abrupt permittivity change. The effects of discontinuous conductivity change were simulated by filling 5 cm diameter petri dishes with 1.4% aqueous KCl and placing them in a much larger, 14 cm diameter petri dish - gap distance varied from about 3 mm to 30 mm. In either case, we will show that these effects are minimal on resultant images, helping to further validate the mapping equation used to construct MIT images. Because of their simplicity, scans reported here did not include coil rotation. To acknowledge the importance of rotation, however, we have devoted a section of this work to illustrate the profound benefits of coil rotation during a scan - though virtual data are used, where coil rotation is more easily specified.

  17. Full-thickness tissue engineered skin constructed with autogenic bone marrow mesenchymal stem cells.

    PubMed

    He, LiJuan; Nan, Xue; Wang, YunFang; Guan, LiDong; Bai, CiXian; Shi, ShuangShuang; Yuan, HongFeng; Chen, Lin; Liu, Daqing; Pei, Xuetao

    2007-08-01

    To explore the feasibility of repairing clinical cutaneous deficiency, autogenic bone marrow mesenchymal stem cells (BMSCs) were isolated and differentiated into epidermal cells and fibroblasts in vitro supplemented with different inducing factors and biomaterials to construct functional tissueengineered skin. The results showed that after 72 h induction, BMSCs displayed morphologic changes such as typical epidermal cell arrangement, from spindle shape to round or oval; tonofibrils, melanosomes and keratohyaline granules were observed under a transmission electronic microscope. The differentiated cells expressed epidermal stem cell surface marker CK19 (59.66% +/- 4.2%) and epidermal cells differentiation marker CK10. In addition, the induced epidermal cells acquired the anti-radiation capacity featured by lowered apoptosis following exposure to UVB. On the other hand, the collagen microfibrils deposition was noticed under a transmission electronic microscope after differentiating into dermis fibroblasts; RT-PCR identified collagen type I mRNA expression in differentiated cells; radioimmunoassay detected the secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8) (up to 115.06 pg/mL and 0.84 ng/mL, respectively). Further in vivo implanting BMSCs with scaffold material shortened skin wound repair significantly. In one word, autogenic BMSCs have the potential to differentiate into epidermal cells and fibroblasts in vitro, and show clinical feasibility acting as epidermis-like and dermis-like seed cells in skin engineering.

  18. Current role of community-acquired methicillin-resistant Staphylococcus aureus among children with skin and soft tissue infections.

    PubMed

    Teran, Carlos G; Sura, Sunitha; Mohamed, Tarek; Lin, Thant; Meadows, Marsha; Cynthia, Donkor; Wong, Sze H

    2012-01-02

    Community-acquired methicillin-resistant Staphylococcus aureus has become a well-established pathogen with alarming rates during the last decade. The current situation of this bacteria in pediatric infections is very limited and motivated us to conduct this study. This is a retrospective and analytical study including patients less than 18 years of age with the diagnosis of skin or soft tissue infections in 2008 and 2009 meeting the criteria of Community-acquired infection. A prevalence of 41.9% among skin and soft tissue infections was found. Inducible resistance to clindamycin was detected in 1.3% of the strains and the infection shows a seasonal predilection for summer (P=0.003); 57.8% of the cases required hospitalization with a mean stay of 3.3±2.5 days. The susceptibility to clindamycin and co-trimoxazole is 88 and 97% respectively. The resistance to erythromycin has reached 92%. The main diagnoses at presentation was gluteal abscess plus cellulitis (34.2%).The prevalence of CA-MRSA is trending up and seems to become a large burden for the health system in our community. Clindamycin is still an excellent option in the community setting since inducible clindamycin resistance is extremely low in this community. Co-trimoxazole should be kept as a reserved drug to avoid the rapid resurgence resistance in the community.

  19. Meshless method with operator splitting technique for transient nonlinear bioheat transfer in two-dimensional skin tissues.

    PubMed

    Zhang, Ze-Wei; Wang, Hui; Qin, Qing-Hua

    2015-01-16

    A meshless numerical scheme combining the operator splitting method (OSM), the radial basis function (RBF) interpolation, and the method of fundamental solutions (MFS) is developed for solving transient nonlinear bioheat problems in two-dimensional (2D) skin tissues. In the numerical scheme, the nonlinearity caused by linear and exponential relationships of temperature-dependent blood perfusion rate (TDBPR) is taken into consideration. In the analysis, the OSM is used first to separate the Laplacian operator and the nonlinear source term, and then the second-order time-stepping schemes are employed for approximating two splitting operators to convert the original governing equation into a linear nonhomogeneous Helmholtz-type governing equation (NHGE) at each time step. Subsequently, the RBF interpolation and the MFS involving the fundamental solution of the Laplace equation are respectively employed to obtain approximated particular and homogeneous solutions of the nonhomogeneous Helmholtz-type governing equation. Finally, the full fields consisting of the particular and homogeneous solutions are enforced to fit the NHGE at interpolation points and the boundary conditions at boundary collocations for determining unknowns at each time step. The proposed method is verified by comparison of other methods. Furthermore, the sensitivity of the coefficients in the cases of a linear and an exponential relationship of TDBPR is investigated to reveal their bioheat effect on the skin tissue.

  20. One-stage Reconstruction of Soft Tissue Defects with the Sandwich Technique: Collagen-elastin Dermal Template and Skin Grafts

    PubMed Central

    Wollina, Uwe

    2011-01-01

    Background: A full-thickness soft tissue defect closure often needs complex procedures. The use of dermal templates can be helpful in improving the outcome. Objective: The objective was to evaluate a sandwich technique combining the dermal collagen–elastin matrix with skin grafts in a one-stage procedure. Materials and Methods: Twenty-three patients with 27 wounds were enrolled in this prospective single-centre observational study. The mean age was 74.8 ± 17.2 years. Included were full-thickness defects with exposed bone, cartilage and/ or tendons. The dermal collagen–elastin matrix was applied onto the wound bed accomplished by skin transplants, i.e. ‘sandwich’ transplantation. In six wounds, the transplants were treated with intermittent negative pressure therapy. Results: The size of defects was ≤875 cm2. The use of the dermal template resulted in a complete and stable granulation in 100% of wounds. Seventeen defects showed a complete closure and 19 achieved a complete granulation with an incomplete closure. There was a marked pain relief. No adverse events were noted due to the dermal template usage. Conclusions: Sandwich transplantation with the collagen–elastin matrix is a useful tool when dealing with full-thickness soft tissue defects with exposed bone, cartilage or tendons. PMID:22279382

  1. Bathing in carbon dioxide-enriched water alters protein expression in keratinocytes of skin tissue in rats

    NASA Astrophysics Data System (ADS)

    Kälsch, Julia; Pott, Leona L.; Takeda, Atsushi; Kumamoto, Hideo; Möllmann, Dorothe; Canbay, Ali; Sitek, Barbara; Baba, Hideo A.

    2016-10-01

    Beneficial effects of balneotherapy using naturally occurring carbonated water (CO2 enriched) have been known since the Middle Ages. Although this therapy is clinically applied for peripheral artery disease and skin disorder, the underlying mechanisms are not fully elucidated. Under controlled conditions, rats were bathed in either CO2-enriched water (CO2 content 1200 mg/L) or tap water, both at 37 °C, for 10 min daily over 4 weeks. Proliferation activity was assessed by Ki67 immunohistochemistry of the epidermis of the abdomen. The capillary density was assessed by immunodetection of isolectin-positive cells. Using cryo-fixed abdominal skin epidermis, follicle cells and stroma tissue containing capillaries were separately isolated by means of laser microdissection and subjected to proteomic analysis using label-free technique. Differentially expressed proteins were validated by immunohistochemistry. Proliferation activity of keratinocytes was not significantly different in the epidermis after bathing in CO2-enriched water, and also, capillary density did not change. Proteomic analysis revealed up to 36 significantly regulated proteins in the analyzed tissue. Based on the best expression profiles, ten proteins were selected for immunohistochemical validation. Only one protein, far upstream element binding protein 2 (FUBP2), was similarly downregulated in the epidermis after bathing in CO2-enriched water with both techniques. Low FUBP2 expression was associated with low c-Myc immune-expression in keratinocytes. Long-term bathing in CO2-enriched water showed a cellular protein response of epithelial cells in the epidermis which was detectable by two different methods. However, differences in proliferation activity or capillary density were not detected in the normal skin.

  2. Nucleotide excision repair is reduced in oral epithelial tissues compared with skin.

    PubMed

    Mitchell, David; Paniker, Lakshmi; Godar, Dianne

    2012-01-01

    Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the signature mutations of UVR. Radioimmunoassay was used to quantify the induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in DNA purified from three reconstructed tissues, EpiDerm(TM) , EpiGingival(TM) and EpiOral(TM) . We observed comparable levels of DNA damage in all tissues immediately after UVR exposure. In contrast, repair was significantly reduced in both oral tissues compared with EpiDerm(TM) . Our data suggest that UVR exposure of oral tissues can result in accumulation of DNA damage and increase the risk for carcinoma and melanoma of the mouth. Because NER is a broad-spectrum defense against DNA damage caused by a variety of agents in addition to UVR, our data suggest that the relatively low NER efficiency observed in oral tissues may have wide-ranging consequences in this highly exposed environment.

  3. Respiratory chain protein turnover rates in mice are highly heterogeneous but strikingly conserved across tissues, ages, and treatments.

    PubMed

    Karunadharma, Pabalu P; Basisty, Nathan; Chiao, Ying Ann; Dai, Dao-Fu; Drake, Rachel; Levy, Nick; Koh, William J; Emond, Mary J; Kruse, Shane; Marcinek, David; Maccoss, Michael J; Rabinovitch, Peter S

    2015-08-01

    The mitochondrial respiratory chain (RC) produces most of the cellular ATP and requires strict quality-control mechanisms. To examine RC subunit proteostasis in vivo, we measured RC protein half-lives (HLs) in mice by liquid chromatography-tandem mass spectrometry with metabolic [(2)H3]-leucine heavy isotope labeling under divergent conditions. We studied 7 tissues/fractions of young and old mice on control diet or one of 2 diet regimens (caloric restriction or rapamycin) that altered protein turnover (42 conditions in total). We observed a 6.5-fold difference in mean HL across tissues and an 11.5-fold difference across all conditions. Normalization to the mean HL of each condition showed that relative HLs were conserved across conditions (Spearman's ρ = 0.57; P < 10(-4)), but were highly heterogeneous between subunits, with a 7.3-fold mean range overall, and a 2.2- to 4.6-fold range within each complex. To identify factors regulating this conserved distribution, we performed statistical analyses to study the correlation of HLs to the properties of the subunits. HLs significantly correlated with localization within the mitochondria, evolutionary origin, location of protein-encoding, and ubiquitination levels. These findings challenge the notion that all subunits in a complex turnover at comparable rates and suggest that there are common rules governing the differential proteolysis of RC protein subunits under divergent cellular conditions.

  4. Heterogeneous nuclear expression of the promyelocytic leukemia (PML) protein in normal and neoplastic human tissues.

    PubMed Central

    Gambacorta, M.; Flenghi, L.; Fagioli, M.; Pileri, S.; Leoncini, L.; Bigerna, B.; Pacini, R.; Tanci, L. N.; Pasqualucci, L.; Ascani, S.; Mencarelli, A.; Liso, A.; Pelicci, P. G.; Falini, B.

    1996-01-01

    The RING-finger promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha gene in the t(15; 17) translocation of acute promyelocytic leukemia. Wild-type PML localizes in the nucleus with a typical speckled pattern that is a consequence of the concentration of the protein within discrete subnuclear domains known as nuclear bodies. Delocalization of PML from nuclear bodies has been documented in acute promyelocytic leukemia cells and suggested to contribute to leukemogenesis. In an attempt to get new insights into the function of the wild-type PML protein and to investigate whether it displays an altered expression pattern in neoplasms other than acute promyelocytic leukemia, we stained a large number of normal and neoplastic human tissues with a new murine monoclonal antibody (PG-M3) directed against the amino-terminal region of PML. As the PG-M3 epitope is partially resistant to fixatives, only cells that overexpress PML are detected by the antibody in microwave-heated paraffin sections. Among normal tissues, PML was characteristically up-regulated in activated epithelioid histiocytes and fibroblasts in a variety of pathological conditions, columnar epithelium in small active thyroid follicles, well differentiated foamy cells in the center of sebaceous glands, and hypersecretory endometria (Arias-Stella). Interferons, the PML of which is a primary target gene, and estrogens are likely to represent some of the cytokines and/or hormones that may be involved in the up-regulation of PML under these circumstances. In keeping with this concept, we found that PML is frequently overexpressed in Hodgkin and Reed-Sternberg cells of Hodgkin's disease, a tumor of cytokine-producing cells. Among solid tumors, overexpression of PML was frequently found in carcinomas of larynx and thyroid (papillary), epithelial thymomas, and Kaposi's sarcoma, whereas carcinomas of the lung, thyroid (follicular), breast, and colon were

  5. Heterogeneity in Subcutaneous Adipose Tissue Morphology and Metabolic Complications in Overweight and Obese Women

    PubMed Central

    Vargas, Gracie; Chandalia, Manisha; Jiang, Yongquan; Davila, Himara; Motamedi, Massoud

    2013-01-01

    Abstract Objective The aim of this study was to assess morphological features of intact adipose tissue (AT) ex vivo from both subcutaneous (s.c.) abdominal and gluteal areas using a novel approach of multiphoton autofluorescence microscopy (MPAM) combined with second harmonic generation microscopy (SHGM), and to assess the relationship between morphological features in the two AT sites and insulin resistance to peripheral glucose disposal. Method This study was a cross-sectional evaluation of AT morphology feature and peripheral insulin resistance. Subjects Fourteen overweight/obese premenopausal women underwent body composition studies, hyperinsulinemic–euglycemic clamps, and needle biopsy of both the s.c. abdominal and gluteal AT areas. MPAM combined with SHGM was used to measure adipocyte maximal diameter and collagen fiber bundle thickness within a sampled image volume after three-dimensional visualization. Results Higher body mass index (BMI) was associated with larger adipocyte diameter in s.c. abdominal, but not gluteal, AT. Higher adipocyte diameter was associated with higher pericellular collagen thickness. Adipocyte diameter in s.c. abdominal, but not gluteal, AT was associated positively with leptin and negatively with adiponectin plasma levels and peripheral glucose disposal rate. The latter correlation was no longer significant after adjustment for collagen thickness. Conclusion In overweight/obese premenopausal women, larger adipocyte diameter in s.c. abdominal, but not gluteal, AT associates with low plasma adiponectin and systemic insulin resistance, and suggests that increased collagen thickness (obesity-related scarring) could contribute to these findings. PMID:23621112

  6. Heterogeneous distribution of a basement membrane heparan sulfate proteoglycan in rat tissues

    PubMed Central

    1987-01-01

    A heparan sulfate proteoglycan (HSPG) synthesized by murine parietal yolk sac (PYS-2) cells has been characterized and purified from culture supernatants. A monospecific polyclonal antiserum was raised against it which showed activity against the HSPG core protein and basement membrane specificity in immunohistochemical studies on frozen tissue sections from many rat organs. However, there was no reactivity with some basement membranes, notably those of several smooth muscle types and cardiac muscle. In addition, it was found that pancreatic acinar basement membranes also lacked the HSPG type recognized by this antiserum. Those basement membranes that lacked the HSPG strongly stained with antisera against laminin and type IV collagen. The striking distribution pattern is possibly indicative of multiple species of basement membrane HSPGs of which one type is recognized by this antiserum. Further evidence for multiple HSPGs was derived from the finding that skeletal neuromuscular junction and liver epithelia also did not contain this type of HSPG, though previous reports have indicated the presence of HSPGs at these sites. The PYS-2 HSPG was shown to be antigenically related to the large, low buoyant density HSPG from the murine Engelbreth-Holm swarm tumor. It was, however, confirmed that only a single population of antibodies was present in the serum. Despite the presence of similar epitopes on these two proteoglycans of different hydrodynamic properties, it was apparent that the PYS-2 HSPG represents a basement membrane proteoglycan of distinct properties reflected in its restricted distribution in vivo. PMID:2959669

  7. Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney

    PubMed Central

    Sato, Yuki; Mii, Akiko; Hamazaki, Yoko; Fujita, Harumi; Nakata, Hirosuke; Masuda, Kyoko; Nishiyama, Shingo; Shibuya, Shinsuke; Haga, Hironori; Ogawa, Osamu; Shimizu, Akira; Narumiya, Shuh; Kaisho, Tsuneyasu; Arita, Makoto; Yanagisawa, Masashi; Sharma, Kumar; Minato, Nagahiro; Kawamoto, Hiroshi

    2016-01-01

    Acute kidney injury (AKI) is a common clinical condition defined as a rapid decline in kidney function. AKI is a global health burden, estimated to cause 2 million deaths annually worldwide. Unlike AKI in the young, which is reversible, AKI in the elderly often leads to end-stage renal disease, and the mechanism that prevents kidney repair in the elderly is unclear. Here we demonstrate that aged but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI. TLT size was associated with impaired renal function and increased expression of proinflammatory cytokines and homeostatic chemokines, indicating a possible contribution of TLTs to sustained inflammation after injury. Notably, resident fibroblasts from a single lineage diversified into p75 neurotrophin receptor+ (p75NTR+) fibroblasts and homeostatic chemokine–producing fibroblasts inside TLTs, and retinoic acid–producing fibroblasts around TLTs. Deletion of CD4+ cells as well as late administration of dexamethasone abolished TLTs and improved renal outcomes. Importantly, aged but not young human kidneys also formed TLTs that had cellular and molecular components similar to those of mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel therapeutic strategy for AKI in the elderly. PMID:27699223

  8. Comparison of Immunomodulation Properties of Porcine Mesenchymal Stromal/Stem Cells Derived from the Bone Marrow, Adipose Tissue, and Dermal Skin Tissue

    PubMed Central

    Ock, Sun-A; Baregundi Subbarao, Raghavendra; Lee, Yeon-Mi; Lee, Jeong-Hyeon; Jeon, Ryoung-Hoon; Lee, Sung-Lim; Park, Ji Kwon; Hwang, Sun-Chul; Rho, Gyu-Jin

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) demonstrate immunomodulation capacity that has been implicated in the reduction of graft-versus-host disease. Accordingly, we herein investigated the capacity of MSCs derived from several tissue sources to modulate both proinflammatory (interferon [IFN] γ and tumor necrosis factor [TNF] α) and immunosuppressive cytokines (transforming growth factor [TGF] β and interleukin [IL] 10) employing xenogeneic human MSC-mixed lymphocyte reaction (MLR) test. Bone marrow-derived MSCs showed higher self-renewal capacity with relatively slow proliferation rate in contrast to adipose-derived MSCs which displayed higher proliferation rate. Except for the lipoprotein gene, there were no marked changes in osteogenesis- and adipogenesis-related genes following in vitro differentiation; however, the histological marker analysis revealed that adipose MSCs could be differentiated into both adipose and bone tissue. TGFβ and IL10 were detected in adipose MSCs and bone marrow MSCs, respectively. However, skin-derived MSCs expressed both IFNγ and IL10, which may render them sensitive to immunomodulation. The xenogeneic human MLR test revealed that MSCs had a partial immunomodulation capacity, as proliferation of activated and resting peripheral blood mononuclear cells was not affected, but this did not differ among MSC sources. MSCs were not tumorigenic when introduced into immunodeficient mice. We concluded that the characteristics of MSCs are tissue source-dependent and their in vivo application requires more in-depth investigation regarding their precise immunomodulation capacities. PMID:26798368

  9. An upgraded camera-based imaging system for mapping venous blood oxygenation in human skin tissue

    NASA Astrophysics Data System (ADS)

    Li, Jun; Zhang, Xiao; Qiu, Lina; Leotta, Daniel F.

    2016-07-01

    A camera-based imaging system was previously developed for mapping venous blood oxygenation in human skin. However, several limitations were realized in later applications, which could lead to either significant bias in the estimated oxygen saturation value or poor spatial resolution in the map of the oxygen saturation. To overcome these issues, an upgraded system was developed using improved modeling and image processing algorithms. In the modeling, Monte Carlo (MC) simulation was used to verify the effectiveness of the ratio-to-ratio method for semi-infinite and two-layer skin models, and then the relationship between the venous oxygen saturation and the ratio-to-ratio was determined. The improved image processing algorithms included surface curvature correction and motion compensation. The curvature correction is necessary when the imaged skin surface is uneven. The motion compensation is critical for the imaging system because surface motion is inevitable when the venous volume alteration is induced by cuff inflation. In addition to the modeling and image processing algorithms in the upgraded system, a ring light guide was used to achieve perpendicular and uniform incidence of light. Cross-polarization detection was also adopted to suppress surface specular reflection. The upgraded system was applied to mapping of venous oxygen saturation in the palm, opisthenar and forearm of human subjects. The spatial resolution of the oxygenation map achieved is much better than that of the original system. In addition, the mean values of the venous oxygen saturation for the three locations were verified with a commercial near-infrared spectroscopy system and were consistent with previously published data.

  10. A heat transfer model of skin tissue for the detection of lesions: sensitivity analysis.

    PubMed

    Cetingül, M Pirtini; Herman, C

    2010-10-07

    In this paper, we study the transient thermal response of skin layers to determine to which extent the surface temperature distribution reflects the properties of subsurface structures, such as benign or malignant lesions. Specifically, we conduct a detailed sensitivity analysis to interpret the changes in the surface temperature distribution as a function of variations in thermophysical properties, blood perfusion rate, metabolic heat generation and thicknesses of skin layers, using a multilayer computational model. These properties can vary from individual to individual or depend on location, external and internal influences, and in certain situations accurate property data are not available in the literature. Therefore, the uncertainties in these data could potentially affect the accuracy of the interpretation/diagnosis of a lesion in a clinical setting. In this study, relevant parameters were varied within characteristic physiological ranges, and differences in the surface temperature response were quantified. It was observed that variations in these parameters have a small influence on the surface temperature distribution. Analysis using this multilayer model was further conducted to determine the sensitivity of transient thermal response to different lesion sizes. This work validates the idea of examining the transient thermal response obtained using a thermal imaging system with the objective of lesion identification. The modeling effort and the sensitivity analysis reported in this paper comprise a portion of a comprehensive research effort involving experimentation on a skin phantom model as well as measurements on patients in a clinical setting, that are currently underway. One of the preliminary results from the ongoing clinical trial is also included to demonstrate the feasibility of the proposed approach.

  11. Identification of human skin from a tissue fragment by detection of squamous cell carcinoma-related antigen using an enzyme immunoassay.

    PubMed

    Kitao, T; Miyaishi, S; Yamamoto, Y; Ishizu, H

    1996-12-02

    A new method of identifying human skin from a tissue fragment by detection of squamous cell carcinoma-related (SCC) antigen, using an enzyme immunoassay, was developed. When an extract was prepared from 0.1 g human skin homogenized with 1 ml of phosphate buffered saline, this method was able to detect SCC antigen in extracts diluted 10(2)-fold. There was no difference in the detection limit between individuals. Species specificity was good, and there was no cross reaction observed with skins from animals. Our method could also discriminate between skin and other organs or tissues, except for esophagus and lung. A practical case to which this method was applied is presented.

  12. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging

    PubMed Central

    Gaur, Meenakshi; Dobke, Marek; Lunyak, Victoria V.

    2017-01-01

    Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology. PMID:28117680

  13. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging.

    PubMed

    Gaur, Meenakshi; Dobke, Marek; Lunyak, Victoria V

    2017-01-20

    Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.

  14. Investigating tissue respiration and skin microhaemocirculation under adaptive changes and the synchronization of blood flow and oxygen saturation rhythms.

    PubMed

    Dunaev, A V; Sidorov, V V; Krupatkin, A I; Rafailov, I E; Palmer, S G; Stewart, N A; Sokolovski, S G; Rafailov, E U

    2014-04-01

    Multi-functional laser non-invasive diagnostic systems allow the study of a number of microcirculatory parameters, including index of blood microcirculation (Im) (by laser Doppler flowmetry, LDF) and oxygen saturation (StO2) of skin tissue (by tissue reflectance oximetry, TRO). This research aimed to use such a system to investigate the synchronization of microvascular blood flow and oxygen saturation rhythms under normal and adaptive change conditions. Studies were conducted on eight healthy volunteers of 21-49 years. These volunteers were observed between one and six months, totalling 422 basic tests (3 min each). Measurements were performed on the palmar surface of the right middle finger and the lower forearm's medial surface. Rhythmic oscillations of LDF and TRO were studied using wavelet analysis. Combined tissue oxygen consumption data for all volunteers during 'adaptive changes' increased relative to normal conditions with and without arteriovenous anastomoses. Data analysis revealed resonance and synchronized rhythms in microvascular blood flow and oxygen saturation as an adaptive change in myogenic oscillation (vasomotion) resulting from exercise and possibly psychoemotional stress. Synchronization of myogenic rhythms during adaptive changes may lead to increased oxygen consumption as a result of increased microvascular blood flow velocity.

  15. Simultaneous optical coherence and multiphoton microscopy of skin-equivalent tissue models

    NASA Astrophysics Data System (ADS)

    Barton, Jennifer K.; Tang, Shuo; Lim, Ryan; Tromberg, Bruce J.

    2007-07-01

    Three-layer skin-equivalent models (rafts) were created consisting of a collagen/fibroblast layer and an air-exposed keratinocyte layer. Rafts were imaged with a tri-modality microscope including optical coherence (OC), two-photon excited fluorescence (TPEF), and second harmonic generation (SHG) channels. Some rafts were stained with Hoechst 33343 or rhodamine 123, and some were exposed to dimethyl sulfoxide (DMSO). OC microscopy revealed signal in cell cytoplasm and nuclear membranes, and a characteristic texture in the collagen/fibroblast layer. TPEF showed signal in cell cytoplasm and from collagen, and stained specimens revealed cell nuclei or mitochondria. There was little SHG in the keratinocyte layer, but strong signal from collagen bundles. Endogenous signals were severely attenuated in DMSO treated rafts; stained samples revealed shrunken and distorted cell structure. OC, TPEF, and SHG can provide complementary and non-destructive information about raft structure and effect of chemical agents.

  16. Pathological considerations of laser-tissue interactions: light microscopic assessment of thermal damage of skin

    NASA Astrophysics Data System (ADS)

    Flotte, Thomas J.; Goetschkes, Margaret

    1992-06-01

    A variety of fixatives and stains were examined for the ability to differentially stain the extracellular matrix components of thermal damage to the skin in an attempt to provide methods for examining the extent of thermal effects. This information is important in comparing different lasers and laser parameters. Four zones of thermal damage were identified including char and three zones of less extensive damage. The lower bounds of the damage with steady state conditions for these zones were 64 - 66 degree(s)C, 80 - 85 degree(s)C, and > 100 degree(s)C. The best choices based on this study include the following: fixative: Bouin's, overall stain: H & E, inner zone stain: Pinkus' acid orcein giemsa, middle zone stain: Movat's pentachrome, and outer zone stain: the modified elastic stain presented in the appendix of this paper.

  17. Microporous Dermal-Mimetic Electrospun Scaffolds Pre-Seeded with Fibroblasts Promote Tissue Regeneration in Full-Thickness Skin Wounds

    PubMed Central

    Bonvallet, Paul P.; Schultz, Matthew J.; Mitchell, Elizabeth H.; Bain, Jennifer L.; Culpepper, Bonnie K.; Thomas, Steven J.; Bellis, Susan L.

    2015-01-01

    Electrospun scaffolds serve as promising substrates for tissue repair due to their nanofibrous architecture and amenability to tailoring of chemical composition. In this study, the regenerative potential of a microporous electrospun scaffold pre-seeded with dermal fibroblasts was evaluated. Previously we reported that a 70% collagen I and 30% poly(Ɛ-caprolactone) electrospun scaffold (70:30 col/PCL) containing 160 μm diameter pores had favorable mechanical properties, supported fibroblast infiltration and subsequent cell-mediated deposition of extracellular matrix (ECM), and promoted more rapid and effective in vivo skin regeneration when compared to scaffolds lacking micropores. In the current study we tested the hypothesis that the efficacy of the 70:30 col/PCL microporous scaffolds could be further enhanced by seeding scaffolds with dermal fibroblasts prior to implantation into skin wounds. To address this hypothesis, a Fischer 344 (F344) rat syngeneic model was employed. In vitro studies showed that dermal fibroblasts isolated from F344 rat skin were able to adhere and proliferate on 70:30 col/PCL microporous scaffolds, and the cells also filled the 160 μm pores with native ECM proteins such as collagen I and fibronectin. Additionally, scaffolds seeded with F344 fibroblasts exhibited a low rate of contraction (~14%) over a 21 day time frame. To assess regenerative potential, scaffolds with or without seeded F344 dermal fibroblasts were implanted into full thickness, critical size defects created in F344 hosts. Specifically, we compared: microporous scaffolds containing fibroblasts seeded for 4 days; scaffolds containing fibroblasts seeded for only 1 day; acellular microporous scaffolds; and a sham wound (no scaffold). Scaffolds containing fibroblasts seeded for 4 days had the best response of all treatment groups with respect to accelerated wound healing, a more normal-appearing dermal matrix structure, and hair follicle regeneration. Collectively these

  18. Monte Carlo simulation of radiation transfer in human skin with geometrically correct treatment of boundaries between different tissues

    NASA Astrophysics Data System (ADS)

    Premru, Jan; Milanič, Matija; Majaron, Boris

    2013-02-01

    In customary implementation of three-dimensional (3D) Monte Carlo (MC) numerical model of light transport in heterogeneous biological structures, the volume of interest is divided into voxels by a rectangular spatial grid. Each voxel is assumed to have homogeneous optical properties and curved boundaries between neighboring tissues inevitably become serrated. This raises some concerns over realism of the modeling results, especially with regard to reflection and refraction on such boundaries. In order to investigate the above concern, we have implemented an augmented 3D MC code, where tissue boundaries (e.g., blood vessel walls) are defined by analytical functions and thus maintain their shape regardless of grid discretization. Results of the customary and augmented model are compared for a few characteristic test geometries, mimicking a cutaneous blood vessel irradiated with a 532 nm laser beam of finite diameter. Our analysis shows that at specific locations inside the vessel, the amount of deposited laser energy can vary between the two models by up to 10%. Even physically relevant integral quantities, such as linear density of the energy absorbed by the vessel, can differ by as much as 30%. Moreover, the values obtained with the customary model vary strongly with discretization step and don't disappear with ever finer discretization. Meanwhile, our augmented model shows no such behavior, indicating that the customary approach suffers from inherent inaccuracies arising from physically flawed treatment of tissue boundaries.

  19. Design and Construction of Artificial Extracellular Matrix (aECM) Proteins from Escherichia coli for Skin Tissue Engineering.

    PubMed

    Low, Pearlie S J; Tjin, Monica S; Fong, Eileen

    2015-06-11

    Recombinant technology is a versatile platform to create novel artificial proteins with tunable properties. For the last decade, many artificial proteins that have incorporated functional domains derived from nature (or created de novo) have been reported. In particular, artificial extracellular matrix (aECM) proteins have been developed; these aECM proteins consist of biological domains taken from fibronectin, laminins and collagens and are combined with structural domains including elastin-like repeats, silk and collagen repeats. To date, aECM proteins have been widely investigated for applications in tissue engineering and wound repair. Recently, Tjin and coworkers developed integrin-specific aECM proteins designed for promoting human skin keratinocyte attachment and propagation. In their work, the aECM proteins incorporate cell binding domains taken from fibronectin, laminin-5 and collagen IV, as well as flanking elastin-like repeats. They demonstrated that the aECM proteins developed in their work were promising candidates for use as substrates in artificial skin. Here, we outline the design and construction of such aECM proteins as well as their purification process using the thermo-responsive characteristics of elastin.

  20. Molecular characterization, expression and methylation status analysis of BMP4 gene in skin tissue of Liaoning cashmere goat during hair follicle cycle.

    PubMed

    Bai, Wen L; Dang, Yun L; Wang, Jiao J; Yin, Rong H; Wang, Ze Y; Zhu, Yu B; Cong, Yu Y; Xue, Hui L; Deng, Liang; Guo, Dan; Wang, Shi Q; Yang, Shu H

    2016-08-01

    Bone morphogenetic protein 4 (BMP4) is a member of the bone morphogenetic protein family (BMPs). It is involved in the development and cycle of hair follicle, as well as, is thought to be a potential candidate gene for cashmere traits in goats. In the present study, we isolated and characterized a full-length open reading frame (ORF) of BMP4 cDNA from the skin tissue of Liaoning cashmere goat, and investigated the transcriptional pattern and methylation status of BMP4 gene in skin tissue of this breed during different stages of hair follicle cycle. The sequence analysis indicated that the isolated cDNA was 1264-bp in length containing a complete ORF of 1230-bp. It encoded a precursor peptide of 409 amino acids with a signal peptide of 19 amino acids. The structural analysis indicated that goat BMP4 contains typical TGF-β propeptide and TGF-β domains. In skin tissue, BMP4 is generally transcribed in an ascendant pattern from anagen to telogen. The methylation level of 5' flanking regulatory region of BMP4 gene might be involved in its mRNA expression in skin tissue: a higher BMP4 methylation level in skin coincides with a lower expression of BMP4 mRNA. These results from the present work provided a foundation for further insight into the functional and regulatory characteristics of BMP4 in the development and cycle of hair follicle in Liaoning Cashmere goat.

  1. Localization and activity of tissue bound cyclic nucleotide phosphodiesterase in normal and lack of changes in psoriatic human skin.

    PubMed

    Mahrle, G; Organos, C E

    1976-12-01

    This study has been undertaken to elucidate the localization and the activity of cyclic nucleotide phosphodiesterase (PDE) in psoriatic epidermis compared to normal. The results showed that the evaluation of cytochemical methods may be difficult because of the various factors which interfere with the reaction and the considerable amount of background staining. Additionally, only the tissue bound particulate enzyme fraction may be demonstrated by cytochemical means. Nevertheless, the method did reveal that the activity of PDE, if any, is localized on the cytoplasmic membranes of the cells, independent of their origin, and not on the cell surface. Moreover, no differences were found between normal and psoriatic skin. It seems, therefore, that the intracellular degradation of cAMP remains unaltered in psoriasis.

  2. Fabrication of aligned poly(lactic acid)-chitosan nanofibers by novel parallel blade collector method for skin tissue engineering.

    PubMed

    Shalumon, K T; Sathish, D; Nair, S V; Chennazhi, K P; Tamura, H; Jayakumar, R

    2012-06-01

    Poly(lactic acid) (PLA) was blended with chitosan (CS) to fabricate electrospun aligned PLA-CS nanofibers. These prepared nanofibers were aligned using a novel collector made of parallel blades which is designed to increase the transversal electric field across the gap. SEM images show that the fiber diameter mostly ranges between 150 +/- 60 nm and Fourier Transform infrared Spectroscopy (FTIR) analysis confirm the presence of PLA and CS. X-Ray Diffraction (XRD) studies explains the amorphous nature of electrospun PLA-CS nanofibers, suitable for faster degradation. Degradation studies confirmed that PLA-CS nanofiber has enhanced degradation than the pure PLA fibers. Cell studies with human dermal fibroblasts (HDF) show the orientation of cells along the direction of fiber alignment. The results indicate that the prepared PLA-CS aligned nanofibers are promising material for skin tissue engineering.

  3. Skin Cancer

    MedlinePlus

    ... States. The two most common types are basal cell cancer and squamous cell cancer. They usually form on the head, face, ... If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments ...

  4. Monte Carlo evaluation of tissue heterogeneities corrections in the treatment of head and neck cancer patients using stereotactic radiotherapy.

    PubMed

    Pokhrel, Damodar; McClinton, Christopher; Sood, Sumit; Badkul, Rajeev; Saleh, Habeeb; Jiang, Hongyu; Lominska, Christopher

    2016-03-01

    The purpose of this study was to generate Monte Carlo computed dose distributions with the X-ray voxel Monte Carlo (XVMC) algorithm in the treatment of head and neck cancer patients using stereotactic radiotherapy (SRT) and compare to heterogeneity corrected pencil-beam (PB-hete) algorithm. This study includes 10 head and neck cancer patients who underwent SRT re-irradiation using heterogeneity corrected pencil-beam (PB-hete) algorithm for dose calculation. Prescription dose was 24-40 Gy in 3-5 fractions (treated 3-5 fractions per week) with at least 95% of the PTV volume receiving 100% of the prescription dose. A stereotactic head and neck localization box was attached to the base of the thermoplastic mask fixation for target localization. The gross tumor volume (GTV) and organs-at-risk (OARs) were contoured on the 3D CT images. The planning target volume (PTV) was generated from the GTV with 0 to 5 mm uniform expansion; PTV ranged from 10.2 to 64.3 cc (average=35.0±17.5 cc). OARs were contoured on the 3D planning CT and consisted of spinal cord, brainstem, optic structures, parotids, and skin. In the BrainLab treatment planning system (TPS), clinically optimal SRT plans were generated using hybrid planning technique (combination of 3D conformal noncoplanar arcs and nonopposing static beams) for the Novalis-Tx linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV-SRS (1000 MU/min) beam. For the purposes of this study, treatment plans were recomputed using XVMC algorithm utilizing identical beam geometry, multileaf positions, and monitor units and compared to the corresponding clinical PB-hete plans. The Monte Carlo calculated dose distributions show small decreases (<1.5%) in calculated dose for D99, Dmean, and Dmax of the PTV coverage between the two algorithms. However, the average target volume encompassed by the prescribed percent dose (Vp) was about 2.5% less with XVMC vs. PB-hete and

  5. Monte Carlo evaluation of tissue heterogeneities corrections in the treatment of head and neck cancer patients using stereotactic radiotherapy.

    PubMed

    Pokhrel, Damodar; McClinton, Christopher; Sood, Sumit; Badkul, Rajeev; Saleh, Habeeb; Jiang, Hongyu; Lominska, Christopher

    2016-03-08

    The purpose of this study was to generate Monte Carlo computed dose distributions with the X-ray voxel Monte Carlo (XVMC) algorithm in the treatment of head and neck cancer patients using stereotactic radiotherapy (SRT) and compare to heterogeneity corrected pencil-beam (PB-hete) algorithm. This study includes 10 head and neck cancer patients who underwent SRT re-irradiation using heterogeneity corrected pencil-beam (PB-hete) algorithm for dose calculation. Prescription dose was 24-40 Gy in 3-5 fractions (treated 3-5 fractions per week) with at least 95% of the PTV volume receiving 100% of the prescription dose. A stereotactic head and neck localization box was attached to the base of the thermoplastic mask fixation for target localization. The gross tumor volume (GTV) and organs-at-risk (OARs) were contoured on the 3D CT images. The planning target volume (PTV) was generated from the GTV with 0 to 5 mm uniform expansion; PTV ranged from 10.2 to 64.3 cc (average = 35.0±17.5 cc). OARs were contoured on the 3D planning CT and consisted of spinal cord, brainstem, optic structures, parotids, and skin. In the BrainLab treatment planning system (TPS), clinically optimal SRT plans were generated using hybrid planning technique (combination of 3D conformal nonco-planar arcs and nonopposing static beams) for the Novalis-Tx linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV-SRS (1000 MU/min) beam. For the purposes of this study, treatment plans were recomputed using XVMC algorithm utilizing identical beam geometry, multileaf positions, and monitor units and compared to the corresponding clinical PB-hete plans. The Monte Carlo calculated dose distributions show small decreases (< 1.5%) in calculated dose for D99, Dmean, and Dmax of the PTV coverage between the two algorithms. However, the average target volume encompassed by the prescribed percent dose (Vp) was about 2.5% less with XVMC vs. PB-hete and

  6. Bilayered, non-cross-linked collagen matrix for regeneration of facial defects after skin cancer removal: a new perspective for biomaterial-based tissue reconstruction.

    PubMed

    Ghanaati, Shahram; Kovács, Adorján; Barbeck, Mike; Lorenz, Jonas; Teiler, Anna; Sadeghi, Nader; Kirkpatrick, Charles James; Sader, Robert

    2016-03-01

    Classically skin defects are covered by split thickness skin grafts or by means of local or regional skin flaps. In the presented case series for the first time a bilayered, non-crossed-linked collagen matrix has been used in an off-label fashion in order to reconstruct facial skin defects following different types of skin cancer resection. The material is of porcine origin and consists of a spongy and a compact layer. The ratio of the two layers is 1:3 in favour of the spongy layer. The aim of the study was to investigate the potential of this matrix for skin regeneration as an alternative to the standard techniques of skin grafts or flaps. Six patients between 39 and 83 years old were included in the study based on a therapeutic trial. The collagen matrix was used in seven defects involving the nose, eyelid, forehead- and posterior scalp regions, and ranging from 1,2 to 6 cm in diameter. Two different head and neck surgeons at two different institutions performed the operations. Each used a different technique in covering the wound following surgery, i.e. with and without a latex-based sheet under the pressure dressing. In three cases cylindrical biopsies were taken after 14 days. In all cases the biomaterial application was performed without any complication and no adverse effects were observed. Clinically, the collagen matrix contributed to a tension-free skin regeneration, independent of the wound dressing used. The newly regenerated skin showed strong similarity to the adjacent normal tissue both in quality and colour. Histological analysis indicated that the spongy layer replaced the defective connective tissue, by providing stepwise integration into the surrounding implantation bed, while the compact layer was infiltrated by mononuclear cells and contributed to its epithelialization by means of a "conductive"process from the surrounding epithelial cells. The clinical and histological data demonstrate that the collagen bilayered matrix used in this series

  7. The Prevalence of S. aureus Skin and Soft Tissue Infections in Patients with Pemphigus.

    PubMed

    Fagheei Aghmiyuni, Zeinab; Khorshidi, Ahmad; Moniri, Rezvan; Soori, Tahereh; Musavi, Seyed Gholam Abbas

    2016-01-01

    Pemphigus vulgaris are autoimmune blistering diseases that may result in significant morbidity and death. Immunosuppressive therapy of pemphigus vulgaris would predispose the patients to infections. The aim of this study was to assess the prevalence of S. aureus infection and PVL gene in patients with pemphigus admitted to dermatology clinic. Materials and Methods. This descriptive study was conducted on 196 pemphigus vulgaris patients (119 males, 77 females) admitted to dermatology clinic between 2014 and 2015. In this study, the diagnosis of pemphigus vulgaris was made by histology, immunofluorescence pattern of perilesional skin, and indirect immunofluorescence testing of serum. Data were collected through a questionnaire. Results. 59.1% of pemphigus vulgaris patients had S. aureus infection. 49 out of 116 were methicillin-resistant. PVL gene was detected in 25 out of 116 S. aureus positive patients. Conclusion. This is the first report of S. aureus infection in pemphigus patients in Iran. More than forty percent of isolates were methicillin-resistant S. aureus. PVL gene carried by methicillin-resistant S. aureus was high in this study.

  8. Factors affecting the mechanical behavior of collagen hydrogels for skin tissue engineering.

    PubMed

    Pensalfini, Marco; Ehret, Alexander E; Stüdeli, Silvia; Marino, Daniela; Kaech, Andres; Reichmann, Ernst; Mazza, Edoardo

    2017-05-01

    The effect of the production factors yielding a functional dermal substitute was investigated by means of monotonic and cyclic uniaxial tensile tests, as well as electron microscopy visualizations. The role of (i) plastic compression, (ii) product incubation, and (iii) cell permanence in the collagenous matrix in order to achieve a skin-like behavior were characterized in terms of material and structural stiffness, in-plane kinematics, and cyclic response, as well as pore size and network density. The plastic compression resulted in a denser and stiffer material, while no corresponding change was observed in the behavior of the entire structure. This was related to the progressive reduction in product thickness and amount of excess water, rather than to formation of new crosslinks between fibers. Contrary, irrespective of the presence of human fibroblasts, the product incubation induced both material and structural stiffening, indicating the formation of a denser network. These results were confirmed by similar evolutions in the construct in-plane kinematics and cyclic stress reduction. Finally, comparison of constructs incubated in different culture media indicated a determinant contribution of the biochemical environment, rather than of the seeded cells, to the achieved mechanical properties. The observed features are relevant in terms of mechanical biocompatibility of the implant and might direct future optimizations of the production process in order to rapidly attain the desired mechanical properties.

  9. The novel antimicrobial peptide PXL150 in the local treatment of skin and soft tissue infections.

    PubMed

    Myhrman, Emma; Håkansson, Joakim; Lindgren, Kerstin; Björn, Camilla; Sjöstrand, Veronika; Mahlapuu, Margit

    2013-04-01

    Dramatic increase in bacterial resistance towards conventional antibiotics emphasises the importance to identify novel, more potent antimicrobial therapies. Antimicrobial peptides (AMPs) have emerged as a promising new group to be evaluated in therapeutic intervention of infectious diseases. Here we describe a novel AMP, PXL150, which demonstrates in vitro a broad spectrum microbicidal action against both Gram-positive and Gram-negative bacteria, including resistant strains. The potent microbicidal activity and broad antibacterial spectrum of PXL150 were not associated with any hemolytic activity. Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) failed to develop resistance towards PXL150 during continued selection pressure. PXL150 caused a rapid depolarisation of cytoplasmic membrane of S. aureus, and dissipating membrane potential is likely one mechanism for PXL150 to kill its target bacteria. Studies in human cell lines indicated that PXL150 has anti-inflammatory properties, which might be of additional benefit. PXL150 demonstrated pronounced anti-infectious effect in an in vivo model of full thickness wounds infected with MRSA in rats and in an ex vivo model of pig skin infected with S. aureus. Subcutaneous or topical application of the peptide in rats did not lead to any adverse reactions. In conclusion, PXL150 may constitute a new therapeutic alternative for local treatment of infections, and further studies are warranted to evaluate the applicability of this AMP in clinical settings.

  10. The Prevalence of S. aureus Skin and Soft Tissue Infections in Patients with Pemphigus

    PubMed Central

    Soori, Tahereh; Musavi, Seyed Gholam Abbas

    2016-01-01

    Pemphigus vulgaris are autoimmune blistering diseases that may result in significant morbidity and death. Immunosuppressive therapy of pemphigus vulgaris would predispose the patients to infections. The aim of this study was to assess the prevalence of S. aureus infection and PVL gene in patients with pemphigus admitted to dermatology clinic. Materials and Methods. This descriptive study was conducted on 196 pemphigus vulgaris patients (119 males, 77 females) admitted to dermatology clinic between 2014 and 2015. In this study, the diagnosis of pemphigus vulgaris was made by histology, immunofluorescence pattern of perilesional skin, and indirect immunofluorescence testing of serum. Data were collected through a questionnaire. Results. 59.1% of pemphigus vulgaris patients had S. aureus infection. 49 out of 116 were methicillin-resistant. PVL gene was detected in 25 out of 116 S. aureus positive patients. Conclusion. This is the first report of S. aureus infection in pemphigus patients in Iran. More than forty percent of isolates were methicillin-resistant S. aureus. PVL gene carried by methicillin-resistant S. aureus was high in this study. PMID:27800178

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

    PubMed Central

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

    2014-01-01

    BACKGROUND Pityriasis alba affects 1% of the world population and about 9.9% of the children in Brazil. However, its etiology remains uncertain. OBJECTIVE The objective of the present study was to evaluate the immunoexpression of factor XIIIa in dermal dendrocytes of skin lesions of pityriasis alba. METHOD Twenty patients with pityriasis alba and 20 patients with atopic dermatitis underwent biopsy. The dermal dendrocytes marked by factor XIIIa were counted by means of immunohistochemical analysis. RESULTS The mean amount of dermal dendrocytes found in the patients with pityriasis alba was 2, whereas in the patients with atopic dermatitis it was 4, with a statistically significant difference between them. A cutoff point of 3 cells/square inch was established to differentiate pityriasis alba from atopic dermatitis, with 80% sensibility and 90% specificity. CONCLUSION We believe that pityriasis alba and atopic dermatitis should be considered different clinical forms within the spectrum of atopic disease, in which sun radiation plays an important role by modulating the progression of the disease. PMID:24770500

  12. Management of Normal Tissue Toxicity Associated With Chemoradiation (Primary Skin, Esophagus, and Lung)

    PubMed Central

    Yazbeck, Victor Y.; Villaruz, Liza; Haley, Marsha; Socinski, Mark A.

    2016-01-01

    Nearly one quarter of patients with lung cancer present with locally advanced disease where concurrent chemoradiotherapy is the current standard of care for patients with good performance status. Cisplatin-based concurrent chemoradiotherapy consistently showed an improvement in survival compared with sequential chemoradiotherapy, at the expense of an increase in the toxicity profile. Over the past decades, several encouraging biomarkers such as transforming growth factor-beta and radioprotective agents such as amifostine were studied but without reaching approval for patient care. We reviewed the prevalence and risk factors for different adverse effects associated with the combined chemoradiotherapy modality, especially dermatitis, mucositis, esophagitis, and pneumonitis. These adverse effects can further be divided into acute, subacute, and chronic. Dermatitis is usually rare and responds well to topical steroids and usual skin care. Acute esophagitis occurs in 30% of patients and is treated with proton pump inhibitors, promotility agents, local anesthetic, and dietary changes. Radiation pneumonitis is a subacute complication seen in 15% of patients and is usually managed with steroids. Chronic adverse effects such as radiation fibrosis and esophageal stricture occur approximately 6 months after completion of radiation therapy and are usually permanent. In this review, complications of chemoradiotherapy for patients with locally advanced lung cancer are delineated, and approaches to their management are described. Given that treatment interruption is associated with a worse outcome, patients are aggressively treated with a curative intent. Therefore, planning for treatment adverse effects improves patient tolerance, compliance, and outcome. PMID:23708070

  13. WE-AB-303-04: A Tissue Model of Cherenkov Emission From the Skin Surface During Megavoltage X-Ray Radiotherapy

    SciTech Connect

    Wiles, A. N.; Loyalka, S. K.; Izaguirre, E. W.

    2015-06-15

    Purpose: To develop a tissue model of Cherenkov radiation emitted from the skin surface during external beam radiotherapy. Imaging Cherenkov radiation emitted from human skin allows visualization of the beam position and potentially surface dose estimates, and our goal is to characterize the optical properties of these emissions. Methods: We developed a Monte Carlo model of Cherenkov radiation generated in a semi-infinite tissue slab by megavoltage x-ray beams with optical transmission properties determined by a two-layered skin model. We separate the skin into a dermal and an epidermal layer in our model, where distinct molecular absorbers modify the Cherenkov intensity spectrum in each layer while we approximate the scattering properties with Mie and Rayleigh scattering from the highly structured molecular organization found in human skin. Results: We report on the estimated distributions of the Cherenkov wavelength spectrum, emission angles, and surface distribution for the modeled irradiated skin surface. The expected intensity distribution of Cherenkov radiation emitted from skin shows a distinct intensity peak around 475 nm, the blue region of the visible spectrum, between a pair of optical absorption bands in hemoglobin and a broad plateau beginning near 600 nm and extending to at least 700 nm where melanin and hemoglobin absorption are both low. We also find that the Cherenkov intensity decreases with increasing angle from the surface normal, the majority being emitted within 20 degrees of the surface normal. Conclusion: Our estimate of the spectral distribution of Cherenkov radiation emitted from skin indicates an advantage to using imaging devices with long wavelength spectral responsivity. We also expect the most efficient imaging to be near the surface normal where the intensity is greatest; although for contoured surfaces, the relative intensity across the surface may appear to vary due to decreasing Cherenkov intensity with increased angle from the

  14. A low dimensional entropy-based descriptor of several tissues in skin cancer histopathology samples

    NASA Astrophysics Data System (ADS)

    Álvarez, Pablo; Corredor, Germán.; García-Arteaga, Juan D.; Romero, Eduardo

    2015-12-01

    The use of low-level visual features to assign high level labels in datasets of histopathology images is a possible solution to the problems derived from manual labeling by experts. However, in many cases, the visual cues are not enough. In this article we propose the use of features derived exclusively from the spatial distribution of the cell nuclei. These features are calculated using the weight of k-nn graphs constructed from the distances between cells. Results show that there are k values with enhanced discriminatory power, especially when comparing cancerous and non-cancerous tissue.

  15. Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

    PubMed

    Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

    2010-07-01

    Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

  16. YAP Regulates the Expression of Hoxa1 and Hoxc13 in Mouse and Human Oral and Skin Epithelial Tissues

    PubMed Central

    Liu, Ming; Zhao, Shuangyun; Lin, Qingjie

    2015-01-01

    Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans. PMID:25691658

  17. YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues.

    PubMed

    Liu, Ming; Zhao, Shuangyun; Lin, Qingjie; Wang, Xiu-Ping

    2015-04-01

    Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans.

  18. Matrigel immobilization on the shish-kebab structured poly(ɛ-caprolactone) nanofibers for skin tissue engineering

    NASA Astrophysics Data System (ADS)

    Jing, Xin; Mi, Hao-Yang; Peng, Xiang-Fang; Turng, Lih-Sheng

    2016-03-01

    Surface properties of tissue engineering scaffolds such as topography, hydrophilicity, and functional groups play a vital role in cell adhesion, migration, proliferation, and apoptosis. First, poly(ɛ-caprolactone) (PCL) shish-kebab scaffolds (PCL-SK), which feature a three-dimensional structure comprised of electrospun PCL nanofibers covered by periodic, self-induced PCL crystal lamellae on the surface, was created to mimic the nanotopography of native collagen fibrils in the extracellular matrix (ECM). Second, matrigel was covalently immobilized on the surface of alkaline hydrolyzed PCL-SK scaffolds to enhance their hydrophilicity. This combined approach not only mimics the nanotopography of native collagen fibrils, but also simulates the surface features of collagen fibrils for cell growth. To investigate the viability of such scaffolds, HEF1 fibroblast cell assays were conducted and the results revealed that the nanotopography of the PCL-SK scaffolds facilitated cell adhesion and proliferation. The matrigel functionalization on PCL-SK scaffolds further enhanced cellular response, which suggested elevated biocompatibility and greater potential for skin tissue engineering applications.

  19. Isthmin 1 Is a Secreted Protein Expressed in Skin, Mucosal Tissues, and NK, NKT, and Th17 Cells

    PubMed Central

    Valle-Rios, Ricardo; Maravillas-Montero, José L.; Burkhardt, Amanda M.; Martinez, Cynthia; Buhren, Bettina Alexandra; Homey, Bernhard; Gerber, Peter Arne; Robinson, Octavio; Hevezi, Peter

    2014-01-01

    Using a comprehensive microarray database of human gene expression, we identified that in mammals, a secreted protein known as isthmin 1 (ISM1) is expressed in skin, mucosal tissues, and selected lymphocyte populations. ISM1 was originally identified in Xenopus brain during development, and it encodes a predicted ∼50-kDa protein containing a signal peptide, a thrombospondin domain, and an adhesion-associated domain. We confirmed the pattern of expression of ISM1 in both human and mouse tissues. ISM1 is expressed by DX5+ lung lymphocytes that include NK and NKT-like cells, and is also expressed by some CD4+ T cells upon activation but its expression increases significantly when CD4+ T cells were polarized to the Th17 lineage in vitro. The presence of IFN-γ during CD4+ T cell polarization inhibits ISM1 expression. Given that ISM1 has been reported to have anti-angiogenic properties, these observations suggest that ISM1 is a mediator of lymphocyte effector functions and may participate in both innate and acquired immune responses. PMID:24956034

  20. Inhibition of UVB-induced nonmelanoma skin cancer: a path from tea to caffeine to exercise to decreased tissue fat.

    PubMed

    Conney, Allan H; Lou, You-Rong; Nghiem, Paul; Bernard, Jamie J; Wagner, George C; Lu, Yao-Ping

    2013-01-01

    Oral administration of green tea, black tea, or caffeine (but not the decaffeinated teas) inhibited ultraviolet B radiation (UVB)-induced skin carcinogenesis in SKH-1 mice. Studies with caffeine indicated that its inhibitory effect on the ATR/Chk1 pathway is an important mechanism for caffeine's inhibition of UVB-induced carcinogenesis. The regular teas or caffeine increased locomotor activity and decreased tissue fat. In these studies, decreased dermal fat thickness was associated with a decrease in the number of tumors per mouse. Administration of caffeine, voluntary exercise, and removal of the parametrial fat pads all stimulated UVB-induced apoptosis, inhibited UVB-induced carcinogenesis, and stimulated apoptosis in UVB-induced tumors. These results suggest that caffeine administration, voluntary exercise, and removal of the parametrial fat pads inhibit UVB-induced carcinogenesis by stimulating UVB-induced apoptosis and by enhancing apoptosis in DNA-damaged precancer cells and in cancer cells. We hypothesize that tissue fat secretes antiapoptotic adipokines that have a tumor promoting effect.

  1. Evaluation of light scattering properties and chromophore concentrations in skin tissue based on diffuse reflectance signals at isosbestic wavelengths of hemoglobin

    NASA Astrophysics Data System (ADS)

    Yokokawa, Takumi; Nishidate, Izumi

    2016-04-01

    We investigate a method to evaluate light-scattering properties and chromophore concentrations in human skin tissue through diffuse reflectance spectroscopy using the reflectance signals acquired at isosbestic wavelengths of hemoglobin (420, 450, 500, and 585 nm). In the proposed method, Monte Carlo simulation-based empirical formulas are used to specify the scattering parameters of skin tissue, such as the scattering amplitude a and the scattering power b, as well as the concentration of melanin C m and the total blood concentration C tb. The use of isosbestic wavelengths of hemoglobin enables the values of C m, C tb, a, and b to be estimated independently of the oxygenation of hemoglobin. The spectrum of the reduced scattering coefficient is reconstructed from the scattering parameters. Experiments using in vivo human skin tissues were performed to confirm the feasibility of the proposed method for evaluating the changes in scattering properties and chromophore concentrations in skin tissue. The experimental results revealed that light scattering is significantly reduced by the application of a glycerol solution, which indicates an optical clearing effect due to osmotic dehydration and the matching of the refractive indices of scatterers in the epidermis.

  2. High Staphylococcus aureus colonization prevalence among patients with skin and soft tissue infections and controls in an urban emergency department.

    PubMed

    Kumar, Neha; David, Michael Z; Boyle-Vavra, Susan; Sieth, Julia; Daum, Robert S

    2015-03-01

    Staphylococcus aureus is a commensal species that can also be a formidable pathogen. In the United States, an epidemic of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has been occurring for the last 15 years. In the context of a study in which we identified patients with skin and soft tissue infections (SSTIs) and randomized them to receive one of two antimicrobial treatment regimens, we assessed S. aureus colonization in the nares, throat, and perianal skin on the day of enrollment and 40 days after therapy. We compared the prevalence of colonization between the SSTI patients and an uninfected control population. A total of 144 subjects and 130 controls, predominantly African American, participated in this study, and 116 returned for a 40-day follow-up visit. Of the SSTI patients, 76% were colonized with S. aureus at enrollment, as were 65% of the controls. Patients were more likely than the controls to be colonized with USA300 MRSA (62/144 [43.1%] versus 11/130 [8.5%], respectively; P < 0.001). The nares were not the most common site of colonization. The colonization prevalence diminished somewhat after antibiotic treatment but remained high. The isolates that colonized the controls were more likely than those in the patients to be methicillin-susceptible S. aureus (MSSA) (74/84 [88.1%] versus 56/106 [52.8%], respectively; P < 0.001). In conclusion, the prevalence of S. aureus colonization among SSTI patients was high and often involved USA300 MRSA. The prevalence diminished somewhat with antimicrobial therapy but remained high at the 40-day follow-up visit. Control subjects were also colonized at a high prevalence but most often with a genetic background not associated with a clinical infection in this study. S. aureus is a commensal species and a pathogen. Plans for decolonization or eradication should take this distinction into account.

  3. Weight Loss via exercise with controlled dietary intake may affect phospholipid profile for cancer prevention in murine skin tissues.

    PubMed

    Ouyang, Ping; Jiang, Yu; Doan, Hieu M; Xie, Linglin; Vasquez, David; Welti, Ruth; Su, Xiaoyu; Lu, Nanyan; Herndon, Betty; Yang, Shie-Shien; Jeannotte, Richard; Wang, Weiqun

    2010-04-01

    Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mechanisms are unclear. This study assessed the effect of exercise with dietary consideration on the phospholipid profile in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin tissues. CD-1 mice were randomly assigned to one of the three groups: ad libitum-fed sedentary control; ad libitum-fed treadmill exercise at 13.4 m/min for 60 min/d, 5 d/wk (Ex+AL); and treadmill-exercised but pair-fed with the same amount as the control (Ex+PF). After 14 weeks, Ex+PF but not Ex+AL mice showed approximately 25% decrease in both body weight and body fat when compared with the controls. Of the total 338 phospholipids determined by electrospray ionization-tandem mass spectrometry, 57 were significantly changed, and 25 species could distinguish effects of exercise and diet treatments in a stepwise discriminant analysis. A 36% to 75% decrease of phosphatidylinositol (PI) levels in Ex+PF mice occurred along with a significant reduction of PI 3-kinase in TPA-induced skin epidermis, as measured by both Western blotting and immunohistochemistry. In addition, approximately 2-fold increase of the long-chain polyunsaturated fatty acids, docosahexaenoic and docosapentaenoic acids, in phosphatidylcholines, phosphatidylethanolamines, and lysophosphatidylethanolamines was observed in the Ex+PF group. Microarray analysis indicated that the expression of fatty acid elongase-1 increased. Taken together, these data indicate that exercise with controlled dietary intake, but not exercise alone, significantly reduced body weight and body fat as well as modified the phospholipid profile, which may contribute to cancer prevention by reducing TPA-induced PI 3-kinase and by enhancing omega-3 fatty acid elongation.

  4. Structural and Surface Compatibility Study of Modified Electrospun Poly(ε-caprolactone) (PCL) Composites for Skin Tissue Engineering.

    PubMed

    Ghosal, Kajal; Manakhov, Anton; Zajíčková, Lenka; Thomas, Sabu

    2017-01-01

    In this study, biodegradable poly(ε-caprolactone) (PCL) nanofibers (PCL-NF), collagen-coated PCL nanofibers (Col-c-PCL), and titanium dioxide-incorporated PCL (TiO2-i-PCL) nanofibers were prepared by electrospinning technique to study the surface and structural compatibility of these scaffolds for skin tisuue engineering. Collagen coating over the PCL nanofibers was done by electrospinning process. Morphology of PCL nanofibers in electrospinning was investigated at different voltages and at different concentrations of PCL. The morphology, interaction between different materials, surface property, and presence of TiO2 were studied by scanning electron microscopy (SEM), Fourier transform IR spectroscopy (FTIR), contact angle measurement, energy dispersion X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). MTT assay and cell adhesion study were done to check biocompatibilty of these scaffolds. SEM study confirmed the formation of nanofibers without beads. FTIR proved presence of collagen on PCL scaffold, and contact angle study showed increment of hydrophilicity of Col-c-PCL and TiO2-i-PCL due to collagen coating and incorporation of TiO2, respectively. EDX and XPS studies revealed distribution of entrapped TiO2 at molecular level. MTT assay and cell adhesion study using L929 fibroblast cell line proved viability of cells with attachment of fibroblasts over the scaffold. Thus, in a nutshell, we can conclude from the outcomes of our investigational works that such composite can be considered as a tissue engineered construct for skin wound healing.

  5. In vivo analysis of tissue by Raman microprobe: examination of human skin lesions and esophagus Barrett's mucosa on an animal model

    NASA Astrophysics Data System (ADS)

    Tfayli, Ali; Piot, Olivier; Derancourt, Sylvie; Cadiot, Guillaume; Diebold, Marie D.; Bernard, Philippe; Manfait, Michel

    2006-02-01

    In the last few years, Raman spectroscopy has been increasingly used for the characterization of normal and pathological tissues. A new Raman system, constituted of optic fibers bundle coupled to an axial Raman spectrometer (Horiba Jobin Yvon SAS), was developed for in vivo investigations. Here, we present in vivo analysis on two tissues: human skin and esophagus mucosa on a rat model. The skin is a directly accessible organ, representing a high diversity of lesions and cancers. Including malignant melanoma, basal cell carcinoma and the squamous cell carcinoma, skin cancer is the cancer with the highest incidence worldwide. Several Raman investigations were performed to discriminate and classify different types of skin lesions, on thin sections of biopsies. Here, we try to characterize in vivo the different types of skin cancers in order to be able to detect them in their early stages of development and to define precisely the exeresis limits. Barrett's mucosa was also studied by in vivo examination of rat's esophagus. Barrett's mucosa, induced by gastro-esophageal reflux, is a pretumoral state that has to be carefully monitored due to its high risk of evolution in adenocarcinoma. A better knowledge of the histological transformation of esophagus epithelium in a Barrett's type will lead to a more efficient detection of the pathology for its early diagnosis. To study these changes, an animal model (rats developing Barrett's mucosa after duodenum - esophagus anastomosis) was used. Potential of vibrational spectroscopy for Barrett's mucosa identification is assessed on this model.

  6. Expression and tissue distribution of hepatocyte growth factor (HGF) and its receptor (c-Met) in alpacas (Vicugna pacos) skins associated with white and brown coat colors.

    PubMed

    Yu, Xiuju; He, Xiaoyan; Jiang, Junbing; He, Junping; Fan, Ruiwen; Wang, Haidong; Geng, Jianjun; Dong, Changsheng

    2015-09-01

    Hepatocyte growth factor (HGF)/c-Met signaling has been considered as a key pathway in both melanocyte development and melanogenesis. To understand better the expression patterns and tissue distribution characterization of HGF and its receptor c-Met in skin of white versus brown alpaca (Vicugna pacos), we detected the tissue distribution of HGF and c-Met using immunohistochemistry and analyzed the expression patterns by using Western blot and quantitative real time PCR (qPCR). Immunohistochemistry analysis demonstrated that HGF staining robustly increased in the dermal papilla and mesenchymal cells of white alpaca skin compared with that of brown. However, c-Met staining showed strongly positive result, particularly inhair matrix and root sheath in brown alpaca skin. Western blot and qPCR results suggested that HGF and c-Met were expressed at significantly high levels in white and brown alpaca skins, respectively, and protein and transcripts possessed the same expression pattern in white and brown alpaca skins. The results suggested that HGF/c-Met signaling functions in alpaca coat color formation offer essential theoretical basis for further exploration of the role of HGF/c-Met signaling in pigment formation.

  7. Low-intensity red and infrared lasers affect mRNA expression of DNA nucleotide excision repair in skin and muscle tissue.

    PubMed

    Sergio, Luiz Philippe S; Campos, Vera Maria A; Vicentini, Solange C; Mencalha, Andre Luiz; de Paoli, Flavia; Fonseca, Adenilson S

    2016-04-01

    Lasers emit light beams with specific characteristics, in which wavelength, frequency, power, fluence, and emission mode properties determine the photophysical, photochemical, and photobiological responses. Low-intensity lasers could induce free radical generation in biological tissues and cause alterations in macromolecules, such as DNA. Thus, the aim of this work was to evaluate excision repair cross-complementing group 1 (ERCC1) and excision repair cross-complementing group 2 (ERCC2) messenger RNA (mRNA) expression in biological tissues exposed to low-intensity lasers. Wistar rat (n = 28, 4 for each group) skin and muscle were exposed to low-intensity red (660 nm) and near-infrared (880 nm) lasers at different fluences (25, 50, and 100 J/cm(2)), and samples of these tissues were withdrawn for RNA extraction, cDNA synthesis, and gene expression evaluation by quantitative polymerase chain reaction. Laser exposure was in continuous wave and power of 100 mW. Data show that ERCC1 and ERCC2 mRNA expressions decrease in skin (p < 0.001) exposed to near-infrared laser, but increase in muscle tissue (p < 0.001). ERCC1 mRNA expression does not alter (p > 0.05), but ERCC2 mRNA expression decreases in skin (p < 0.001) and increases in muscle tissue (p < 0.001) exposed to red laser. Our results show that ERCC1 and ERCC2 mRNA expression is differently altered in skin and muscle tissue exposed to low-intensity lasers depending on wavelengths and fluences used in therapeutic protocols.

  8. Microbiology of skin and soft tissue infections in the age of community-acquired methicillin-resistant Staphylococcus aureus.

    PubMed

    Ray, G Thomas; Suaya, Jose A; Baxter, Roger

    2013-05-01

    The objectives of this study were to determine the etiology of skin and soft-tissue infections (SSTIs) in a general population, and to describe patient characteristics, SSTI types, frequency of microbiologic testing, and the role of methicillin-resistant Staphylococcus aureus (MRSA) over time. Using electronic databases, we identified SSTI episodes and microbiologic testing among members of a large US health plan. Between 2006 and 2009, 648699 SSTI episodes were identified, of which 23% had a specimen, of which 15% were blood. A pathogen was identified in 58% of SSTI cultures. S. aureus was the most common pathogen (80% of positive cultures). Half of S. aureus isolates were MRSA. Among cellulitis and abscess episodes with a positive blood culture, 21% were methicillin-sensitive S. aureus, 16% were MRSA, 21% were beta-hemolytic streptococci and 28% were Gram negative bacteria. Between 1998 and 2009, the percentage of SSTIs for which a culture was obtained increased from 11% to 24%. In SSTI episodes with a culture-confirmed pathogen, MRSA increased from 5% in 1998 to 9% in 2001 to 42% in 2005, decreasing to 37% in 2009. These data can inform the choice of antibiotics for treatment of SSTIs.

  9. Practices and Procedures to Prevent the Transmission of Skin and Soft Tissue Infections in High School Athletes

    PubMed Central

    Fritz, Stephanie A.; Long, Marcus; Gaebelein, Claude J.; Martin, Madeline S.; Hogan, Patrick G.; Yetter, John

    2013-01-01

    Skin and soft tissue infections (SSTI) 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 transmission. Of 1,642 (37%) respondents, 61% received MRSA educational information during the past year and 32% indicated their school had written guidelines for managing SSTI in athletes. Coaches and athletic directors aware of written guidelines reported a lower incidence of SSTI in student athletes (26%) compared to those without written policies (34%, p=0.03). When confronted with SSTI, 49% of respondents referred student athletes to the school nurse or a physician. A relationship exists between school policies for SSTI management and lower incidence of SSTI. Educational initiatives by school nurses in conjunction with athletic staff may lead to practices that limit SSTI in this at-risk population. PMID:22472636

  10. Managing skin and soft-tissue infection and nosocomial pneumonia caused by MRSA: a 2014 follow-up survey.

    PubMed

    Dryden, Matthew; Andrasevic, Arjana Tambic; Bassetti, Matteo; Bouza, Emilio; Chastre, Jean; Baguneid, Mo; Esposito, Silvano; Giamarellou, Helen; Gyssens, Inge; Nathwani, Dilip; Unal, Serhat; Voss, Andreas; Wilcox, Mark

    2015-04-24

    As a follow-up to our 2009 survey, in order to explore opinion and practice on the epidemiology and management of meticillin-resistant Staphylococcus aureus (MRSA) in Europe, we conducted a second survey to elicit current opinions on this topic, particularly around antibiotic choice, dose, duration and route of administration. We also aimed to further understand how the management of MRSA has evolved in Europe during the past 5 years. Members of an expert panel of infectious diseases specialists convened in London (UK) in January 2014 to identify and discuss key issues in the management of MRSA. Following this meeting, a survey was developed comprising 36 questions covering a wide range of topics on MRSA complicated skin and soft-tissue infection and nosocomial pneumonia management. The survey instrument, a web-based questionnaire, was sent to the International Society of Chemotherapy for distribution to registered European infection societies and their members. This article reports the survey results from the European respondents. At the time of the original survey, the epidemiology of MRSA varied significantly across Europe and there were differing views on best practice. The current findings suggest that the epidemiology of healthcare-associated MRSA in Europe is, if anything, even more polarised, whilst community-acquired MRSA has become much more common. However, there now appears to be a much greater knowledge of current treatment/management options, and antimicrobial stewardship has moved forward considerably in the 5 years since the last survey.

  11. In-vivo Measurement of Complex Relative Permittivity for Human Skin Tissues Using Open-Ended Coaxial Probe

    NASA Astrophysics Data System (ADS)

    Sato, Yusuke; Hirata, Akimasa; Fujiwara, Osamu

    We made in-vivo measurement of the complex relative permittivity of palm and sole in the frequency range from 100 MHz to 40 GHz with a network analyzer and an open-ended coaxial probe, which was compared with Gabriel in-vitro data for skin tissue to reveal that the in-vivo measurement results are mostly lower than the in-vitro data. For validation, we measured the dielectric constant of Teflon sheet with respect to its thickness from 0.05 mm to 5.00 mm, which showed that the open-ended coaxial probe provides sufficient measurement accuracy for Teflon with a thickness of over 0.5 mm, however, the probe data can be affected by the material beneath the Teflon with a thickness of less than 0.5 mm. This means that the in-vivo palm data derive from the epidermis and the dermis including blood, while the in-vivo sole data come from the epidermis. For further investigation, under the assumption that in-vitro data derive from a mixture of epidermis and blood, we calculated the complex relative permittivity for the compound from the Litchtenecker's law of exponent to show a possibility that due to the inclusion of blood, in-vitro measurement may provide a higher relative permittivity than in-vivo measurement.

  12. Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins

    PubMed Central

    Berlon, Nicholas R.; Qi, Robert; Sharma-Kuinkel, Batu K.; Joo, Hwang-Soo; Park, Lawrence P.; George, Dennis; Thaden, Joshua T.; Messina, Julia A.; Maskarinec, Stacey A.; Mueller-Premru, Manica; Athan, Eugene; Tattevin, Pierre; Pericas, Juan M.; Woods, Christopher W.; Otto, Michael; Fowler, Vance G.

    2016-01-01

    Summary Background Phenol-soluble modulins (PSMs) are amphipathic, pro-inflammatory proteins secreted by most Staphylococcus aureus isolates. This study tested the hypothesis that in vitro PSM production levels are associated with specific clinical phenotypes. Methods 177 methicillin-resistant S. aureus (MRSA) isolates from infective endocarditis (IE), skin and soft tissue infection (SSTI), and hospital-acquired/ventilator-associated pneumonia (HAP) were matched by geographic origin, then genotyped using spa-typing. In vitro PSM production was measured by high performance liquid chromatography/mass spectrometry. Statistical analysis was performed using Chi-squared or Kruskal–Wallis tests as appropriate. Results Spa type 1 was significantly more common in SSTI isolates (62.7% SSTI; 1.7% IE; 16.9% HAP; p < 0.0001) while HAP and IE isolates were more commonly spa type 2 (0% SSTI; 37.3% IE; 40.7% HAP; p < 0.0001). USA300 isolates produced the highest levels of PSMs in vitro. SSTI isolates produced significantly higher quantities of PSMα1-4, PSMβ1, and δ-toxin than other isolates (p < 0.001). These findings persisted when USA300 isolates were excluded from analysis. PMID:26079275

  13. Practices and procedures to prevent the transmission of skin and soft tissue infections in high school athletes.

    PubMed

    Fritz, Stephanie A; Long, Marcus; Gaebelein, Claude J; Martin, Madeline S; Hogan, Patrick G; Yetter, John

    2012-10-01

    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 transmission. Of 1,642 (37%) respondents, 61% received MRSA educational information during the past year and 32% indicated their school had written guidelines for managing SSTIs in athletes. Coaches and athletic directors aware of written guidelines reported a lower incidence of SSTIs in student athletes (26%) compared to those without written policies (34%, p = .03). When confronted with SSTIs, 49% of respondents referred student athletes to the school nurse or a physician. A relationship exists between school policies for SSTI management and lower incidence of SSTIs. Educational initiatives by school nurses in conjunction with athletic staff may lead to practices that limit SSTIs in this at-risk population.

  14. Complicated skin and soft tissue infection with Mycobacterium fortuitum following excision of a sebaceous cyst in Taiwan.

    PubMed

    Tsai, Shih-Chen; Chen, Li-Hsin; Liao, Hsien-Hua; Chiang, Chih-Yu; Lin, Wea-Lung; Chen, Shiuan-Chih; Tsao, Shih-Ming; Hung, Hung-Chang; Lee, Yuan-Ti

    2016-12-30

    Mycobacterium fortuitum group (M. fortuitum), also known as rapidly growing Mycobacteria, can cause pyogenic infections in human beings, most commonly in immunocompromised patients. Herein, we present a 40-year-old immunocompetent male patient who underwent planned excision of a sebaceous cyst in the abdominal wall. He suffered from tender erythematous lesions with purulent discharge around the healing wound that developed 2 weeks after surgery. Gram stain, bacterial and fungal culture results of the wound were negative. A diagnosis of non-tuberculous mycobacteria was made from a wound culture from the area of operative debridement, which was subsequently confirmed to be M. fortuitum group using PCR-restriction fragment length polymorphism analysis of the hsp65 gene. The patient received 4 weeks of parenteral imipenem/cilastatin 500 mg every 6 hours and amikacin 500 mg every 12 hours, plus oral clarithromycin 500 mg twice daily, and the wound recovered completely. He was discharged and followed up regularly at our outpatient clinic, and continued taking oral ciprofloxacin and clarithromycin 500 mg twice daily for 6 months. This case highlights the importance of strict aseptic precautions even during minor procedures, and also the characteristics of M. fortuitum infections in immunocompetent patients, which usually develop as localized postsurgical wound infections. We also share our experience in successfully treating a M. fortuitum complicated skin and soft tissue infection.

  15. Molecular characterization of Staphylococcus aureus isolates causing skin and soft tissue infections in patients from Malakand, Pakistan.

    PubMed

    Madzgalla, S; Syed, M A; Khan, M A; Rehman, S S; Müller, E; Reissig, A; Ehricht, R; Monecke, S

    2016-09-01

    Comparatively few studies have been published describing Staphylococcus aureus/MRSA epidemiology in Central Asia including Pakistan. Here, we report the genotyping of Staphylococcus aureus strains (that include both methicillin-susceptible and methicillin-resistant Staphylococcus aureus) from community- and hospital-acquired skin and soft-tissue infections in a tertiary care hospital in the Malakand district of the Khyber Pakhtunkhwa Province of Pakistan. Forty-five isolates of Staphylococcus aureus were characterized by microarray hybridization. Twenty isolates (44 %) were MRSA, whereas 22 (49 %) were PVL-positive. Fourteen isolates (31 %) harboured both mecA and PVL genes. The dominant clones were CC121-MSSA (n = 15, 33 %) and the PVL-positive "Bengal Bay Clone" (ST772-MRSA-V; n = 13, 29 %). The PVL-positive CC8-MRSA-IV strain "USA300" was found once. The pandemic ST239-MRSA-III strain was absent, although it has previously been observed in Pakistan. These observations require a re-assessment of schemes for initial antibiotic therapy to cover MRSA and they emphasise the need for a rapid and non-molecular test for PVL.

  16. Electrospun Poly(L-Lactic Acid)-co-Poly(ϵ-Caprolactone) Nanofibres Containing Silver Nanoparticles for Skin-Tissue Engineering.

    PubMed

    Jin, Guorui; Prabhakaran, Molamma P; Nadappuram, Binoy P; Singh, Gurdev; Kai, Dan; Ramakrishna, Seeram

    2012-01-01

    Silver nanoparticles (AgNPs) and silver ions (Ag(+)) show growth-inhibitory activity against microorganisms and have been used for decades as antibacterial agents in various fields. To fabricate a nanofibrous scaffold which is antibacterial against bacteria and non-toxic to cells, we electrospun composite poly(L-lactic acid)-co-poly(ϵ-caprolactone) nanofibres containing silver nanoparticles (PLLCL-AgNPs) with different concentrations (0.25, 0.50 and 0.75 wt%) of silver nitrate (AgNO3) in PLLCL. The diameters of the electrospun PLLCL-AgNPs nanofibres decreased with the increase of AgNO3 concentration in PLLCL solutions. Human skin fibroblasts cultured on the scaffolds showed that the PLLCL nanofibres containing lesser amounts of AgNPs (0.25 wt%) had better cell proliferation and retained the cell morphology similar to the phenotype observed on tissue culture plates (control). The antibacterial activity of AgNPs in PLLCL nanofibres was investigated against Staphylococcus aureus and Salmonella enterica and the antimicrobial activity was found to increase with the increasing concentration of nanoparticles present in the scaffold. Based on our studies, we propose that PLLCL nanofibres containing 0.25 wt% AgNO3 or PLLCL-Ag(25), favors cell proliferation and inhibits bacteria and could be a suitable substrate for wound healing.

  17. The role of primary care prescribers in the diagnosis and management of community-associated methicillin-resistant Staphylococcus aureus skin and soft tissue infections.

    PubMed

    Lawrence, Kenneth R; Golik, Monica V; Davidson, Lisa

    2009-01-01

    Nosocomial infections caused by methicillin-resistant Staphylococcus aureus were first reported in the United States in the early 1960s. Beginning in the 1990s, healthy individuals from the community with no risk factors for resistant bacteria began presenting with methicillin-resistant Staphylococcus aureus infections, acquiring the name "community-associated methicillin-resistant Staphylococcus aureus" (CA-MRSA). CA-MRSA has a tendency to affect the skin and skin structures, generally in the form of abscesses and furuncles, carbuncles, and cellulitis. Cases of invasive infections including bacteremia, endocarditis, and necrotizing pneumonia have also been reported. A patient complaint of a "spider bite" is frequently associated with CA-MRSA. CA-MRSA and the traditional health care-associated methicillin-resistant Staphylococcus aureus are distinguished by their genetic composition, virulence factors, and susceptibility patterns to non-beta-lactam antibiotics. Appropriate management of CA-MRSA skin and skin structure infections includes incision and drainage of infected tissue and appropriate antimicrobial therapy. It has been suggested that when prevalence of CA-MRSA within a community eclipses 10%-15%, empiric use of non-beta-lactam antibiotics with in vitro activity against CA-MRSA be initiated when treating skin and skin structure infections. CA-MRSA retains susceptibility to a range of older antibiotics available in oral formulations such as minocycline, doxycycline, sulfamethoxazole-trimethoprim, moxifloxacin, levofloxacin, and clindamycin. Local susceptibility patterns and individual patient factors should guide the selection of antibiotics.

  18. A novel method for single sample multi-axial nanoindentation of hydrated heterogeneous tissues based on testing great white shark jaws.

    PubMed

    Ferrara, Toni L; Boughton, Philip; Slavich, Eve; Wroe, Stephen

    2013-01-01

    Nanomechanical testing methods that are suitable for a range of hydrated tissues are crucial for understanding biological systems. Nanoindentation of tissues can provide valuable insights into biology, tissue engineering and biomimetic design. However, testing hydrated biological samples still remains a significant challenge. Shark jaw cartilage is an ideal substrate for developing a method to test hydrated tissues because it is a unique heterogeneous composite of both mineralized (hard) and non-mineralized (soft) layers and possesses a jaw geometry that is challenging to test mechanically. The aim of this study is to develop a novel method for obtaining multidirectional nanomechanical properties for both layers of jaw cartilage from a single sample, taken from the great white shark (Carcharodon carcharias). A method for obtaining multidirectional data from a single sample is necessary for examining tissue mechanics in this shark because it is a protected species and hence samples may be difficult to obtain. Results show that this method maintains hydration of samples that would otherwise rapidly dehydrate. Our study is the first analysis of nanomechanical properties of great white shark jaw cartilage. Variation in nanomechanical properties were detected in different orthogonal directions for both layers of jaw cartilage in this species. The data further suggest that the mineralized layer of shark jaw cartilage is less stiff than previously posited. Our method allows multidirectional nanomechanical properties to be obtained from a single, small, hydrated heterogeneous sample. Our technique is therefore suitable for use when specimens are rare, valuable or limited in quantity, such as samples obtained from endangered species or pathological tissues. We also outline a method for tip-to-optic calibration that facilitates nanoindentation of soft biological tissues. Our technique may help address the critical need for a nanomechanical testing method that is applicable

  19. Skin optics

    SciTech Connect

    van Gemert, M.J.; Jacques, S.L.; Sterenborg, H.J.; Star, W.M.

    1989-12-01

    Quantitative dosimetry in the treatment of skin disorders with (laser) light requires information on propagation of light in the skin related to the optical properties of the individual skin layers. This involves the solution of the integro-differential equation of radiative transfer in a model representing skin geometry, as well as experimental methods to determine the optical properties of each skin layer. These activities are unified under the name skin optics. This paper first reviews the current status of tissue optics, distinguishing between the cases of: dominant absorption, dominant scattering, and scattering about equal to absorption. Then, previously published data as well as some current unpublished data on (human) stratum corneum, epidermis and dermis, have been collected and/or (re)analyzed in terms of absorption coefficient, scattering coefficient, and anisotropy factor of scattering. The results are that the individual skin layers show strongly forward scattering (anisotropy factors between 0.7 and 0.9). The absorption and scattering data show that for all wavelengths considered scattering is much more important than absorption. Under such circumstances, solutions to the transport equation for a multilayer skin model and finite beam laser irradiation are currently not yet available. Hence, any quantitative dosimetry for skin treated with (laser) light is currently lacking.

  20. [Investigation of SCCmec types and Panton-Valentine leukocidin in community-acquired and nosocomial Staphylococcus aureus strains: comparing skin and soft tissue infections to the other infections].

    PubMed

    Gülmez, Dolunay; Sancak, Banu; Ercis, Serpil; Karakaya, Jale; Hasçelik, Gülşen

    2012-07-01

    Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are important health care problems since they are usually multidrug resistant. Although MRSA is isolated especially from nosocomial infections, community-acquired MRSA infections are increasing. Methicillin resistance is due to the expression of mecA gene, which is located on SCCmec gene cassette. Different SCCmec types can be detected in hospital-acquired and community-acquired (CA-) MRSA strains. CA-MRSA strains might harbour Panton-Valentine leukocidin (PVL), an important virulence factor in skin and soft tissue infections. Strains carrying PVL has the ability to penetrate undamaged skin and cause more severe infections. The aim of this study was to detect SCCmec types and PVL gene in S.aureus strains isolated from skin and soft tissue infections and to compare with strains isolated from other infections in a university hospital in Ankara, Turkey. S.aureus strains isolated from skin and soft tissue infections (n= 285) and a control group consisting of 161 strains isolated from other infections (53 blood, 48 lower respiratory tract samples, 30 sterile body fluids, 30 genitourinary tract samples) chosen by stratification and random selection method, were included in the study. Among skin and soft tissue infection strains 46.7% were from the hospitalized patients and 48.4% of skin and soft tissue infection strains were from female patients. The mean age of the skin and soft tissue infection patients was 45.5 years. Among the control strains 60.9% were from the hospitalized patients and 41.6% of the control patients were female. The mean age of the control patients was 50.2 years. Strains were identified by the Phoenix system (Becton Dickinson, USA) and identification was confirmed by tube coagulase test. Methicillin resistance was determined by the Phoenix system which determines both oxacillin and cefoxitin minimum inhibitor concentrations and, confirmed by oxacillin agar screening and

  1. Ovarian teratoma displaying a wide variety of tissue components in a broiler chicken (Gallus Domesticus): morphological heterogeneity of pluripotential germ cell during tumorigenesis

    PubMed Central

    Ohfuji, S.

    2016-01-01

    Spontaneous ovarian teratoma was found in a seven-week-old female Chunky broiler chicken that was slaughtered for food. On post-mortem inspection, a spherical tumor mass attaching to a juvenile ovary was found in the abdominal cavity. Histopathologically, the tumor was comprised of immature mesenchymal stroma and a variety of mature tissue elements of mesodermal and ectodermal origin. In addition, there were multiple indistinguishable tissue elements, which showed no malignant cytological features but were unidentifiable as to corresponding embryological layer of origin. These heterogeneous teratoma tissues consisted of a variety of glandular, cystic, duct-like, and tubular structures, some of which exhibited a lining by a mixture of both keratinizing/non-keratinizing stratified squamous epithelial cells and cuboidal/columnar epithelial cells. The ovarian tetatoma was considered a benign and congenital one. The highly diverse differentiation of the teratoma might have manifested a morphological aspect of intrinsic character of the pluripotential germ cells during tumorigenesis. PMID:27303655

  2. Accuracy of dose measurements and calculations within and beyond heterogeneous tissues for 6 MV photon fields smaller than 4 cm produced by Cyberknife

    SciTech Connect

    Wilcox, Ellen E.; Daskalov, George M.

    2008-06-15

    For the small radiation field sizes used in stereotactic radiosurgery, lateral electronic disequilibrium and steep dose gradients exist in a large portion of these fields, requiring the use of high-resolution measurement techniques. These relatively large areas of electronic disequilibrium make accurate dosimetry as well as dose calculation more difficult, and this is exacerbated in regions of tissue heterogeneity. Tissue heterogeneity was considered insignificant in the brain where stereotactic radiosurgery was first used. However, as this technique is expanded to the head and neck and other body sites, dose calculations need to account for dose perturbations in and beyond air cavities, lung, and bone. In a previous study we have evaluated EBT Gafchromic film (International Specialty Products, Wayne, NJ) for dosimetry and characterization of the Cyberknife radiation beams and found that it was comparable to other common detectors used for small photon beams in solid water equivalent phantoms. In the present work EBT film is used to measure dose in heterogeneous slab phantoms containing lung and bone equivalent materials for the 6 MV radiation beams of diameter 7.5 to 40 mm produced by the Cyberknife (Accuray, Sunnyvale, CA). These measurements are compared to calculations done with both the clinically utilized Raytrace algorithm as well as the newly developed Monte Carlo based algorithm available on the Cyberknife treatment planning system. Within the low density material both the measurements and Monte Carlo calculations correctly model the decrease in dose produced by a loss of electronic equilibrium, whereas the Raytrace algorithm incorrectly predicts an enhancement of dose in this region. Beyond the low density material an enhancement of dose is correctly calculated by both algorithms. Within the high density bone heterogeneity the EBT film measurements represent dose to unit density tissue in bone and agree with the Monte Carlo results when corrected to dose

  3. Protective effects of β-glucan against oxidative injury induced by 2.45-GHz electromagnetic radiation in the skin tissue of rats.

    PubMed

    Ceyhan, Ali Murat; Akkaya, Vahide Baysal; Güleçol, Şeyma Celik; Ceyhan, Betül Mermi; Özgüner, Fehmi; Chen, WenChieh

    2012-09-01

    In recent times, there is widespread use of 2.45-GHz irradiation-emitting devices in industrial, medical, military and domestic application. The aim of the present study was to investigate the effect of 2.45-GHz electromagnetic radiation (EMR) on the oxidant and antioxidant status of skin and to examine the possible protective effects of β-glucans against the oxidative injury. Thirty-two male Wistar albino rats were randomly divided into four equal groups: control; sham exposed; EMR; and EMR + β-glucan. A 2.45-GHz EMR emitted device from the experimental exposure was applied to the EMR group and EMR + β-glucan group for 60 min daily, respectively, for 4 weeks. β-glucan was administered via gavage at a dose of 50 mg/kg/day before each exposure to radiation in the treatment group. The activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), as well as the concentration of malondialdehyde (MDA) were measured in tissue homogenates of the skin. Exposure to 2.45-GHz EMR caused a significant increase in MDA levels and CAT activity, while the activities of SOD and GSH-Px decreased in skin tissues. Systemic β-glucan significantly reversed the elevation of MDA levels and the reduction of SOD activities. β-glucan treatment also slightly enhanced the activity of CAT and prevented the depletion of GSH-Px activity caused by EMR, but not statistically significantly. The present study demonstrated the role of oxidative mechanisms in EMR-induced skin tissue damages and that β-glucan could ameliorate oxidative skin injury via its antioxidant properties.

  4. Risk of Skin and Soft Tissue Infections among Children Found to be Staphylococcus aureus MRSA USA300 Carriers

    PubMed Central

    Immergluck, Lilly Cheng; Jain, Shabnam; Ray, Susan M.; Mayberry, Robert; Satola, Sarah; Parker, Trisha Chan; Yuan, Keming; Mohammed, Anaam; Jerris, Robert C.

    2017-01-01

    Introduction The purpose of this study was to examine community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) carriage and infections and determine risk factors associated specifically with MRSA USA300. Methods We conducted a case control study in a pediatric emergency department. Nasal and axillary swabs were collected, and participants were interviewed for risk factors. The primary outcome was the proportion of S. aureus carriers among those presenting with and without a skin and soft tissue infection (SSTI). We further categorized S. aureus carriers into MRSA USA300 carriers or non-MRSA USA300 carriers. Results We found the MRSA USA300 carriage rate was higher in children less than two years of age, those with an SSTI, children with recent antibiotic use, and those with a family history of SSTI. MRSA USA300 carriers were also more likely to have lower income compared to non-MRSA USA300 carriers and no S. aureus carriers. Rates of Panton-Valentine leukocidin (PVL) genes were higher in MRSA carriage isolates with an SSTI, compared to MRSA carriage isolates of patients without an SSTI. There was an association between MRSA USA300 carriage and presence of PVL in those diagnosed with an abscess. Conclusion Children younger than two years were at highest risk for MRSA USA300 carriage. Lower income, recent antibiotic use, and previous or family history of SSTI were risk factors for MRSA USA300 carriage. There is a high association between MRSA USA300 nasal/axillary carriage and presence of PVL in those with abscesses. PMID:28210352

  5. Characterization of community-associated Staphylococcus aureus from skin and soft-tissue infections: a multicenter study in China.

    PubMed

    Liu, Ying; Xu, Zhe; Yang, Zhou; Sun, Juan; Ma, Lin

    2016-12-21

    We evaluated the epidemiological and molecular features of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and methicillin-sensitive S. aureus (MSSA) from children and adult patients with skin and soft-tissue infections (SSTIs) in China. Prospective community-acquired S. aureus SSTI surveillance was conducted in 23 hospitals over a 24-month period. Susceptibility to 16 antimicrobials was evaluated using the agar dilution method. StatApriori was used to determine statistically significant association trends. The genotypic characteristics of CA-MRSA isolates were tested by staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) typing, and multilocus sequence typing. The presence of Panton-Valentine leukocidin (pvl) genes was determined. Overall, 71.6% (1946/2716) of cases were community-associated S. aureus. CA-MRSA accounted for 2.6% (51). Out of 1895 methicillin-sensitive S. aureus strains, 97.3% were resistant to erythromycin, 96.6% to penicillin and 89.1% to clindamycin. No S. aureus strains were resistant to vancomycin. Thirteen sequence types (STs) and 17 spa types were detected among the CA-MRSA strains. The most prevalent sequence type was ST121 (19/51, 37.3%), followed by ST59 (13/51, 25.5%). In addition, t437 was predominant, accounting for 43.1% (22/51). Only five (9.8%) of the CA-MRSA strains harbored pvl genes. There were no significant differences in antibiotic sensitivity profiles between ST121 and non-ST121 MRSA isolates. However, ST121 strains tended to be more resistant to cefazolin, whereas non-ST121 strains were more resistant to chloramphenicol. In conclusion, CA-MRSA infections are rare among Chinese SSTI patients. MRSA strains in China have diverse genetic backgrounds, with ST121 being the predominant clone. Fusidic acid and mupirocin remain effective for topical treatment.

  6. RNA-Seq Analysis of the Host Response to Staphylococcus aureus Skin and Soft Tissue Infection in a Mouse Model.

    PubMed

    Brady, Rebecca A; Bruno, Vincent M; Burns, Drusilla L

    2015-01-01

    Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTI), which are primarily self-limiting. We conducted a comprehensive analysis of the host transcriptome during a S. aureus SSTI to provide insight on the protective mechanisms that thwart these infections. We utilized a murine SSTI model in which one ear is epicutaneously challenged while the other is not. We then harvested these infected and uninfected ears, as well as ears from naïve mice, at one, four, and seven days post-challenge, and performed RNA sequencing (RNA-seq) using the Illumina platform. RNA-seq data demonstrated a robust response at the site of infection. Comparison of gene expression profiles between infected ears and the non-infected ears of challenged mice defined the local response to infection, while comparisons of expression profiles of non-infected ears from challenged mice to ears of naïve mice revealed changes in gene expression levels away from the site indicative of a systemic response. Over 1000 genes exhibited increased expression locally at all tested time points. The local response was more robust than the systemic response. Through evaluation of the RNA-seq data using the Upstream Regulator Analytic as part of the Ingenuity Pathway Analysis software package, we found that changes in the activation and inhibition of regulatory pathways happen first locally, and lag behind systemically. The activated pathways are highly similar at all three time points during SSTI, suggesting a stable global response over time. Transcript increases and pathway activation involve pro- and anti-inflammatory mediators, chemotaxis, cell signaling, keratins, and TH1/TH17 cytokines. Transcript decreases and pathway inhibition demonstrate that metabolic genes and anti-inflammatory pathways are repressed. These data provide insight on the host responses that may aid in resolution of this self-limited S. aureus infection, and may shed light on potential immune correlates of

  7. Molecular Epidemiology of Staphylococcus aureus among Patients with Skin and Soft Tissue Infections in Two Chinese Hospitals

    PubMed Central

    Gu, Fei-Fei; Chen, Ye; Dong, De-Ping; Song, Zhen; Guo, Xiao-Kui; Ni, Yu-Xing; Han, Li-Zhong

    2016-01-01

    Background: Staphylococcus aureus is one of the predominant causes of skin and soft tissue infections (SSTIs), but limited data were available regarding the characterization of S. aureus from SSTIs patients in Jiangsu Province in China. We aimed to investigate the molecular epidemiology of S. aureus among SSTIs patients in two hospitals of Jiangsu Province. Methods: Sixty-two patients with SSTIs from two Chinese hospitals in Jiangsu Province were enrolled in this study, and 62 S. aureus isolates were collected from February 2014 to January 2015. S. aureus isolates were characterized by antimicrobial susceptibility testing, toxin gene detection, and molecular typing with sequence type, Staphylococcus protein A gene type, accessory gene regulator (agr) group, and Staphylococcal cassette chromosome mec type. Results: Sixteen (25.8%) methicillin-resistant S. aureus (MRSA) isolates were detected, and there was no isolate found resistant to vancomycin, teicoplanin, sulfamethoxazole-trimethoprim, and linezolid. The sei was the toxin gene most frequently found, and no lukS/F-PV-positive isolates were detected among the SSTIs’ patients. Molecular analysis revealed that ST398 (10/62, 16.1%; 2 MRSA and 8 methicillin-susceptible S. aureus) to be the dominant clone, followed by ST5 (8/62, 12.9%) and ST7 (8/62, 12.9%). Conclusions: The livestock ST398 was the most common clone among patients with S. aureus SSTIs in Jiangsu Province, China. Surveillance and further studies on the important livestock ST398 clone in human infections are necessarily requested. PMID:27647191

  8. Characterization of community-associated Staphylococcus aureus from skin and soft-tissue infections: a multicenter study in China

    PubMed Central

    Liu, Ying; Xu, Zhe; Yang, Zhou; Sun, Juan; Ma, Lin

    2016-01-01

    We evaluated the epidemiological and molecular features of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and methicillin-sensitive S. aureus (MSSA) from children and adult patients with skin and soft-tissue infections (SSTIs) in China. Prospective community-acquired S. aureus SSTI surveillance was conducted in 23 hospitals over a 24-month period. Susceptibility to 16 antimicrobials was evaluated using the agar dilution method. StatApriori was used to determine statistically significant association trends. The genotypic characteristics of CA-MRSA isolates were tested by staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) typing, and multilocus sequence typing. The presence of Panton–Valentine leukocidin (pvl) genes was determined. Overall, 71.6% (1946/2716) of cases were community-associated S. aureus. CA-MRSA accounted for 2.6% (51). Out of 1895 methicillin-sensitive S. aureus strains, 97.3% were resistant to erythromycin, 96.6% to penicillin and 89.1% to clindamycin. No S. aureus strains were resistant to vancomycin. Thirteen sequence types (STs) and 17 spa types were detected among the CA-MRSA strains. The most prevalent sequence type was ST121 (19/51, 37.3%), followed by ST59 (13/51, 25.5%). In addition, t437 was predominant, accounting for 43.1% (22/51). Only five (9.8%) of the CA-MRSA strains harbored pvl genes. There were no significant differences in antibiotic sensitivity profiles between ST121 and non-ST121 MRSA isolates. However, ST121 strains tended to be more resistant to cefazolin, whereas non-ST121 strains were more resistant to chloramphenicol. In conclusion, CA-MRSA infections are rare among Chinese SSTI patients. MRSA strains in China have diverse genetic backgrounds, with ST121 being the predominant clone. Fusidic acid and mupirocin remain effective for topical treatment. PMID:27999423

  9. Different gene expression of skin tissues between mice with weight controlled by either calorie restriction or physical exercise.

    PubMed

    Lu, Jia; Xie, Linglin; Sylvester, Jessica; Wang, Jiasong; Bai, Jianfa; Baybutt, Richard; Wang, Weiqun

    2007-04-01

    Cancer prevention by weight control via dietary calorie restriction (DCR) and/or exercise has been demonstrated in animal models. To understand the underlying mechanisms, we compared phorbol ester (TPA)-induced gene expression profiles in DCR- or exercise-treated mouse skin tissues. SENCAR mice were randomly assigned to one of the following groups: ad libitum-fed sedentary control, ad libitum-fed exercise (AE), exercise but pair-fed at the amount of the control (PE), and 20% DCR. After 10 weeks, both body weight and fat composition significantly decreased in the DCR and PE groups compared with the controls. Weight loss was not observed in the AE group due, at least in part, to increased food intake. Among 39,000 transcripts with 45,101 probe sets measured by Affymetrix microarray, we identified 411, 110, and 67 genes that showed >or=1.5-fold and significant changes by DCR, AE, and PE, respectively. Gene ontology showed a profound impact on gene expression by DCR in 21 biologic process categories. Although PE and AE had a moderate impact on gene expression, the similarity of gene expression pattern altered by PE was relatively closer to DCR, whereas AE was closer to the control. The results of 22 cancer-related gene expression patterns, especially for certain oncogenes, further supported that PE appeared to be a better alternative than AE to DCR-like cancer prevention. The impact on gene expression pattern was associated with the effect on weight loss (i.e., DCR > PE > AE). Overall, this study demonstrated for the first time that weight control via decreasing energy intake or increasing energy expenditure resulted in the different modes of gene expression. DCR showed profound inhibitory impact on the expression of genes relevant to cancer risks. Furthermore, exercise along with limited calorie intake appears to be a better method for reducing weight and cancer risk compared with exercise alone.

  10. RNA-Seq Analysis of the Host Response to Staphylococcus aureus Skin and Soft Tissue Infection in a Mouse Model

    PubMed Central

    Brady, Rebecca A.; Bruno, Vincent M.; Burns, Drusilla L.

    2015-01-01

    Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTI), which are primarily self-limiting. We conducted a comprehensive analysis of the host transcriptome during a S. aureus SSTI to provide insight on the protective mechanisms that thwart these infections. We utilized a murine SSTI model in which one ear is epicutaneously challenged while the other is not. We then harvested these infected and uninfected ears, as well as ears from naïve mice, at one, four, and seven days post-challenge, and performed RNA sequencing (RNA-seq) using the Illumina platform. RNA-seq data demonstrated a robust response at the site of infection. Comparison of gene expression profiles between infected ears and the non-infected ears of challenged mice defined the local response to infection, while comparisons of expression profiles of non-infected ears from challenged mice to ears of naïve mice revealed changes in gene expression levels away from the site indicative of a systemic response. Over 1000 genes exhibited increased expression locally at all tested time points. The local response was more robust than the systemic response. Through evaluation of the RNA-seq data using the Upstream Regulator Analytic as part of the Ingenuity Pathway Analysis software package, we found that changes in the activation and inhibition of regulatory pathways happen first locally, and lag behind systemically. The activated pathways are highly similar at all three time points during SSTI, suggesting a stable global response over time. Transcript increases and pathway activation involve pro- and anti-inflammatory mediators, chemotaxis, cell signaling, keratins, and TH1/TH17 cytokines. Transcript decreases and pathway inhibition demonstrate that metabolic genes and anti-inflammatory pathways are repressed. These data provide insight on the host responses that may aid in resolution of this self-limited S. aureus infection, and may shed light on potential immune correlates of

  11. Mupirocin and chlorhexidine resistance in Staphylococcus aureus in patients with community-onset skin and soft tissue infections.

    PubMed

    Fritz, Stephanie A; Hogan, Patrick G; Camins, Bernard C; Ainsworth, Ali J; Patrick, Carol; Martin, Madeline S; Krauss, Melissa J; Rodriguez, Marcela; Burnham, Carey-Ann D

    2013-01-01

    Decolonization measures, including mupirocin and chlorhexidine, are often prescribed to prevent Staphylococcus aureus skin and soft tissue infections (SSTI). The objective of this study was to determine the prevalence of high-level mupirocin and chlorhexidine resistance in S. aureus strains recovered from patients with SSTI before and after mupirocin and chlorhexidine administration and to determine whether carriage of a mupirocin- or chlorhexidine-resistant strain at baseline precluded S. aureus eradication. We recruited 1,089 patients with community-onset SSTI with or without S. aureus colonization. In addition to routine care, 483 patients were enrolled in a decolonization trial: 408 received intranasal mupirocin (with or without antimicrobial baths), and 258 performed chlorhexidine body washes. Patients were followed for up to 12 months with repeat colonization cultures. All S. aureus isolates were tested for high-level mupirocin and chlorhexidine resistance. At baseline, 23/1,089 (2.1%) patients carried a mupirocin-resistant S. aureus strain and 10/1,089 (0.9%) patients carried chlorhexidine-resistant S. aureus. Of 4 patients prescribed mupirocin, who carried a mupirocin-resistant S. aureus strain at baseline, 100% remained colonized at 1 month compared to 44% of the 324 patients without mupirocin resistance at baseline (P = 0.041). Of 2 patients prescribed chlorhexidine, who carried a chlorhexidine-resistant S. aureus strain at baseline, 50% remained colonized at 1 month compared to 48% of the 209 patients without chlorhexidine resistance at baseline (P = 1.0). The overall prevalence of mupirocin and chlorhexidine resistance is low in S. aureus isolates recovered from outpatients, but eradication efforts were less successful in patients carrying a mupirocin-resistant S. aureus strain at baseline.

  12. Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur Mustard Injury to Human Skin

    DTIC Science & Technology

    2004-05-01

    skin have not been possible for ethical reasons. Therefore, we have used an approach that has allowed us to identify sites and pathways of sulfur...morphologic features of human skin to a high degree and ing epithelial morphogenesis of the embryoid body, J Cell Biol 153:811-822, demonstrates that

  13. Successful treatment of skin and soft tissue infection due to carbapenem-resistant Acinetobacter baumannii by ampicillin-sulbactam and meropenem combination therapy.

    PubMed

    Hiraki, Yoichi; Yoshida, Mayumi; Masuda, Yoko; Inoue, Daisuke; Tsuji, Yasuhiro; Kamimura, Hidetoshi; Karube, Yoshiharu; Takaki, Kazutaka; Kawano, Fumio

    2013-12-01

    In recent years, carbapenem-resistant Acinetobacter baumannii infections have been responsible for outbreaks in medical facilities. A 35-year-old Japanese woman developed a skin and soft tissue infection due to carbapenem-resistant A. baumannii. The isolate was resistant to antibiotics other than ampicillin-sulbactam and colistin, suggesting drug resistance due to carbapenemase production by OXA-23. We selected a combination therapy consisting of intravenous ampicillin-sulbactam and meropenem. No changes were observed in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, or serum creatinine during therapy, and carbapenem-resistant A. baumannii was not detected in wound exudates 3 days after therapy initiation. In our patient's case, combination therapy with ampicillin-sulbactam and meropenem was successful. Thus, combination therapy with ampicillin-sulbactam and meropenem is effective against skin and soft tissue infection due to carbapenem-resistant A. baumannii. Combination therapy with intravenous ampicillin-sulbactam and meropenem may be an option for skin and soft tissue infections due to carbapenem-resistant A. baumannii.

  14. Fullerene-C60/liposome complex: Defensive effects against UVA-induced damages in skin structure, nucleus and collagen type I/IV fibrils, and the permeability into human skin tissue.

    PubMed

    Kato, Shinya; Aoshima, Hisae; Saitoh, Yasukazu; Miwa, Nobuhiko

    2010-01-21

    We previously reported biological safety of fullerene-C60 (C60) incorporated in liposome consisting of hydrogenated lecithin and glycine soja sterol, as Liposome-Fullerene (0.5% aqueous phase; a particle size, 76nm; Lpsm-Flln), and its cytoprotective activity against UVA. In the present study, Lpsm-Flln was administered on the surface of three-dimensional human skin tissue model, rinsed out before each UVA-irradiation at 4 J/cm(2), and thereafter added again, followed by 19-cycle-repetition for 4 days (sum: 76 J/cm(2)). UVA-caused corneum scaling and disruption of epidermis layer were detected by scanning electron microscopy. Breakdown of collagen type I/IV, DNA strand cleavage and pycnosis/karyorrhexis were observed in vertical cross-sections of UVA-irradiated skin models visualized with fluorescent immunostain or Hoechst 33342 stain. These skin damages were scarcely repressed by liposome alone, but appreciably repressed by Lpsm-Flln of 250 ppm, containing 0.75 ppm of C60-equivalent to a 1/3300-weight amount vs. the whole liposome. Upon administration with Lpsm-Flln [16.7 microM (12 ppm): C60-equivalent] on human abdomen skin biopsies mounted in Franz diffusion cells, C60 permeated after 24h into the epidermis at 1.86 nmol/g tissue (1.34 ppm), corresponding to 0.3% of the applied amount and a 9.0-fold dilution rate, but C60 was not detected in the dermis by HPLC, suggesting no necessity for considering a toxicity of C60 due to systemic circulation via dermal veins. Thus Lpsm-Flln has a potential to be safely utilized as a cosmetic anti-oxidative ingredient for UVA-protection.

  15. Antimicrobial resistance profile of Staphylococcus aureus isolates obtained from skin and soft tissue infections of outpatients from a university hospital in Recife - PE, Brazil*

    PubMed Central

    Caraciolo, Fabiana Beserra; Maciel, Maria Amélia Vieira; dos Santos, Josemir Belo; Rabelo, Marcelle Aquino; Magalhães, Vera

    2012-01-01

    BACKGROUND Staphylococcus aureus has a notable ability to acquire resistance to antibiotics, and methicillin resistance represents a growing public health problem. Methicillin-resistant S. aureus (MRSA) has also become important outside the hospital environment, particularly in the United States. In Brazil, since 2005, cases of community skin infections caused by MRSA have been reported, but resistance studies involving outpatients are scarce. OBJECTIVE To know the resistance profile of S. aureus involved in skin and soft tissue infections of patients seen at the Dermatology outpatient clinic of a university hospital in Recife, Pernambuco State, northeastern Brazil. METHODS Prospective study involving 30 patients with skin and soft tissue infections, seen at the Dermatology outpatient clinic from May until November 2011. To evaluate the susceptibility of S. aureus to antibiotics, the disk diffusion method and oxacillin screening agar were used. RESULTS From a total of 30 samples of skin lesions, 19 (63%) had positive culture for S. aureus. The following resistance patterns of S. aureus were observed: penicillin, 95%; tetracycline, 32%; erythromycin, 21%; gentamicin, 16%; cefoxitin, 11%; oxacillin, 11%; trimethoprim-sulfamethoxazole, 11%; chloramphenicol, 11%; clindamycin, 5% ; and ciprofloxacin, 0%. One of the identified MRSA was obtained from a patient without risk factors for its acquisition, and was resistant, beyond to the beta-lactams, only to tetracycline. CONCLUSIONS With regard to the resistance patterns of S. aureus, resistances to tetracycline, erythromycin and gentamicin were the highest. It was documented, for the first time in Pernambuco, a case of skin infection caused by community-associated MRSA. PMID:23197204

  16. The optical diagnostics of parameters of biological tissues of human intact skin in near-infrared range

    NASA Astrophysics Data System (ADS)

    Petruk, Vasyl; Kvaternyuk, Sergii; Bolyuh, Boris; Bolyuh, Dmitry; Dronenko, Vladimir; Harasim, Damian; Annabayev, Azamat

    2016-09-01

    Melanoma skin is difficult to diagnose in the early stages of development despite its location outside. Melanoma is difficult to visually differentiate from benign melanocytic nevi. In the work we investigated parameters of human intact skin in near-infrared range for different racial and gender groups. This allows to analyze statistical differences in the coefficient of diffuse reflection and use them in the differential diagnosis of cancer by optical methods subject.

  17. The electric field induced in the brain by magnetic stimulation: a 3-D finite-element analysis of the effect of tissue heterogeneity and anisotropy.

    PubMed

    Miranda, Pedro C; Hallett, Mark; Basser, Peter J

    2003-09-01

    We investigate the effect of tissue heterogeneity and anisotropy on the electric field and current density distribution induced in the brain during magnetic stimulation. Validation of the finite-element (FE) calculations in a homogeneous isotropic sphere showed that the magnitude of the total electric field can be calculated to within an error of approximately 5% in the region of interest, even in the presence of a significant surface charge contribution. We used a high conductivity inclusion within a sphere of lower conductivity to simulate a lesion due to an infarct. Its effect is to increase the electric field induced in the surrounding low conductivity region. This boost is greatest in the vicinity of interfaces that lie perpendicular to the current flow. For physiological values of the conductivity distribution, it can reach a factor of 1.6 and extend many millimeters from the interface. We also show that anisotropy can significantly alter the electric field and current density distributions. Either heterogeneity or anisotropy can introduce a radial electric field component, not present in a homogeneous isotropic conductor. Heterogeneity and anisotropy are predicted to significantly affect the distribution of the electric field induced in the brain. It is, therefore, expected that anatomically faithful FE models of individual brains which incorporate conductivity tensor data derived from diffusion tensor measurements, will provide a better understanding of the location of possible stimulation sites in the brain.

  18. Skin and soft tissue infections in intercontinental travellers and the import of multi-resistant Staphylococcus aureus to Europe.

    PubMed

    Nurjadi, D; Friedrich-Jänicke, B; Schäfer, J; Van Genderen, P J J; Goorhuis, A; Perignon, A; Neumayr, A; Mueller, A; Kantele, A; Schunk, M; Gascon, J; Stich, A; Hatz, C; Caumes, E; Grobusch, M P; Fleck, R; Mockenhaupt, F P; Zanger, P

    2015-06-01

    Staphylococcus aureus is emerging globally. Treatment of infections is complicated by increasing antibiotic resistance. We collected clinical data and swabs of returnees with skin and soft tissue infections (SSTI) at 13 travel-clinics in Europe (www.staphtrav.eu). Sixty-two percent (196/318) SSTI patients had S. aureus-positive lesions, of which almost two-thirds (122/196) were Panton-Valentine leukocidin (PVL) positive. PVL was associated with disease severity, including hospitalization for SSTI (OR 5.2, 95% CI 1.5-18.2). In returnees with SSTI, longer travel and more intense population contact were risk factors for nasal colonization with PVL-positive S. aureus. Imported S. aureus frequently proved resistant to trimethoprim-sulfamethoxazole (21%), erythromycin (21%), tetracycline (20%), ciprofloxacin (13%), methicillin (12%) and clindamycin (8%). Place of exposure was significantly (p < 0.05) associated with predominant resistance phenotypes and spa genotypes: Latin America (methicillin; t008/CC24/304), Africa (tetracycline, trimethoprim-sulfamethoxazole; t084/CC84, t314/singleton, t355/CC355), South Asia (trimethoprim-sulfamethoxazole, ciprofloxacin; t021/CC21/318), South-East Asia (clindamycin; t159/CC272). USA300-like isolates accounted for 30% of all methicillin-resistant S. aureus imported to Europe and were predominantly (71%) acquired in Latin America. Multi-resistance to non-β-lactams were present in 24% of imports and associated with travel to South Asia (ORcrude 5.3, 95% CI 2.4-11.8), even after adjusting for confounding by genotype (ORadjusted 3.8, 95% 1.5-9.5). Choosing randomly from compounds recommended for the empiric treatment of severe S. aureus SSTI, 15% of cases would have received ineffective antimicrobial therapy. These findings call for the development of regionally stratified guidance on the antibiotic management of severe imported S. aureus disease and put the infected and colonized traveller at the centre of interventions against the

  19. Efficacy and safety of daptomycin for skin and soft tissue infections: a systematic review with trial sequential analysis

    PubMed Central

    Liu, Chao; Mao, Zhi; Yang, Mengmeng; Kang, Hongjun; Liu, Hui; Pan, Liang; Hu, Jie; Luo, Jun; Zhou, Feihu

    2016-01-01

    Background Skin and soft tissue infections (SSTIs) are significant indications for antibiotic treatment. Daptomycin, a novel antibiotic, has been registered and licensed to be used in the treatment of these infections. However, its efficacy and safety remain controversial. Objective The objective of this study was to conduct a systematic review with trial sequential analysis (TSA) to evaluate the efficacy and safety of daptomycin for the treatment of SSTIs and to analyze whether the available sample size has been large enough and is conclusive. Methods PubMed, the Cochrane Library, and EMBASE were searched for published randomized controlled trials (RCTs) that compared daptomycin with other antibiotics in adult patients with SSTIs up to February 2016. Results This meta-analysis included eight randomized controlled trials (n=2,002). There was no difference in either the clinical success rate (intention-to-treat population: relative risk [RR] =1.04, 95% confidence interval [CI] =0.99–1.10, P=0.12; clinically evaluable population: RR =1.00, 95% CI =0.97–1.04, P=0.82) or the microbiological success rate (RR =1.00, 95% CI =0.95–1.06, P=0.92) between the daptomycin and comparator groups for treating SSTIs, which was confirmed by TSA. Compared with vancomycin, daptomycin exhibited no advantage in increasing the clinical success rate (RR =1.03, 95% CI =0.95–1.13, P=0.47), and this was also confirmed by TSA. All-cause mortality, overall treatment-related adverse events, and creatine phosphokinase events were similar between these two groups. Conclusion Daptomycin and comparator drugs are equally efficacious with regard to clinical and microbiological success for patients with SSTIs, and TSA showed that no additional randomized controlled trials are required. Although daptomycin is a good alternative when other antibiotics are contraindicated for patients with SSTIs and it can serve as a first-line treatment for SSTIs, clinicians should be aware of potential adverse

  20. Specific Behaviors Predict Staphylococcus aureus Colonization and Skin and Soft Tissue Infections Among Human Immunodeficiency Virus-Infected Persons.

    PubMed

    Crum-Cianflone, Nancy F; Wang, Xun; Weintrob, Amy; Lalani, Tahaniyat; Bavaro, Mary; Okulicz, Jason F; Mende, Katrin; Ellis, Michael; Agan, Brian K

    2015-04-01

    Background.  Few data exist on the incidence and risk factors of Staphylococcus aureus colonization and skin and soft tissue infections (SSTIs) among patients infected with human immunodeficiency virus (HIV). Methods.  Over a 2-year period, we prospectively evaluated adults infected with HIV for incident S aureus colonization at 5 body sites and SSTIs. Cox proportional hazard models using time-updated covariates were performed. Results.  Three hundred twenty-two participants had a median age of 42 years (interquartile range, 32-49), an HIV duration of 9.4 years (2.7-17.4), and 58% were on highly active antiretroviral therapy (HAART). Overall, 102 patients (32%) became colonized with S aureus with an incidence rate of 20.6 (95% confidence interval [CI], 16.8-25.0) per 100 person-years [PYs]. Predictors of colonization in the final multivariable model included illicit drug use (hazard ratios [HR], 4.26; 95% CI, 1.33-13.69) and public gym use (HR 1.66, 95% CI, 1.04-2.66), whereas antibacterial soap use was protective (HR, 0.50; 95% CI, 0.32-0.78). In a separate model, perigenital colonization was associated with recent syphilis infection (HR, 4.63; 95% CI, 1.01-21.42). Fifteen percent of participants developed an SSTI (incidence rate of 9.4 cases [95% CI, 6.8-12.7] per 100 PYs). Risk factors for an SSTI included incident S aureus colonization (HR 2.52; 95% CI, 1.35-4.69), public shower use (HR, 2.59; 95% CI, 1.48-4.56), and hospitalization (HR 3.54; 95% CI, 1.67-7.53). The perigenital location for S aureus colonization was predictive of SSTIs. Human immunodeficiency virus-related factors (CD4 count, HIV RNA level, and HAART) were not associated with colonization or SSTIs. Conclusions.  Specific behaviors, but not HIV-related factors, are predictors of colonization and SSTIs. Behavioral modifications may be the most important strategies in preventing S aureus colonization and SSTIs among persons infected with HIV.

  1. A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture.

    PubMed

    Wagner, Ilka; Materne, Eva-Maria; Brincker, Sven; Süssbier, Ute; Frädrich, Caroline; Busek, Mathias; Sonntag, Frank; Sakharov, Dmitry A; Trushkin, Evgeny V; Tonevitsky, Alexander G; Lauster, Roland; Marx, Uwe

    2013-09-21

    Current in vitro and animal tests for drug development are failing to emulate the systemic organ complexity of the human body and, therefore, to accurately predict drug toxicity. In this study, we present a multi-organ-chip capable of maintaining 3D tissues derived from cell lines, primary cells and biopsies of various human organs. We designed a multi-organ-chip with co-cultures of human artificial liver microtissues and skin biopsies, each a (1)/100,000 of the biomass of their original human organ counterparts, and have successfully proven its long-term performance. The system supports two different culture modes: i) tissue exposed to the fluid flow, or ii) tissue shielded from the underlying fluid flow by standard Transwell® cultures. Crosstalk between the two tissues was observed in 14-day co-cultures exposed to fluid flow. Applying the same culture mode, liver microtissues showed sensitivity at different molecular levels to the toxic substance troglitazone during a 6-day exposure. Finally, an astonishingly stable long-term performance of the Transwell®-based co-cultures could be observed over a 28-day period. This mode facilitates exposure of skin at the air-liquid interface. Thus, we provide here a potential new tool for systemic substance testing.

  2. “Serious skin & soft tissue infections in rheumatoid arthritis patients taking anti-tumor necrosis factor alpha drugs: a nested case–control study”

    PubMed Central

    2013-01-01

    Background Anti-tumor necrosis factor alpha (anti-TNF) drugs are very effective for the treatment of rheumatoid arthritis but may increase the risk of serious bacterial infections. We assessed the association between the risk of serious skin and soft tissue infections (SSSTI) and the use of these agents in rheumatoid arthritis patients (RA). Methods We conducted a nested case–control study among rheumatoid arthritis patients in the Veterans Integrated Service Network 20 from 2000–2008. We identified rheumatoid arthritis patients with SSSTI, matched them to three sets of RA controls and used conditional logistic regression to compare the risk of SSSTI between patients treated and those not treated with an anti-TNF drug, after adjusting for known confounders and important covariates. Limited by the design, we could not assess (absolute) risk but only relative risk in terms of association. Results Among the 97 cases and 291 controls, 90 percent were male, 62 percent white, with a mean age of 63 years. Twenty percent received anti-TNF drugs during the study period. Thirty-nine percent of cases and 15 percent of controls died, (OR 3.5, 95% CI: 2.033, 6.11, p <0.01). Diabetes mellitus (37%), kidney disease (16%) and a history of skin infections (27%) were common among cases. Based on conditional logistic regression, anti-TNF use was not significantly associated with skin and soft tissue infections (OR 1.1, 95% CI: 0.61-2.03, p = 0.92). However, patients with diabetes mellitus (OR 2.5, 95% CI: 1.53-4.13, p = 0.01) or a prior history of skin infection (OR 5.7, 95% CI: 2.87-11.43, p <0.01) were more likely to have skin and soft tissue infections. Conclusion Use of anti-TNF therapy among RA patients was not associated with an increased risk of SSSTI, but patients with diabetes mellitus and those with a history of prior skin infection were significantly more likely to have SSSTI and mortality was higher among cases than controls in this veteran cohort. PMID:24498926

  3. Patients With Burns Versus Patients With Complex Skin and Soft-Tissue Disease: An Analysis of Outcomes in the United States.

    PubMed

    Maximus, Steven; Phelan, Michael; Joe, Victor C

    2016-01-01

    With the incidence of burns decreasing nationally, burn units are caring for more patients with nonburn conditions. The American Burn Association National Burn Repository does not currently report data regarding patients cared for in burn units without a diagnosis of burn. Using the National Inpatient Sample, we examined if there was a difference in characteristics and outcomes of patients admitted for burns compared with those with a primary admitting diagnosis of necrotizing skin infections and soft-tissue infections and exfoliative skin conditions. This is a retrospective study querying the National Inpatient Sample database to identify 56,102 patients from 2007 to 2012 who were admitted with a diagnosis of a burn (burn group). This group was then compared with 375,857 patients who had a primary admitting diagnosis of a necrotizing skin and/or soft-tissue infection or exfoliative skin conditions (nonburn group). Clinical and demographic variables were analyzed to determine characteristics of each patient group including length of stay, disposition, complications, comorbidities, and mortality. The average age of the nonburn group was 63.7 years, whereas the average age of the burn group was 40.1 years. Overall length of stay was higher in the nonburn patients than in burn patients (10.5 vs 8.4 days, P < .001). Nonburn patients had a higher rate of medical comorbidities. Nonburn patients had higher rates of mortality (6.9% vs 2.7%) and complications. After adjusting for confounders, such as age, gender, ethnicity, and comorbidities, the nonburn group was found to have higher rates of all recorded complications. Burn patients were more likely to undergo a major operating room procedure (39.3% vs 28.1%) and routine discharge (68.4% vs 26.3%) compared with the nonburn group. Patients with necrotizing skin and soft-tissue infections and exfoliative skin conditions are older, have more comorbidities, higher complication rates, and higher mortality rates than burn

  4. Optical devices used for image analysis of pigmented skin lesions: a proposal for quality assurance protocol using tissue-like phantoms.

    PubMed

    Lualdi, M; Colombo, A; Carrara, M; Scienza, L; Tomatis, S; Marchesini, R

    2006-12-07

    Different technological tools have been developed to aid in the diagnosis of pigmented skin lesions, including cameras working with conventional RGB colour systems, epiluminescence microscopy and spectrophotometric methods using visible and near infrared wavelengths. All the different procedures should provide in an objective and reproducible fashion quantitative measurements of the colour and shape features of a given skin mole. At present, many devices have been introduced in experimental stages for clinical diagnosis, mainly used to provide to the clinicians an objective, computer-assisted second opinion. As for any diagnostic instruments, optical devices should also be subjected to a dedicated quality assurance protocol in order to evaluate the response repeatability of each device (intra-instrument agreement) and to check the accordance among the responses of different devices (inter-instrument agreement). The aim of this study was to design a quality assurance protocol for optical devices dedicated to image analysis of pigmented skin lesions and, in case, to detect cutaneous melanoma by using suitable tissue-like phantoms as standard references that enable testing of both hardware and software components. As an example, we report the results of intra-instrument and inter-instrument agreement when the protocol was applied on a series of 30 SpectroShade instruments, a novel optical device based on multi-spectral image analysis of colour and shape features of pigmented skin lesion.

  5. Laser capture microdissection of cervical human papillomavirus infections: copy number of the virus in cancerous and normal tissue and heterogeneous DNA methylation.

    PubMed

    Kalantari, Mina; Garcia-Carranca, Alejandro; Morales-Vazquez, Claudia Dalia; Zuna, Rosemary; Montiel, Delia Perez; Calleja-Macias, Itzel E; Johansson, Bo; Andersson, Sonia; Bernard, Hans-Ulrich

    2009-08-01

    Research on the pathogenicity of human papillomaviruses (HPVs) during cervical carcinogenesis often relies on the study of homogenized tissue or cultured cells. This approach does not detect molecular heterogeneities within the infected tissue. It is desirable to understand molecular properties in specific histological contexts. We asked whether laser capture microdissection (LCM) of archival cervical tumors in combination with real-time polymerase chain reaction and bisulfite sequencing permits (i) sensitive DNA diagnosis of small clusters of formalin-fixed cells, (ii) quantification of HPV DNA in neoplastic and normal cells, and (iii) analysis of HPV DNA methylation, a marker of tumor progression. We analyzed 26 tumors containing HPV-16 or 18. We prepared DNA from LCM dissected thin sections of 100 to 2000 cells, and analyzed aliquots corresponding to between nine and 70 cells. We detected nine to 630 HPV-16 genome copies and one to 111 HPV-18 genome copies per tumor cell, respectively. In 17 of the 26 samples, HPV DNA existed in histologically normal cells distant from the margins of the tumors, but at much lower concentrations than in the tumor, suggesting that HPVs can infect at low levels without pathogenic changes. Methylation of HPV DNA, a biomarker of integration of the virus into cellular DNA, could be measured only in few samples due to limited sensitivity, and indicated heterogeneous methylation patterns in small clusters of cancerous and normal cells. LCM is powerful to study molecular parameters of cervical HPV infections like copy number, latency and epigenetics.

  6. A data-driven soft sensor for needle deflection in heterogeneous tissue using just-in-time modelling.

    PubMed

    Rossa, Carlos; Lehmann, Thomas; Sloboda, Ronald; Usmani, Nawaid; Tavakoli, Mahdi

    2016-12-10

    Global modelling has traditionally been the approach taken to estimate needle deflection in soft tissue. In this paper, we propose a new method based on local data-driven modelling of needle deflection. External measurement of needle-tissue interactions is collected from several insertions in ex vivo tissue to form a cloud of data. Inputs to the system are the needle insertion depth, axial rotations, and the forces and torques measured at the needle base by a force sensor. When a new insertion is performed, the just-in-time learning method estimates the model outputs given the current inputs to the needle-tissue system and the historical database. The query is compared to every observation in the database and is given weights according to some similarity criteria. Only a subset of historical data that is most relevant to the query is selected and a local linear model is fit to the selected points to estimate the query output. The model outputs the 3D deflection of the needle tip and the needle insertion force. The proposed approach is validated in ex vivo multilayered biological tissue in different needle insertion scenarios. Experimental results in five different case studies indicate an accuracy in predicting needle deflection of 0.81 and 1.24 mm in the horizontal and vertical lanes, respectively, and an accuracy of 0.5 N in predicting the needle insertion force over 216 needle insertions.

  7. Phase-resolved functional optical coherence tomography: simultaneous imaging of in situ tissue structure, blood flow velocity, standard deviation, birefringence, and Stokes vectors in human skin

    NASA Astrophysics Data System (ADS)

    Ren, Hongwu; Ding, Zhihua; Zhao, Yonghua; Miao, Jianjun; Nelson, J. Stuart; Chen, Zhongping

    2002-10-01

    We describe a phase-resolved functional optical coherence tomography system that can simultaneously yield in situ images of tissue structure, blood flow velocity, standard deviation, birefringence, and the Stokes vectors in human skin. Multifunctional images were obtained by processing of analytical interference fringe signals derived from two perpendicular polarization-detection channels. The blood flow velocity and standard deviation images were obtained by comparison of the phases from pairs of analytical signals in neighboring A-lines in the same polarization state. The analytical signals from two polarization-diversity detection channels were used to determine the four Stokes vectors for four reference polarization states. From the four Stokes vectors, the birefringence image, which is not sensitive to the orientation of the optical axis in the sample, was obtained. Multifunctional in situ images of a port wine stain birthmark in human skin are presented.

  8. Mastocytosis in children and adults: clinical disease heterogeneity

    PubMed Central

    Nedoszytko, Bogusław; Górska, Aleksandra; Żawrocki, Anton; Sobjanek, Michał; Kozlowski, Dariusz

    2012-01-01

    Mastocytosis is a clonal disease of the hematopoietic stem cell. The condition consists of a heterogeneous group of disorders characterized by a pathological accumulation of mast cells in tissues including the skin, bone marrow, liver, spleen and the lymph nodes. Mastocytosis is a rare disease which occurs both in children and adults. Childhood onset mastocytosis is usually cutaneous and transient while in adults the condition commonly progresses to a systemic form. The heterogeneity of clinical presentation of mastocytosis is typically related to the tissue mast cell burden, symptoms due to the release of mast cell mediators, the type of skin lesions, the patient's age at the onset and associated haematological disorders. Therefore, a multidisciplinary approach is recommended. The present article provides an overview of clinical symptoms, diagnostic criteria and treatment of mastocytosis to facilitate the diagnosis and management of mastocytosis patients in clinical practice. PMID:22852012

  9. Mastocytosis in children and adults: clinical disease heterogeneity.

    PubMed

    Lange, Magdalena; Nedoszytko, Bogusław; Górska, Aleksandra; Zawrocki, Anton; Sobjanek, Michał; Kozlowski, Dariusz

    2012-07-04

    Mastocytosis is a clonal disease of the hematopoietic stem cell. The condition consists of a heterogeneous group of disorders characterized by a pathological accumulation of mast cells in tissues including the skin, bone marrow, liver, spleen and the lymph nodes. Mastocytosis is a rare disease which occurs both in children and adults. Childhood onset mastocytosis is usually cutaneous and transient while in adults the condition commonly progresses to a systemic form. The heterogeneity of clinical presentation of mastocytosis is typically related to the tissue mast cell burden, symptoms due to the release of mast cell mediators, the type of skin lesions, the patient's age at the onset and associated haematological disorders. Therefore, a multidisciplinary approach is recommended. The present article provides an overview of clinical symptoms, diagnostic criteria and treatment of mastocytosis to facilitate the diagnosis and management of mastocytosis patients in clinical practice.

  10. Healing and evaluating guinea pig skin incision after surgical suture and laser tissue by welding using in vivo Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Alimova, A.; Sriramoju, V.; Chakraverty, R.; Muthukattil, R.; Alfano, R. R.

    2010-02-01

    Changes in collagen in the wound during the healing process of guinea pig skin following surgical incisions and LTW was evaluated using in vivo, using Raman spectroscopy. Raman spectroscopy provided information regarding the internal structure of the proteins. After the incisions were closed either by suturing or by LTW the ratio of the Raman peaks of the amide III (1247 cm-1) band to a peak at 1326 cm-1 used to evaluate the progression of collagen deposition. Histopathology was used as the gold standard. LTW skin demonstrated better healing than sutured skin, exhibiting minimal hyperkeratosis, minimal collagen deposition, near-normal surface contour, and minimal loss of dermal appendages. This work is important to plastic surgery.

  11. Micro Regional Heterogeneity of 64Cu-ATSM and 18F-FDG Uptake in Canine Soft Tissue Sarcomas: Relation to Cell Proliferation, Hypoxia and Glycolysis

    PubMed Central

    Zornhagen, Kamilla Westarp; Hansen, Anders E.; Oxboel, Jytte; Clemmensen, Andreas E.; El Ali, Henrik H.; Kristensen, Annemarie T.; Kjær, Andreas

    2015-01-01

    Objectives Tumour microenvironment heterogeneity is believed to play a key role in cancer progression and therapy resistance. However, little is known about micro regional distribution of hypoxia, glycolysis and proliferation in spontaneous solid tumours. The overall aim was simultaneous investigation of micro regional heterogeneity of 64Cu-ATSM (hypoxia) and 18F-FDG (glycolysis) uptake and correlation to endogenous markers of hypoxia, glycolysis, proliferation and angiogenesis to better therapeutically target aggressive tumour regions and prognosticate outcome. Methods Exploiting the different half-lives of 64Cu-ATSM (13h) and 18F-FDG (2h) enabled simultaneous investigation of micro regional distribution of hypoxia and glycolysis in 145 tumour pieces from four spontaneous canine soft tissue sarcomas. Pairwise measurements of radioactivity and gene expression of endogenous markers of hypoxia (HIF-1α, CAIX), glycolysis (HK2, GLUT1 and GLUT3), proliferation (Ki-67) and angiogenesis (VEGFA and TF) were performed. Dual tracer autoradiography was compared with Ki-67 immunohistochemistry. Results Micro regional heterogeneity in hypoxia and glycolysis within and between tumour sections of each tumour piece was observed. The spatial distribution of 64Cu-ATSM and 18F-FDG was rather similar within each tumour section as reflected in moderate positive significant correlations between the two tracers (ρ = 0.3920–0.7807; p = 0.0180 –<0.0001) based on pixel-to-pixel comparisons of autoradiographies and gamma counting of tumour pieces. 64Cu-ATSM and 18F-FDG correlated positively with gene expression of GLUT1 and GLUT3, but negatively with HIF-1α and CAIX. Significant positive correlations were seen between Ki-67 gene expression and 64Cu-ATSM (ρ = 0.5578, p = 0.0004) and 18F-FDG (ρ = 0.4629–0.7001, p = 0.0001–0.0151). Ki-67 gene expression more consistently correlated with 18F-FDG than with 64Cu-ATSM. Conclusions Micro regional heterogeneity of hypoxia and glycolysis

  12. Skin and soft tissue concentrations of tedizolid (formerly torezolid), a novel oxazolidinone, following a single oral dose in healthy volunteers

    PubMed Central

    Sahre, Martina; Sabarinath, Sreedharan; Grant, Maria; Seubert, Christoph; DeAnda, Carisa; Prokocimer, Philippe

    2013-01-01

    Plasma concentrations of antimicrobial drugs have long been used to correlate exposure with effect, yet one cannot always assume that unbound plasma and tissue concentrations are similar. Knowledge about unbound tissue concentrations is important in the development of antimicrobial drugs, since most infections are localised in tissues. Therefore, a clinical microdialysis study was conducted to evaluate the distribution of tedizolid (TR-700), the active moiety of the antimicrobial prodrug tedizolid phosphate (TR-701), into interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissues following a single oral 600 mg dose of tedizolid phosphate in fasting conditions. Twelve healthy adult subjects were enrolled. Two microdialysis probes were implanted into the thigh of each subject, one into the vastus medialis muscle and one into subcutaneous adipose tissue. Probes were calibrated using retrodialysis. Dialysate samples were collected every 20 min for 12 h following a single oral dose of 600 mg tedizolid phosphate, and blood samples were drawn over 24 h. Unbound tedizolid levels in plasma were similar to those in muscle and adipose tissue. The ratios of unbound (free) AUC in tissues over unbound AUC in plasma (fAUCtissue/fAUCplasma) were 1.1 ± 0.2 and 1.2 ± 0.2 for adipose and muscle tissue, respectively. The median half-life was 8.1, 9.2 and 9.6 h for plasma, adipose tissue and muscle tissue, respectively. Mean protein binding was 87.2 ± 1.8%. The study drug was very well tolerated. The results of this study show that tedizolid distributes well into ISF of adipose and muscle tissues. Unbound levels of tedizolid in plasma, adipose tissue and muscle tissue were well correlated. Free plasma levels are indicative of unbound levels in the ISF of muscle and adipose tissues. PMID:22584101

  13. Oxytetracycline depletion from skin-on fillet tissue of coho salmon fed oxytetracycline medicated feed in freshwater at temperatures less than 9°C

    USGS Publications Warehouse

    Meinertz, Jeffery R.; Gaikowski, Mark P.; Stehly, Guy R.; Gingerich, William H.; Evered, Joy A.

    2001-01-01

    Oxytetracycline (OTC) is a broad spectrum antibacterial agent approved in the USA for treating certain bacterial diseases in salmonids cultured in freshwater at temperatures greater than or equal to 9°C. This study was conducted to provide the information necessary to expand the OTC label to include treatment of diseased salmonids cultured in freshwater at temperatures below 9°C. The study was designed to treat juvenile coho salmon (Oncorhynchus kisutch) with OTC-medicated feed and determine the depletion of OTC from the skin-on fillet tissue. Oxytetracycline depletion was evaluated in juvenile coho salmon (weight range, 13–62 g) fed OTC-medicated feed at a rate of 88.2 mg OTC/kg body weight/day for 10 days. Pairs of skin-on fillets were taken from individual fish on days 4 and 10 during the treatment phase and on days 1, 4, 8, 14, and 19 during the depletion phase. Water temperatures during the study period ranged from 4.1°C to 8.5°C. The OTC concentrations in medicated feed and skin-on fillets were determined with high-performance liquid chromatography methods. The maximum mean OTC concentration in fillet tissue was 932 ng/g, 1 day after the last treatment and decreased to 32 ng/g 19 days after the last treatment. The log-linear loss of OTC from the fillet tissue was biphasic with a terminal phase half-life of 4.9 days.

  14. Comparative Genomic, MicroRNA, and Tissue Analyses Reveal Subtle Differences between Non-Diabetic and Diabetic Foot Skin

    PubMed Central

    Ramirez, Horacio A.; Liang, Liang; Pastar, Irena; Rosa, Ashley M.; Stojadinovic, Olivera; Zwick, Thomas G.; Kirsner, Robert S.; Maione, Anna G.; Garlick, Jonathan A.; Tomic-Canic, Marjana

    2015-01-01

    Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular

  15. Skin Dictionary

    MedlinePlus

    ... your skin, hair, and nails Skin dictionary Camp Discovery Good Skin Knowledge lesson plans and activities Video library Find a ... your skin, hair, and nails Skin dictionary Camp Discovery Good Skin Knowledge lesson plans and activities Video library Find a ...

  16. Within subject heterogeneity in tissue-level post-yield mechanical and material properties in human trabecular bone.

    PubMed

    Carretta, Roberto; Stüssi, Edgar; Müller, Ralph; Lorenzetti, Silvio

    2013-08-01

    The ability to determine patient-specific mechanical properties of trabecular bone is needed for a reliable estimation of fracture risks. Tissue mechanics and material composition are important factors that contribute to trabecular bone performance, but only a few studies have investigated the post-yield behaviour of human trabecular bone, and limited knowledge for modelling is available about ultimate properties needed. Aim of this paper was to investigate absolute values and deviation of mechanical and material properties of human trabecular bone at the tissue level, in a healthy and osteoporotic donor. A combination of tensile and bending tests of single trabeculae up to failure, μCT measurement of sample geometry and finite element analysis were incorporated to determine mechanical properties. The samples were analysed with Raman spectroscopy to evaluate the material composition. High within-subject variability was found, for both the healthy and osteoporotic donor. Nevertheless, the two donors could be separated by analysing the ultimate strain and post-yield work, as well as two of the material parameters (B-type carbonate substitution ratio and collagen cross-link ratio). It indicates that tissue level properties seem to be relevant also for macroscopic mechanical behaviour. These findings also suggest that the mechanical variability for the inelastic region at the tissue level may be associated with varying material properties, while until yielding occurs our data does not suggest any connection between the mechanical and the investigated material. Finally, a set of mechanical properties of human bone have been reported that are a relevant reference for computational studies and FE analysis.

  17. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients

    PubMed Central

    Møller, Mia; Strand, Siri Hundtofte; Mundbjerg, Kamilla; Liang, Gangning; Gill, Inderbir; Haldrup, Christa; Borre, Michael; Høyer, Søren; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard

    2017-01-01

    Prostate cancer (PC) diagnosis is based on histological evaluation of prostate needle biopsies, which have high false negative rates. Here, we investigated if cancer-associated epigenetic field effects in histologically normal prostate tissue may be used to increase sensitivity for PC. We focused on nine genes (AOX1, CCDC181 (C1orf114), GABRE, GAS6, HAPLN3, KLF8, MOB3B, SLC18A2, and GSTP1) known to be hypermethylated in PC. Using quantitative methylation-specific PCR, we analysed 66 malignant and 134 non-malignant tissue samples from 107 patients, who underwent ultrasound-guided prostate biopsy (67 patients had at least one cancer-positive biopsy, 40 had exclusively cancer-negative biopsies). Hypermethylation was detectable for all genes in malignant needle biopsy samples (AUC: 0.80 to 0.98), confirming previous findings in prostatectomy specimens. Furthermore, we identified a four-gene methylation signature (AOX1xGSTP1xHAPLN3xSLC18A2) that distinguished histologically non-malignant biopsies from patients with vs. without PC in other biopsies (AUC = 0.65; sensitivity = 30.8%; specificity = 100%). This signature was validated in an independent patient set (59 PC, 36 adjacent non-malignant, and 9 normal prostate tissue samples) analysed on Illumina 450 K methylation arrays (AUC = 0.70; sensitivity = 40.6%; specificity = 100%). Our results suggest that a novel four-gene signature may be used to increase sensitivity for PC diagnosis through detection of epigenetic field effects in histologically non-malignant prostate tissue samples. PMID:28084441

  18. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients.

    PubMed

    Møller, Mia; Strand, Siri Hundtofte; Mundbjerg, Kamilla; Liang, Gangning; Gill, Inderbir; Haldrup, Christa; Borre, Michael; Høyer, Søren; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard

    2017-01-13

    Prostate cancer (PC) diagnosis is based on histological evaluation of prostate needle biopsies, which have high false negative rates. Here, we investigated if cancer-associated epigenetic field effects in histologically normal prostate tissue may be used to increase sensitivity for PC. We focused on nine genes (AOX1, CCDC181 (C1orf114), GABRE, GAS6, HAPLN3, KLF8, MOB3B, SLC18A2, and GSTP1) known to be hypermethylated in PC. Using quantitative methylation-specific PCR, we analysed 66 malignant and 134 non-malignant tissue samples from 107 patients, who underwent ultrasound-guided prostate biopsy (67 patients had at least one cancer-positive biopsy, 40 had exclusively cancer-negative biopsies). Hypermethylation was detectable for all genes in malignant needle biopsy samples (AUC: 0.80 to 0.98), confirming previous findings in prostatectomy specimens. Furthermore, we identified a four-gene methylation signature (AOX1xGSTP1xHAPLN3xSLC18A2) that distinguished histologically non-malignant biopsies from patients with vs. without PC in other biopsies (AUC = 0.65; sensitivity = 30.8%; specificity = 100%). This signature was validated in an independent patient set (59 PC, 36 adjacent non-malignant, and 9 normal prostate tissue samples) analysed on Illumina 450 K methylation arrays (AUC = 0.70; sensitivity = 40.6%; specificity = 100%). Our results suggest that a novel four-gene signature may be used to increase sensitivity for PC diagnosis through detection of epigenetic field effects in histologically non-malignant prostate tissue samples.

  19. An efficient computational approach to characterize DSC-MRI signals arising from three-dimensional heterogeneous tissue structures.

    PubMed

    Semmineh, Natenael B; Xu, Junzhong; Boxerman, Jerrold L; Delaney, Gary W; Cleary, Paul W; Gore, John C; Quarles, C Chad

    2014-01-01

    The systematic investigation of susceptibility-induced contrast in MRI is important to better interpret the influence of microvascular and microcellular morphology on DSC-MRI derived perfusion data. Recently, a novel computational approach called the Finite Perturber Method (FPM), which enables the study of susceptibility-induced contrast in MRI arising from arbitrary microvascular morphologies in 3D has been developed. However, the FPM has lower efficiency in simulating water diffusion especially for complex tissues. In this work, an improved computational approach that combines the FPM with a matrix-based finite difference method (FDM), which we call the Finite Perturber the Finite Difference Method (FPFDM), has been developed in order to efficiently investigate the influence of vascular and extravascular morphological features on susceptibility-induced transverse relaxation. The current work provides a framework for better interpreting how DSC-MRI data depend on various phenomena, including contrast agent leakage in cancerous tissues and water diffusion rates. In addition, we illustrate using simulated and micro-CT extracted tissue structures the improved FPFDM along with its potential applications and limitations.

  20. Determination of the exposure parameters that maximise the concentrations of the anaesthetic/sedative eugenol in rainbow trout (Oncorhynchus mykiss) skin-on fillet tissue.

    PubMed

    Meinertz, J R; Porcher, S T; Smerud, J R; Gaikowski, M P

    2014-01-01

    Studies were conducted to determine the anaesthetic/sedative concentrations and durations that would maximise anaesthetic/sedative residue concentrations in rainbow trout (Oncorhynchus mykiss) skin-on fillet tissue. Rainbow trout (167-404 g) were exposed to 50 mg l(-1) AQUI-S(®) 20E (10% active ingredient, eugenol) in 17°C freshwater for durations up to 1440 min, 100 and 250 mg l(-1) AQUI-S(®) 20E for durations up to 240 min, and 500 and 1000 mg l(-1) AQUI-S(®) 20E for durations up to 90 min. Fish exposed to 100 mg l(-1) AQUI-S(®) 20E for durations of 30, 60, 120 and 240 min had the greatest eugenol concentrations in the fillet tissue, 50, 58, 54 and 62 µg g(-1), respectively. All other exposure concentrations and durations resulted in significantly lower eugenol concentrations, i.e. all < 39 µg g(-1).

  1. Determination of the exposure parameters that maximise the concentrations of the anaesthetic/sedative eugenol in rainbow trout (Oncorhynchus mykiss) skin-on fillet tissue

    USGS Publications Warehouse

    Meinertz, Jeffery R.; Porcher, Scott T.; Smerud, Justin R.

    2014-01-01

    Studies were conducted to determine the anaesthetic/sedative concentrations and durations that would maximize anaesthetic/sedative residue concentrations in rainbow trout (Oncorhynchus mykiss) skin-on fillet tissue. Rainbow trout (167–404 g) were exposed to 50 mg l−1 AQUI-S® 20E (10% active ingredient, eugenol) in 17°C freshwater for durations up to 1440 min, 100 and 250 mg l−1 AQUI-S® 20E for durations up to 240 min, and 500 and 1000 mg l−1 AQUI-S® 20E for durations up to 90 min. Fish exposed to 100 mg l−1 AQUI-S® 20E for durations of 30, 60, 120 and 240 min had the greatest eugenol concentrations in the fillet tissue, 50, 58, 54 and 62 µg g−1, respectively. All other exposure concentrations and durations resulted in significantly lower eugenol concentrations, i.e. all −1.

  2. A simple and efficient method for DNA extraction from skin and paraffin-embedded tissues applicable to T-cell clonality assays.

    PubMed

    Sidorova, Julia V; Biderman, Bella V; Nikulina, Elena E; Sudarikov, Andrey B

    2012-01-01

    PCR-based clonality assay of rearranged T-cell receptor genes gamma and beta (TCRG and TCRB) in a number of cases could be essential to discriminate between cutaneous T-cell lymphomas and reactive lymphoproliferative lesions in the skin. However, extraction of good-quality DNA from skin specimens (especially formalin-fixed paraffin-embedded) remains a challenge. Common procedures, being labour-intensive and time-consuming and requiring toxic solvents such as phenol and chloroform, still may end up with DNA sample of insufficient quality. We herewith present a simple and efficient method for DNA isolation based on ammonia extraction of tissue, followed by neutralization and simultaneous salting out of proteins with acetic acid. We have analysed 30 samples - 24 fresh (16 skin, two spleen and six lymph node) and six paraffin-embedded. Standard procedure (proteinase K digestion, followed by phenol/chloroform extraction) has been carried out simultaneously. We observed good PCR signal for TCRG rearrangements in 30 samples processed with the new protocol and only in 20 extracted with proteinase K/phenol/chloroform. For TCRB, the success rate was 29 of 30 with the new protocol, compared to 11 of 30 with conventional protocol. The proposed method of DNA extraction should improve the value of T-cell clonality assay, because insufficient DNA quality and quantity may bias analysis towards monoclonality and therefore cause false-positive results.

  3. Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castrationresistant prostate cancer: a report from the PETRUS prospective study

    PubMed Central

    Massard, Christophe; Oulhen, Marianne; Le Moulec, Sylvestre; Auger, Nathalie; Foulon, Stéphanie; Abou-Lovergne, Aurélie; Billiot, Fanny; Valent, Alexander; Marty, Virginie; Loriot, Yohann; Fizazi, Karim; Vielh, Philippe; Farace, Francoise

    2016-01-01

    Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR-amplification and TMPRSS2-ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively. By comparing CellSearch and filtration (ISET)-enrichment combined to four color immunofluorescent staining, we showed that CellSearch and ISET isolated distinct subpopulations of CTCs: CTCs undergoing epithelial-to-mesenchymal transition, CTC clusters and large CTCs with cytomorphological characteristics but no detectable markers were isolated using ISET. Epithelial CTCs detected by the CellSearch were mostly lost during the ISET-filtration. AR-amplification was detected in CellSearch-captured CTCs, but not in ISET-enriched CTCs which harbor exclusively AR gain of copies. Eighty-eight percent concordance for ERG-rearrangement was observed between metastatic biopsies and CTCs even if additional ERG-alteration patterns were detected in ISET-enriched CTCs indicating a higher heterogeneity in CTCs. Molecular screening of metastatic biopsies is achievable in a multicenter context. Our data indicate that CTCs detected by the CellSearch and the ISET-filtration systems are not only phenotypically but also genetically different. Close attention must be paid to CTC characterization since neither approach tested here fully reflects the tremendous phenotypic and genetic heterogeneity present in CTCs from mCRPC patients. PMID:27391263

  4. Biocompatible Silk Noil-Based Three-Dimensional Carded-Needled Nonwoven Scaffolds Guide the Engineering of Novel Skin Connective Tissue.

    PubMed

    Chiarini, Anna; Freddi, Giuliano; Liu, Daisong; Armato, Ubaldo; Dal Prà, Ilaria

    2016-08-01

    Retracting hypertrophic scars resulting from healed burn wounds heavily impact on the patients' life quality. Biomaterial scaffolds guiding burned-out skin regeneration could suppress or lessen scar retraction. Here we report a novel silk noil-based three-dimensional (3D) nonwoven scaffold produced by carding and needling with no formic acid exposure, which might improve burn healing. Once wetted, it displays human skin-like physical features and a high biocompatibility. Human keratinocyte-like cervical carcinoma C4-I cells seeded onto the carded-needled nonwovens in vitro quickly adhered to them, grew, and actively metabolized glutamine releasing lactate. As on plastic, they released no proinflammatory IL-1β, although secreting tumor necrosis factor-alpha, an inducer of the autocrine mitogen amphiregulin in such cells. Once grafted into interscapular subcutaneous tissue of mice, carded-needled nonwovens guided the afresh assembly of a connective tissue enveloping the fibroin microfibers and filling the interposed voids within 3 months. Fibroblasts and a few poly- or mononucleated macrophages populated the engineered tissue. Besides, its extracellular matrix contained thin sparse collagen fibrils and a newly formed vascular network whose endothelin-1-expressing endothelial cells grew first on the fibroin microfibrils and later expanded into the intervening matrix. Remarkably, no infiltrates of inflammatory leukocytes and no packed collagen fibers bundles among fibroin microfibers, no fibrous capsules at the grafts periphery, and hence no foreign body response was obtained at the end of 3 months of observation. Therefore, we posit that silk noil-based 3D carded-needled nonwoven scaffolds are tools for translational medicine studies as they could guide connective tissue regeneration at deep burn wounds averting scar retraction with good functional results.

  5. Fibrous hydrogel scaffolds with cells embedded in the fibers as a potential tissue scaffold for skin repair.

    PubMed

    Lin, Hsin-Yi; Peng, Chih-Wei; Wu, Wei-Wen

    2014-01-01

    A novel approach was undertaken to create a potential skin wound dressing. L929 fibroblast cells and alginate solution were simultaneously dispensed into a calcium chloride solution using a three-dimensional plotting system to manufacture a fibrous alginate scaffold with interconnected pores. These cells were then embedded in the alginate hydrogel fibers of the scaffold. A conventional scaffold with cells directly seeded on the fiber surface was used as a control. The encapsulated fibroblasts made using the co-dispensing method distributed homogeneously within the scaffold and showed the delayed formation of large cell aggregates compared to the control. The cells embedded in the hydrogel fibers also deposited more type I collagen in the extracellular matrix and expressed higher levels of fgf11 and fn1 than the control, indicating increased cellular proliferation and attachment. The results indicate that the novel co-dispensing alginate scaffold may promote skin regeneration better than the conventional directly-seeded scaffold.

  6. Characteristics of Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) Strains Isolated from Skin and Soft-Tissue Infections in Uruguay

    PubMed Central

    Pardo, Lorena; Machado, Virginia; Mollerach, Marta; Mota, María Inés; Tuchscherr, Lorena P. N.; Gadea, Pilar; Gardella, Noella; Sordelli, Daniel O.; Vola, Magdalena; Schelotto, Felipe; Varela, Gustavo

    2009-01-01

    We analyzed 90 nonduplicates community-associated methicillin-resistant S. aureus (CA-MRSA) strains isolated from skin and soft-tissue infections. All strains were mecA positive. Twenty-four of the 90 strains showed inducible macrolide-lincosamide-streptogramin B resistance. All strains produced α-toxin; 96% and 100% of them displayed positive results for lukS-F and cna genes, respectively. Eigthy-five strains expressed capsular polysaccharide serotype 8. Six different pulsotypes were discriminated by pulsed-field gel electrophoresis (PFGE) and three predominant groups of CA-MRSA strains (1, 2, and 4) were identified, in agreement with phenotypic and genotypic characteristics. Strains of group 1 (pulsotype A, CP8+, and Panton-Valentine leukocidin (PVL)+) were the most frequently recovered and exhibited a PFGE band pattern identical to other CA-MRSA strains previously isolated in Uruguay and Brazil. Three years after the first local CA-MRSA report, these strains are still producing skin and soft-tissue infections demonstrating the stability over time of this community-associated emerging pathogen. PMID:20016669

  7. Patterns of Emphysema Heterogeneity

    PubMed Central

    Valipour, Arschang; Shah, Pallav L.; Gesierich, Wolfgang; Eberhardt, Ralf; Snell, Greg; Strange, Charlie; Barry, Robert; Gupta, Avina; Henne, Erik; Bandyopadhyay, Sourish; Raffy, Philippe; Yin, Youbing; Tschirren, Juerg; Herth, Felix J.F.

    2016-01-01

    Background Although lobar patterns of emphysema heterogeneity are indicative of optimal target sites for lung volume reduction (LVR) strategies, the presence of segmental, or sublobar, heterogeneity is often underappreciated. Objective The aim of this study was to understand lobar and segmental patterns of emphysema heterogeneity, which may more precisely indicate optimal target sites for LVR procedures. Methods Patterns of emphysema heterogeneity were evaluated in a representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive pulmonary disease (COPD) patients from the COPDGene study. High-resolution computerized tomography analysis software was used to measure tissue destruction throughout the lungs to compute heterogeneity (≥ 15% difference in tissue destruction) between (inter-) and within (intra-) lobes for each patient. Emphysema tissue destruction was characterized segmentally to define patterns of heterogeneity. Results Segmental tissue destruction revealed interlobar heterogeneity in the left lung (57%) and right lung (52%). Intralobar heterogeneity was observed in at least one lobe of all patients. No patient presented true homogeneity at a segmental level. There was true homogeneity across both lungs in 3% of the cohort when defining heterogeneity as ≥ 30% difference in tissue destruction. Conclusion Many LVR technologies for treatment of emphysema have focused on interlobar heterogeneity and target an entire lobe per procedure. Our observations suggest that a high proportion of patients with emphysema are affected by interlobar as well as intralobar heterogeneity. These findings prompt the need for a segmental approach to LVR in the majority of patients to treat only the most diseased segments and preserve healthier ones. PMID:26430783

  8. Characterization of clinical strains of MSSA, MRSA and MRSE isolated from skin and soft tissue infections and the antibacterial activity of ZnO nanoparticles.

    PubMed

    Ansari, Mohammad Azam; Khan, Haris M; Khan, Aijaz A; Sultan, Asfia; Azam, Ameer

    2012-04-01

    Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is an important cause of pyogenic skin and soft tissue infections (SSTIs). MRSA is an important pathogen in the healthcare sector that has neither been eliminated from the hospital nor community environment. In humans, S. aureus causes superficial lesions in the skin and localized abscesses, pyogenic meningitis/encephalitis, osteomyelitis, septic arthritis, invasive endocarditis, pneumonia, urinary tract infections and septicemia. Investigations focused in the search of other alternatives for the treatment of MRSA infections are in progress. Among the range of compounds whose bactericidal activity is being investigated, ZnO nanoparticles (ZnO-NPs) appears most promising new unconventional antibacterial agent that could be helpful to confront this and other drug-resistant bacteria. The aim of present study is to investigate the antibacterial potential of ZnO-NPs against Staphylococcus species isolated from the pus and wounds swab from the patients with skin and soft tissue infections in a tertiary care hospital of north India. ZnO-NPs (≈19.82 nm) synthesized by sol-gel process were characterized using scanning electron microscopy, X-ray diffraction , and Atomic force microscopy. The antibacterial potential was assessed using time-dependent growth inhibition assay, well diffusion test, MIC and MBC test and colony forming units methods. ZnO-NPs inhibited bacterial growth of methicillin-sensitive S. aureus (MSSA), MRSA and methicillin-resistant S. epidermidis (MRSE) strains and were effective bactericidal agents that were not affected by drug-resistant mechanisms of MRSA and MRSE.

  9. Antigen-Presenting Cells in the Skin.

    PubMed

    Kashem, Sakeen W; Haniffa, Muzlifah; Kaplan, Daniel H

    2017-02-06

    Professional antigen-presenting cells (APCs) in the skin include dendritic cells, monocytes, and macrophages. They are highly dynamic, with the capacity to enter skin from the peripheral circulation, patrol within tissue, and migrate through lymphatics to draining lymph nodes. Skin APCs are endowed with antigen sensing, processing, and presenting machinery and play key roles in initiating, modulating, and resolving cutaneous inflammation. Skin APCs are a highly heterogeneous population with functionally specialized subsets that are developmentally imprinted and modulated by local tissue microenvironmental and inflammatory cues. This review explores recent advances that have allowed for a more accurate taxonomy of APC subsets found in both mouse and human skin. It also examines the functional specificity of individual APC subsets and their collaboration with other immune cell types that together promote adaptive T cell and regional cutaneous immune responses during homeostasis, inflammation, and disease. Expected final online publication date for the Annual Review of Immunology Volume 35 is April 26, 2017 . Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  10. TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds.

    PubMed

    Qi, Yu; Jiang, Dongsheng; Sindrilaru, Anca; Stegemann, Agatha; Schatz, Susanne; Treiber, Nicolai; Rojewski, Markus; Schrezenmeier, Hubert; Vander Beken, Seppe; Wlaschek, Meinhard; Böhm, Markus; Seitz, Andreas; Scholz, Natalie; Dürselen, Lutz; Brinckmann, Jürgen; Ignatius, Anita; Scharffetter-Kochanek, Karin

    2014-02-01

    Proper activation of macrophages (Mφ) in the inflammatory phase of acute wound healing is essential for physiological tissue repair. However, there is a strong indication that robust Mφ inflammatory responses may be causal for the fibrotic response always accompanying adult wound healing. Using a complementary approach of in vitro and in vivo studies, we here addressed the question of whether mesenchymal stem cells (MSCs)-due to their anti-inflammatory properties-would control Mφ activation and tissue fibrosis in a murine model of full-thickness skin wounds. We have shown that the tumor necrosis factor-α (TNF-α)-stimulated protein 6 (TSG-6) released from MSCs in co-culture with activated Mφ or following injection into wound margins suppressed the release of TNF-α from activated Mφ and concomitantly induced a switch from a high to an anti-fibrotic low transforming growth factor-β1 (TGF-β1)/TGF-β3 ratio. This study provides insight into what we believe to be a previously undescribed multifaceted role of MSC-released TSG-6 in wound healing. MSC-released TSG-6 was identified to improve wound healing by limiting Mφ activation, inflammation, and fibrosis. TSG-6 and MSC-based therapies may thus qualify as promising strategies to enhance tissue repair and to prevent excessive tissue fibrosis.

  11. Effect of diabetes and fasting on GLUT-4 (muscle/fat) glucose-transporter expression in insulin-sensitive tissues. Heterogeneous response in heart, red and white muscle.

    PubMed Central

    Camps, M; Castelló, A; Muñoz, P; Monfar, M; Testar, X; Palacín, M; Zorzano, A

    1992-01-01

    1. GLUT-4 glucose-transporter protein and mRNA levels were assessed in heart, red muscle and white muscle, as well as in brown and white adipose tissue from 7-day streptozotocin-induced diabetic and 48 h-fasted rats. 2. In agreement with previous data, white adipose tissue showed a substantial decrease in GLUT-4 mRNA and protein levels in response to both diabetes and fasting. Similarly, GLUT-4 mRNA and protein markedly decreased in brown adipose tissue in both insulinopenic conditions. 3. Under control conditions, the level of expression of GLUT-4 protein content differed substantially in heart, red and white skeletal muscle. Thus GLUT-4 protein was maximal in heart, and red muscle had a greater GLUT-4 content compared with white muscle. In spite of the large differences in GLUT-4 protein content, GLUT-4 mRNA levels were equivalent in heart and red skeletal muscle. 4. In heart, GLUT-4 mRNA decreased to a greater extent than GLUT-4 protein in response to diabetes and fasting. In contrast, red muscle showed a greater decrease in GLUT-4 protein than in mRNA in response to diabetes or fasting, and in fact no decrease in GLUT-4 mRNA content was detectable in fasting. On the other hand, preparations of white skeletal muscle showed a substantial increase in GLUT-4 mRNA under both insulinopenic conditions, and that was concomitant to either a modest decrease in GLUT-4 protein in diabetes or to no change in fasting. 5. These results indicate that (a) the effects of diabetes and fasting are almost identical and lead to changes in GLUT-4 expression that are tissue-specific, (b) white adipose tissue, brown adipose tissue and heart respond similarly to insulin deficiency by decreasing GLUT-4 mRNA to a larger extent than GLUT-4 protein, and (c) red and white skeletal muscle respond to insulinopenic conditions in a heterogeneous manner which is characterized by enhanced GLUT-4 mRNA/protein ratios. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:1554359

  12. Inactivation of Human Nevus Tissue Using High Hydrostatic Pressure for Autologous Skin Reconstruction: A Novel Treatment for Giant Congenital Melanocytic Nevi.

    PubMed

    Jinno, Chizuru; Morimoto, Naoki; Mahara, Atsushi; Liem, Pham Hieu; Sakamoto, Michiharu; Ogino, Shuichi; Kakudo, Natsuko; Inoie, Masukazu; Fujisato, Toshia; Kusumoto, Kenji; Suzuki, Shigehiko; Yamaoka, Tetsuji

    2015-11-01

    Giant congenital melanocytic nevi are intractable lesions associated with a risk of melanoma. High hydrostatic pressure (HHP) technology is a safe physical method for producing decellularized tissues without chemicals. We have reported that HHP can inactivate cells present in various tissues without damaging the native extracellular matrix (ECM). The objectives of this study were to inactivate human nevus tissue using HHP and to explore the possibility of reconstructing skin using inactivated nevus in combination with cultured epidermis (CE). Human nevus specimens 8 mm in diameter were pressurized by HHP at 100, 200, 500, and 1000 MPa for 10 min. The viability of specimens just after HHP, outgrowth of cells, and viability after cultivation were evaluated to confirm the inactivation by HHP. Histological evaluation using hematoxylin-eosin staining and immunohistochemical staining for type IV collagen was performed to detect damage to the ECM of the nevus. The pressurized nevus was implanted into the subcutis of nude mice for 6 months to evaluate the retention of human cells. Then, human CE was applied on the pressurized nevus and implanted into the subcutis of nude mice. The viability of pressurized nevus was not detected just after HHP and after cultivation, and outgrowth of fibroblasts was not observed in the 200, 500, and 1000 MPa groups. Human cells were not observed after 6 months of implantation in these groups. No apparent damage to the ECM was detected in all groups; however, CE took on nevus in the 200 and 500 MPa groups, but not in the 1000 MPa group. These results indicate that human nevus tissue was inactivated by HHP at more than 200 MPa; however, HHP at 1000 MPa might cause damage that prevents the take of CE. In conclusion, all cells in nevus specimens were inactivated after HHP at more than 200 MPa and this inactivated nevus could be used as autologous dermis for covering full-thickness skin defects after nevus removal. HHP between 200 and 500 MPa

  13. Effects of Diaspirin Crosslinked Hemoglobin (DCLHb) on microcirculation and local tissue pO2 of striated skin muscle following resuscitation from hemorrhagic shock.

    PubMed

    Hungerer, Sven; Nolte, Dirk; Botzlar, Andreas; Messmer, Konrad

    2006-01-01

    The hemoglobin based oxygen carrier (HBOC) Diaspirin Crosslinked Hemoglobin (DCLHb) has been developed to substitute not only the blood volume, but also to restore the oxygen-carrying properties of blood during hemorrhagic shock. However, it has been suggested that HBOCs may enhance the formation of free oxygen radicals through the release of free iron ions via the Haber-Weiss reaction. The aim of this study was to investigate the effects of DCLHb on the microcirculation, leukocyte-endothelial cell interaction and local tissue oxygenation in striated skin muscle of Syrian golden hamsters during and after resuscitation from hemorrhagic shock. In particular we focused on the local tissue oxygenation after resuscitation with DCLHb (hemoglobin content 10 g%) compared to resuscitation using autologous blood diluted to a hemoglobin content of 10 g%. Hemorrhagic shock was induced for 45 minutes by bleeding the animals at a rate of 33 ml/kg BW maintaining a mean arterial pressure of 30 +/- 5 mmHg. Animals were resuscitated either with 33 ml/kg BW 6% Dextran-60.000 or with 10 g% DCLHb. The control group received shed blood diluted with Ringers to a hemoglobin content of 10 g%. Intravital microscopy was used for investigation of the microcirculatory parameters and a multiwire platinum surface electrode for measurement of local tissue pO2 in striated skin muscle in the dorsal skinfold chamber of Syrian golden hamsters. Resuscitation from hemorrhagic shock with 10 g% AUB revealed significant increase of leukocytes rolling in postcapillary venules at 30 to 120 minutes after resuscitation compared to baseline values. DCLHb turned out to reduce the number of firmly adherent leukocytes after resuscitation compared to 10 g% AUB. Microvascular permeability as an indicator for functional endothelial integrity revealed no significant differences between the groups. DCLHb and 10 g% AUB led to a significant increase in local tissue oxygenation after resuscitation from hemorrhagic shock

  14. Comparison of structural changes in skin and amnion tissue grafts for transplantation induced by gamma and electron beam irradiation for sterilization.

    PubMed

    Mrázová, H; Koller, J; Kubišová, K; Fujeríková, G; Klincová, E; Babál, P

    2016-06-01

    Sterilization is an important step in the preparation of biological material for transplantation. The aim of the study is to compare morphological changes in three types of biological tissues induced by different doses of gamma and electron beam radiation. Frozen biological tissues (porcine skin xenografts, human skin allografts and human amnion) were irradiated with different doses of gamma rays (12.5, 25, 35, 50 kGy) and electron beam (15, 25, 50 kGy). Not irradiated specimens served as controls. The tissue samples were then thawn and fixed in 10 % formalin, processed by routine paraffin technique and stained with hematoxylin and eosin, alcian blue at pH 2.5, orcein, periodic acid Schiff reaction, phosphotungstic acid hematoxylin, Sirius red and silver impregnation. The staining with hematoxylin and eosin showed vacuolar cytoplasmic changes of epidermal cells mainly in the samples of xenografts irradiated by the lowest doses of gamma and electron beam radiation. The staining with orcein revealed damage of fine elastic fibers in the xenograft dermis at the dose of 25 kGy of both radiation types. Disintegration of epithelial basement membrane, especially in the xenografts, was induced by the dose of 15 kGy of electron beam radiation. The silver impregnation disclosed nuclear chromatin condensation mainly in human amnion at the lowest doses of both radiation types and disintegration of the fine collagen fibers in the papillary dermis induced by the lowest dose of electron beam and by the higher doses of gamma radiation. Irradiation by both, gamma rays and the electron beam, causes similar changes on cells and extracellular matrix, with significant damage of the basement membrane and of the fine and elastic and collagen fibers in the papillary dermis, the last caused already by low dose electron beam radiation.

  15. Skin Diseases: Skin Health and Skin Diseases

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...

  16. Tissue heterogeneity in structure and conductivity contribute to cell survival during irreversible electroporation ablation by ``electric field sinks''

    NASA Astrophysics Data System (ADS)

    Golberg, Alexander; Bruinsma, Bote G.; Uygun, Basak E.; Yarmush, Martin L.

    2015-02-01

    Irreversible electroporation (IRE) is an emerging, minimally invasive technique for solid tumors ablation, under clinical investigation for cancer therapy. IRE affects only the cell membrane, killing cells while preserving the extracellular matrix structure. Current reports indicate tumors recurrence rate after IRE averaging 31% of the cases, of which 10% are local recurrences. The mechanisms for these recurrences are not known and new explanations for incomplete cell death are needed. Using finite elements method for electric field distribution, we show that presence of vascular structures with blood leads to the redistribution of electric fields leading to the areas with more than 60% reduced electric field strength in proximity to large blood vessels and clustered vessel structures. In an in vivo rat model of liver IRE ablation, we show that cells located in the proximity of larger vessel structures and in proximity of clustered vessel structures appear less affected by IRE ablation than cells in the tissue parenchyma or in the proximity of small, more isolated vessels. These findings suggest a role for ``electric field sinks'' in local tumors recurrences after IRE and emphasize the importance of the precise mapping of the targeted organ structure and conductivity for planning of electroporation procedures.

  17. Tissue heterogeneity in structure and conductivity contribute to cell survival during irreversible electroporation ablation by "electric field sinks".

    PubMed

    Golberg, Alexander; Bruinsma, Bote G; Uygun, Basak E; Yarmush, Martin L

    2015-02-16

    Irreversible electroporation (IRE) is an emerging, minimally invasive technique for solid tumors ablation, under clinical investigation for cancer therapy. IRE affects only the cell membrane, killing cells while preserving the extracellular matrix structure. Current reports indicate tumors recurrence rate after IRE averaging 31% of the cases, of which 10% are local recurrences. The mechanisms for these recurrences are not known and new explanations for incomplete cell death are needed. Using finite elements method for electric field distribution, we show that presence of vascular structures with blood leads to the redistribution of electric fields leading to the areas with more than 60% reduced electric field strength in proximity to large blood vessels and clustered vessel structures. In an in vivo rat model of liver IRE ablation, we show that cells located in the proximity of larger vessel structures and in proximity of clustered vessel structures appear less affected by IRE ablation than cells in the tissue parenchyma or in the proximity of small, more isolated vessels. These findings suggest a role for "electric field sinks" in local tumors recurrences after IRE and emphasize the importance of the precise mapping of the targeted organ structure and conductivity for planning of electroporation procedures.

  18. Tissue heterogeneity in structure and conductivity contribute to cell survival during irreversible electroporation ablation by “electric field sinks”

    PubMed Central

    Golberg, Alexander; Bruinsma, Bote G.; Uygun, Basak E.; Yarmush, Martin L.

    2015-01-01

    Irreversible electroporation (IRE) is an emerging, minimally invasive technique for solid tumors ablation, under clinical investigation for cancer therapy. IRE affects only the cell membrane, killing cells while preserving the extracellular matrix structure. Current reports indicate tumors recurrence rate after IRE averaging 31% of the cases, of which 10% are local recurrences. The mechanisms for these recurrences are not known and new explanations for incomplete cell death are needed. Using finite elements method for electric field distribution, we show that presence of vascular structures with blood leads to the redistribution of electric fields leading to the areas with more than 60% reduced electric field strength in proximity to large blood vessels and clustered vessel structures. In an in vivo rat model of liver IRE ablation, we show that cells located in the proximity of larger vessel structures and in proximity of clustered vessel structures appear less affected by IRE ablation than cells in the tissue parenchyma or in the proximity of small, more isolated vessels. These findings suggest a role for “electric field sinks” in local tumors recurrences after IRE and emphasize the importance of the precise mapping of the targeted organ structure and conductivity for planning of electroporation procedures. PMID:25684630

  19. Absorption of Iontophoresis-Driven 2% Lidocaine With Epinephrine in the Tissues at 5 mm Below the Surface of the Skin

    PubMed Central

    Draper, David O.; Coglianese, Mark; Castel, Chris

    2011-01-01

    Context: In a recent study, we were unable to measure lidocaine in the human calf at a 5-mm depth via iontophoresis. We surmised that this might be due to a lack of epinephrine in the compound. Because epinephrine is a vasoconstrictor, it might allow the drug to pass beyond the capillaries and be delivered to the deeper tissues. Objective: To determine if iontophoresis could deliver lidocaine with epinephrine 5 mm under the surface of human skin, as measured by microdialysis. Design: Descriptive laboratory study. Setting: Therapeutic modalities research laboratory. Patients or Other Participants: Ten volunteers (5 males, 5 females; age, 15–28 years) with less than 5 mm of adipose tissue in the area we measured and with no allergies to lidocaine participated. The measurement area had been free of any injury, swelling, or infection for at least 3 months before the study. Intervention(s): We inserted a microdialysis probe 0.5 cm under the skin of the right lower leg. Next, microdialysis was performed through this area for 60 minutes, which allowed local skin blood flow to return to baseline. We then performed iontophoresis at 40 mA/min using 2 mL of 2% lidocaine. Iontophoresis was performed over this area for 10.5 minutes to collect the lidocaine samples. After this stage, the electrode was left in place for another 50 minutes for a total of 60 minutes. Main Outcome Measure(s): The samples of the drug were analyzed via reverse-phase high-performance liquid chromatography (RP-HPLC) in the chemistry department. Results: The RP-HPLC analysis confirmed the presence of lidocaine in all 10 participants. The mean concentration of lidocaine detected at the 5-mm depth was calculated as 3.63 mg/mL (greater than 18% of delivered concentration). Conclusions: We found that 2% lidocaine can be delivered up to 5 mm below the surface of the skin when the drug compound contains epinephrine and when passive delivery occurs for at least 50 minutes after the active delivery has

  20. Bimodal spectroscopy for in vivo characterization of hypertrophic skin tissue: pre-clinical experimentation, spectral data selection and classification

    NASA Astrophysics Data System (ADS)

    Liu, Honghui; Gisquet, Héloïse; Guillemin, F.; Blondel, Walter C. P. M.

    2011-07-01

    Objective: The objective of this study was two folds: firstly, we would like to investigate the efficiency of bimodal spectroscopic technique in characterization of hypertrophic scarring tissue deliberately created on a preclinical model (rabbit's ear); on the other hand, we evaluate the inhibition effect of an anti-inflammatory medication (tacrolimus) on hypertrophic formation in scar by using our bimodal spectroscopic system. Study design: This study was conducted on 20 New Zealand Rabbits receiving hypertrophic scarring treatment on their ears. Fluorescence and Diffuse Reflectance spectra were collected from each scar, amongst which some had received tacrolimus treatment. Features were extracted from corrected spectral data and analyzed to classify the scarring tissues into hypertrophic or non-hypertrophic. Diagnostic algorithms were developed with the use of k-NN classifier and validated by comparing to histological classification result with Leave-one- out cross validation. Results and discussion: The accuracy of our bimodal spectroscopy method for detecting hypertrophic scarring scar tissue was good (sensibility: 90.84%, specificity: 94.44%). The features used for classification were mainly extracted from the spectra exited at 360, 410 and 420 nm. This indicates that the difference between the spectra acquired from hypertrophic and non-hypertrophic tissue may be due to the different intensity distribution of several fluorophores (collagen,elastin and NADH) excited in this range, or to the change in proportion of tissue layers (epidermis and dermis) explored by the CEFS in use.

  1. UVA exposure of human skin reconstructed in vitro induces apoptosis of dermal fibroblasts: subsequent connective tissue repair and implications in photoaging.

    PubMed

    Bernerd, F; Asselineau, D

    1998-09-01

    The skin reconstructed in vitro has been previously shown to be a useful model to investigate the effects of UVB exposure (Bernerd and Asselineau, 1997). The present study describes the response to UVA irradiation. Major alterations were observed within the dermal compartment. Apoptosis of fibroblasts located in the superficial area of the dermal equivalent was observed as soon as 6 h after irradiation, leading to their disappearance after 48 h. This effect was obtained without major alterations of epidermal keratinocytes suggesting a differential cell type sensitivity to UVA radiations. In addition, collagenase I was secreted by dermal fibroblasts. The UVA dermal effects could be observed even after removal of the epidermis during the post irradiation period, demonstrating that they were independent of the keratinocyte response. The analysis of the tissue regeneration during the following 2 weeks revealed a connective tissue repair via fibroblasts proliferation, migration and active synthesis of extracellular matrix proteins such as fibronectin and procollagen I. This cellular recolonization of the superficial part of the dermal equivalent was due to activation of surviving fibroblasts located deeply in the dermal equivalent. The direct damage in the dermis and the subsequent connective tissue repair may contribute to the formation of UVA-induced dermal alterations.

  2. Effect of tissue-engineered chitosan-poly(vinyl alcohol) nanofibrous scaffolds on healing of burn wounds of rat skin.

    PubMed

    Gholipour-Kanani, A; Bahrami, S H; Samadi-Kochaksaraie, A; Ahmadi-Tafti, H; Rabbani, S; Kororian, A; Erfani, E

    2012-12-01

    Chitosan-poly(vinyl alcohol) (Cs:PVA) nanofibrous scaffolds were electrospun from 2:3 (wt/wt) Cs:PVA solution dissolved in 80% acetic acid. In vivo study was carried out on the dorsum skin of rat which burnt with a hot brass cylinder. The scaffolds were applied in two forms, that is, acellular (n=6) and cell-seeded with mesenchymal stem cells (n=6). Macroscopic measurements of wound area showed good aspect healing effect of scaffolds in comparison with control wounds specially in 15 days post operating. Pathological studies were done on the wounds to investigate the healing effects. The healing process of the wound covered with Cs/PVA nanofibrous scaffolds was much rapid compared to untreated wounds. However, the presence of stem cells on this scaffolds accelerated the wound healing process owing to their ability of collagen regeneration.

  3. Dual Effects of Bisphosphonates on Ectopic Skin and Vascular Soft Tissue Mineralization versus Bone Microarchitecture in a Mouse Model of Generalized Arterial Calcification of Infancy.

    PubMed

    Li, Qiaoli; Kingman, Joshua; Sundberg, John P; Levine, Michael A; Uitto, Jouni

    2016-01-01

    Generalized arterial calcification of infancy is an intractable ectopic mineralization disorder caused by mutations in the ENPP1 gene, resulting in reduced plasma inorganic pyrophosphate (PPi) levels. We previously characterized the Enpp1(asj) mutant mouse as a model of generalized arterial calcification of infancy, and we have now explored the potential efficacy of bisphosphonates, nonhydrolyzable PPi analogs, in preventing ectopic mineralization in these mice. The mice were maintained on either basic diet (control) or diets containing etidronate or alendronate in three different concentrations (experimental). Considering low bioavailability of bisphosphonates when administered orally, subsequent studies tested the mice with subcutaneous injections of etidronate. The treatments were initiated at 4 weeks of age, and the degree of mineralization was assessed at 12 weeks of age by quantitation of calcium deposits in the muzzle skin containing dermal sheath of vibrissae and in aorta. We found that bisphosphonate treatments significantly reduced mineralization in skin and aorta. These changes in treated mice were accompanied with restoration of their bone microarchitecture, determined by microcomputed tomography. The inhibitory capacity of bisphosphonates, with mechanistic implications, was confirmed in a cell-based mineralization assay in vitro. Collectively, these results suggest that bisphosphonate treatment may be beneficial by a dual effect for preventing ectopic soft tissue mineralization while correcting decreased bone mineralization in generalized arterial calcification of infancy caused by ENPP1 mutations.

  4. Surveillance of physician-diagnosed skin and soft tissue infections consistent with methicillin-resistant Staphylococcus aureus (MRSA) among Nebraska high school athletes, 2008-2012.

    PubMed

    Buss, Bryan F; Connolly, Susan

    2014-02-01

    Though historically confined to hospital settings, methicillin-resistant Staphylococcus aureus (MRSA) has received increasing attention in the wider community, particularly among athletes. A 2007-2008 investigation in Nebraska concluded that MRSA skin infections were an emerging problem among the state's student athletes. Statewide surveillance was subsequently conducted during 4 school years (2008-2012) to estimate incidence of skin and soft tissue infections (SSTI) consistent with MRSA among student athletes. High school athletic officials completed Internet-based surveys following winter and fall sport seasons. Over 3 school years, incidence estimates per 10,000 athletes decreased substantially from 20.9 (2008-2009) to 11.3 (2010-2011) among football players and from 60.8 (2008-2009) to 28.1 (2010-2011) among wrestlers. Following the 2011-2012 sport seasons, however, incidence estimates increased to 16.6 per 10,000 football players and 43.3 per 10,000 wrestlers. School nurses should support school officials to prioritize prevention and control efforts for SSTI, including MRSA.

  5. Pathophysiology and burden of infection in patients with diabetes mellitus and peripheral vascular disease: focus on skin and soft-tissue infections.

    PubMed

    Dryden, M; Baguneid, M; Eckmann, C; Corman, S; Stephens, J; Solem, C; Li, J; Charbonneau, C; Baillon-Plot, N; Haider, S

    2015-09-01

    Diabetes mellitus affects 284 million adults worldwide and is increasing in prevalence. Accelerated atherosclerosis in patients with diabetes mellitus contributes an increased risk of developing cardiovascular diseases including peripheral vascular disease (PVD). Immune dysfunction, diabetic neuropathy and poor circulation in patients with diabetes mellitus, especially those with PVD, place these patients at high risk for many types of typical and atypical infections. Complicated skin and soft-tissue infections (cSSTIs) are of particular concern because skin breakdown in patients with advanced diabetes mellitus and PVD provides a portal of entry for bacteria. Patients with diabetes mellitus are more likely to be hospitalized with cSSTIs and to experience related complications than patients without diabetes mellitus. Patients with PVD requiring lower extremity bypass are also at high risk of surgical site and graft infections. Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent causative pathogen in cSSTIs, and may be a significant contributor to surgical site infections, especially in patients who are colonized with MRSA on hospital admission. Patients with cSSTIs and diabetes mellitus or PVD experience lower clinical success rates than patients without these comorbidities, and may also have a longer length of hospital stay and higher risk of adverse drug events. Clinicians should be vigilant in recognizing the potential for infection with multi-drug-resistant organisms, especially MRSA, in these populations and initiating therapy with appropriate antibiotics.

  6. Targeting Staphylococcus aureus α-Toxin as a Novel Approach to Reduce Severity of Recurrent Skin and Soft-Tissue Infections

    PubMed Central

    Sampedro, Georgia R.; DeDent, Andrea C.; Becker, Russell E. N.; Berube, Bryan J.; Gebhardt, Michael J.; Cao, Hongyuan; Bubeck Wardenburg, Juliane

    2014-01-01

    Staphyococcus aureus frequently causes recurrent skin and soft-tissue infection (SSTI). In the pediatric population, elevated serum antibody targeting S. aureus α-toxin is correlated with a reduced incidence of recurrent SSTI. Using a novel model of recurrent SSTI, we demonstrated that expression of α-toxin during primary infection increases the severity of recurrent disease. Antagonism of α-toxin by either a dominant-negative toxin mutant or a small molecule inhibitor of the toxin receptor ADAM10 during primary infection reduces reinfection abscess severity. Early neutralization of α-toxin activity during S. aureus SSTI therefore offers a new therapeutic strategy to mitigate primary and recurrent disease. PMID:24740631

  7. Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation.

    PubMed

    Burnworth, B; Popp, S; Stark, H-J; Steinkraus, V; Bröcker, E B; Hartschuh, W; Birek, C; Boukamp, P

    2006-07-27

    Non-melanoma skin cancers, in particular keratoacanthomas (KAs) and squamous cell carcinomas (SCCs), have become highly frequent tumor types especially in immune-suppressed transplant patients. Nevertheless, little is known about essential genetic changes. As a paradigm of 'early' changes, that is, changes still compatible with tumor regression, we studied KAs by comparative genomic hybridization and show that gain of chromosome 11q is not only one of the most frequent aberration (8/18), but in four tumors also the only aberration. Furthermore, 11q gain correlated with amplification of the cyclin D1 locus (10/14), as determined by fluorescence in situ hybridization, and overexpression of cyclin D1 protein (25/31), as detected by immunohistochemistry. For unraveling the functional consequence, we overexpressed cyclin D1 in HaCaT skin keratinocytes. These cells only gained little growth advantage in conventional and in organotypic co-cultures. However, although the control vector-transfected cells formed a well-stratified and orderly differentiated epidermis-like epithelium, they showed deregulation of tissue architecture with an altered localization of proliferation and impaired differentiation. The most severe phenotype was seen in a clone that additionally upregulated cdk4 and p21. These cells lacked terminal differentiation, exhibited a more autonomous growth in vitro and in vivo and even formed tumors in two injection sites with a growth pattern resembling that of human KAs. Thus, our results identify 11q13 gain/cyclin D1 overexpression as an important step in KA formation and point to a function that exceeds its known role in proliferation by disrupting tissue organization and thereby allowing abnormal growth.

  8. Oxygenation and perfusion monitoring with a hyperspectral camera system for chemical based tissue analysis of skin and organs.

    PubMed

    Holmer, Amadeus; Tetschke, Florian; Marotz, Jörg; Malberg, Hagen; Markgraf, Wenke; Thiele, Christine; Kulcke, Axel

    2016-11-01

    The monitoring of free flaps, free transplants or organs for transplantation still poses a problem in medicine. Available systems for the measurement of perfusion and oxygenation can only perform localized measurements and usually need contact with the tissue. Contact free hyperspectral imaging and near-infrared spectroscopy (NIRS) for the analysis of tissue oxygenation and perfusion have been used in many scientific studies with good results. But up to now the clinical and scientific application of this technology has been hindered by the lack of hyperspectral measurement systems usable in clinical practice. We will introduce the application of a new hyperspectral camera system for the quick and robust recording of remission spectra in the combined VIS and NIR spectral range with high spectral and spatial resolution. This new system can be applied for the clinical monitoring of free flaps and organs providing high quality oxygenation and perfusion images.

  9. Longitudinal label-free tracking of cell death dynamics in living engineered human skin tissue with a multimodal microscope

    PubMed Central

    Zhao, Youbo; Marjanovic, Marina; Chaney, Eric J.; Graf, Benedikt W.; Mahmassani, Ziad; Boppart, Marni D.; Boppart, Stephen A.

    2014-01-01

    We demonstrate real-time, longitudinal, label-free tracking of apoptotic and necrotic cells in living tissue using a multimodal microscope. The integrated imaging platform combines multi-photon microscopy (MPM, based on two-photon excitation fluorescence), optical coherence microscopy (OCM), and fluorescence lifetime imaging microscopy (FLIM). Three-dimensional (3-D) co-registered images are captured that carry comprehensive information of the sample, including structural, molecular, and metabolic properties, based on light scattering, autofluorescence intensity, and autofluorescence lifetime, respectively. Different cell death processes, namely, apoptosis and necrosis, of keratinocytes from different epidermal layers are longitudinally monitored and investigated. Differentiation of the two cell death processes in a complex living tissue environment is enabled by quantitative image analysis and high-confidence classification processing based on the multidimensional, cross-validating imaging data. These results suggest that despite the limitations of each individual label-free modality, this multimodal imaging approach holds the promise for studies of different cell death processes in living tissue and in vivo organs. PMID:25360383

  10. Differences in Gene Expression and Cytokine Release Profiles Highlight the Heterogeneity of Distinct Subsets of Adipose Tissue-Derived Stem Cells in the Subcutaneous and Visceral Adipose Tissue in Humans

    PubMed Central

    Perrini, Sebastio; Ficarella, Romina; Picardi, Ernesto; Cignarelli, Angelo; Barbaro, Maria; Nigro, Pasquale; Peschechera, Alessandro; Palumbo, Orazio; Carella, Massimo; De Fazio, Michele; Natalicchio, Annalisa; Laviola, Luigi; Pesole, Graziano; Giorgino, Francesco

    2013-01-01

    Differences in the inherent properties of adipose tissue-derived stem cells (ASC) may contribute to the biological specificity of the subcutaneous (Sc) and visceral (V) adipose tissue depots. In this study, three distinct subpopulations of ASC, i.e. ASCSVF, ASCBottom, and ASCCeiling, were isolated from Sc and V fat biopsies of non-obese subjects, and their gene expression and functional characteristics were investigated. Genome-wide mRNA expression profiles of ASCSVF, ASCBottom and ASCCeiling from Sc fat were significantly different as compared to their homologous subsets of V-ASCs. Furthermore, ASCSVF, ASCCeiling and ASCBottom from the same fat depot were also distinct from each other. In this respect, both principal component analysis and hierarchical clusters analysis showed that ASCCeiling and ASCSVF shared a similar pattern of closely related genes, which was highly different when compared to that of ASCBottom. However, larger variations in gene expression were found in inter-depot than in intra-depot comparisons. The analysis of connectivity of genes differently expressed in each ASC subset demonstrated that, although there was some overlap, there was also a clear distinction between each Sc-ASC and their corresponding V-ASC subsets, and among ASCSVF, ASCBottom, and ASCCeiling of Sc or V fat depots in regard to networks associated with regulation of cell cycle, cell organization and development, inflammation and metabolic responses. Finally, the release of several cytokines and growth factors in the ASC cultured medium also showed both inter- and intra-depot differences. Thus, ASCCeiling and ASCBottom can be identified as two genetically and functionally heterogeneous ASC populations in addition to the ASCSVF, with ASCBottom showing the highest degree of unmatched gene expression. On the other hand, inter-depot seem to prevail over intra-depot differences in the ASC gene expression assets and network functions, contributing to the high degree of specificity

  11. Depletion of the chloramine-T marker residue, para-toluenesulfonamide, from skin-on fillet tissue of hybrid striped bass, rainbow trout, and yellow perch

    USGS Publications Warehouse

    Meinertz, J.R.; Stehly, G.R.; Greseth, Shari L.; Gaikowski, M.P.; Gingerich, W.H.

    2004-01-01

    Waterborne exposure to n-sodium-n-chloro-p-toluenesulfonamide (chloramine-T) is an effective treatment for controlling fish mortalities caused by bacterial gill disease (BGD). Currently, data are being generated to gain United States Food and Drug Administration (FDA) approval for the use of chloramine-T in aquaculture. As part of the data required for an approval, depletion of the chloramine-T marker residue (para-toluenesulfonamide [p-TSA]) from the edible fillet tissue of exposed fish must be determined. Hybrid striped bass (Morone saxatilis??Morone chrysops; mean weight 357 g), rainbow trout (Oncorhynchus mykiss; mean weight 457 g), and yellow perch (Perca flavescens; mean weight 144 g) were exposed to 20 mg/l of chloramine-T for 60 min on 4 consecutive days (the most aggressive treatment expected for approved use in the United States). Groups of fish (n=15 or 19) were sampled immediately after the last treatment and periodically through 48 or 168 h after the treatment phase. Duplicate subsamples of skin-on fillet tissue from each fish were analyzed for p-TSA. Mean p-TSA concentrations in fillet tissue from fish sampled immediately after the last treatment were 142 ng/g (hybrid striped bass), 97 ng/g (rainbow trout), and 150 ng/g (yellow perch). Mean p-TSA concentrations at terminal sample times were 94 (168 h; hybrid striped bass), 74 (48 h; rainbow trout), and 35 ng/g (168 h; yellow perch). The half-lives of p-TSA in fillet tissue from fish near or at market size were 11.4 (hybrid striped bass), 4.3 (rainbow trout), and 3.2 days (yellow perch).

  12. Three-Dimensional In Vitro Skin and Skin Cancer Models Based on Human Fibroblast-Derived Matrix.

    PubMed

    Berning, Manuel; Prätzel-Wunder, Silke; Bickenbach, Jackie R; Boukamp, Petra

    2015-09-01

    Three-dimensional in vitro skin and skin cancer models help to dissect epidermal-dermal and tumor-stroma interactions. In the model presented here, normal human dermal fibroblasts isolated from adult skin self-assembled into dermal equivalents with their specific fibroblast-derived matrix (fdmDE) over 4 weeks. The fdmDE represented a complex human extracellular matrix that was stabilized by its own heterogeneous collagen fiber meshwork, largely resembling a human dermal in vivo architecture. Complemented with normal human epidermal keratinocytes, the skin equivalent (fdmSE) thereof favored the establishment of a well-stratified and differentiated epidermis and importantly allowed epidermal regeneration in vitro for at least 24 weeks. Moreover, the fdmDE could be used to study the features of cutaneous skin cancer. Complementing fdmDE with HaCaT cells in different stages of malignancy or tumor-derived cutaneous squamous cell carcinoma cell lines, the resulting skin cancer equivalents (fdmSCEs) recapitulated the respective degree of tumorigenicity. In addition, the fdmSCE invasion phenotypes correlated with their individual degree of tissue organization, disturbance in basement membrane organization, and presence of matrix metalloproteinases. Together, fdmDE-based models are well suited for long-term regeneration of normal human epidermis and, as they recapitulate tumor-specific growth, differentiation, and invasion profiles of cutaneous skin cancer cells, also provide an excellent human in vitro skin cancer model.

  13. Elemental analysis of tissue pellets for the differentiation of epidermal lesion and normal skin by laser-induced breakdown spectroscopy

    PubMed Central

    Moon, Youngmin; Han, Jung Hyun; Shin, Sungho; Kim, Yong-Chul; Jeong, Sungho

    2016-01-01

    By laser induced breakdown spectroscopy (LIBS) analysis of epidermal lesion and dermis tissue pellets of hairless mouse, it is shown that Ca intensity in the epidermal lesion is higher than that in dermis, whereas Na and K intensities have an opposite tendency. It is demonstrated that epidermal lesion and normal dermis can be differentiated with high selectivity either by univariate or multivariate analysis of LIBS spectra with an intensity ratio difference by factor of 8 or classification accuracy over 0.995, respectively. PMID:27231610

  14. Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia

    PubMed Central

    Harder, Yves; Schmauss, Daniel; Wettstein, Reto; Egaña, José T.; Weiss, Fabian; Weinzierl, Andrea; Schuldt, Anna; Machens, Hans-Günther; Menger, Michael D.; Rezaeian, Farid

    2014-01-01

    Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are still occurring, particularly in reconstructive flap surgery. Multiple experimental flap models have been developed to analyze underlying causes and mechanisms and to investigate treatment strategies to prevent ischemic complications. The limiting factor of most models is the lacking possibility to directly and repetitively visualize microvascular architecture and hemodynamics. The goal of the protocol was to present a well-established mouse model affiliating these before mentioned lacking elements. Harder et al. have developed a model of a musculocutaneous flap with a random perfusion pattern that undergoes acute persistent ischemia and results in ~50% necrosis after 10 days if kept untreated. With the aid of intravital epi-fluorescence microscopy, this chamber model allows repetitive visualization of morphology and hemodynamics in different regions of interest over time. Associated processes such as apoptosis, inflammation, microvascular leakage and angiogenesis can be investigated and correlated to immunohistochemical and molecular protein assays. To date, the model has proven feasibility and reproducibility in several published experimental studies investigating the effect of pre-, peri- and postconditioning of ischemically challenged tissue. PMID:25489743

  15. Cell Type-dependent Gene Transcription Profile in Three Dimensional Human Skin Tissue Model Exposed to Low Doses of Ionizing Radiation: Implications for Medical Exposures

    SciTech Connect

    Freiin von Neubeck, Claere H.; Shankaran, Harish; Karin, Norman J.; Kauer, Paula M.; Chrisler, William B.; Wang, Xihai; Robinson, Robert J.; Waters, Katrina M.; Tilton, Susan C.; Sowa, Marianne B.

    2012-04-17

    The concern over possible health risks from exposures to low doses of ionizing radiation has been driven largely by the increase in medical exposures, the routine implementation of X-ray backscatter devices for airport security screening, and, most recently, the nuclear incident in Japan. Due to a paucity of direct epidemiological data at very low doses, cancer risk must be estimated from high dose exposure scenarios. However, there is increasing evidence that low and high dose exposures result in different signaling events and may have different mechanisms of cancer induction. We have examined the radiation induced temporal response of an in vitro three dimensional (3D) human skin tissue model using microarray-based transcriptional profiling. Our data shows that exposure to 100 mGy of X-rays is sufficient to affect gene transcription. Cell type specific analysis showed significant changes in gene expression with the levels of > 1400 genes altered in the dermis and > 400 genes regulated in the epidermis. The two cell types rarely exhibited overlapping responses at the mRNA level. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) measurements validated the microarray data in both regulation direction and value. Key pathways identified relate to cell cycle regulation, immune responses, hypoxia, reactive oxygen signaling, and DNA damage repair. We discuss in particular the role of proliferation and emphasizing how the disregulation of cellular signaling in normal tissue may impact progression towards radiation induced secondary diseases.

  16. Differential response of human adipose tissue-derived mesenchymal stem cells, dermal fibroblasts, and keratinocytes to burn wound exudates: potential role of skin-specific chemokine CCL27.

    PubMed

    van den Broek, Lenie J; Kroeze, Kim L; Waaijman, Taco; Breetveld, Melanie; Sampat-Sardjoepersad, Shakun C; Niessen, Frank B; Middelkoop, Esther; Scheper, Rik J; Gibbs, Susan

    2014-01-01

    Many cell-based regenerative medicine strategies toward tissue-engineered constructs are currently being explored. Cell-cell interactions and interactions with different biomaterials are extensively investigated, whereas very few studies address how cultured cells will interact with soluble wound-healing mediators that are present within the wound bed after transplantation. The aim of this study was to determine how adipose tissue-derived mesenchymal stem cells (ASC), dermal fibroblasts, and keratinocytes will react when they come in contact with the deep cutaneous burn wound bed. Burn wound exudates isolated from deep burn wounds were found to contain many cytokines, including chemokines and growth factors related to inflammation and wound healing. Seventeen mediators were identified by ELISA (concentration range 0.0006-9 ng/mg total protein), including the skin-specific chemokine CCL27. Burn wound exudates activated both ASC and dermal fibroblasts, but not keratinocytes, to increase secretion of CXCL1, CXCL8, CCL2, and CCL20. Notably, ASC but not fibroblasts or keratinocytes showed significant increased secretion of vascular endothelial growth factor (5-fold) and interleukin-6 (253-fold), although when the cells were incorporated in bi-layered skin substitute (SS) these differences were less pronounced. A similar discrepancy between ASC and dermal fibroblast mono-cultures was observed when recombinant human-CCL27 was used instead of burn wound exudates. Although CCL27 did not stimulate the secretion of any of the wound-healing mediators by keratinocytes, these cells, in contrast to ASC or dermal fibroblasts, showed increased proliferation and migration. Taken together, these results indicate that on transplantation, keratinocytes are primarily activated to promote wound closure. In contrast, dermal fibroblasts and, in particular, ASC respond vigorously to factors present in the wound bed, leading to increased secretion of angiogenesis/granulation tissue formation

  17. Skin Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Skin Cancer What is Skin Cancer? Skin cancer is the most common type ... of approximately 9,480 Americans in 2013. Can Skin Cancer Be Treated? Most basal cell and squamous ...

  18. [Skin diseases and obesity].

    PubMed

    Guerra-Segovia, Carolina; Ocampo-Candiani, Jorge

    2015-01-01

    Obesity is a public health problem worldwide. It predominates in industrialized countries; however, it is prevalent in all nations. It is defined as a condition of excess adipose tissue and is the result of changes in lifestyle, excessive consumption of energy-dense foods with poor nutritional value, physical inactivity and the reduction of open space where one can practice a sport. Although obesity is associated with multiple diseases, it is important to stress that the metabolic changes caused by it affect skin physiology and play a predisposing factor for the development of skin diseases. Very little has been studied on the impact of obesity on the skin. The purpose of this article is to review the most frequently skin diseases in obesity. Some skin pathologies in obesity are caused by changes in skin physiology, others are related to insulin resistance or constitute an exacerbating factor for dermatitis. This article covers the clinical features of obesity related skin disease and its management.

  19. The Mice Drawer System (MDS) Tissue Sharing Programme: effect of space conditions on skin metabolic activity and vascularization and potential impact of radiations in mice.

    NASA Astrophysics Data System (ADS)

    Nusgens, Betty; Lambert, Charles; Liu, Yi; Cancedda, Ranieri; Tavella, Sara; Ruggiu, Alessandra; Colige, Alain

    Our aim was to investigate the effect of prolonged microgravity on skin physiology in mice and to identify potentially altered metabolic and vascular parameters. Osteoporosis-induced microgravity is a well documented space flight problem in Man and animals.We have previously demonstrated that fibroblasts from the dermis also sense and react to mechanical forces issued from the surrounding extracellular matrix. Conversely, fibroblasts are able to remodel their environment by a dynamic process of synthesis and degradation. Fibroblasts and cells of the vascular network also react to soluble mediators secreted by the keratinocytes such as IL-1, IL-6, VEGF, .... Skin fibroblasts upon relaxation of mechanical tension adopt a catabolic phenotype and produce significant amount of IL-1 and IL-6, of various matrix metalloproteinases (MMP) while the collagen synthesis is reduced. In microgravity, we have shown that the expression of MMP-1 and IL-6 by dermal fibroblasts is increased indicating that cell might interpret micro-gravity as a mechanical relaxation. This concept is supported by a reduction of the actin stress fibers and focal adhesions in fibroblasts in microgravity. Altogether, microgravity might alter metabolic equilibrium of the skin and perhaps of other soft connective tissues such as tendons or interstitial matrix of internal organs. The Mice Drawer System (MDS) is an Italian Space Agency facility which is able to support mice onboard the International Space Station during long-duration exploration missions by providing living space, food, water, ventilation and light-ing. Details on the mission that took place from August 28, 2009 to November 27, 2009, can be found at the URL indicated below. A similar ground control mission has been performed using the same wild type and transgenic mice overexpressing OSF-1. Upon receiving mice at KSC, the team has collected pieces of skin that were handled for histological, transcriptomic and biochemical analyses. The

  20. Fullerene-C60 derivatives prevent UV-irradiation/ TiO2-induced cytotoxicity on keratinocytes and 3D-skin tissues through antioxidant actions.

    PubMed

    Kato, Shinya; Aoshima, Hisae; Saitoh, Yasukazu; Miwa, Nobuhiko

    2014-05-01

    Microcorpuscular titanium dioxide (TiO2), a useful sunscreen agent, photocatalyzes generation of reactive oxygen species (ROS). We assessed protective effects of fullerene-C60 derivatives or microcolloidal platinum (Pt) against ultraviolet ray (UV)-irradiation in the presence of TiO2 in vitro. UV-irradiation (8 J/cm2, mixed UVA and UVB) in the presence of 15 ppm TiO2 on HaCaT keratinocytes decreased cell viability as quantified by WST-1 assay, and increased both intracellular ROS and cell-membrane-lipid peroxidation, as quantified by nitroblue-tetrazolium (NBT) assay and diphenyl-1-pyrenylphosphine (DPPP) assay, respectively, whereas all of three phototoxicity-related symptoms were appreciably repressed almost to UV-unirradiational levels by pretreatment with polyvinylpyrrolidone-entrapped fullerene-C60 (C60/PVP) or fullerene-C60 dissolved in squalane (C60/Sqn) in a dose-dependent manner of C60, but scarcely by PVP alone or Sqn alone. In contrast, Pt repressed intracellular ROS generation, but did not prevent either peroxidation of cell-membrane-lipid or cell mortality. Then in the epidermis of 3-dimensional human skin tissue model, UV-irradiation in the presence of TiO2 extensively induced two symptoms such as ROS-generation around perinuclear regions and membrane-lipid peroxidation, both of which were repressed by C60/PVP or C60/Sqn, whereas Pt did not prevent membrane-lipid peroxidation adequately. Thus the advantageous application of the lipophilic antioxidant fullerene-C60 which effectively protects cell membrane against peroxidation. In conclusion, fullerene-C60 can be expected to serve as an antioxidant for scavenging of TiO2-photocatalyzed ROS in the skin surface, and therefore provide a functional improvement of TiO2-containing sunscreens.

  1. Development of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) fibers for skin tissue engineering: effects of topography, mechanical, and chemical stimuli.

    PubMed

    Kuppan, Purushothaman; Vasanthan, Kirthanashri S; Sundaramurthi, Dhakshinamoorthy; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2011-09-12

    Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), a biodegradable polyester, was electrospun to form defect-free fibers with high surface-area-to-volume ratio for skin regeneration. Several parameters such as solvent ratio, polymer concentration, applied voltage, flow rate, and tip-to-target distance were optimized to achieve defect-free morphology. The average diameter of the PHBV fibers was 724 ± 91 nm. PHBV was also solvent-cast to form 2-D films, and its mechanical properties, porosity, and degradation rates were compared with PHBV fibers. Our results demonstrate that PHBV fibers exhibited higher porosity, increased ductility, and faster degradation rate when compared with PHBV 2-D films (p < 0.05). In vitro studies with PHBV fibers and 2-D films were carried out to evaluate the adhesion, viability, proliferation, and gene expression of human skin fibroblasts. Cells adhered and proliferated on both PHBV fibers and 2-D films. However, the proliferation of cells on the surface of PHBV fibers was comparable to tissue culture polystyrene (TCPS, control) (p > 0.05). The gene expression of collagen I and elastin was significantly up-regulated when compared with TCPS control, whereas collagen III was down-regulated on PHBV fibers and 2-D film after 14 days in culture. The