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Sample records for skin tissue heterogeneity

  1. Nanofibrous asymmetric membranes self-organized from chemically heterogeneous electrospun mats for skin tissue engineering.

    PubMed

    Wu, Chaoxi; Chen, Tian; Xin, Yanjiao; Zhang, Zhen; Ren, Zhe; Lei, Jing; Chu, Bin; Wang, Yifei; Tang, Shunqing

    2016-01-01

    Asymmetric membranes, which mimic the structure and functions of human skin, have been extensively pursued as ideal skin tissue engineering constructs. In this study, we demonstrated that nanostructured asymmetric membranes can be prepared by the self-organization of chemically heterogeneous bilayer electrospun membranes in aqueous solutions. Structurally, the skin layer consists of hydrophobic β-glucan butyrate nanofibers and its inner layer consists of hydrophilic β-glucan acetate nanofibers. After the electrospinning process, both of the layers are in a dense state. When placed in water, the skin layer absorbs little water and still remains dense, but the fibers in the inner layer become extensively hydrated and spontaneously reorganize into a fully stretched structure, resulting in a significant volume increase and a density decrease of the inner layer. SEM imaging showed that β-glucan ester nanofibers exhibited a bead-free and uniform structure. Contact angle measurement and swelling tests showed that the inner layer was highly hydrophilic with extensive swelling, but the skin layer was highly hydrophobic with little swelling. Mechanical tests indicated that the nanofibrous asymmetric membranes had good mechanical properties in both the dry and wet states. In vitro cytocompatibility tests showed that nanofibrous asymmetric membranes could promote the adhesion and proliferation of fibroblasts and keratinocytes. A preliminary in vivo study performed on a full thickness mouse skin wound model demonstrated that the nanofibrous asymmetric membranes significantly accelerated the wound healing process by promoting re-epithelialization, tissue remodeling and collagen deposition. Taken together, our study provides a novel model for the design and fabrication of nanostructured asymmetric membranes, and our β-glucan based nanofibrous asymmetric membranes could be used as an advanced platform for skin tissue engineering. PMID:27327625

  2. Impact of Tissue Heterogeneity on Noninvasive Near-Infrared Glucose Measurements in Interstitial Fluid of Rat Skin

    PubMed Central

    Alexeeva, Natalia V; Arnold, Mark A

    2010-01-01

    Background Movement of the optical interface used to collect noninvasive near-infrared spectra is known to dramatically increase prediction errors for glucose concentration measurements within the interstitial fluid of living rat skin. Prediction errors increase by more than 2.5-fold when the interface is moved before each non-invasive measurement compared to measurements where the interface position is constant throughout. Chemical heterogeneity of the skin matrix is examined as a possible mechanism for the strong sensitivity to the interface placement during noninvasive measurements conducted from transmission near-infrared absorption spectroscopy. Method Microspectroscopy was performed over a region of the near-infrared spectrum (4000–5000 cm−1) to map the concentrations of water, collagen protein, fat, and keratin protein within the skin tissue matrix through which noninvasive spectra are collected. Maps were created for multiple samples of skin excised from male and female animals. Sets of near-infrared spectra were constructed to simulate noninvasive spectra in accord with the basic tissue composition found from the microspectroscopic maps with added information corresponding to a span of glucose concentrations ranging from 5 to 35 mM and Gaussian-distributed noise. Results Microspectroscopic maps of rat skin reveal similar patterns of heterogeneity for major chemical components of skin samples excised from both male and female animals. These maps demonstrate concentration domains with dimensions similar to the size of the fiber interface used to collect noninvasive spectra. Partial least squares calibration models generated from sets of simulated spectra demonstrate increases in prediction errors for glucose when the spectral matrix is changed in accord with the degree of chemical heterogeneity displayed in the skin maps. Prediction errors typically increase between 100 and 1000% when comparing errors generated from spectra that represent a single tissue

  3. [Skin and soft tissue infections].

    PubMed

    Piso, R J; Bassetti, S

    2012-03-14

    Skin- and Soft tissue infections are a frequent problem in hospital as well as in ambulatory care. Diagnostic procedures and treatment principles have to include the most frequent pathogens. While the acute forms of skin and soft tissue infections, with, necrotising fasciitis as important exception, rarely cause diagnostic or therapeutic problem, the treatment of patients with recurrent furunculosis, chronic wounds and diabetic feet is often difficult and frustration for patients and physicians. This article gives an overview of the most important problems and treatment strategies. PMID:22419138

  4. Skin and Soft Tissue Infections.

    PubMed

    Ramakrishnan, Kalyanakrishnan; Salinas, Robert C; Agudelo Higuita, Nelson Ivan

    2015-09-15

    Skin and soft tissue infections result from microbial invasion of the skin and its supporting structures. Management is determined by the severity and location of the infection and by patient comorbidities. Infections can be classified as simple (uncomplicated) or complicated (necrotizing or nonnecrotizing), or as suppurative or nonsuppurative. Most community-acquired infections are caused by methicillin-resistant Staphylococcus aureus and beta-hemolytic streptococcus. Simple infections are usually monomicrobial and present with localized clinical findings. In contrast, complicated infections can be mono- or polymicrobial and may present with systemic inflammatory response syndrome. The diagnosis is based on clinical evaluation. Laboratory testing may be required to confirm an uncertain diagnosis, evaluate for deep infections or sepsis, determine the need for inpatient care, and evaluate and treat comorbidities. Initial antimicrobial choice is empiric, and in simple infections should cover Staphylococcus and Streptococcus species. Patients with complicated infections, including suspected necrotizing fasciitis and gangrene, require empiric polymicrobial antibiotic coverage, inpatient treatment, and surgical consultation for debridement. Superficial and small abscesses respond well to drainage and seldom require antibiotics. Immunocompromised patients require early treatment and antimicrobial coverage for possible atypical organisms. PMID:26371732

  5. MicroRNAs in skin tissue engineering.

    PubMed

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

    2015-07-01

    35.2 million annual cases in the U.S. require clinical intervention for major skin loss. To meet this demand, the field of skin tissue engineering has grown rapidly over the past 40 years. Traditionally, skin tissue engineering relies on the "cell-scaffold-signal" approach, whereby isolated cells are formulated into a three-dimensional substrate matrix, or scaffold, and exposed to the proper molecular, physical, and/or electrical signals to encourage growth and differentiation. However, clinically available bioengineered skin equivalents (BSEs) suffer from a number of drawbacks, including time required to generate autologous BSEs, poor allogeneic BSE survival, and physical limitations such as mass transfer issues. Additionally, different types of skin wounds require different BSE designs. MicroRNA has recently emerged as a new and exciting field of RNA interference that can overcome the barriers of BSE design. MicroRNA can regulate cellular behavior, change the bioactive milieu of the skin, and be delivered to skin tissue in a number of ways. While it is still in its infancy, the use of microRNAs in skin tissue engineering offers the opportunity to both enhance and expand a field for which there is still a vast unmet clinical need. Here we give a review of skin tissue engineering, focusing on the important cellular processes, bioactive mediators, and scaffolds. We further discuss potential microRNA targets for each individual component, and we conclude with possible future applications. PMID:25953499

  6. Tissue engineering of cultured skin substitutes.

    PubMed

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

    2005-01-01

    Skin replacement has been a challenging task for surgeons ever since the introduction of skin grafts by Reverdin in 1871. Recently, skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements. This has been fostered by the dramatically improved survival rates of major burns where the availability of autologous normal skin for grafting has become one of the limiting factors. The ideal properties of a temporary and a permanent skin substitute have been well defined. Tissue-engineered skin replacements: cultured autologous keratinocyte grafts, cultured allogeneic keratinocyte grafts, autologous/allogeneic composites, acellular biological matrices, and cellular matrices including such biological substances as fibrin sealant and various types of collagen, hyaluronic acid etc. have opened new horizons to deal with such massive skin loss. In extensive burns it has been shown that skin substitution with cultured grafts can be a life-saving measure where few alternatives exist. Future research will aim to create skin substitutes with cultured epidermis that under appropriate circumstances may provide a wound cover that could be just as durable and esthetically acceptable as conventional split-thickness skin grafts. Genetic manipulation may in addition enhance the performance of such cultured skin substitutes. If cell science, molecular biology, genetic engineering, material science and clinical expertise join their efforts to develop optimized cell culture techniques and synthetic or biological matrices then further technical advances might well lead to the production of almost skin like new tissue-engineered human skin products resembling natural human skin. PMID:16202208

  7. Novel living skin replacement biotherapy approach for wounded skin tissues.

    PubMed

    LaFrance, M L; Armstrong, D W

    1999-04-01

    A novel living skin replacement (LSR) biotherapy concept, addressing the challenging problems related to tissue regeneration and wound healing, is presented for the treatment of skin burns, traumatic injuries and ulcerations. LSR combines elements of cell therapy along with those of tissue engineering to allow for the regeneration of wounded skin. It takes advantage of biodegradable microspheres onto which donor skin epidermal and dermal cells can be attached and expanded in vitro for subsequent direct application down to the deepest recesses of the wound bed. The key element of the biotherapy is the ability of the skin cells to migrate freely from the microspheres into the wound for regeneration of the tissues. The large surface to volume ratio of the microspheres allows for the delivery of appropriate cell numbers while minimizing the amount of biomaterial to be resorbed. This novel approach presents a number of advantages over existing therapies including facilitated cell manipulations, ease of storage and transportation, rapid clinical intervention due to the elimination of any surgical suturing or stapling, and a more natural three-dimensional tissue remodeling and anatomical compliance. Preliminary in vitro and in vivo evidence of the LSR functionality and its potential benefits is presented. PMID:10358222

  8. [Tissue engineered skin and regenerative wound repair].

    PubMed

    Han, Chun-mao; Wang, Xin-gang

    2013-04-01

    Various skin defects resulting from mechanical injury, burns, chronic ulcers, and resection of tumor etc. are very common in clinic. The traditional treatment measure, such as grafting of autologous split-thickness skin remains the gold standard. However, its limitations are obvious, such as shortage of donor sites, creation of new injury, and scar formation. To realize regenerative or scarless repair of tissue defects has always been the dream of human being. The advent of tissue engineered skin (TES) provides an ideal access to tissue regeneration. After decades of development, several kinds of TES products have been developed and used in clinic, with promising effects. However, a large number of basic scientific problems regarding TES, as well as difficulties in translation of basic research to bedside should be taken into serious consideration. This article presents a comprehensive overview of strategies of construction of TES, the role of TES in regenerative wound repair, and its opportunities and challenges. PMID:23985197

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

    PubMed

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

    2015-11-01

    Advances in cell culture methods, multidisciplinary research, clinical need to replace lost skin tissues and regulatory need to replace animal models with alternative test methods has led to development of three dimensional models of human skin. In general, these in vitro models of skin consist of keratinocytes cultured over fibroblast-populated dermal matrices. Accumulating evidences indicate that mesenchyme-derived signals are essential for epidermal morphogenesis, homeostasis and differentiation. Various studies show that fibroblasts isolated from different tissues in the body are dynamic in nature and are morphologically and functionally heterogeneous subpopulations. Further, these differences seem to be dictated by the local biological and physical microenvironment the fibroblasts reside resulting in "positional identity or memory". Furthermore, the heterogeneity among the fibroblasts play a critical role in scarless wound healing and complete restoration of native tissue architecture in fetus and oral mucosa; and excessive scar formation in diseased states like keloids and hypertrophic scars. In this review, we summarize current concepts about the heterogeneity among fibroblasts and their role in various wound healing environments. Further, we contemplate how the insights on fibroblast heterogeneity could be applied for the development of next generation organotypic skin models. PMID:26344860

  10. Heterogeneous genetic profiles in soft tissue myoepitheliomas.

    PubMed

    Hallor, Karolin H; Teixeira, Manuel R; Fletcher, Christopher D M; Bizarro, Susana; Staaf, Johan; Domanski, Henryk A; von Steyern, Fredrik Vult; Panagopoulos, Ioannis; Mandahl, Nils; Mertens, Fredrik

    2008-11-01

    Myoepithelioma, mixed tumor and parachordoma are uncommon soft tissue tumors thought to represent morphological variants of a single tumor type. The genetic basis of these neoplasms is poorly understood. However, they morphologically resemble mixed tumor of the salivary glands (also known as pleomorphic adenoma), a tumor characterized by deregulated expression of PLAG1 or HMGA2. To evaluate a possible genetic relationship between these soft tissue and salivary gland tumors, PLAG1 expression levels and the genomic status of PLAG1 and HMGA2 were investigated in five soft tissue myoepitheliomas and one pleomorphic adenoma. In addition, all tumors were cytogenetically investigated and whole genome DNA copy number imbalances were studied in five of them. The genetic profiles were heterogeneous and the only aberration common to all soft tissue myoepitheliomas was a minimally deleted region of 3.55 Mb in chromosome band 19p13. Recurrent deletion of CDKN2A suggests that inactivation of this tumor suppressor gene is pathogenetically important in a subset. Furthermore, PLAG1 rearrangement was found in a soft tissue tumor from a patient previously treated for a salivary pleomorphic adenoma, indicating either metastasis of the salivary gland lesion or that some soft tissue tumors develop through the same mechanisms as their salivary gland counterparts. PMID:18604193

  11. [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. PMID:26259741

  12. 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.

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

    PubMed Central

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

    2014-01-01

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

  14. Role of tissue thickness on depth of morphologic skin damage

    NASA Astrophysics Data System (ADS)

    RajaMahmood, T. L. I.; Mat Jafri, M. Z.; Omar, Khalid M.

    2013-05-01

    Different zonal areas of the skins have different thickness and different adnexal composition. For this reason, the power density and exposure duration have to be adjusted to the area that being treated. The effects of laser expose to the different area of the skin has been studied by using the power density of 20.31 W/cm2 and the times when the cracking sound heard is the explosive duration recorded for each area of the skins. As a result, the histologic sections revealed that the explosive duration varied significantly with the difference in thickness of the skin tissue. Also, the expanding spaces between hair follicles and its surrounding tissue as well as denaturation of collagen fiberswere shownin each skin section and were mainly affected by the photothermal effect produced from the CO2 laser-skin tissue interaction.

  15. 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)

  16. 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. PMID:23834768

  17. 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.

  18. Polyethylene glycol diffusion in ex vivo skin tissue

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

    Optical clearing of the rat skin under the action of polyethylene glycol (PEG) with molecular weight 300 and 400 Dalton was studied ex vivo. The collimated transmittance was measured at the wavelength range 500-900 nm. It was found that collimated transmittance of skin samples increased, whereas weight, thickness and area of the samples decreased during PEG penetration in skin tissue. A mechanism of the optical clearing under the action of PEG is discussed. Taking into account the kinetics of volume and thickness of the skin samples, diffusion coefficient of PEGs in skin tissue has been estimated as (1.83±2.22)×10-6 cm2/s and (1.70±1.47)×10-6 cm2/s for PEG-300 and PEG-400, respectively. 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.

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

    PubMed

    Arvelo, Francisco

    2007-09-01

    Tissue engineering is the new science that has come to make possible the growth of new organ tissue from small fragments of healthy tissue, thus partially or totally restoring the lost functions of ill tissues or organs, as shown by the achievements made with the culture of skin, cornea or cartilage. Thus far, this new science is able to ensure the recovery of lost functions and, doubtlessly, in a near future will be capable of developing tissues and organs not unlike natural ones. In our laboratory we have began the development of tissue engineering techniques for the successful construction of in vitro skin with the aim at mid term of producing cornea and cartilage. In a first clinical trial, these techniques were applied in the treatment of chronic skin lesions and the advantages and reach of these new tools were demonstrated for the effective solution of problems with would otherwise not be easily solved through the use of conventional treatments. PMID:17853796

  20. 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

  1. Non-linear microscopy and spectroscopy of skin tissues

    NASA Astrophysics Data System (ADS)

    Palero, Jonathan A.; Latouche, Gwendal; de Bruijn, Henri"tte S.; Gerritsen, Hans C.; Sterenborg, Henricus J. C. M.

    2005-11-01

    We combined a non-linear microscope with a sensitive prism-based spectrograph and employed it for the imaging of the auto fluorescence of skin tissues. The system has a sub-micron spatial resolution and a spectral resolution of better than 5 nm. The spectral images contain signals arising from two-photon excited fluorescence (TPEF) of endogenous fluorophores in the skin and from second harmonic generation (SHG) produced by the collagen fibers, which have non-centrosymmetric structure. Non-linear microscopy has the potential to image deep into optically thick specimens because it uses near-infrared (NIR) laser excitation. In addition, the phototoxicity of the technique is comparatively low. Here, the technique is used for the spectral imaging of unstained skin tissue sections. We were able to image weak cellular autofluorescence as well as strong collagen SHG. The images were analyzed by spectral unmixing and the results exhibit a clear spectral signature for the different skin layers.

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

    PubMed Central

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

    2016-01-01

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

  3. Multiscale Approach to Characterize Mechanical Properties of Tissue Engineered Skin.

    PubMed

    Tupin, S; Molimard, J; Cenizo, V; Hoc, T; Sohm, B; Zahouani, H

    2016-09-01

    Tissue engineered skin usually consist of a multi-layered visco-elastic material composed of a fibrillar matrix and cells. The complete mechanical characterization of these tissues has not yet been accomplished. The purpose of this study was to develop a multiscale approach to perform this characterization in order to link the development process of a cultured skin to the mechanical properties. As a proof-of-concept, tissue engineered skin samples were characterized at different stages of manufacturing (acellular matrix, reconstructed dermis and reconstructed skin) for two different aging models (using cells from an 18- and a 61-year-old man). To assess structural variations, bi-photonic confocal microscopy was used. To characterize mechanical properties at a macroscopic scale, a light-load micro-mechanical device that performs indentation and relaxation tests was designed. Finally, images of the internal network of the samples under stretching were acquired by combining confocal microscopy with a tensile device. Mechanical properties at microscopic scale were assessed. Results revealed that adding cells during manufacturing induced structural changes, which provided higher elastic modulus and viscosity. Moreover, senescence models exhibited lower elastic modulus and viscosity. This multiscale approach was efficient to characterize and compare skin equivalent samples and permitted the first experimental assessment of the Poisson's ratio for such tissues. PMID:26942585

  4. Macrophage heterogeneity in tissues: phenotypic diversity and functions

    PubMed Central

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

    2014-01-01

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

  5. 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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

    Nilsson, Gert E.; Leahy, Martin J.

    2010-02-01

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

  8. 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.

  9. 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

  10. 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.

  11. Quantifying thermal modifications on laser welded skin tissue

    NASA Astrophysics Data System (ADS)

    Tabakoglu, Hasim Ö.; Gülsoy, Murat

    2011-02-01

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

  12. 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

  13. Minced Skin for Tissue Engineering of Epithelialized Subcutaneous Tunnels

    PubMed Central

    Fossum, Magdalena; Zuhaili, Baraa; Hirsch, Tobias; Spielmann, Malte; Reish, Richard G.; Mehta, Priyesh

    2009-01-01

    We used minced, autologous skin for neoepithelialization of surgically created subcutaneous tunnels in a large animal model. Partial-thickness skin grafts were harvested from the back region of five 50–60 kg Yorkshire pigs. The skin was minced to 0.8 × 0.8 × 0.3 mm particles. Silicone-latex tubes were covered with fibrin, rolled in minced skin, and placed in subcutaneous tunnels created in the abdominal area. For comparison, single cell suspensions of keratinocytes and fibroblasts in fibrin or fibrin only were transplanted on tubes. Tunnels were extracted after 14, 21, and 28 days for microscopic evaluation. All tubes transplanted with minced skin particles showed neoepithelialization. The epithelium was stratified and differentiated after 2 weeks in vivo, and the stratum corneum was directed toward the implanted tube. No epithelium formed from tubes transplanted with single cell suspensions, and only sparse keratinocytes could be detected by serial sectioning and immunostaining on day 14, but not later. No epithelial lining was found in tunnels with fibrin-only-coated tubes. Epithelial cysts could be found the first 2 weeks after transplantation in the minced skin group but not later. In conclusion, a minced skin technique could serve as a potential source for tissue engineering of tubular conduits for reconstructive purposes of the urethra and for cutaneous stomas for bladder catheterization, or intestinal irrigations. The method would have the advantage of being simple and expeditious and not requiring in vitro culturing. PMID:19292681

  14. Thermal effects of X-band microwaves on skin tissues

    NASA Astrophysics Data System (ADS)

    Song, Kyo D.; Yoon, Hargsoon; Lee, Kunik; Kim, Jaehwan; Choi, Sang H.

    2012-04-01

    Microwave can be used as a power carrier to implanted medical devices wirelessly, which is regarded as one of the attractive features for medical applications. The loss mechanism of microwave transmission through lossy media often appears as a thermal effect due to the absorption of microwave. Such a thermal effect on human tissue has not rigorously studied yet. The thermal effect on living tissues was experimentally tested with animal skins to understand the absorption characteristics of microwave. In this paper, the frequency range of microwave used for the tests was from 6 GHz to 13 GHz.

  15. 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

  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

    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)

  18. 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.

  19. Bacteremic skin and soft tissue infection caused by Prevotella loescheii

    PubMed Central

    2014-01-01

    Background Anaerobes are a major component of gut flora. They play an important role in the pathogenesis of infections resulting from breaches in mucus membranes. Because of the difficulties in cultivating and identifying it, their role continues to be undermined. The purpose of this paper is to report a case of Prevotella loescheii bacteremic skin and soft tissue infection and review the literature. Case presentation A 42-year-old Caucasian man was admitted for an elective bariatric surgery. A lengthy intensive care unit stay and buttocks decubitus ulcers complicated his post-operative course. After being transferred to a long-term care facility, the decubitus ulcer became secondarily infected with multiple bacteria including P. loescheii; an anaerobe that grew in blood and wound cultures. The patient was treated successfully with aggressive surgical debridement, antibiotics and subsequent wound care. Conclusion P. loescheii colonizes the gut and plays an important role in periodontal infections. In rare occasions and under suitable circumstances, it can infect skin and soft tissues as well as joints. Given the difficulties in isolating anaerobes in the microbiology lab, considering this bacterium alongside other anaerobes in infections of devitalized tissue is indicated even if cultures were reported negative. PMID:24661318

  20. Aminoguanidine cream ameliorates skin tissue microenvironment in diabetic rats

    PubMed Central

    Tian, Ming; Qing, Chun; Niu, Yiwen; Dong, Jiaoyun; Cao, Xiaozan; Song, Fei; Ji, Xiaoyun

    2016-01-01

    Introduction The aim of the study was to explore the effect of aminoguanidine cream on the skin tissue microenvironment in diabetic rats. Material and methods A total of 51 healthy male Sprague Dawley (SD) rats were randomly divided into three groups: the diabetes group (n = 18), the aminoguanidine group (n = 18) and the control group (n = 15). Rats in the diabetes group and aminoguanidine group were injected with 65 mg/kg streptozotocin to induce the diabetes model, and in the control group with citrate buffer. After successful induction of diabetes, the back hair of all rats was stripped by barium sulfide, and the aminoguanidine group was treated with aminoguanidine cream using disinfected cotton swabs twice every day for 40 days, while the diabetes and control groups were treated with the cream matrix. The pathological changes of skin were observed by HE staining, while the content of inflammatory cytokines (TNF-α, IL-8, ICAM and IL-1α) and the antioxidant indexes (T-AOC, GSH-PX, MPO MDA H2O2) were examined using commercial kits. Results After 40 days of treatment, the diabetes group manifested tissue lesions, whereas the aminoguanidine group seemed normal. Compared with the diabetes group, the content of inflammatory cytokines TNF-α, IL-8, ICAM and IL-1α was dramatically lower in the aminoguanidine group. T-AOC in all groups underwent dramatic changes and returned to normal finally. The activities of GSH-PX and MPO and content of H2O2 in the diabetes group were all higher than those in the aminoguanidine group. Conclusions Aminoguanidine may have a good systemic effect on alleviating the pathological changes of skin tissue in diabetic rats, which may be attributed to the regulation of GSH-PX, TNF-α, IL-8, ICAM and IL-1α. PMID:26925135

  1. Skin and soft tissue infections in the military.

    PubMed

    Lamb, Lucy; Morgan, M

    2013-09-01

    Skin and soft tissue infections (SSTI) are common in military populations regularly living and training in close contact with each other. The majority of such infections are simple and can be easily treated with antibiotics and appropriate infection control practices. Some, however, can progress to become complex and even life threatening, such as Panton-Valentine Leukocidin (PVL)-associated staphylococcus aureus pneumonia, or Streptococcus pyogenes necrotising fasciitis, which carry a mortality rate of up to 65% and 30%, respectively. This review focuses on the most important SSTIs and those more commonly affecting military personnel with advice on how they are best managed. PMID:24109144

  2. Soft tissue sarcomas in skin: presentations and management.

    PubMed

    Patt, Joshua C; Haines, Nikkole

    2016-06-01

    Soft tissue sarcomas are a rare but heterogeneous family of malignant tumors that are predominantly found deep to the integumentary layer. Only a small number of these primary mesenchymal tumors actually originate from the dermal layers. A systematic approach to the evaluation and workup of these neoplasms can prevent inappropriate management. After staging evaluation, most of these tumors are primarily managed with en-bloc surgical resection. Other adjuvant therapies routinely employed include chemotherapy and radiation therapy. Proper treatment typically involves participation of a multidisciplinary care team for optimal outcome. General principles and treatment strategies will be discussed along with a review of the more common cutaneous manifestations of sarcoma. PMID:27178697

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-05-01

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

  7. 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

  8. Tissue Heterogeneity in IMRT Dose Calculation for Lung Cancer

    SciTech Connect

    Pasciuti, Katia; Iaccarino, Giuseppe; Strigari, Lidia; Malatesta, Tiziana; Benassi, Marcello; Di Nallo, Anna Maria; Mirri, Alessandra; Pinzi, Valentina; Landoni, Valeria

    2011-07-01

    The aim of this study was to evaluate the differences in accuracy of dose calculation between 3 commonly used algorithms, the Pencil Beam algorithm (PB), the Anisotropic Analytical Algorithm (AAA), and the Collapsed Cone Convolution Superposition (CCCS) for intensity-modulated radiation therapy (IMRT). The 2D dose distributions obtained with the 3 algorithms were compared on each CT slice pixel by pixel, using the MATLAB code (The MathWorks, Natick, MA) and the agreement was assessed with the {gamma} function. The effect of the differences on dose-volume histograms (DVHs), tumor control, and normal tissue complication probability (TCP and NTCP) were also evaluated, and its significance was quantified by using a nonparametric test. In general PB generates regions of over-dosage both in the lung and in the tumor area. These differences are not always in DVH of the lung, although the Wilcoxon test indicated significant differences in 2 of 4 patients. Disagreement in the lung region was also found when the {Gamma} analysis was performed. The effect on TCP is less important than for NTCP because of the slope of the curve at the level of the dose of interest. The effect of dose calculation inaccuracy is patient-dependent and strongly related to beam geometry and to the localization of the tumor. When multiple intensity-modulated beams are used, the effect of the presence of the heterogeneity on dose distribution may not always be easily predictable.

  9. Tissue heterogeneity in IMRT dose calculation for lung cancer.

    PubMed

    Pasciuti, Katia; Iaccarino, Giuseppe; Strigari, Lidia; Malatesta, Tiziana; Benassi, Marcello; Di Nallo, Anna Maria; Mirri, Alessandra; Pinzi, Valentina; Landoni, Valeria

    2011-01-01

    The aim of this study was to evaluate the differences in accuracy of dose calculation between 3 commonly used algorithms, the Pencil Beam algorithm (PB), the Anisotropic Analytical Algorithm (AAA), and the Collapsed Cone Convolution Superposition (CCCS) for intensity-modulated radiation therapy (IMRT). The 2D dose distributions obtained with the 3 algorithms were compared on each CT slice pixel by pixel, using the MATLAB code (The MathWorks, Natick, MA) and the agreement was assessed with the γ function. The effect of the differences on dose-volume histograms (DVHs), tumor control, and normal tissue complication probability (TCP and NTCP) were also evaluated, and its significance was quantified by using a nonparametric test. In general PB generates regions of over-dosage both in the lung and in the tumor area. These differences are not always in DVH of the lung, although the Wilcoxon test indicated significant differences in 2 of 4 patients. Disagreement in the lung region was also found when the Γ analysis was performed. The effect on TCP is less important than for NTCP because of the slope of the curve at the level of the dose of interest. The effect of dose calculation inaccuracy is patient-dependent and strongly related to beam geometry and to the localization of the tumor. When multiple intensity-modulated beams are used, the effect of the presence of the heterogeneity on dose distribution may not always be easily predictable. PMID:20970989

  10. Simulation of Electron-Beam Irradiation of Skin Tissue Model

    SciTech Connect

    Miller, John H.; Suleiman, Atef; Chrisler, William B.; Sowa, Marianne B.

    2011-01-03

    Monte Carlo simulation of electrons stopping in liquid water was used to model the penetration and dose distribution of electron beams incident on the full-thickness EpiDermTM skin model (MatTek, Ashland, VA). This 3D tissue model has a fully developed basement membrane separating an epidermal layer of keratinocytes in various stages of differentiation from a dermal layer of fibroblast embedded in collagen. The simulations were motivated by a desire to selectively expose the epidermal layer to low linear-energy-transfer (LET) radiation in the presence of a non-irradiated dermal layer. Using the variable energy electron microbeam at the Pacific Northwest National Laboratory (PNNL) as a model of device characteristics and irradiation geometry, we find that at the highest beam energy available (90 keV), the estimated 90th percentile of penetration remains in the epidermal layer. To investigate the depth-dose distribution, we calculated lineal energy spectra for 10um thick layers near the 10th, 50th, and 90th percentile of penetration by the 90 keV electron beam. Biphasic spectra showed an increasing component of "stoppers" with increasing depth. Despite changes in the lineal energy spectra, the main effect on dose deposition with increasing depth is the screening effect of tissue above the layer of interest.

  11. Skin and Soft Tissue Infection (Cellulitis) (Beyond the Basics)

    MedlinePlus

    ... skin infections are discussed separately. (See "Patient education: Methicillin-resistant Staphylococcus aureus (MRSA) (Beyond the Basics)" and "Patient ... be caused by a skin infection known as methicillin-resistant Staphylococcus aureus (MRSA). This is discussed separately. (See " ...

  12. Proteolytic Processing Causes Extensive Heterogeneity of Tissue Matrilin Forms*

    PubMed Central

    Ehlen, Harald W. A.; Sengle, Gerhard; Klatt, Andreas R.; Talke, Anja; Müller, Stefan; Paulsson, Mats; Wagener, Raimund

    2009-01-01

    The matrilins are a family of multidomain extracellular matrix proteins with adapter functions. The oligomeric proteins have a bouquet-like structure and bind to a variety of different ligands whereby the avidity of their interactions is dependent on the number of subunits and domains present. Here we show the contribution of post-translational proteolytic processing to the heterogeneity of matrilins seen in tissue extracts and cell culture supernatants. A cleavage site after two glutamate residues in the hinge region close to the C-terminal coiled-coil oligomerization domain is conserved among the matrilins. Cleavage at this site yields molecules that lack almost complete subunits. The processing is least pronounced in matrilin-1 and particularly complex in matrilin-2, which contains additional cleavage sites. Replacement of the hinge region in matrilin-4 by the matrilin-1 hinge region had no marked effect on the processing. A detailed study revealed that matrilin-4 is processed already in the secretory pathway and that the activation of the responsible enzymes is dependent on proprotein convertase activity. Matrilin-3 and -4, but not matrilin-1 subunits present in matrilin-1/-3 hetero-oligomers, were identified as substrates for ADAMTS4 and ADAMTS5, whereas ADAMTS1 did not cleave any matrilin. A neo-epitope antibody raised against the N terminus of the C-terminal cleavage product of matrilin-4 detected processed matrilin-4 in cultures of primary chondrocytes as well as on cartilage sections showing that the conserved cleavage site is used in vivo. PMID:19531486

  13. Simultaneous imaging of blood flow and hemoglobin concentration change in skin tissue using NIR speckle patterns

    NASA Astrophysics Data System (ADS)

    Aizu, Yoshihisa; Hirata, Tatsuya; Maeda, Takaaki; Nishidate, Izumi; Yokoi, Naomichi

    2009-07-01

    We propose a method for imaging simultaneously blood flow and hemoglobin concentration change in skin tissue using speckle patterns acquired at two wavelengths of 780 and 830 nm. Experimental results demonstrate that the method is useful for time-varying analysis of blood circulation in human forearm skin tissue from one set of sequential speckle images.

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  15. Schnitzler syndrome: heterogeneous immunopathological findings involving IgM-skin interactions.

    PubMed

    Lipsker, D; Spehner, D; Drillien, R; Schmitt, P; Cribier, B; Heid, E; Humbel, R L; Grosshans, E

    2000-05-01

    The Schnitzler syndrome is the association of chronic urticaria, intermittent fever, osteosclerotic bone lesions and a monoclonal IgM gammopathy. It is not yet firmly established whether the monoclonal immunoglobulin component plays a part in the pathophysiology of the urticarial lesions. Immunoblotting on epidermal and dermal human skin extracts as well as immunoelectron microscopic (IEM) studies on Lowicryl K4M-embedded skin sections were performed in three patients with the Schnitzler syndrome. Western blotting on epidermal extracts showed the presence of IgM-kappa antiskin autoantibodies in two patients. These antibodies displayed the same isotype as the monoclonal components and recognized a 280-290-kDa antigen in one patient and a 200-kDa antigen in the other patient. IEM studies showed sparse IgM deposits in the epidermis, around the keratinocytes, near the desmosomes in one patient and dense deposits below the lamina densa, in the region of the anchoring fibrils, in another patient. Antiskin IgM autoantibodies of the same isotype as their monoclonal gammopathies can be present in the serum of some patients with the Schnitzler syndrome. These IgM antibodies seem to deposit in vivo in the epidermis and at the dermal-epidermal junction, in the region of the anchoring fibrils. These findings suggest that the monoclonal gammopathy plays a part in the pathophysiology of the skin rash. They also suggest patient heterogeneity both in the skin antigens that are recognized as well as in their localization. PMID:10809854

  16. 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

  17. Tissue Engineered Skin Substitutes Created by Laser-Assisted Bioprinting Form Skin-Like Structures in the Dorsal Skin Fold Chamber in Mice

    PubMed Central

    Michael, Stefanie; Sorg, Heiko; Peck, Claas-Tido; Koch, Lothar; Deiwick, Andrea; Chichkov, Boris; Vogt, Peter M.; Reimers, Kerstin

    2013-01-01

    Tissue engineering plays an important role in the production of skin equivalents for the therapy of chronic and especially burn wounds. Actually, there exists no (cellularized) skin equivalent which might be able to satisfactorily mimic native skin. Here, we utilized a laser-assisted bioprinting (LaBP) technique to create a fully cellularized skin substitute. The unique feature of LaBP is the possibility to position different cell types in an exact three-dimensional (3D) spatial pattern. For the creation of the skin substitutes, we positioned fibroblasts and keratinocytes on top of a stabilizing matrix (Matriderm®). These skin constructs were subsequently tested in vivo, employing the dorsal skin fold chamber in nude mice. The transplants were placed into full-thickness skin wounds and were fully connected to the surrounding tissue when explanted after 11 days. The printed keratinocytes formed a multi-layered epidermis with beginning differentiation and stratum corneum. Proliferation of the keratinocytes was mainly detected in the suprabasal layers. In vitro controls, which were cultivated at the air-liquid-interface, also exhibited proliferative cells, but they were rather located in the whole epidermis. E-cadherin as a hint for adherens junctions and therefore tissue formation could be found in the epidermis in vivo as well as in vitro. In both conditions, the printed fibroblasts partly stayed on top of the underlying Matriderm® where they produced collagen, while part of them migrated into the Matriderm®. In the mice, some blood vessels could be found to grow from the wound bed and the wound edges in direction of the printed cells. In conclusion, we could show the successful 3D printing of a cell construct via LaBP and the subsequent tissue formation in vivo. These findings represent the prerequisite for the creation of a complex tissue like skin, consisting of different cell types in an intricate 3D pattern. PMID:23469227

  18. Point-of-care instrument for monitoring tissue health during skin graft repair

    NASA Astrophysics Data System (ADS)

    Gurjar, R. S.; Seetamraju, M.; Zhang, J.; Feinberg, S. E.; Wolf, D. E.

    2011-06-01

    We have developed the necessary theoretical framework and the basic instrumental design parameters to enable mapping of subsurface blood dynamics and tissue oxygenation for patients undergoing skin graft procedures. This analysis forms the basis for developing a simple patch geometry, which can be used to map by diffuse optical techniques blood flow velocity and tissue oxygenation as a function of depth in subsurface tissue.skin graft, diffuse correlation analysis, oxygen saturation.

  19. Alterations of Dermal Connective Tissue Collagen in Diabetes: Molecular Basis of Aged-Appearing Skin

    PubMed Central

    Argyropoulos, Angela J.; Robichaud, Patrick; Balimunkwe, Rebecca Mutesi; Fisher, Gary J.; Hammerberg, Craig; Yan, Yan

    2016-01-01

    Alterations of the collagen, the major structural protein in skin, contribute significantly to human skin connective tissue aging. As aged-appearing skin is more common in diabetes, here we investigated the molecular basis of aged-appearing skin in diabetes. Among all known human matrix metalloproteinases (MMPs), diabetic skin shows elevated levels of MMP-1 and MMP-2. Laser capture microdissection (LCM) coupled real-time PCR indicated that elevated MMPs in diabetic skin were primarily expressed in the dermis. Furthermore, diabetic skin shows increased lysyl oxidase (LOX) expression and higher cross-linked collagens. Atomic force microscopy (AFM) further indicated that collagen fibrils were fragmented/disorganized, and key mechanical properties of traction force and tensile strength were increased in diabetic skin, compared to intact/well-organized collagen fibrils in non-diabetic skin. In in vitro tissue culture system, multiple MMPs including MMP-1 and MM-2 were induced by high glucose (25 mM) exposure to isolated primary human skin dermal fibroblasts, the major cells responsible for collagen homeostasis in skin. The elevation of MMPs and LOX over the years is thought to result in the accumulation of fragmented and cross-linked collagen, and thus impairs dermal collagen structural integrity and mechanical properties in diabetes. Our data partially explain why old-looking skin is more common in diabetic patients. PMID:27104752

  20. Vital roles of stem cells and biomaterials in skin tissue engineering.

    PubMed

    Mohd Hilmi, Abu Bakar; Halim, Ahmad Sukari

    2015-03-26

    Tissue engineering essentially refers to technology for growing new human tissue and is distinct from regenerative medicine. Currently, pieces of skin are already being fabricated for clinical use and many other tissue types may be fabricated in the future. Tissue engineering was first defined in 1987 by the United States National Science Foundation which critically discussed the future targets of bioengineering research and its consequences. The principles of tissue engineering are to initiate cell cultures in vitro, grow them on scaffolds in situ and transplant the composite into a recipient in vivo. From the beginning, scaffolds have been necessary in tissue engineering applications. Regardless, the latest technology has redirected established approaches by omitting scaffolds. Currently, scientists from diverse research institutes are engineering skin without scaffolds. Due to their advantageous properties, stem cells have robustly transformed the tissue engineering field as part of an engineered bilayered skin substitute that will later be discussed in detail. Additionally, utilizing biomaterials or skin replacement products in skin tissue engineering as strategy to successfully direct cell proliferation and differentiation as well as to optimize the safety of handling during grafting is beneficial. This approach has also led to the cells' application in developing the novel skin substitute that will be briefly explained in this review. PMID:25815126

  1. Vital roles of stem cells and biomaterials in skin tissue engineering

    PubMed Central

    Mohd Hilmi, Abu Bakar; Halim, Ahmad Sukari

    2015-01-01

    Tissue engineering essentially refers to technology for growing new human tissue and is distinct from regenerative medicine. Currently, pieces of skin are already being fabricated for clinical use and many other tissue types may be fabricated in the future. Tissue engineering was first defined in 1987 by the United States National Science Foundation which critically discussed the future targets of bioengineering research and its consequences. The principles of tissue engineering are to initiate cell cultures in vitro, grow them on scaffolds in situ and transplant the composite into a recipient in vivo. From the beginning, scaffolds have been necessary in tissue engineering applications. Regardless, the latest technology has redirected established approaches by omitting scaffolds. Currently, scientists from diverse research institutes are engineering skin without scaffolds. Due to their advantageous properties, stem cells have robustly transformed the tissue engineering field as part of an engineered bilayered skin substitute that will later be discussed in detail. Additionally, utilizing biomaterials or skin replacement products in skin tissue engineering as strategy to successfully direct cell proliferation and differentiation as well as to optimize the safety of handling during grafting is beneficial. This approach has also led to the cells’ application in developing the novel skin substitute that will be briefly explained in this review. PMID:25815126

  2. Tissue Specific Heterogeneity in Effector Immune Cell Response

    PubMed Central

    Tufail, Saba; Badrealam, Khan Farheen; Sherwani, Asif; Gupta, Umesh D.; Owais, Mohammad

    2013-01-01

    Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct “homing codes” (adhesion molecules and chemokine receptors) during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A) and sunlight (vitamin D3) prime dendritic cells, imprinting them to play centre stage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue-tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues along with giving an overview of tissue tropism in B cells. PMID:23986763

  3. Revascularization of autogenous skin grafts placed on irradiated tissue

    SciTech Connect

    Ueda, M.; Torii, S.; Kaneda, T.; Oka, T.

    1982-08-01

    Vascular changes in rat skin after irradiation were examined microangiographically. Revascularization of the skin transplanted during the chronic stage after irradiation was also studied. The results obtained through these examinations revealed higher vascular densities at the acute and the subacute stages, and low values at the chronic stages compared with those of the control. Furthermore, when the skin grafts were transplanted to the irradiated beds in the chronic stage, primary revascularization was scant, and the inhibited capillary proliferation in the recipient sites prevented new vessel penetration. This explains why grafts transplanted to previously irradiated beds fail to survive.

  4. Mechanical Tissue Optical Clearing Devices: Enhancement of Light Penetration in Ex-Vivo Porcine Skin and Adipose Tissue

    PubMed Central

    Milner, Thomas E.; Baranov, Stepan; Nelson, J. Stuart

    2008-01-01

    Background and Objective The complex morphological structure of tissue and associated variations in the indices of refraction of components therein, provides a highly scattering medium for visible and near-infrared wavelengths of light. Tissue optical clearing permits delivery of light deeper into tissue, potentially improving the capabilities of various light-based therapeutic techniques, such as adipose tissue removal or reshaping. Study Design/ Materials and Methods We report results of a study to evaluate effectiveness of novel mechanical tissue optical clearing devices (TOCD) using white light photography and infrared imaging radiometry (IIR). The TOCD consists of a pin array and vacuum pressure source applied directly to the skin surface. IIR images recorded light absorption and temperature increase of ex vivo porcine skin and adipose during laser irradiation (980 and 1210 nm) before and after TOCD application. Results White light photographic images of in vivo human skin demonstrated localized compression and altered visual appearance, indicative of water and blood movement in skin. White light photographic images also showed increased visible light transport through regions of ex vivo porcine skin compressed by TOCD pins. Rate of heating in sub-dermal adipose regions beneath TOCD pins was two-fold higher following TOCD application. Conclusions Results of our study suggest that mechanical optical clearing may provide a means to deliver increased light fluence to dermal and adipose tissues. PMID:19065559

  5. Tissue engineered skin for diabetic foot ulcers: a meta-analysis

    PubMed Central

    Li, Xuedong; Xu, Geliang; Chen, Jianqiu

    2015-01-01

    To evaluate the effectiveness of tissue engineered skin in the management of diabetic foot ulcer. We searched PubMed, EMBASE and ISI Web of Science database in order to obtain the randomized controlled trial with interventions of tissue engineered skin. A meta-analysis was used to compare the effectiveness between tissue engineered skin and conventional treatment in the patients with diabetic foot ulcer. This meta-analysis was performed by STATA 11 software. The risk factor was analyzed by random effect model pooled odds ratio (OR) and 95% confidence interval (CI). Moreover, the funnel plot was used to assess the published bias of articles. Eight studies were included, and a total of 1060 cases were involved for this meta-analysis. The OR of tissue engineered skin for diabetic foot ulcers was 1.76 (95% CI: 1.35-2.30). A subgroup analysis was conducted for different types of tissue engineering skin, combined OR was 1.91 (95% CI: 1.12-3.27) for Derma graft, 2.05 (95% CI: 1.20-3.50) for Graft skin and 1.57 (95% CI: 0.91-2.70) for Hyalo graft 3D. Applying tissue engineered skin is more effective in the improvement of wound closure in patients with diabetic foot ulcers, compared with conventional treatment. PMID:26770419

  6. 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. PMID:26275343

  7. Newer treatment options for skin and soft tissue infections.

    PubMed

    Raghavan, Murugan; Linden, Peter K

    2004-01-01

    In recent years, serious skin and soft tissue infections (SSTIs) caused by multidrug resistant pathogens have become more common. While the majority of SSTIs are caused by Staphylococcus aureus or beta-haemolytic streptococci that are methicillin/oxacillin susceptible, the emergence of methicillin-resistant and vancomycin-resistant community-acquired and nosocomial Gram-positive pathogens has created a need for different therapeutic agents, such as linezolid, quinupristin/dalfopristin, daptomycin, and newer generation carbapenems and fluoroquinolones. This review focuses on agents presently in clinical development for the treatment of SSTIs caused by Gram-positive pathogens such as staphylococci, streptococci and enterococci including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE). Newer-generation carbapenems, such as meropenem and ertapenem, are characterised by a broad-spectrum of activity against Gram-positive and -negative aerobes and anaerobes, and are resistant to hydrolysis by many beta-lactamases. Current-generation fluoroquinolones, such as levofloxacin, moxifloxacin and gatifloxacin, have demonstrated better eradication rates for S. aureus than conventional penicillin and cephalosporins. These antimicrobial agents can be used to treat methicillin-susceptible staphylococcal and streptococcal strains. Oxazolidinones, streptogramin combinations and cyclic lipopeptides have novel mechanisms of action and have been studied in several multinational phase III clinical trials in the treatment of complicated and uncomplicated SSTIs. They possess a broad spectrum of activity against multidrug-resistant pathogens, including MRSA and VRE. Linezolid has been shown to be active against a wide variety of community-acquired and nosocomial antimicrobial-resistant pathogens with comparability to vancomycin, as well as resulting in reduced lengths of hospital stay. Cyclic lipopeptides such as daptomycin have a unique mechanism of action

  8. A diffusion approximation model of light transport in multilayered skin tissue

    NASA Astrophysics Data System (ADS)

    Makropoulou, M.; Kaselouris, E.; Drakaki, E.; Serafetinides, A. A.; Sianoudis, J. A.

    2007-07-01

    In dermatology, biophotonic methods offer high sensitivity and non-invasive measurements of skin tissue optical properties, in various physiological and pathological conditions. There are numerous skin processes, which can be examined and characterized using diagnostic optical spectroscopy, as the monitoring of skin aging, diagnosis of benign and malignant cutaneous lesions, dosimetry in photodynamic therapy (PDT), etc. Several mathematical models have been used to calculate the tissue optical properties from experimental measurements and to predict the light propagation in soft tissues, like skin, based on transport theory or Monte Carlo modeling. This work analyses the phenomena which are observed experimentally during the irradiation of skin, such as the absorption, reflectance, scattering, fluorescence and transmission of laser light. The study was carried out on animal skin samples, extracted post-mortem. In this work we also tried to evaluate the utility of diffusion approximation modeling for measuring the light intensity distribution in the skin samples with cw visible laser beam (λ=632.8 nm). The diffusion theory model was tested for the simulation results of the spatial light distribution within a five-layer model of animal skin tissue. We have studied the dependence towards the depth and the radial distance of the photon density of the incident radiation.

  9. 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.

  10. Skin tissue engineering advances in severe burns: review and therapeutic applications.

    PubMed

    Chua, Alvin Wen Choong; Khoo, Yik Cheong; Tan, Bien Keem; Tan, Kok Chai; Foo, Chee Liam; Chong, Si Jack

    2016-01-01

    Current advances in basic stem cell research and tissue engineering augur well for the development of improved cultured skin tissue substitutes: a class of products that is still fraught with limitations for clinical use. Although the ability to grow autologous keratinocytes in-vitro from a small skin biopsy into sheets of stratified epithelium (within 3 to 4 weeks) helped alleviate the problem of insufficient donor site for extensive burn, many burn units still have to grapple with insufficient skin allografts which are used as intermediate wound coverage after burn excision. Alternatives offered by tissue-engineered skin dermal replacements to meet emergency demand have been used fairly successfully. Despite the availability of these commercial products, they all suffer from the same problems of extremely high cost, sub-normal skin microstructure and inconsistent engraftment, especially in full thickness burns. Clinical practice for severe burn treatment has since evolved to incorporate these tissue-engineered skin substitutes, usually as an adjunct to speed up epithelization for wound closure and/or to improve quality of life by improving the functional and cosmetic results long-term. This review seeks to bring the reader through the beginnings of skin tissue engineering, the utilization of some of the key products developed for the treatment of severe burns and the hope of harnessing stem cells to improve on current practice. PMID:27574673

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

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

  12. 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.

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

    PubMed

    Arvelo, Francisco; Pérez, Pedro; Cotte, Carlos

    2004-01-01

    The aim of this "in vitro" study was to develop a new system for keratinocyte culture on a dermal equivalent that enables treatment of different skin injuries. The keratinocyte where obtained from primary cell cultures derived from skin biopsies, seeded over a fibrin matrix enhanced with live human fibroblast. Cells growing over the dermal equivalent, rapidly confluences and a stratified epithelium was obtained within 20-25 days culture. Detachment of composite culture from flask is a simple and quick procedure with no need for chemical or enzyme treatments. The method described provides a number of advantages which include the large expansion of keratinocyte from the primary cell cultures without the need of a feeder layer, the availability of plasma from blood banks, and the versatile and safe manipulation of composite obtained "in vitro". All these facts allow to assure that this system could result very efficient for the treatment of all type of skin injuries. PMID:15916167

  14. 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

  15. Analysis and classification of normal and pathological skin tissue spectra using neural networks

    NASA Astrophysics Data System (ADS)

    Bruch, Reinhard F.; Afanasyeva, Natalia I.; Gummuluri, Satyashree

    2000-07-01

    An innovative spectroscopic diagnostic method has been developed for investigation of different regions of normal human skin tissue, as well as cancerous and precancerous conditions in vivo, ex vivo and in vitro. This new method is a combination of fiber-optical evanescent wave Fourier Transform infrared (FEW-FTIR) spectroscopy and fiber optic techniques using low-loss, highly flexible and nontoxic fiber optical sensors. The FEW-FTIR technique is nondestructive and very sensitive to changes of vibrational spectra in the IR region without heating and staining and thus altering the skin tissue. A special software package was developed for the treatment of the spectra. This package includes a database, programs for data preparation and presentation, and neural networks for classification of disease states. An unsupervised neural competitive learning neural network is implemented for skin cancer diagnosis. In this study, we have investigated and classified skin tissue in the range of 1400 to 1800 cm-1 using these programs. The results of our surface analysis of skin tissue are discussed in terms of molecular structural similarities and differences as well as in terms of different skin states represented by eleven different skin spectra classes.

  16. A statistical measure of tissue heterogeneity with application to 3D PET sarcoma data.

    PubMed

    O'Sullivan, Finbarr; Roy, Supratik; Eary, Janet

    2003-07-01

    In vivo measurement of local tissue characteristics by modern bioimaging techniques such as positron emission tomography (PET) provides the opportunity to analyze quantitatively the role that tissue heterogeneity may play in understanding biological function. This paper develops a statistical measure of the heterogeneity of a tissue characteristic that is based on the deviation of the distribution of the tissue characteristic from a unimodal elliptically contoured spatial pattern. An efficient algorithm is developed for computation of the measure based on volumetric region of interest data. The technique is illustrated by application to data from PET imaging studies of fluorodeoxyglucose utilization in human sarcomas. A set of 74 sarcoma patients (with five-year follow-up survival information) were evaluated for heterogeneity as well as a number of other potential prognostic indicators of survival. A Cox proportional hazards analysis of these data shows that the degree of heterogeneity of the sarcoma is the major risk factor associated with patient death. Some theory is developed to analyze the asymptotic statistical behavior of the heterogeneity estimator. In the context of data arising from Poisson deconvolution (PET being the prime example), the heterogeneity estimator, which is a non-linear functional of the PET image data, is consistent and converges at a rate that is parametric in the injected dose. PMID:12925510

  17. 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.

  18. 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. PMID:26171294

  19. 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

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

    NASA Astrophysics Data System (ADS)

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

    2002-06-01

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

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

    NASA Astrophysics Data System (ADS)

    Alonso, Sergio; Bär, Markus

    2013-04-01

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

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

    PubMed

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

    2015-01-01

    Based on the electrical properties of biological tissues, bioimpedance measurement technology can be employed to collect physiologic and pathologic information by measuring changes in human bioimpedance. When an alternating current (AC) is applied as a detection signal to a tissue, the current field distribution, which is affected by skin effect, is related to both the bioimpedance of the tissue and the AC frequency. These relations would possibly reduce the accuracy and reliability of the measurement. In this study, an electromagnetic theory-based method, in which cylindrical conductor were divided into layers, was used to obtain current field distribution models of human limbs. Model simulations were conducted in MATLAB. The skin effect phenomenon and its characteristics in human tissues at different frequencies were observed, thus providing essential data on skin effect, which are useful in the development of bioimpedance measurement technology. PMID:26406033

  4. Apoptosis and mitosis in tumours of the skin and subcutaneous tissues of the dog.

    PubMed

    Martin De Las Mulas, J; Millan, Y; Ruiz-Villamor, E; Bautista, M J; Rollon, E; Espinosa De Los Monteros, A

    1999-04-01

    The presence of apoptotic cell death was evaluated in routinely processed tissue samples of 39 neoplasms of the skin and subcutaneous tissues of the dog using the method of terminal deoxynucleotidyl transferase (T d T) mediated deoxyuridine-5'-triphosphate (d UTP)-biotin nick end labelling (TUNEL). The degree of apoptosis was related to the frequency of mitosis, an index of cell proliferation. The correlation between the apoptotic index (AI), the percentage of positive cells after randomly enumerating 1000 cells and the mitotic count (MC), the number of mitotic figures in 10 fields at a magnification of 400 times was assessed by the Spearman non-parametric correlation test. TUNEL signals were observed in all types of tumours as brown products detected in non-pyknotic nuclei, in non-identifiable rounded structures (so-called apoptotic bodies) and occasionally in the cytoplasm, either singly or in combination. An inverse relationship between AI and MC was observed in benign tumours, while no correlation was found between AI and MC in either malignant or locally invasive tumours. Among benign tumours, intracutaneous cornifying epithelioma, fibroma, haemangioma and Schwannoma had high AI and low MC, while histiocytomas had low AI and high MC and pilomatrixomas low AI and MC. All malignant tumours had low AI and high MC, except for fibrosarcomas, which had high AI and MC. Finally, higher heterogeneity was observed among locally invasive tumours, as they had high AI and low MC (squamous cell carcinomas), and low AI with either low MC (haemangiopericytomas) or high MC (basal cell tumours). The classification of the tumours according to their AI (>15.8% high and <15.8% low) and MC (>9 high, <9 low) did not reflect the clinical behaviour of some tumour types. PMID:10208892

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

    PubMed

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

    2013-06-01

    Burn injury-mediated destruction of the skin barrier normally induces microbial invasion, in turn leading to the development of systemic infection and occasional septic shock by the release of endotoxins. The objective of this work was to study the influence of lipopolysaccharide (LPS) on the biological characteristics of normal skin fibroblasts and to elucidate the influence of LPS in the initial stage of skin wound healing. Twenty patients with hypertrophic scar in proliferative stage were selected randomly and primary cultures were established from fibroblasts derived from their hypertrophic scar tissue and normal skin. Normal skin fibroblasts of passage 3 were stimulated with different concentrations of LPS. LPS stimulated the proliferation and collagen synthesis of fibroblasts within a certain extent of concentrations (0.005-0.5 μg/mL) (P < 0.05), whereas at a concentration of 1 μg/mL inhibited the proliferation and collagen synthesis of fibroblasts (P < 0.05). Collagen synthesis by normal skin fibroblasts after LPS stimulation mimicked those derived from hypertrophic scar tissue. LPS of 0.1 μg/mL had significant effect on normal skin fibroblasts-continuous passage of these fibroblasts resulted in ultrastructural pattern similar to fibroblasts derived from hypertrophic scar tissue, and the findings was substantiated by hematoxylin and eosin staining and immunohistochemistry detection of proliferation cell nuclear antigen, type I procollagen and α-smooth muscle actin. Our results suggest that LPS might convert normal skin fibroblasts to hypertrophic scar tissue fibroblasts and participate in the formation of hypertrophic scar; hence, appropriate concentration of LPS may have no effect or be beneficial to skin wound healing, whereas excessive concentration of LPS may delay the time of wound healing. PMID:23653386

  6. Homeostatic Tissue Responses in Skin Biopsies from NOMID Patients with Constitutive Overproduction of IL-1β

    PubMed Central

    Aubert, Pamela; Suárez-Fariñas, Mayte; Mitsui, Hiroshi; Johnson-Huang, Leanne M.; Harden, Jamie Lynn; Pierson, Katherine C.; Dolan, Joseph G.; Novitskaya, Inna; Coats, Israel; Estes, Jacob; Cowen, Edward W.; Plass, Nicole; Lee, Chyi-Chia Richard; Sun, Hong-Wei

    2012-01-01

    The autoinflammatory disorder, Neonatal-onset Multisystem Inflammatory Disease (NOMID) is the most severe phenotype of disorders caused by mutations in CIAS1 that result in increased production and secretion of active IL-1β. NOMID patients present with systemic and organ-specific inflammation of the skin, central nervous system and bone, and respond dramatically to treatment with IL-1 blocking agents. We compared the cellular infiltrates and transcriptome of skin biopsies from patients with NOMID (n = 14) before treatment (lesional (LS) and non-lesional (pre-NL) skin) and after treatment (post-NL) with the IL-1 blocker anakinra (recombinant IL-1 receptor antagonist, Kineret®, Swedish Orphan Biovitrum AB, SOBI), to normal skin (n = 5) to assess tissue responses in the context of untreated and treated disease. Abundant neutrophils distinguish LS skin from pre-NL and post-NL skin. CD11c+ dermal dendritic cells and CD163+ macrophages expressed activated caspase-1 and are a likely source of cutaneous IL-1 production. Treatment with anakinra led to the disappearance of neutrophils, but CD3+ T cells and HLA-DR+ cells remained elevated. Among the upregulated genes IL-6, IL-8, TNF, IL-17A, CCL20, and the neutrophil defensins DEFA1 and DEFA3 were differentially regulated in LS tissues (compared to normal skin). Important significantly downregulated pathways in LS skin included IL-1R/TLR signaling, type I and II cytokine receptor signaling, mitochondrial dysfunction, and antigen presentation. The differential expression and regulation of microRNAs and pathways involved in post-transcriptional modification were suggestive of epigenetic modification in the chronically inflamed tissue. Overall, the dysregulated genes and pathways suggest extensive “adaptive” mechanisms to control inflammation and maintain tissue homeostasis, likely triggered by chronic IL-1 release in the skin of patients with NOMID. PMID:23226210

  7. 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

  8. 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

  9. The confounding effects of source isotopic heterogeneity on consumer-diet and tissue-tissue stable isotope relationships.

    PubMed

    Codron, Daryl; Sponheimer, Matt; Codron, Jacqui; Newton, Ian; Lanham, John L; Clauss, Marcus

    2012-08-01

    Stable isotope analysis of consumer tissues document patterns of resource use because data are linearly related to isotope compositions of their source(s) (i.e., food, water, etc.). Deviations in parameters estimated for these relationships can arise from variations in consumer tissue-diet spacing (Δ(TS)) and the level of isotopic heterogeneity in the source(s). We present a set of simple hypotheses that distinguish between the effects of Δ(TS) and source isotope heterogeneity. The latter may arise via mixed diets, during tissue turnover, or by isotopic routing of dietary components. We apply these concepts to stable carbon and nitrogen isotope relationships between gut contents and body tissues of large mammal herbivores from mixed C(3)/C(4) South African savannas and test predictions based on the compound- and/or time-specific data archived within each material. Predicted effects of source isotope heterogeneity are readily detected in carbon isotope relationships between materials representing different time periods or comprising bulk versus protein-only diet components. Differences in Δ(TS) of carbon isotopes across mammal herbivore species with very different feeding niches (and diet isotope compositions) are likely to be small or non-existent in these habitats. Variations in Δ(TS) estimated for nitrogen isotopes are much greater, leading to inconsistencies that cannot be explained by diet or trophic level effects alone. The effects of source heterogeneity on isotopic relationships generate numerical artefacts that have been misinterpreted as variations in Δ(TS). We caution against generalized application of hypotheses based on assumptions of source isotopic homogeneity, even for single diets commonly used in laboratory studies. More careful consideration of how heterogeneity affects consumer-diet relationships is needed for many field and laboratory systems. PMID:22349754

  10. 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

  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. PMID:26939692

  12. 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. PMID:26954709

  13. Low-intensity infrared lasers alter actin gene expression in skin and muscle tissue

    NASA Astrophysics Data System (ADS)

    Fonseca, A. S.; Mencalha, A. L.; Campos, V. M. A.; Ferreira-Machado, S. C.; Peregrino, A. A. F.; Magalhães, L. A. G.; Geller, M.; Paoli, F.

    2013-02-01

    The biostimulative effect of low-intensity lasers is the basis for treatment of diseases in soft tissues. However, data about the influence of biostimulative lasers on gene expression are still scarce. The aim of this work was to evaluate the effects of low-intensity infrared lasers on the expression of actin mRNA in skin and muscle tissue. Skin and muscle tissue of Wistar rats was exposed to low-intensity infrared laser radiation at different fluences and frequencies. One and 24 hours after laser exposure, tissue samples were withdrawn for total RNA extraction, cDNA synthesis and evaluation of actin gene expression by quantitative polymerase chain reaction. The data obtained show that laser radiation alters the expression of actin mRNA differently in skin and muscle tissue of Wistar rats depending of the fluence, frequency and time after exposure. The results could be useful for laser dosimetry, as well as to justify the therapeutic protocols for treatment of diseases of skin and muscle tissues based on low-intensity infrared laser radiation.

  14. 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

  15. In vivo enhancement of sensory perception recovery in a tissue-engineered skin enriched with laminin.

    PubMed

    Caissie, René; Gingras, Marie; Champigny, Marie-France; Berthod, François

    2006-05-01

    The use of autologous reconstructed skin appears to be a promising treatment for the permanent coverage of deep and extensive burns. However, the capability of reconstructed skin transplanted on wounds to promote recovery of sensory perception is a major concern. Our aim was to assess the effect of laminin on cutaneous nerve regeneration. We prepared collagen-chitosan sponges enriched with 0, 1, 10 or 50 microg of laminin/sponge to produce tissue-engineered reconstructed skins by culture of human fibroblasts and keratinocytes, then grafted on the back of athymic mice for 120 days. Immunohistochemical studies demonstrated that there were 7 times more neurofilament 150 kD-positive nerve fibers migrating in the graft in the samples enriched with 10 microg laminin/sponge, compared to reconstructed skin without laminin, 120 days after graft. A significant improvement in the current perception threshold of the Abeta and Adelta nerve fibers was measured using a Neurometer in all grafts enriched with laminin. In addition, the type C nerve fibers reached an identical current perception threshold than mouse skin, in all reconstructed skins enriched or not with laminin. We conclude that the use of a tissue-engineered autologous skin graft enriched with laminin has the potential to efficiently optimize cutaneous sensory nerve regeneration in vivo. PMID:16448695

  16. Combination of Er:YAG laser and CO2 laser treatment on skin tissue.

    PubMed

    Anayb Baleg, Sana Mohammed; Bidin, Noriah; Suan, Lau Pik; Sidi Ahmad, Muhammad Fakarruddin; Krishnan, Ganesan; Johari, Abd Rahman; Hamid, Asmah

    2015-01-01

    Skin is the most important organ in our body, as it protects us from external environmental effects. Study the ability of the skin to stretch and the histological examinations of irradiated tissues have significant values in scientific and medical applications. Only a few studies have been done to study the correlation between epidermis ablation and the changes that occur at dermal levels when using dual lasers in ablative resurfacing mode. The aim of this work is to determine this correlation and to estimate the effects of multiple pulses on induced collagen remodeling and the strength of skin exposed with dual lasers in an in vivo rat model. All laser exposures led to mark improvement in the skin's strength compared to their own controls. The histological investigation indicated that there was a thickness loss in the epidermis layer with the induction of deep collagen coagulation in the dermis layer as the dual laser pulses increased. Additionally, more collagen fibers were remolded in the treated samples by dual wavelengths. We conclude that by combining dual lasers with multiple pulses targeted at not only the epidermis layer of the skin, it could also induce some heat diffusion in the dermis layer which causes more coagulation of collagen fibers. The tensile results confirmed by our histological data demonstrate that the strength of irradiated skin with dual wavelengths increased more than using both lasers separately on the skin tissue since more collagen is induced. PMID:25327511

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

    PubMed

    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. PMID:22507867

  18. 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. PMID:23399174

  19. 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

  20. GPU-based Monte Carlo simulation for light propagation in complex heterogeneous tissues.

    PubMed

    Ren, Nunu; Liang, Jimin; Qu, Xiaochao; Li, Jianfeng; Lu, Bingjia; Tian, Jie

    2010-03-29

    As the most accurate model for simulating light propagation in heterogeneous tissues, Monte Carlo (MC) method has been widely used in the field of optical molecular imaging. However, MC method is time-consuming due to the calculations of a large number of photons propagation in tissues. The structural complexity of the heterogeneous tissues further increases the computational time. In this paper we present a parallel implementation for MC simulation of light propagation in heterogeneous tissues whose surfaces are constructed by different number of triangle meshes. On the basis of graphics processing units (GPU), the code is implemented with compute unified device architecture (CUDA) platform and optimized to reduce the access latency as much as possible by making full use of the constant memory and texture memory on GPU. We test the implementation in the homogeneous and heterogeneous mouse models with a NVIDIA GTX 260 card and a 2.40GHz Intel Xeon CPU. The experimental results demonstrate the feasibility and efficiency of the parallel MC simulation on GPU. PMID:20389700

  1. [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. PMID:24566790

  2. Wound Tissue Can Utilize a Polymeric Template to Synthesize a Functional Extension of Skin

    NASA Astrophysics Data System (ADS)

    Yannas, I. V.; Burke, J. F.; Orgill, D. P.; Skrabut, E. M.

    1982-01-01

    Prompt and long-term closure of full-thickness skin wounds in guinea pigs and humans is achieved by applying a bilayer polymeric membrane. The membrane comprises a top layer of a silicone elastomer and a bottom layer of a porous cross-linked network of collagen and glycosaminoglycan. The bottom layer can be seeded with a small number of autologous basal cells before grafting. No immunosuppression is used and infection, exudation, and rejection are absent. Host tissue utilizes the sterile membrane as a culture medium to synthesize neoepidermal and neodermal tissue. A functional extension of skin over the entire wound area is formed in about 4 weeks.

  3. Availability of thiazone as an enhancer for optical clearing of skin tissue in vitro

    NASA Astrophysics Data System (ADS)

    Jiang, Jingying; Chen, Wei; Wang, Ruikang K.; Xu, Kexin

    2008-02-01

    Dimethyl sulfoxside (DMSO) has been used as enhancer for tissue optical clearing technique. However, due to its potential toxicity and possible side effects, taking clearing effects and clinical availability into accounts, a new enhancer will be needed in order to facilitate practical application of tissue optical clearing technique to non-invasive light-based diagnostic and imaging technique. In this talk, it is our aim to introduce a new skin penetration promoter, thiazone, used in the fields of pharmaceutic industry, cosmetic, etc and investigate its availability as a new enhancer for tissue optical clearing technique. Firstly, we analyzed its structure, physical and chemical properties. And then we performed experimental investigation of the effect of DMSO and thiazone as enhancers mixed with polyethylene glycol (PEG) respectively on optical clearing of porcine skin tissue in vitro. Results of direct observation from camera reveal that thiazone has a higher penetration enhancing effect when compared with DMSO as an enhancer when porcine skin was topically impregnated by different mixed-solutions. Optical property parameters, obtained by using double integrating-spheres system and Inverse Adding-Doubling (IAD) method, showed that thiazone led to almost similar reduction in scattering to DMSO did during the same time period. Therefore, in terms of optical application and clinical safety, thiazone could be a better choice than DMSO as an enhancer for optical clearing of skin tissue.

  4. Resistance to 1,25-dihydroxyvitamin D. Association with heterogeneous defects in cultured skin fibroblasts

    SciTech Connect

    Liberman, U.A.; Eil, C.; Marx, S.J.

    1983-02-01

    We evaluated the interaction of (/sup 3/H)1,25(OH)/sub 2/D/sub 3/ with skin fibroblasts cultured from normal subjects or from affected members of six kindreds with rickets and resistance to 1-alpha, 25(OH)/sub 2/D (1,25(OH)/sub 2/D). We analyzed two aspects of the radioligand interaction; nuclear uptake with dispersed, intact cells at 37 degrees C and binding at 0 degrees C with soluble extract (cytosol) prepared from cells disrupted in buffer containing 300 mM KCl and 10 mM sodium molybdate. With normal fibroblasts the affinity and capacity of nuclear uptake of (/sup 3/H)1,25(OH)/sub 2/D/sub 3/ were 0.5 nM and 10,300 sites per cell, respectively; for binding with cytosol these were 0.13 nM and 8,900 sites per cell, respectively. In all cases where the radioligand bound with high affinity in nucleus or cytosol, the nucleus- or cytosol-associated radioligand exhibited normal sedimentation velocity on sucrose density gradients. When two kindreds exhibited similar patterns (i.e. pattern a or c) with the analyses of cultured fibroblasts, clinical features in affected members suggested that the underlying genetic defects were not identical. In conclusion: (a) Fibroblasts cultured from human skin manifest nuclear uptake and cytosol binding of (/sup 3/H)1,25(OH)/sub 2/D/sub 3/ that is an expression of the genes determining these processes in target tissues. (b) Based upon data from clinical evaluations and from analyses of cultured fibroblasts, severe resistance to 1,25(OH)/sub 2/D resulted from five or six distinct genetic mutations in six kindreds.

  5. Resistance to 1,25-dihydroxyvitamin D. Association with heterogeneous defects in cultured skin fibroblasts

    SciTech Connect

    Liberman, U.A.; Eil, C.; Marx, S.J.

    1983-02-01

    The authors evaluated the interaction of (/sub 3/H)1,25(OH)/sup 2/D3 with skin fibroblasts cultured from normal subjects or from affected members of six kindreds with rickets and resistance to 1-alpha, 25(OH)/sub 2/D (1,25(OH)/sub 2/D). They analyzed two aspects of the radioligand interaction; nuclear uptake with dispersed, intact cells at 37 degrees C and binding at 0 degrees C with soluble extract (cytosol) prepared from cells disrupted in buffer. With normal fibroblasts the affinity and capacity of nuclear uptake of (/sub 3/H)1,25(OH)/sup 2/D3 were 0.5 nM and 10,300 sites per cell, respectively; for binding with cytosol these were 0.13 nM and 8,900 sites per cell, respectively. The following four patterns of interaction with (/sub 3/H)1,25(OH)/sup 2/D3 were observed with cells cultured from affected patients. In all cases where the radioligand bound with high affinity in nucleus or cytosol, the nucleus- or cytosol-associated radioligand exhibited normal sedimentation velocity on sucrose density gradients. When two kindreds exhibited similar patterns (i.e. pattern a or c) with the analyses of cultured fibroblasts, clinical features in affected members suggested that the underlying genetic defects were not identical. In conclusion: (a) Fibroblasts cultured from human skin manifest nuclear uptake and cytosol binding of (/sub 3/H)1,25(OH)/sup 2/D3 that is an expression of the genes determining these processes in target tissues. (b) Based upon data from clinical evaluations and from analyses of cultured fibroblasts, severe resistance to 1,25(OH)/sup 2/D resulted from five or six distinct genetic mutations in six kindreds.

  6. The effects of refractive index heterogeneity within kidney tissue on multiphoton fluorescence excitation microscopy.

    PubMed

    Young, P A; Clendenon, S G; Byars, J M; Dunn, K W

    2011-05-01

    Although multiphoton fluorescence excitation microscopy has improved the depth at which useful fluorescence images can be collected in biological tissues, the reach of multiphoton fluorescence excitation microscopy is nonetheless limited by tissue scattering and spherical aberration. Scattering can be reduced in fixed samples by mounting in a medium whose refractive index closely matches that of the fixed material. Using optical 'clearing', the effects of refractive index heterogeneity on signal attenuation with depth are investigated. Quantitative measurements show that by mounting kidney tissue in a high refractive index medium, less than 50% of signal attenuates in 100 μm of depth. PMID:21118239

  7. 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. PMID:24677536

  8. 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.

  9. 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.

  10. 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.

  11. 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. PMID:26556717

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  13. [The Effects of Skin Thickness on Optical Transmission Characteristics in Fruits Tissues].

    PubMed

    Shi, Shu-ning; Tan, Zuo-jun; Xie, Jing; Lu, Jun

    2015-07-01

    Fruit quality inspection techniques play a very important role in the production and consumption of fruits. In the field of quality non-destructive inspection and grading for fruits, the light-based techniques using optical properties of fruit products were widely used as one of the most practical and the most successful techniques. Quantitative understanding of light interaction with fruits is critical to designing better optical systems for inspection of food quality. In this paper, a fruit model consisted of two layer tissues was developed using Monte Carlo simulations to explore the light transport process and properties in the pome fruits, such as apples and mandarins, which were used as the thin-skinned and thick-skinned fruits respectively. The simulation results obtained are based on the assumption that the light source is a Gaussian beam at the wavelength 808 nm. This paper reports that the effects of skin thickness on light transmission characteristics in fruit tissues, including diffuse reflectance, transmittance, absorptivity, penetration depth etc. The inspection efficiency of flesh tissues was also demonstrated. The results indicated that the transmittance and the penetration depth decreases with the fruit skin increasing. As for the absorbed energy density, the fruit skin tissues have the wider distribution at the radial distance than the fruit flesh tissues. The absorbed energy density always tended to decrease with the inside depth of the fruit tissues increasing, especially decreased more apparently at the radial direction. The diffuse reflectance at the radial distance from 0.2 to 1.2 cm decreased with the decreasing of fruit skin, however it showed the inverse relationship in the radial distance range from 1.2 to 4.0 cm, the diffuse reflectance decreases with the increasing fruit skin. This paper proposed that the interaction between light and fruits skin in transmission or reflective approach, should be considered for developing optical

  14. Chitosan-collagen scaffolds with nano/microfibrous architecture for skin tissue engineering.

    PubMed

    Sarkar, Soumi Dey; Farrugia, Brooke L; Dargaville, Tim R; Dhara, Santanu

    2013-12-01

    In this study, a hierarchical nano/microfibrous chitosan/collagen scaffold that approximates structural and functional attributes of native extracellular matrix has been developed for applicability in skin tissue engineering. Scaffolds were produced by electrospinning of chitosan followed by imbibing of collagen solution, freeze-drying, and subsequent cross-linking of two polymers. Scanning electron microscopy showed formation of layered scaffolds with nano/microfibrous architechture. Physicochemical properties of scaffolds including tensile strength, swelling behavior, and biodegradability were found satisfactory for intended application. 3T3 fibroblasts and HaCaT keratinocytes showed good in vitro cellular response on scaffolds thereby indicating the matrices, cytocompatible nature. Scaffolds tested in an ex vivo human skin equivalent wound model, as a preliminary alternative to animal testing, showed keratinocyte migration and wound re-epithelization-a prerequisite for healing and regeneration. Taken together, the herein proposed chitosan/collagen scaffold, shows good potential for skin tissue engineering. PMID:23606420

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

    PubMed

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

    2014-01-01

    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. PMID:25057963

  16. 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.

  17. Fish collagen/alginate/chitooligosaccharides integrated scaffold for skin tissue regeneration application.

    PubMed

    Chandika, Pathum; Ko, Seok-Chun; Oh, Gun-Woo; Heo, Seong-Yeong; Nguyen, Van-Tinh; Jeon, You-Jin; Lee, Bonggi; Jang, Chul Ho; Kim, GeunHyung; Park, Won Sun; Chang, Wonseok; Choi, Il-Whan; Jung, Won-Kyo

    2015-11-01

    An emerging paradigm in wound healing techniques is that a tissue-engineered skin substitute offers an alternative approach to create functional skin tissue. Here we developed a fish collagen/alginate (FCA) sponge scaffold that was functionalized by different molecular weights of chitooligosaccharides (COSs) with the use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as a cross-linking agent. The effects of cross-linking were analyzed by Fourier transform infrared spectroscopy. The results indicate that the homogeneous materials blending and cross-linking intensity were dependent on the molecular weights of COSs. The highly interconnected porous architecture with 160-260μm pore size and over 90% porosity and COS's MW driven swelling and retention capacity, tensile property and in vitro biodegradation behavior guaranteed the FCA/COS scaffolds for skin tissue engineering application. Further improvement of these properties enhanced the cytocompatibility of all the scaffolds, especially the scaffolds containing COSs with MW in the range of 1-3kDa (FCA/COS1) showed the best cytocompatibility. These physicochemical, mechanical, and biological properties suggest that the FCA/COS1 scaffold is a superior candidate that can be used for skin tissue regeneration. PMID:26306410

  18. Molecular Signatures of Tissue-Specific Microvascular Endothelial Cell Heterogeneity in Organ Maintenance and Regeneration

    PubMed Central

    Nolan, Daniel J.; Ginsberg, Michael; Israely, Edo; Palikuqi, Brisa; Poulos, Michael G.; James, Daylon; Ding, Bi-Sen; Schachterle, William; Liu, Ying; Rosenwaks, Zev; Butler, Jason M.; Xiang, Jenny; Rafii, Arash; Shido, Koji; Rabbany, Sina Y.; Elemento, Olivier; Rafii, Shahin

    2013-01-01

    SUMMARY Microvascular endothelial cells (ECs) within different tissues are endowed with distinct but as yet unrecognized structural, phenotypic, and functional attributes. We devised EC purification, cultivation, profiling, and transplantation models that establish tissue-specific molecular libraries of ECs devoid of lymphatic ECs or parenchymal cells. These libraries identify attributes that confer ECs with their organotypic features. We show that clusters of transcription factors, angiocrine growth factors, adhesion molecules, and chemokines are expressed in unique combinations by ECs of each organ. Furthermore, ECs respond distinctly in tissue regeneration models, hepatectomy, and myeloablation. To test the data set, we developed a transplantation model that employs generic ECs differentiated from embryonic stem cells. Transplanted generic ECs engraft into regenerating tissues and acquire features of organotypic ECs. Collectively, we demonstrate the utility of informational databases of ECs toward uncovering the extravascular and intrinsic signals that define EC heterogeneity. These factors could be exploited therapeutically to engineer tissue-specific ECs for regeneration. PMID:23871589

  19. Classifying tissue samples from measurements on cells with within-class tissue sample heterogeneity

    PubMed Central

    Yamal, Jose-Miguel; Follen, Michele; Guillaud, Martial; Cox, Dennis D.

    2011-01-01

    We consider here the problem of classifying a macro-level object based on measurements of embedded (micro-level) observations within each object, for example, classifying a patient based on measurements on a collection of a random number of their cells. Classification problems with this hierarchical, nested structure have not received the same statistical understanding as the general classification problem. Some heuristic approaches have been developed and a few authors have proposed formal statistical models. We focus on the problem where heterogeneity exists between the macro-level objects within a class. We propose a model-based statistical methodology that models the log-odds of the macro-level object belonging to a class using a latent-class variable model to account for this heterogeneity. The latent classes are estimated by clustering the macro-level object density estimates. We apply this method to the detection of patients with cervical neoplasia based on quantitative cytology measurements on cells in a Papanicolaou smear. Quantitative cytology is much cheaper and potentially can take less time than the current standard of care. The results show that the automated quantitative cytology using the proposed method is roughly equivalent to clinical cytopathology and shows significant improvement over a statistical model that does not account for the heterogeneity of the data. PMID:21642388

  20. 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.

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

    PubMed

    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. PMID:26822943

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

    PubMed Central

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

    2012-01-01

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

  3. 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. PMID:22853915

  4. Metabolomics reveals the heterogeneous secretome of two entomopathogenic fungi to ex vivo cultured insect tissues.

    PubMed

    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

  5. 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

  6. Human Skin Cells That Express Stage-Specific Embryonic Antigen 3 Associate with Dermal Tissue Regeneration

    PubMed Central

    Vega Crespo, Agustin; Awe, Jason P.; Reijo Pera, Renee

    2012-01-01

    Abstract Stage-specific embryonic antigen 3 (SSEA3) is a glycosphingolipid that has previously been used to identify cells with stem cell-like, multipotent, and pluripotent characteristics. A rare subpopulation of SSEA3-expressing cells exists in the dermis of adult human skin. These SSEA3-expressing cells undergo a significant increase in cell number in response to injury, suggesting a possible role in regeneration. These SSEA3-expressing regeneration-associated (SERA) cells were derived through primary cell culture, purified by fluorescence-activated cell sorting (FACS), and characterized. Longer in vitro culture of the primary skin cells led to lower SSEA3 expression stability after FACS-based purification, suggesting that the current culture conditions may need to be optimized to permit the large-scale expansion of SERA cells. The SERA cells demonstrated a global transcriptional state that was most similar to bone marrow- and fat-derived mesenchymal stem cells (MSCs), and the highest expressing SSEA3-expressing cells co-expressed CD105 (clone 35). However, while a rare population of MSCs was observed in primary human skin cell cultures that could differentiate into adipocytes, osteoblasts, or chondrocytes, SERA cells did not possess this differentiation capacity, suggesting that there are at least two different rare subpopulations in adult human skin primary cultures. The identification, efficient purification, and large-scale expansion of these rare subpopulations (SERA cells and MSCs) from heterogeneous adult human skin primary cell cultures may have applications for future patient-specific cellular therapies. PMID:23514702

  7. 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.

  8. 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.

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

    PubMed

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

    2013-12-01

    Tissue-resident memory T cells (T(RM) cells) provide superior protection against infection in extralymphoid tissues. Here we found that CD103(+)CD8(+) T(RM) cells developed in the skin from epithelium-infiltrating precursor cells that lacked expression of the effector-cell marker KLRG1. A combination of entry into the epithelium plus local signaling by interleukin 15 (IL-15) and transforming growth factor-β (TGF-β) was required for the formation of these long-lived memory cells. Notably, differentiation into T(RM) cells resulted in the progressive acquisition of a unique transcriptional profile that differed from that of circulating memory cells and other types of T cells that permanently reside in skin epithelium. We provide a comprehensive molecular framework for the local differentiation of a distinct peripheral population of memory cells that forms a first-line immunological defense system in barrier tissues. PMID:24162776

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

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

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

    PubMed

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

    2015-01-01

    The skin, being a multi-layered material, is responsible for protecting the human body from the mechanical, bacterial, and viral insults. The skin tissue may display different mechanical properties according to the anatomical locations of a body. However, these mechanical properties in different anatomical regions and at different loading directions (axial and circumferential) of the mice body to date have not been determined. In this study, the axial and circumferential loads were imposed on the mice skin samples. The elastic modulus and maximum stress of the skin tissues were measured before the failure occurred. The nonlinear mechanical behavior of the skin tissues was also computationally investigated through a suitable constitutive equation. Hyperelastic material model was calibrated using the experimental data. Regardless of the anatomic locations of the mice body, the results revealed significantly different mechanical properties in the axial and circumferential directions and, consequently, the mice skin tissue behaves like a pure anisotropic material. The highest elastic modulus was observed in the back skin under the circumferential direction (6.67 MPa), while the lowest one was seen in the abdomen skin under circumferential loading (0.80 MPa). The Ogden material model was narrowly captured the nonlinear mechanical response of the skin at different loading directions. The results help to understand the isotropic/anisotropic mechanical behavior of the skin tissue at different anatomical locations. They also have implications for a diversity of disciplines, i.e., dermatology, cosmetics industry, clinical decision making, and clinical intervention. PMID:25266627

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

    NASA Astrophysics Data System (ADS)

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

    2007-07-01

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

  13. Real-time simulation of contact and cutting of heterogeneous soft-tissues.

    PubMed

    Courtecuisse, Hadrien; Allard, Jérémie; Kerfriden, Pierre; Bordas, Stéphane P A; Cotin, Stéphane; Duriez, Christian

    2014-02-01

    This paper presents a numerical method for interactive (real-time) simulations, which considerably improves the accuracy of the response of heterogeneous soft-tissue models undergoing contact, cutting and other topological changes. We provide an integrated methodology able to deal both with the ill-conditioning issues associated with material heterogeneities, contact boundary conditions which are one of the main sources of inaccuracies, and cutting which is one of the most challenging issues in interactive simulations. Our approach is based on an implicit time integration of a non-linear finite element model. To enable real-time computations, we propose a new preconditioning technique, based on an asynchronous update at low frequency. The preconditioner is not only used to improve the computation of the deformation of the tissues, but also to simulate the contact response of homogeneous and heterogeneous bodies with the same accuracy. We also address the problem of cutting the heterogeneous structures and propose a method to update the preconditioner according to the topological modifications. Finally, we apply our approach to three challenging demonstrators: (i) a simulation of cataract surgery (ii) a simulation of laparoscopic hepatectomy (iii) a brain tumor surgery. PMID:24440853

  14. Fatal skin and soft tissue infection of multidrug resistant Acinetobacter baumannii: A case report

    PubMed Central

    Ali, Aqsa; Botha, John; Tiruvoipati, Ravindranath

    2014-01-01

    INTRODUCTION Acinetobacter baumannii is usually associated with respiratory tract, urinary tract and bloodstream infections. Recent reports suggest that it is increasingly causing skin and soft tissue infections. It is also evolving as a multidrug resistant organism that can be difficult to treat. We present a fatal case of multidrug resistant A. baumannii soft tissue infection and review of relevant literature. PRESENTATION OF CASE A 41 year old morbidly obese man, with history of alcoholic liver disease presented with left superficial pre-tibial abrasions and cellulitis caused by multidrug resistant (MDR) A. baumannii. In spite of early antibiotic administration he developed extensive myositis and fat necrosis requiring extensive and multiple surgical debridements. He deteriorated despite appropriate antibiotic therapy and multiple surgical interventions with development of multi-organ failure and died. DISCUSSION Managing Acinetobacter infections remains difficult due to the array of resistance and the pathogens ability to develop new and ongoing resistance. The early diagnosis of necrotizing soft tissue infection may be challenging, but the key to successful management of patients with necrotizing soft tissue infection are early recognition and complete surgical debridement. CONCLUSION A. baumannii is emerging as an important cause of severe, life-threatening soft tissue infections. Multidrug resistant A. baumannii soft tissue infections may carry a high mortality in spite of early and aggressive treatment. Clinicians need to consider appropriate early empirical antibiotic coverage or the use of combination therapy to include MDR A. baumannii as a cause of skin and soft tissue infections. PMID:25016080

  15. [Cellular reaction of the skin and underlying tissues on prolonged acupuncture needle introduction].

    PubMed

    Kobozeva, L P; Michunskaia, A B; Mukhina, M M; Chadaev, N V; Pozdniakov, O M

    2010-01-01

    The changes of a skin and hypodermic are studied at the prolonged introduction (till 3 months) original acupuncture needles under a skin of an auricle and neck at rats by the technique Muhina M.M. In early terms in an introduction place develops an aseptic (or septic) inflammation reaching of peak in 1-2 weeks. On a measure reduction of inflammatory reaction activation of epydermis (keratinocites) which acquire from periphery an acupuncture needle is marked, isolating it from surrounding tissues and forming the implant channel (acustract). Formation process of acustract comes to the end through 2 - 2,5 months. PMID:20806469

  16. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology.

    PubMed

    Xu, Tao; Zhao, Weixin; Zhu, Jian-Ming; Albanna, Mohammad Z; Yoo, James J; Atala, Anthony

    2013-01-01

    This study was designed to develop a versatile method for fabricating complex and heterogeneous three-dimensional (3D) tissue constructs using simultaneous ink-jetting of multiple cell types. Human amniotic fluid-derived stem cells (hAFSCs), canine smooth muscle cells (dSMCs), and bovine aortic endothelial cells (bECs), were separately mixed with ionic cross-linker calcium chloride (CaCl(2)), loaded into separate ink cartridges and printed using a modified thermal inkjet printer. The three cell types were delivered layer-by-layer to pre-determined locations in a sodium alginate-collagen composite located in a chamber under the printer. The reaction between CaCl(2) and sodium alginate resulted in a rapid formation of a solid composite gel and the printed cells were anchored in designated areas within the gel. The printing process was repeated for several cycles leading to a complex 3D multi-cell hybrid construct. The biological functions of the 3D printed constructs were evaluated in vitro and in vivo. Each of the printed cell types maintained their viability and normal proliferation rates, phenotypic expression, and physiological functions within the heterogeneous constructs. The bioprinted constructs were able to survive and mature into functional tissues with adequate vascularization in vivo. These findings demonstrate the feasibility of fabricating complex heterogeneous tissue constructs containing multiple cell types using inkjet printing technology. PMID:23063369

  17. Mathematical modelling of transcriptional heterogeneity identifies novel markers and subpopulations in complex tissues

    PubMed Central

    Wang, Niya; Hoffman, Eric P.; Chen, Lulu; Chen, Li; Zhang, Zhen; Liu, Chunyu; Yu, Guoqiang; Herrington, David M.; Clarke, Robert; Wang, Yue

    2016-01-01

    Tissue heterogeneity is both a major confounding factor and an underexploited information source. While a handful of reports have demonstrated the potential of supervised computational methods to deconvolute tissue heterogeneity, these approaches require a priori information on the marker genes or composition of known subpopulations. To address the critical problem of the absence of validated marker genes for many (including novel) subpopulations, we describe convex analysis of mixtures (CAM), a fully unsupervised in silico method, for identifying subpopulation marker genes directly from the original mixed gene expressions in scatter space that can improve molecular analyses in many biological contexts. Validated with predesigned mixtures, CAM on the gene expression data from peripheral leukocytes, brain tissue, and yeast cell cycle, revealed novel marker genes that were otherwise undetectable using existing methods. Importantly, CAM requires no a priori information on the number, identity, or composition of the subpopulations present in mixed samples, and does not require the presence of pure subpopulations in sample space. This advantage is significant in that CAM can achieve all of its goals using only a small number of heterogeneous samples, and is more powerful to distinguish between phenotypically similar subpopulations. PMID:26739359

  18. Influence trend of temperature distribution in skin tissue generated by different exposure dose pulse laser

    NASA Astrophysics Data System (ADS)

    Shan, Ning; Wang, Zhijing; Liu, Xia

    2014-11-01

    Laser is widely applied in military and medicine fields because of its excellent capability. In order to effectively defend excess damage by laser, the thermal processing theory of skin tissue generated by laser should be carried out. The heating rate and thermal damage area should be studied. The mathematics model of bio-tissue heat transfer that is irradiated by laser is analyzed. And boundary conditions of bio-tissue are discussed. Three layer FEM grid model of bio-tissue is established. The temperature rising inducing by pulse laser in the tissue is modeled numerically by adopting ANSYS software. The changing trend of temperature in the tissue is imitated and studied under the conditions of different exposure dose pulse laser. The results show that temperature rising in the tissue depends on the parameters of pulse laser largely. In the same conditions, the pulse width of laser is smaller and its instant power is higher. And temperature rising effect in the tissue is very clear. On the contrary, temperature rising effect in the tissue is lower. The cooling time inducing by temperature rising effect in the tissue is longer along with pulse separation of laser is bigger. And the temperature difference is bigger in the pulse period.

  19. Visualizing depth and thickness of a local blood region in skin tissue using diffuse reflectance images.

    PubMed

    Nishidate, Izumi; Maeda, Takaaki; Aizu, Yoshihisa; Niizeki, Kyuichi

    2007-01-01

    A method is proposed for visualizing the depth and thickness distribution of a local blood region in skin tissue using diffuse reflectance images at three isosbestic wavelengths of hemoglobin: 420, 585, and 800 nm. Monte Carlo simulation of light transport specifies a relation among optical densities, depth, and thickness of the region under given concentrations of melanin in epidermis and blood in dermis. Experiments with tissue-like agar gel phantoms indicate that a simple circular blood region embedded in scattering media can be visualized with errors of 6% for the depth and 22% for the thickness to the given values. In-vivo measurements on human veins demonstrate that results from the proposed method agree within errors of 30 and 19% for the depth and thickness, respectively, with values obtained from the same veins by the conventional ultrasound technique. Numerical investigation with the Monte Carlo simulation of light transport in the skin tissue is also performed to discuss effects of deviation in scattering coefficients of skin tissue and absorption coefficients of the local blood region from the typical values of the results. The depth of the local blood region is over- or underestimated as the scattering coefficients of epidermis and dermis decrease or increase, respectively, while the thickness of the region agrees well with the given values below 1.2 mm. Decreases or increases of hematocrit value give over- or underestimation of the thickness, but they have almost no influence on the depth. PMID:17994894

  20. Automated segmentations of skin, soft-tissue, and skeleton, from torso CT images

    NASA Astrophysics Data System (ADS)

    Zhou, Xiangrong; Hara, Takeshi; Fujita, Hiroshi; Yokoyama, Ryujiro; Kiryu, Takuji; Hoshi, Hiroaki

    2004-05-01

    We have been developing a computer-aided diagnosis (CAD) scheme for automatically recognizing human tissue and organ regions from high-resolution torso CT images. We show some initial results for extracting skin, soft-tissue and skeleton regions. 139 patient cases of torso CT images (male 92, female 47; age: 12-88) were used in this study. Each case was imaged with a common protocol (120kV/320mA) and covered the whole torso with isotopic spatial resolution of about 0.63 mm and density resolution of 12 bits. A gray-level thresholding based procedure was applied to separate the human body from background. The density and distance features to body surface were used to determine the skin, and separate soft-tissue from the others. A 3-D region growing based method was used to extract the skeleton. We applied this system to the 139 cases and found that the skin, soft-tissue and skeleton regions were recognized correctly for 93% of the patient cases. The accuracy of segmentation results was acceptable by evaluating the results slice by slice. This scheme will be included in CAD systems for detecting and diagnosing the abnormal lesions in multi-slice torso CT images.

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

    PubMed

    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

  3. Evaluation of cryo-preserved skin tissues using two-photon microscopy

    NASA Astrophysics Data System (ADS)

    Riemann, Iris; Beier, Axel; Schwarz, Martin; Dörr, Daniel; Stracke, Frank; Zimmermann, Heiko

    2010-02-01

    If no fresh skin samples can be obtained or used, it is important for research and industries to have models and stored tissue samples as close to the native state as possible at disposal. One way to preserve tissues for a longer timeframe is to use deep freezing cryo-techniques. Unfortunately much damage can be induced during the cooling and the thawing processes like disruption of cells and extra-cellular matrices due to the formation of ice crystals. This could lead to a disturbance of the united cell structure up to the point of a loss of cell viability. Two-photon microscopy is able to gather information about cells and tissue components via excitation of the autofluorescence deep inside the sample with a high resolution in both, frozen and thawed states. It is possible to monitor the samples before and after and, important, observe events during the freezing process like the formation of ice crystals. To determine the state of skin tissues after slow rate freezing and the quick process of vitrification, the samples were examined with two-photon microscopy. To establish an optimized freezing-protocol for skin tissues, morphological changes, changes in autofluorescence of endogenous fluorophores (NADH, keratin, flavins, elastin) or changes in second harmonic generation of collagen fibres could provide information about the quality of the used freezing parameters and protective additives and lead to an optimized freezing-protocol with a new set of parameters to obtain mostly intact tissue samples. Multiphoton microscopy has been established as a useful tool for optical in situ quality control of frozen tissues.

  4. Tissue kallikrein in cardiovascular, cerebrovascular and renal diseases and skin wound healing.

    PubMed

    Chao, Julie; Shen, Bo; Gao, Lin; Xia, Chun-Fang; Bledsoe, Grant; Chao, Lee

    2010-04-01

    Tissue kallikrein (KLK1) processes low-molecular weight kininogen to produce vasoactive kinins, which exert biological functions via kinin receptor signaling. Using various delivery approaches, we have demonstrated that tissue kallikrein through kinin B2 receptor signaling exhibits a wide spectrum of beneficial effects by reducing cardiac and renal injuries, restenosis and ischemic stroke, and by promoting angiogenesis and skin wound healing, independent of blood pressure reduction. Protection by tissue kallikrein in oxidative organ damage is attributed to the inhibition of apoptosis, inflammation, hypertrophy and fibrosis. Tissue kallikrein also enhances neovascularization in ischemic heart and limb. Moreover, tissue kallikrein/kinin infusion not only prevents but also reverses kidney injury, inflammation and fibrosis in salt-induced hypertensive rats. Furthermore, there is a wide time window for kallikrein administration in protection against ischemic brain infarction, as delayed kallikrein infusion for 24 h after cerebral ischemia in rats is effective in reducing neurological deficits, infarct size, apoptosis and inflammation. Importantly, in the clinical setting, human tissue kallikrein has been proven to be effective in the treatment of patients with acute brain infarction when injected within 48 h after stroke onset. Finally, kallikrein promotes skin wound healing and keratinocyte migration by direct activation of protease-activated receptor 1. PMID:20180644

  5. Review of tissue penetration and clinical efficacy of enoxacin in skin and skin structure infections and in osteomyelitis.

    PubMed

    Pankey, G A

    1989-01-01

    Enoxacin achieves a high penetration into skin tissue and blister fluid, reaching a maximum serum concentration (Cmax) of 3.7 mg/L at a time to reach maximum concentration (tmax) of 1.9 hours and a blister-fluid Cmax of 2.9 mg/L at a tmax of 3.7 hours after an oral dose of 600 mg. The half-life of enoxacin is 6.2 hours in serum and 7.2 hours in blister fluid. In a multicentre, open, non-comparative trial, clinical cure or improvement in skin or skin structure infections was achieved after oral administration of enoxacin 200 to 600 mg twice daily in 88% of 196 evaluable patients. Overall satisfactory bacteriological response was obtained in 76% of patients. In a multicentre, randomised, double-blind trial comparing oral enoxacin 400 mg twice daily with cephalexin 500 mg twice daily, satisfactory clinical outcome was achieved in 92% of 73 evaluable patients receiving enoxacin and in 99% of 72 evaluable patients receiving cephalexin. Furthermore, there was no statistically significant difference between the bacteriological efficacy of the 2 agents. In 3 single-centre trials, satisfactory clinical results were achieved in 75 to 100% of patients, and satisfactory bacteriological results occurred in 47 to 76% of patients after administration of oral enoxacin 400 mg twice daily for 7 to 14 days. In vitro uptake of enoxacin in bone leads to a concentration of 300 micrograms/g, with 83% being retained by bone after 3 washings with saline at pH 7.2. Clinical trials involving oral enoxacin in osteomyelitis are currently under way. PMID:2653695

  6. 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. PMID:22823443

  7. 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. PMID:25128085

  8. On the influence of soft tissue coverage in the determination of bone kinematics using skin markers.

    PubMed

    Taylor, William R; Ehrig, Rainald M; Duda, Georg N; Schell, Hanna; Seebeck, Petra; Heller, Markus O

    2005-07-01

    Accurate measurement of underlying bone positions is important for the understanding of normal movement and function, as well as for addressing clinical musculoskeletal or post-injury problems. Non-invasive measurement techniques are limited by the analysis technique and movement of peripheral soft tissues that can introduce significant measurement errors in reproducing the kinematics of the underlying bones when using external skin markers. Reflective markers, skeletally mounted to the right hind limb of three Merino-mix sheep were measured simultaneously with markers attached to the skin of each segment, during repetitions of gait trials. The movement of the skin markers relative to the underlying bone positions was then assessed using the Point Cluster Technique (PCT), raw averaging and the Optimal Common Shape Technique (OCST), a new approach presented in this manuscript. Errors in the position of the proximal joint centre, predicted from the corresponding skin markers, were shown to be phasic and strongly associated with the amount soft tissue coverage, averaging 8.5 mm for the femur, 2.8 for the tibia and 2.0 for the metatarsus. Although the results show a better prediction of bone kinematics associated with the Optimal Common Shape Technique, these errors were large for all three assessment techniques and much greater than the differences between the various techniques. Whilst individual markers moved up to 4 mm from the optimal marker set configuration, average peak errors of up to 16, 5 and 3 mm (hip, knee and tibio-metatarsal joints respectively) were observed, suggesting that a large amount of kinematic noise is produced from the synchronous shifting of marker sets, potentially as a result of underlying muscle firing and the inertial effects of heel impact. Current techniques are therefore limited in their ability to determine the kinematics of underlying bones based on skin markers, particularly in segments with more pronounced soft tissue coverage

  9. Quantification of ultrasonic texture intra-heterogeneity via volumetric stochastic modeling for tissue characterization

    PubMed Central

    Al-Kadi, Omar S.; Chung, Daniel Y.F.; Carlisle, Robert C.; Coussios, Constantin C.; Noble, J. Alison

    2015-01-01

    Intensity variations in image texture can provide powerful quantitative information about physical properties of biological tissue. However, tissue patterns can vary according to the utilized imaging system and are intrinsically correlated to the scale of analysis. In the case of ultrasound, the Nakagami distribution is a general model of the ultrasonic backscattering envelope under various scattering conditions and densities where it can be employed for characterizing image texture, but the subtle intra-heterogeneities within a given mass are difficult to capture via this model as it works at a single spatial scale. This paper proposes a locally adaptive 3D multi-resolution Nakagami-based fractal feature descriptor that extends Nakagami-based texture analysis to accommodate subtle speckle spatial frequency tissue intensity variability in volumetric scans. Local textural fractal descriptors – which are invariant to affine intensity changes – are extracted from volumetric patches at different spatial resolutions from voxel lattice-based generated shape and scale Nakagami parameters. Using ultrasound radio-frequency datasets we found that after applying an adaptive fractal decomposition label transfer approach on top of the generated Nakagami voxels, tissue characterization results were superior to the state of art. Experimental results on real 3D ultrasonic pre-clinical and clinical datasets suggest that describing tumor intra-heterogeneity via this descriptor may facilitate improved prediction of therapy response and disease characterization. PMID:25595523

  10. Adipose-Derived Mesenchymal Stromal/Stem Cells: Tissue Localization, Characterization, and Heterogeneity

    PubMed Central

    Baer, Patrick C.; Geiger, Helmut

    2012-01-01

    Adipose tissue as a stem cell source is ubiquitously available and has several advantages compared to other sources. It is easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose-derived mesenchymal stromal/stem cells (ASCs) yields a high amount of stem cells, which is essential for stem-cell-based therapies and tissue engineering. Several studies have provided evidence that ASCs in situ reside in a perivascular niche, whereas the exact localization of ASCs in native adipose tissue is still under debate. ASCs are isolated by their capacity to adhere to plastic. Nevertheless, recent isolation and culture techniques lack standardization. Cultured cells are characterized by their expression of characteristic markers and their capacity to differentiate into cells from meso-, ecto-, and entodermal lineages. ASCs possess a high plasticity and differentiate into various cell types, including adipocytes, osteoblasts, chondrocytes, myocytes, hepatocytes, neural cells, and endothelial and epithelial cells. Nevertheless, recent studies suggest that ASCs are a heterogeneous mixture of cells containing subpopulations of stem and more committed progenitor cells. This paper summarizes and discusses the current knowledge of the tissue localization of ASCs in situ, their characterization and heterogeneity in vitro, and the lack of standardization in isolation and culture methods. PMID:22577397

  11. Temporomandibular joint dysfunction. Connective tissue variations in skin biopsy and mitral valve function.

    PubMed

    Westling, L; Holm, S; Wallentin, I

    1992-12-01

    Ten women with temporomandibular joint dysfunction and general joint hypermobility (score, 4 to 8) and 10 symptom-free female volunteers without systemic laxity (score, 0 to 2) were selected for the study. A biopsy of connective tissue from arm skin found that the total collagen concentrations were lower and the proteoglycan values were higher in the hypermobile TMJ patients than in the control subjects. The mitral region of the heart was inspected by echocardiography. Eight patients and four controls had slightly abnormal echocardiographic findings. Two patients fulfilled the criteria for mitral valve prolapse. The patients had significantly more musculoskeletal complaints than did the controls. The study suggests an association between joint hypermobility, abnormal skin connective tissue composition, mitral valve malfunction, and musculoskeletal disorders in young women with TMJ dysfunction, especially internal derangement. PMID:1488224

  12. Properties and Biocompatibility of Chitosan and Silk Fibroin Blend Films for Application in Skin Tissue Engineering

    PubMed Central

    Luangbudnark, Witoo; Viyoch, Jarupa; Laupattarakasem, Wiroon; Surakunprapha, Palakorn; Laupattarakasem, Pisamai

    2012-01-01

    Chitosan/silk fibroin (CS/SF) blend films were prepared and evaluated for feasibility of using the films as biomaterial for skin tissue engineering application. Fourier transform infrared spectroscopy and differential scanning calorimetry analysis indicated chemical interaction between chitosan and fibroin. Chitosan enhanced β-sheet conformation of fibroin and resulted in shifting of thermal degradation of the films. Flexibility, swelling index, and enzyme degradation were also increased by the chitosan content of the blend films. Biocompatibility of the blend films was determined by cultivation with fibroblast cells. All films showed no cytotoxicity by XTT assay. Fibroblast cells spread on CS/SF films via dendritic extensions, and cell-cell interactions were noted. Cell proliferation on CS/SF films was also demonstrated, and their phenotype was examined by the expression of collagen type I gene. These results showed possibility of using the CS/SF films as a supporting material for further study on skin tissue engineering. PMID:22701367

  13. In vivo model of wound healing based on transplanted tissue-engineered skin.

    PubMed

    Geer, David J; Swartz, Daniel D; Andreadis, Stelios T

    2004-01-01

    Advances in understanding the complex process of wound healing and development of novel growth factor and gene therapies would benefit from models that mimic closely the physiology of human wounds. To this end, we developed a hybrid wound-healing model based on human tissue-engineered skin transplanted onto athymic mice. Grafted tissues were infiltrated with mouse mesenchymal cells as native and foreign dermal regions fused together. Immunohistochemical staining for human involucrin revealed that the transplanted epithelium maintained its human origin, whereas the dermis was infiltrated by numerous mouse fibroblasts and blood vessels. Grafted tissues were wounded with a 4-mm punch to create full-thickness excisional wounds. At 1 and 2 weeks, the tissues were excised and assessed for reepithelialization, differentiation, and neovascularization. Interestingly, the average rate of keratinocyte migration (120 microm/day) was similar to migration rates observed in human subjects and significantly lower than migration in mouse epidermis. Immunohistochemical staining for keratin 10, laminin, and involucrin revealed a normal pattern of differentiation in the neoepidermis. Neovascularization was significantly elevated in the granulation tissue at 1 week and subsided to the level of unwounded tissue at 2 weeks postwounding. Our data suggest that skin equivalents grafted to a mouse model may serve as a realistic model of human wound regeneration. Because skin equivalents can be prepared with patient cells and genetically modified to stimulate or suppress gene expression, this model may be ideal for addressing mechanistic questions and evaluating the efficacy of biomaterials and gene therapeutics for promoting wound healing. PMID:15363158

  14. 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. PMID:24781885

  15. Hot topics in the diagnosis and management of skin and soft-tissue infections.

    PubMed

    Esposito, Silvano; Bassetti, Matteo; Bonnet, Eric; Bouza, Emilio; Chan, Monica; De Simone, Giuseppe; Dryden, Matthew; Gould, Ian; Lye, David Chien; Saeed, Kordo; Segreti, John; Unal, Serhat; Yalcin, Ata Nevzat

    2016-07-01

    Eighteen hot topics regarding the diagnosis and management of skin and soft-tissue infections (SSTIs) were selected and reviewed by members of the SSTI Working Group of the International Society of Chemotherapy (ISC). Despite the large amount of literature available on the issue selected, there are still many unknowns with regard to many of them and further studies are required to answer these challenging issues that face clinicians on a daily basis. PMID:27216380

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

    PubMed

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

    2016-01-01

    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. PMID:27431614

  17. Heterogeneous receptor binding of classical quaternary muscarinic antagonists. I. Bovine tissue distribution.

    PubMed

    Roffel, A F; Ensing, K; in 't Hout, W G; de Zeeuw, R A; Zaagsma, J

    1991-01-01

    In competition experiments with the tertiary radioligand [3H]dexetimide, classical quaternary muscarinic antagonists like ipratropium bromide and N-methylscopolamine bromide distinguished two muscarinic binding sites in bovine brain (total brain minus cerebellum) membranes, in contrast to their tertiary analogues, atropine and scopolamine, which recognized only one binding site. This binding behavior was found to be almost identical in bovine striatal membranes, both in terms of binding affinities and proportions of high (Q1) and low (Q2) affinity binding sites. Both in total brain and in striatal membranes, the Q1/Q2 binding heterogeneity was independent of pirenzepine binding heterogeneity (M1/M2). In peripheral tissues, the binding properties of quaternary muscarinic antagonists varied. Whereas tertiary as well as quaternary compounds showed only high affinity binding towards muscarinic receptors in bovine atrial and left ventricular membranes, heterogeneous binding behavior was observed with quaternary but not with tertiary antagonists in bovine tracheal smooth muscle membranes. The tissue distribution found in the present study suggests that bovine tracheal smooth muscle contraction studies might shed light on the functional significance of the anomalous binding behavior of quaternary muscarinic antagonists. PMID:1824191

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

    NASA Astrophysics Data System (ADS)

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

    2002-05-01

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

  19. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

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

  1. Heterogeneous Tissue Characterization Using Ultrasound: A Comparison of Fractal Analysis Backscatter Models on Liver Tumors.

    PubMed

    Al-Kadi, Omar S; Chung, Daniel Y F; Coussios, Constantin C; Noble, J Alison

    2016-07-01

    Assessment of tumor tissue heterogeneity via ultrasound has recently been suggested as a method for predicting early response to treatment. The ultrasound backscattering characteristics can assist in better understanding the tumor texture by highlighting the local concentration and spatial arrangement of tissue scatterers. However, it is challenging to quantify the various tissue heterogeneities ranging from fine to coarse of the echo envelope peaks in tumor texture. Local parametric fractal features extracted via maximum likelihood estimation from five well-known statistical model families are evaluated for the purpose of ultrasound tissue characterization. The fractal dimension (self-similarity measure) was used to characterize the spatial distribution of scatterers, whereas the lacunarity (sparsity measure) was applied to determine scatterer number density. Performance was assessed based on 608 cross-sectional clinical ultrasound radiofrequency images of liver tumors (230 and 378 representing respondent and non-respondent cases, respectively). Cross-validation via leave-one-tumor-out and with different k-fold methodologies using a Bayesian classifier was employed for validation. The fractal properties of the backscattered echoes based on the Nakagami model (Nkg) and its extend four-parameter Nakagami-generalized inverse Gaussian (NIG) distribution achieved best results-with nearly similar performance-in characterizing liver tumor tissue. The accuracy, sensitivity and specificity of Nkg/NIG were 85.6%/86.3%, 94.0%/96.0% and 73.0%/71.0%, respectively. Other statistical models, such as the Rician, Rayleigh and K-distribution, were found to not be as effective in characterizing subtle changes in tissue texture as an indication of response to treatment. Employing the most relevant and practical statistical model could have potential consequences for the design of an early and effective clinical therapy. PMID:27056610

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

    NASA Astrophysics Data System (ADS)

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

    2012-05-01

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

  3. 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.

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

    PubMed

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

    2016-08-01

    Cutaneous psoriasis (e.g., psoriasis vulgaris (PsV)) and psoriatic arthritis (PsA) are complex heterogeneous diseases thought to have similar pathophysiology. The soluble and cellular mediators of these closely related diseases are being elucidated through genetic approaches such as genome-wide association studies (GWAS), as well as animal and molecular models. Novel therapeutics targeting these mediators (IL-12, IL-23, IL-17, IL-17 receptor, TNF) are effective in treating both the skin and joint manifestations of psoriasis, reaffirming the shared pathophysiology of PsV and PsA. However, the molecular and cellular interactions between skin and joint disease have not been well characterized. Clearly, PsV and PsA are highly variable in terms of their clinical manifestations, and this heterogeneity can partially be explained by differences in HLA-associations (HLA-Cw*0602 versus HLA-B*27, for example). In addition, there are numerous other genetic susceptibility loci (LCE3, CARD14, NOS2, NFKBIA, PSMA6, ERAP1, TRAF3IP2, IL12RB2, IL23R, IL12B, TNIP1, TNFAIP3, TYK2) and geoepidemiologic factors that contribute to the wide variability seen in psoriasis. Herein, we review the complex interplay between the genetic, cellular, ethnic, and geographic mediators of psoriasis, focusing on the shared mechanisms of PsV and PsA. PMID:26780035

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

    PubMed Central

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

    2014-01-01

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

  6. 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. PMID:25336949

  7. Tissue Characterization after a New Disaggregation Method for Skin Micro-Grafts Generation.

    PubMed

    Purpura, Valeria; Bondioli, Elena; Graziano, Antonio; Trovato, Letizia; Melandri, Davide; Ghetti, Martina; Marchesini, Andrea; Cusella De Angelis, Maria Gabriella; Benedetti, Laura; Ceccarelli, Gabriele; Riccio, Michele

    2016-01-01

    Several new methods have been developed in the field of biotechnology to obtain autologous cellular suspensions during surgery, in order to provide one step treatments for acute and chronic skin lesions. Moreover, the management of chronic but also acute wounds resulting from trauma, diabetes, infections and other causes, remains challenging. In this study we describe a new method to create autologous micro-grafts from cutaneous tissue of a single patient and their clinical application. Moreover, in vitro biological characterization of cutaneous tissue derived from skin, de-epidermized dermis (Ded) and dermis of multi-organ and/or multi-tissue donors was also performed. All tissues were disaggregated by this new protocol, allowing us to obtain viable micro-grafts. In particular, we reported that this innovative protocol is able to create bio-complexes composed by autologous micro-grafts and collagen sponges ready to be applied on skin lesions. The clinical application of autologous bio-complexes on a leg lesion was also reported, showing an improvement of both re-epitalization process and softness of the lesion. Additionally, our in vitro model showed that cell viability after mechanical disaggregation with this system is maintained over time for up to seven (7) days of culture. We also observed, by flow cytometry analysis, that the pool of cells obtained from disaggregation is composed of several cell types, including mesenchymal stem cells, that exert a key role in the processes of tissue regeneration and repair, for their high regenerative potential. Finally, we demonstrated in vitro that this procedure maintains the sterility of micro-grafts when cultured in Agar dishes. In summary, we conclude that this new regenerative approach can be a promising tool for clinicians to obtain in one step viable, sterile and ready to use micro-grafts that can be applied alone or in combination with most common biological scaffolds. PMID:26967938

  8. 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

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tissue adhesive with adjunct wound closure device... DEVICES Surgical Devices § 878.4011 Tissue adhesive with adjunct wound closure device for topical approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for...

  9. 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

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tissue adhesive with adjunct wound closure device... DEVICES Surgical Devices § 878.4011 Tissue adhesive with adjunct wound closure device for topical approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for...

  10. 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

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tissue adhesive with adjunct wound closure device... DEVICES Surgical Devices § 878.4011 Tissue adhesive with adjunct wound closure device for topical approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for...

  11. 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

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tissue adhesive with adjunct wound closure device... DEVICES Surgical Devices § 878.4011 Tissue adhesive with adjunct wound closure device for topical approximation of skin. (a) Identification. A tissue adhesive with adjunct wound closure device intended for...

  12. Amniotic fluid for ex vivo skin preservation: a comparative study of tissue preservation solutions.

    PubMed

    Buseman, Jason; Rinker, Alexander B; Rinker, Brian

    2013-12-01

    Ex vivo skin preservation is important for skin banks, burn centers, and in research; however, the optimal preservation solution is not known. Human amniotic fluid (HAF), in addition to its role in fetal wound healing, has promise as an effective and readily available preservation solution. The purpose of this study was to compare the efficacy of several solutions, including HAF, in full-thickness skin preservation. Human amniotic fluid was obtained from patients undergoing amniocentesis. Full-thickness skin obtained during abdominoplasty was divided into 1-cm(2) samples. These specimens were preserved in either saline, HAF from a single patient, pooled HAF, University of Wisconsin solution, or custodial histidine-tryptophan-ketoglutarate solution at 4°C. There were 5 samples in each group. Specimens were examined for keratinocyte survival at 7, 14, 21, 28, and 35 days using the trypan blue assay. The first 200 cells identified were counted to calculate the degree of cell death. Comparisons were made between the groups, and a multivariable repeated-measures analysis was performed to determine statistical significance, which was defined as P < 0.05. The individual and pooled HAF showed greater keratinocyte survival than the other solutions, at each time point. The difference was statistically significant (P < 0.05) when compared to saline and custodial solution but not statistically significant when compared to University of Wisconsin solution. When used as a tissue preservation solution, HAF produces superior keratinocyte survival than several commercially available solutions. Amniotic fluid, nature's tissue preservation solution, may be an inexpensive, readily available alternative for use in skin banks, burn centers, and research. PMID:24231574

  13. 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.

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

    PubMed

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

    2016-01-01

    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

  15. 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

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

    PubMed

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

    2009-01-01

    The object of this study was to investigate whether laser-induced skin autofluorescence (LIF) and/or light reflectance spectra could provide a useful contrast between basal cell carcinoma (BCC) tissues and the surrounding healthy skin. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a nitrogen laser (lambda = 337 nm) for excitation of autofluorescence and a tungsten halogen lamp for the reflectance measurements. The ex vivo spectroscopic results were correlated with the histopathology images to distinguish the areas of BCC from those of the surrounding health skin. A simple spectral analysis technique was also applied for better skin diagnosis. In conclusion, it seems that LIF and reflectance spectra could be used to differentiate neoplastic from normal skin tissue using an appropriate classification model analysis. PMID:19365155

  17. Poly(L-lactide-co-glycolide) thin films can act as autologous cell carriers for skin tissue engineering.

    PubMed

    Zuber, Aleksandra; Borowczyk, Julia; Zimolag, Eliza; Krok, Malgorzata; Madeja, Zbigniew; Pamula, Elzbieta; Drukala, Justyna

    2014-06-01

    Degradable aliphatic polyesters such as polylactides, polyglycolides and their copolymers are used in several biomedical and pharmaceutical applications. We analyzed the influence of poly(L-lactide-co-glycolide) (PLGA) thin films on the adhesion, proliferation, motility and differentiation of primary human skin keratinocytes and fibroblasts in the context of their potential use as cell carriers for skin tissue engineering. We did not observe visible differences in the morphology, focal contact appearance, or actin cytoskeleton organization of skin cells cultured on PLGA films compared to those cultured under control conditions. Moreover, we did not detect biologically significant differences in proliferative activity, migration parameters, level of differentiation, or expression of vinculin when the cells were cultured on PLGA films and tissue culture polystyrene. Our results indicate that PLGA films do not affect the basic functions of primary human skin keratinocytes and fibroblasts and thus show acceptable biocompatibility in vitro, paving the way for their use as biomaterials for skin tissue engineering. PMID:24825569

  18. 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.

  19. 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.

  20. Characteristics and Young's Modulus of Collagen Fibrils from Expanded Skin Using Anisotropic Controlled Rate Self-Inflating Tissue Expander.

    PubMed

    Manssor, Nur Aini S; Radzi, Zamri; Yahya, Noor Azlin; Mohamad Yusof, Loqman; Hariri, Firdaus; Khairuddin, Nurul Hayah; Abu Kasim, Noor Hayaty; Czernuszka, Jan T

    2016-01-01

    Mechanical properties of expanded skin tissue are different from normal skin, which is dependent mainly on the structural and functional integrity of dermal collagen fibrils. In the present study, mechanical properties and surface topography of both expanded and nonexpanded skin collagen fibrils were evaluated. Anisotropic controlled rate self-inflating tissue expanders were placed beneath the skin of sheep's forelimbs. The tissue expanders gradually increased in height and reached equilibrium in 2 weeks. They were left in situ for another 2 weeks before explantation. Expanded and normal skin samples were surgically harvested from the sheep (n = 5). Young's modulus and surface topography of collagen fibrils were measured using an atomic force microscope. A surface topographic scan showed organized hierarchical structural levels: collagen molecules, fibrils and fibers. No significant difference was detected for the D-banding pattern: 63.5 ± 2.6 nm (normal skin) and 63.7 ± 2.7 nm (expanded skin). Fibrils from expanded tissues consisted of loosely packed collagen fibrils and the width of the fibrils was significantly narrower compared to those from normal skin: 153.9 ± 25.3 and 106.7 ± 28.5 nm, respectively. Young's modulus of the collagen fibrils in the expanded and normal skin was not statistically significant: 46.5 ± 19.4 and 35.2 ± 27.0 MPa, respectively. In conclusion, the anisotropic controlled rate self-inflating tissue expander produced a loosely packed collagen network and the fibrils exhibited similar D-banding characteristics as the control group in a sheep model. However, the fibrils from the expanded skin were significantly narrower. The stiffness of the fibrils from the expanded skin was higher but it was not statistically different. PMID:26836267

  1. Evaluation of surrogate tissues as indicators of drug activity in a melanoma skin model.

    PubMed

    Parekh, Palak R; Choudhuri, Rohini; Weyemi, Urbain; Martin, Olga A; Bonner, William M; Redon, Christophe E

    2016-08-01

    The development of novel cancer treatments is a challenging task, partly because results from model systems often fail to predict drug efficacy in humans, and also tumors are often inaccessible for biochemical analysis, preventing effective monitoring of drug activity in vivo. Utilizing a model system, we evaluated the use of drug-induced DNA damage in surrogate tissues as indicators of drug efficacy. Samples of a commercially available melanoma skin model (Mattek MLNM-FT-A375) containing keratinocyte and fibroblast layers with melanoma nodules were subjected to various chemotherapeutic regimens for one, four, or eight days. At these times they were analyzed for DNA double-stranded breaks (γH2AX foci) and apoptosis (TUNEL). A wide range of drug responses in both tumor and normal tissues were observed and cataloged. For the melanoma, the most common drug response was apoptosis. The basal keratinocyte layer, which was the most reliable indicator of drug response in the melanoma skin model, responded with γH2AX foci formation that was abrupt and transient. The relationships between tumor and surrogate tissue drug responses are complex, indicating that while surrogate tissue drug responses may be useful clinical tools, careful control of variables such as the timing of sampling may be important in interpreting the results. PMID:27339860

  2. The potential applications of fibrin-coated electrospun polylactide nanofibers in skin tissue engineering.

    PubMed

    Bacakova, Marketa; Musilkova, Jana; Riedel, Tomas; Stranska, Denisa; Brynda, Eduard; Zaloudkova, Margit; Bacakova, Lucie

    2016-01-01

    Fibrin plays an important role during wound healing and skin regeneration. It is often applied in clinical practice for treatment of skin injuries or as a component of skin substitutes. We prepared electrospun nanofibrous membranes made from poly(l-lactide) modified with a thin fibrin nanocoating. Fibrin surrounded the individual fibers in the membrane and also formed a thin fibrous mesh on several places on the membrane surface. The cell-free fibrin nanocoating remained stable in the cell culture medium for 14 days and did not change its morphology. On membranes populated with human dermal fibroblasts, the rate of fibrin degradation correlated with the degree of cell proliferation. The cell spreading, mitochondrial activity, and cell population density were significantly higher on membranes coated with fibrin than on nonmodified membranes, and this cell performance was further improved by the addition of ascorbic acid in the cell culture medium. Similarly, fibrin stimulated the expression and synthesis of collagen I in human dermal fibroblasts, and this effect was further enhanced by ascorbic acid. The expression of beta1-integrins was also improved by fibrin, and on pure polylactide membranes, it was slightly enhanced by ascorbic acid. In addition, ascorbic acid promoted deposition of collagen I in the form of a fibrous extracellular matrix. Thus, the combination of nanofibrous membranes with a fibrin nanocoating and ascorbic acid seems to be particularly advantageous for skin tissue engineering. PMID:26955273

  3. I. Microwave Apparatus for Exposing Tissue and the Effect of the Radiation on Skin Respiration

    PubMed Central

    Lawrence, J. C.

    1968-01-01

    An apparatus was designed which enabled small pieces of skin to be exposed to a uniform field of microwaves at χ-band (8,730 MHz). This was used to investigate the effect of these microwaves at selected energy levels on the metabolism of skin. It was shown that skin cultured in vitro exhibited a graded response to microwave energy, and a doseresponse curve was constructed from this data. The ED50 of this curve was 4,740 mW./sq. cm. applied for 1 second. Microscopical examination of three-day cultures of skin showed that histological abnormalities occurred if the specimens were exposed to intensities of microwaves causing more than 30% respiratory damage. The energy level at the ED30 was 2,880 mW./sq. cm. applied for 1 second. Results were consistent with the hypothesis that tissue damage caused by irradiation with microwaves was due to the energy absorbed by the specimen being converted to heat. PMID:5663427

  4. 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. PMID:19837098

  5. 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. PMID:21888762

  6. Biofilm formation by Staphylococcus aureus isolates from skin and soft tissue infections.

    PubMed

    Kwiecinski, Jakub; Kahlmeter, Gunnar; Jin, Tao

    2015-05-01

    Many diseases caused by Staphylococcus aureus are associated with biofilm formation. However, the ability of S. aureus isolates from skin and soft tissue infections to form biofilms has not yet been investigated. We tested 160 isolates from patients with various skin infections for biofilm-forming capacity in different growth media. All the isolates formed biofilms, the extent of which depended on the type of growth medium. The thickest biofilms were formed when both plasma and glucose were present in the broth; in this case, S. aureus incorporated host fibrin into the biofilm's matrix. There were no differences in the biofilm formation between isolates from different types of skin infections, except for a particularly good biofilm formation by isolates from diabetic wounds and a weaker biofilm formation by isolates from impetigo. In conclusion, biofilm formation is a universal behavior of S. aureus isolates from skin infections. In some cases, such as in diabetic wounds, a particularly strong biofilm formation most likely contributes to the chronic and recurrent character of the infection. Additionally, as S. aureus apparently uses host fibrin as part of the biofilm structure, we suggest that plasma should be included more frequently in in vitro biofilm studies. PMID:25586078

  7. 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

  8. Premalignant and Malignant Skin Lesions in Two Recipients of Vascularized Composite Tissue Allografts (Face, Hands).

    PubMed

    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

  9. IL-13 from intraepithelial lymphocytes regulates tissue homeostasis and protects against carcinogenesis in the skin

    PubMed Central

    Dalessandri, Tim; Crawford, Greg; Hayes, Mark; Castro Seoane, Rocio; Strid, Jessica

    2016-01-01

    The skin is under constant renewal and exposure to environmental challenges. How homeostasis is maintained alongside protective mechanisms against damage is unclear. Among the basal epithelial cells (ECs) is a population of resident intraepithelial lymphocytes (IELs) that provide host-protective immune surveillance. Here we show that IELs cross-communicate with ECs via the production of IL-13. Skin ECs are activated by IEL-derived IL-13, enabling a canonical EC stress response. In the absence of IL-13, or canonical IEL, the skin has decreased ability to repair its barrier and increased susceptibility to cutaneous carcinogenesis. IL-13 controls the rate of EC movement through the epidermis, which might explain the importance of IL-13 for epidermal integrity and its suppressive effect on skin carcinogenesis. These findings show that IL-13 acts as a molecular bridge between IELs and ECs, and reveal a critical host-defensive role for type-2 immunity in regulating EC tissue homeostasis and carcinogenesis. PMID:27357235

  10. 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

  11. Chitosan as a Modifying Component of Artificial Scaffold for Human Skin Tissue Engineering.

    PubMed

    Romanova, O A; Grigor'ev, T E; Goncharov, M E; Rudyak, S G; Solov'yova, E V; Krasheninnikov, S T; Saprykin, V P; Sytina, E V; Chvalun, S N; Pal'tsev, M A; Panteleev, A A

    2015-08-01

    We compared the structure and mechanical properties of scaffolds based on pure collagen, pure chitosan, and a mixture of these polymers. The role of the composition and structure of scaffolds in the maintenance of cell functions (proliferation, differentiation, and migration) was demonstrated in two experimental models: homogeneous tissue analogues (scaffold populated by fibroblasts) and complex skin equivalents (fibroblasts and keratinocytes). In contrast to collagen scaffolds, pure chitosan inhibited the growth of fibroblasts that did not form contacts with chitosan fibers, but formed specific cellular conglomerates, spheroids, and lose their ability to synthesize natural extracellular matrix. However, the use of chitosan as an additive stimulated proliferative activity of fibroblasts on collagen, which can be associated with improvement of mechanical properties of the collagen scaffolds. The effectiveness of chitosan as an additional cross-linking agent also manifested in its ability to improve significantly the resistance of collagen scaffolds to fibroblast contraction in comparison with glutaraldehyde treatment. Polymer scaffolds (without cells) accelerated complete healing of skin wounds in vivo irrespective of their composition healing, pure chitosan sponge being most effective. We concluded that the use of chitosan as the scaffold for skin equivalents populated with skin cells is impractical, whereas it can be an effective modifier of polymer scaffolds. PMID:26395628

  12. 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

  13. 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.

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

    PubMed

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

    2015-05-01

    This paper presents a method for real-time augmented reality of internal liver structures during minimally invasive hepatic surgery. Vessels and tumors computed from pre-operative CT scans can be overlaid onto the laparoscopic view for surgery guidance. Compared to current methods, our method is able to locate the in-depth positions of the tumors based on partial three-dimensional liver tissue motion using a real-time biomechanical model. This model permits to properly handle the motion of internal structures even in the case of anisotropic or heterogeneous tissues, as it is the case for the liver and many anatomical structures. Experimentations conducted on phantom liver permits to measure the accuracy of the augmentation while real-time augmentation on in vivo human liver during real surgery shows the benefits of such an approach for minimally invasive surgery. PMID:26357206

  15. Suspended, Shrinkage-Free, Electrospun PLGA Nanofibrous Scaffold for Skin Tissue Engineering.

    PubMed

    Ru, Changhai; Wang, Feilong; Pang, Ming; Sun, Lining; Chen, Ruihua; Sun, Yu

    2015-05-27

    Electrospinning is a technique for creating continuous nanofibrous networks that can architecturally be similar to the structure of extracellular matrix (ECM). However, the shrinkage of electrospun mats is unfavorable for the triggering of cell adhesion and further growth. In this work, electrospun PLGA nanofiber assemblies are utilized to create a scaffold. Aided by a polypropylene auxiliary supporter, the scaffold is able to maintain long-term integrity without dimensional shrinkage. This scaffold is also able to suspend in cell culture medium; hence, keratinocyte cells seeded on the scaffold are exposed to air as required in skin tissue engineering. Experiments also show that human skin keratinocytes can proliferate on the scaffold and infiltrate into the scaffold. PMID:25941905

  16. 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.

  17. 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

  18. Tissue repair genes: the TiRe database and its implication for skin wound healing.

    PubMed

    Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E

    2016-04-19

    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

  19. 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. PMID:26344279

  20. Facial skin and soft tissue infection caused by Mycobacterium wolinskyi associated with cosmetic procedures

    PubMed Central

    2013-01-01

    Background Mycobacteirum wolinskyi is a member of the Mycobacterium smegmatis group, which is less frequently found in clinical settings than other nontuberculous mycobacterium (NTM) species. However, its clinical significance has recently increased in opportunistic infections. This case is the first report of facial skin and soft tissue infection by M. wolinskyi complicating cosmetic procedures. Case presentation A 56-year-old Asian female patient with a history of receiving multiple facial cosmetic procedures over the preceding 2 years was admitted to our institution with swelling, local pain, and erythema on the right cheek. Mycobacteirum fortuitum complex isolated from a pus culture was identified as M. wolinskyi by rpoB sequencing. Metallic foreign bodies and abscess were detected by radiologic imaging. The pus was incised and drained. Treatment comprised clarithromycin (500 mg every 12 h), amikacin (200 mg every 8 h), and ciprofloxacin (400 mg every 6 h). Conclusion We report the first case of facial skin and soft tissue infection with M. wolinskyi after multiple cosmetic procedures of filler injection and laser lipolysis. Increased occurrence of NTM infection in nosocomial settings suggests the importance of appropriate treatment including culturing and rpoB gene sequencing when patients who have undergone cosmetic procedures display symptoms and signs of soft tissue infection indicative of NTM infection. PMID:24131522

  1. 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

  2. [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. PMID:18513892

  3. Molecular composition of type VI collagen. Evidence for chain heterogeneity in mammalian tissues and cultured cells.

    PubMed Central

    Kielty, C M; Boot-Handford, R P; Ayad, S; Shuttleworth, C A; Grant, M E

    1990-01-01

    The chain composition and relative abundance of type VI collagen synthesized by cells cultured from foetal bovine nuchal ligament and skin were compared with those of the type VI collagen present in these foetal tissues. Immunoprecipitation of intact collagen VI from medium and cell layers of nuchal ligament fibroblasts and skin fibroblasts at confluence revealed collagen type VI molecules with a chain composition consistent with an [alpha 1(VI)alpha 2(VI)alpha 3(VI)] monomeric assembly. Maintenance of cells in a post-confluent quiescent state promoted a marked phenotypic change in these ratios, with increased concentrations of assemblies composed of equimolar ratios of alpha 1(VI) and alpha 2(VI) chains detected in the medium of these cultures. Analysis of steady-state concentrations of mRNA for alpha 1(VI) and alpha 2(VI) chains revealed these species to be present in increased abundance at post-confluence in all the cultures, but no corresponding increase was observed in the alpha 3(VI) mRNA. In order to assess the physiological significance of these observations, the chain composition of the collagen VI content of the corresponding foetal tissues was assessed by Western blotting after extraction in guanidinium isothiocyanate under reducing conditions. Extracts of nuchal ligament revealed a collagen VI chain composition consistent with a heterotrimeric chain assembly. In contrast, the skin extracts revealed an abundance of alpha 1(VI) and alpha 2(VI) chains with only traces of the alpha 3(VI) chain detected. Increased equimolar concentrations of the alpha 1(VI)-chain and alpha 2(VI)-chain mRNAs in skin again reflected the increased concentrations of these polypeptide chains. Type VI collagen was present in greater abundance both in the nuchal ligament and in the corresponding nuchal-ligament fibroblast cultures. The results indicate that the chain composition of type VI collagen is subject to modulation at the level of transcription as a result of variations in

  4. 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].

  5. 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

  6. Stable-hydrogen isotope heterogeneity in keratinous materials: mass spectrometry and migratory wildlife tissue subsampling strategies.

    PubMed

    Wassenaar, Leonard I; Hobson, Keith A

    2006-01-01

    Stable-hydrogen isotope measurements (deltaD) of biological tissues have gained widespread acceptance in wildlife and forensic studies, especially in tracking geographical movements of birds and other species. Continuous-flow isotope-ratio mass spectrometry enables high-throughput deltaD analyses to be conducted on tissue samples as small as 0.15 mg, compared with conventional offline analyses that require 7-10 mg. This reduction in sample size has raised concerns regarding intra-sample hydrogen isotopic variance due to potential biological heterogeneities that could exceed interpretations of geospatial origin. To help resolve this, feathers were obtained from captive birds to examine isotopic variance expected due to sample size, location, and heterogeneity factors, and from selected wild birds to examine isotopic variance due to these and to additional dietary or location changes during feather growth. Captive bird feathers were sub-sampled along the vane on either side of a single feather at masses of 0.25, 0.35, 0.45, 0.6, 1.0 and 2.0 mg, and along the rachis. The results showed consistency of feather deltaD measurements across a wide range of sample masses. Within-feather deltaD isotopic variance for captive and some wild birds was as low as +/-3 per thousand for vane material, which corresponds to a geospatial resolution of about 1 degree of latitude in central North America. Intra-sample variance for the rachis was +/-5 per thousand, with lower deltaD values for both wild and captive birds. However, given the extraordinary intra-feather deltaD variance observed in some wild species, we recommend researchers first carefully assess the degree of intra- and inter-sample hydrogen isotopic variation in the selected tissue growth period for the species of interest before geospatial interpretations of origin are attempted. PMID:16862621

  7. 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.

  8. Nitric oxide nanoparticle technology: a novel antimicrobial agent in the context of current treatment of skin and soft tissue infection.

    PubMed

    Englander, Laura; Friedman, Adam

    2010-06-01

    Staphylococcus aureus infections account for the majority of skin and soft tissue infections in the United States. Staphylococcus aureus is rapidly evolving resistance to contemporary topical as well as systemic antibiotics. Alternatives to current treatment options for skin and soft tissue infections are needed for more effective treatment now and in the future. Nitric oxide's proven roles in both wound repair and as an antimicrobial agent make it an excellent candidate for the treatment of skin infections. Recent attempts at novel nitric oxide therapies, in the form of nitric oxide donors, have shown limited potential in treating cutaneous infection. However, more recent developments in nitric oxide delivery, using nitric oxide nanoparticle technology, demonstrate substantial promise in the promotion of wound repair and eradication of skin and soft tissue infections. PMID:20725551

  9. 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. PMID:27023906

  10. Ultrahigh Detective Heterogeneous Photosensor Arrays with In-Pixel Signal Boosting Capability for Large-Area and Skin-Compatible Electronics.

    PubMed

    Kim, Jaehyun; Kim, Jaekyun; Jo, Sangho; Kang, Jingu; Jo, Jeong-Wan; Lee, Myungwon; Moon, Juhyuk; Yang, Lin; Kim, Myung-Gil; Kim, Yong-Hoon; Park, Sung Kyu

    2016-04-01

    An ultra-thin and large-area skin-compatible heterogeneous organic/metal-oxide photosensor array is demonstrated which is capable of sensing and boosting signals with high detectivity and signal-to-noise ratio. For the realization of ultra-flexible and high-sensitive heterogeneous photosensor arrays on a polyimide substrate having organic sensor arrays and metal-oxide boosting circuitry, solution-processing and room-temperature alternating photochemical conversion routes are applied. PMID:26928606

  11. Effect of microwaves at X-band on guinea-pig skin in tissue culture: 3. Effect of pulsed microwaves on skin respiration and biochemistry

    PubMed Central

    Carney, S. A.; Lawrence, J. C.; Ricketts, C. R.

    1970-01-01

    Carney, S. A., Lawrence, J. C., and Ricketts, C. R. (1970).Brit. J. industr. Med.,27, 72-76. Effect of microwaves at X-band on guinea-pig skin in tissue culture. 3. Effect of pulsed microwaves on skin respiration and biochemistry. Small pieces of guinea-pig skin were exposed to known power densities of pulsed microwaves at X-band (9·6 GHz). The pulse duration was 0·25 microsecond and the pulse repetition frequency 4 KHz. The peak power was thus 1,000 times the mean power. Otherwise conditions were closely comparable with those of previous experiments using continuous microwaves. After exposure the skin was maintained on a nutrient medium in vitro. The respiration of the skin and the uptake of 35S-sulphate, 32P-phosphate, and 14C-L-proline into skin constituents were reduced by exposure. The reduction was very similar to that observed after exposure to the same mean power density of continuous microwaves. The effects are believed to be attributable to heating of the skin. PMID:5418922

  12. Radioresistance of granulation tissue-derived cells from skin wounds combined with total body irradiation.

    PubMed

    Dai, Tingyu; Chen, Zelin; Tan, Li; Shi, Chunmeng

    2016-04-01

    Combined radiation and wound injury (CRWI) occurs following nuclear explosions and accidents, radiological or nuclear terrorism, and radiation therapy combined with surgery. CRWI is complicated and more difficult to heal than single injuries. Stem cell‑based therapy is a promising treatment strategy for CRWI, however, sourcing stem cells remains a challenge. In the present study, the granulation tissue-derived cells (GTCs) from the skin wounds (SWs) of CRWI mice (C‑GTCs) demonstrated a higher radioresistance to the damage caused by combined injury, and were easier to isolate and harvest when compared with bone marrow‑derived mesenchymal stromal cells (BMSCs). Furthermore, the C-GTCs exhibited similar stem cell-associated properties, such as self-renewal and multilineage differentiation capacity, when compared with neonatal dermal stromal cells (DSCs) and GTCs from unirradiated SWs. Granulation tissue, which is easy to access, may present as an optimal autologous source of stem/progenitor cells for therapeutic applications in CRWI. PMID:26936439

  13. 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.

  14. An in-vitro investigation of skin tissue soldering using gold nanoshells and diode laser.

    PubMed

    Nourbakhsh, Mohammad S; Khosroshahi, Mohammad E

    2011-01-01

    Gold-coated silica core nanoparticles have an optical response dictated by the plasmon resonance (PR). The wavelength at which the resonance occurs depends on the core and shell size, allowing nanoshells to be tailored for particular applications. The purpose of this study is to synthesize and use different concentrations of gold nanoshells as exogenous material for in-vitro skin tissue soldering and also to examine the effect of laser-soldering parameters on the properties of repaired skin. Two mixtures of albumin solder and different concentrations of gold nanoshells were prepared. A full-thickness incision of 2 × 20 mm(2) was made on the surface and after addition of mixtures it was irradiated by an 810-nm diode laser at different power densities. The changes of tensile strength σ(t) due to temperature rise, number of scan (N(s)), and scan velocity (V(s)) were investigated. The results showed at constant laser power density (I), σ(t) of repaired incisions increases by increasing the concentration of gold nanoshells, N(s) and decreasing V(s). It is therefore important to consider the trade-off between the scan velocity and the skin temperature for achieving an optimum operating condition. In our case, this corresponds to σ(t) = 1,610 g/cm(2) at I ∼ 60 Wcm(-2), T ∼ 65°C, Ns = 10 and Vs = 0.2 mms(-1). PMID:20623244

  15. 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.

  16. Fibrin-Induced Skin Fibrosis in Mice Deficient in Tissue Plasminogen Activator

    PubMed Central

    de Giorgio-Miller, Alexander; Bottoms, Steve; Laurent, Geoffrey; Carmeliet, Peter; Herrick, Sarah

    2005-01-01

    The deposition of fibrin is an integral part of the tissue repair process, but its persistence is also associated with a number of fibrotic conditions. This study addressed the hypothesis that reduced fibrinolysis and fibrin persistence are associated with an enhanced accumulation of collagen and the development of skin fibrosis. Decreased fibrinolysis was confirmed in fibrin gel cultures that contained human dermal fibroblasts plus the specific plasmin inhibitor α2-antiplasmin or dermal fibroblasts isolated from plasminogen activator (PA)-deficient mice. Collagen accumulation was significantly increased in the presence of inhibitor and in tPA-deficient, but not uPA-deficient, fibroblasts compared with controls. These findings were also confirmed using a skin fibrosis model in which multiple injections of fibrin were given subcutaneously to PA-deficient mice. Injection sites from tPA-deficient mice displayed significantly increased collagen levels compared with uPA-deficient mice and wild-type controls. Up-regulation of fibroblast procollagen gene expression and reduced activation of pro-MMP-1 appeared to mediate the increase in collagen by human dermal fibroblasts in the presence of α2-antiplasmin. These findings suggest that persistent fibrin is associated with enhanced collagen accumulation that may result in the development of fibrotic skin disorders in which reduced fibrinolysis is a feature. PMID:16127152

  17. Children hospitalized with skin and soft tissue infections: a guide to antibacterial selection and treatment.

    PubMed

    Vayalumkal, Joseph V; Jadavji, Tajdin

    2006-01-01

    Skin and soft tissue infections in children are an important cause for hospitalization. A thorough history and physical examination can provide clues to the pathogens involved. Collection of purulent discharge from lesions should be completed prior to initiating antimicrobial therapy, and results of bacteriologic studies (Gram stain and culture) should guide therapeutic decisions. The main pathogens involved in these infections are Staphylococcus aureus and group A beta-hemolytic streptococci, but enteric organisms also play a role especially in nosocomial infections. Increasing antibacterial resistance is becoming a major problem in the treatment of these infections worldwide. Specifically, the rise of methicillin-resistant S. aureus and glycopeptide-resistant S. aureus pose challenges for the future. Infections of the skin and soft tissues can be broadly classified based on the extent of tissue involvement. Superficial infections such as erysipelas, cellulitis, bullous impetigo, bite infections, and periorbital cellulitis may require hospitalization and parenteral antibacterials. Deeper infections such as orbital cellulitis, necrotizing fasciitis, and pyomyositis require surgical intervention as well as parenteral antibacterial therapy. Surgery plays a key role in the treatment of abscesses and for the debridement of necrotic tissue in deep infections. Intravenous immunoglobulin, as an adjunctive therapy, can be helpful in treating necrotizing fasciitis. For most infections an antistaphylococcal beta-lactam antibacterial is first-line therapy. Third-generation cephalosporins and beta-lactam/beta-lactamase inhibitor antibacterials as well as clindamycin or metronidazole are often required to provide broad-spectrum coverage for polymicrobial infections.Special populations, such as immunocompromised children, those with an allergy to penicillins, and those that acquire infections in hospitals, require specific antibacterial strategies. These usually involve broader

  18. 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.

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

    PubMed

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

    2015-01-01

    The complexity of biological tissue morphogenesis makes in silico simulations of such system very interesting in order to gain a better understanding of the underlying mechanisms ruling the development of multicellular tissues. This complexity is mainly due to two elements: firstly, biological tissues comprise a large amount of cells; secondly, these cells exhibit complex interactions and behaviors. To address these two issues, we propose two tools: the first one is a virtual cell model that comprise two main elements: firstly, a mechanical structure (membrane, cytoskeleton, and cortex) and secondly, the main behaviors exhibited by biological cells, i.e., mitosis, growth, differentiation, molecule consumption, and production as well as the consideration of the physical constraints issued from the environment. An artificial chemistry is also included in the model. This virtual cell model is coupled to an agent-based formalism. The second tool is a simulator that relies on the OpenCL framework. It allows efficient parallel simulations on heterogenous devices such as micro-processors or graphics processors. We present two case studies validating the implementation of our model in our simulator: cellular proliferation controlled by cell signalling and limb growth in a virtual organism. PMID:26451816

  20. 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

  1. Collagen structural alterations contribute to stiffening of tissue after split-thickness skin grafting.

    PubMed

    Rosin, Nicole L; Agabalyan, Natacha; Olsen, Katherine; Martufi, Giampaol; Gabriel, Vincent; Biernaskie, Jeff; Di Martino, Elena S

    2016-03-01

    The gold standard treatment for full thickness injuries of the skin is autologous split-thickness skin grafting. This involves harvesting the epidermis and superficial dermis from healthy skin and transplanting it onto the prepared wound bed. The donor site regenerates spontaneously, but the appendages and cellular components from the dermal layer are excluded from the graft. As a result, the new tissue is inferior; the healed graft site is dry/itchy, has decreased elasticity, increased fragility, and altered sensory function. Because this dermal layer is composed of collagen and other extracellular matrix proteins, the aim was to characterize the changes in the dermal collagen after split thickness grafting that could contribute to a deficit in functionality. This will serve as a baseline for future studies designed to improve skin function using pharmacological or cell-based therapies for skin repair. A xenograft model whereby human split-thickness grafts were implanted into full-thickness defects on immunocompromised (athymic Nu/Nu) mice was used. The grafts were harvested 4 and 8 weeks later. The collagen microstructure was assessed with second harmonic generation with dual-photon microscopy and light polarization analysis. Collagen fiber stiffness and engagement stretch were estimated by fitting the results of biaxial mechanical tensile tests to a histo-mechanical constitutive model. The stiffness of the collagen fibril-proteoglycan complex increased from 682 ± 226 kPa/sr to 1016 ± 324 kPa/sr between 4 and 8 weeks postgrafting. At the microstructural level there were significant decreases in both thickness of collagen fibers (3.60 ± 0.34 μm vs. 2.10 ± 0.27 μm) and waviness ratio (2.04 ± 0.17 vs. 1.43 ± 0.08) of the collagen fibers postgrafting. The decrease of the macroscopic engagement stretch from 1.19 ± 0.11 to 1.09 ± 0.08 over time postgrafting mirrored the decrease in waviness measured at the microscopic level

  2. Data on CUX1 isoforms in idiopathic pulmonary fibrosis lung and systemic sclerosis skin tissue sections.

    PubMed

    Ikeda, Tetsurou; Fragiadaki, Maria; Shi-Wen, Xu; Ponticos, Markella; Khan, Korsa; Denton, Christopher; Garcia, Patricia; Bou-Gharios, George; Yamakawa, Akio; Morimoto, Chikao; Abraham, David

    2016-09-01

    This data article contains complementary figures related to the research article entitled, "Transforming growth factor-β-induced CUX1 isoforms are associated with fibrosis in systemic sclerosis lung fibroblasts" (Ikeda et al. (2016) [2], http://dx.doi.org/10.1016/j.bbrep.2016.06.022), which presents that TGF-β increased CUX1 binding in the proximal promoter and enhancer of the COL1A2 and regulated COL1. Further, in the scleroderma (SSc) lung and diffuse alveolar damage lung sections, CUX1 localized within the α- smooth muscle actin (α-SMA) positive cells (Fragiadaki et al., 2011) [1], "High doses of TGF-beta potently suppress type I collagen via the transcription factor CUX1" (Ikeda et al., 2016) [2]. Here we show that CUX1 isoforms are localized within α-smooth muscle actin-positive cells in SSc skin and idiopathic pulmonary fibrosis (IPF) lung tissue sections. In particular, at the granular and prickle cell layers in the SSc skin sections, CUX1 and α-SMA are co-localized. In addition, at the fibrotic loci in the IPF lung tissue sections, CUX1 localized within the α-smooth muscle actin (α-SMA) positive cells. PMID:27583344

  3. A novel gellan-PVA nanofibrous scaffold for skin tissue regeneration: Fabrication and characterization.

    PubMed

    Vashisth, Priya; Nikhil, Kumar; Roy, Partha; Pruthi, Parul A; Singh, Rajesh P; Pruthi, Vikas

    2016-01-20

    In this investigation, we have introduced novel electrospun gellan based nanofibers as a hydrophilic scaffolding material for skin tissue regeneration. These nanofibers were fabricated using a blend mixture of gellan with polyvinyl alcohol (PVA). PVA reduced the repulsive force of resulting solution and lead to formation of uniform fibers with improved nanostructure. Field emission scanning electron microscopy (FESEM) confirmed the average diameter of nanofibers down to 50 nm. The infrared spectra (IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis evaluated the crosslinking, thermal stability and highly crystalline nature of gellan-PVA nanofibers, respectively. Furthermore, the cell culture studies using human dermal fibroblast (3T3L1) cells established that these gellan based nanofibrous scaffold could induce improved cell adhesion and enhanced cell growth than conventionally proposed gellan based hydrogels and dry films. Importantly, the nanofibrous scaffold are biodegradable and could be potentially used as a temporary substrate/or biomedical graft to induce skin tissue regeneration. PMID:26572421

  4. Fabrication of robust Antheraea assama fibroin nanofibrous mat using ionic liquid for skin tissue engineering.

    PubMed

    Srivastava, Chandra Mohan; Purwar, Roli

    2016-11-01

    Electrospinning is an emerging technique used for fabrication of nanofibrous mats for skin tissue engineering applications. The aim of this study centered on fabrication of muga fibroin electrospun mats by using ionic liquid and its characterizations. The muga fibroin extracted from cocoon of Antheraea assama is dissolved in 1-butyl, 3-methyl imidazolium acetate (BMIMAc), a green solvent, to prepare a dope solution for electrospinning. The molecular weight, rheology and structural properties of dope solution are characterized. The process parameters of electrospinning machine such as voltage and concentration of dope solution are varied to obtain nanofibrous mats. The nanofibrous mat having average fiber diameter of 160nm are obtained from 10% w/v concentration of muga fibroin in BMIMAc with an applied voltage of 20KV. The mechanical, structural, physical and thermal properties of muga nanofibrous mat (MNF) are analyzed and compare with muga cast film. The cytocompatibility test is performed using L929 fibroblast cells. It is observed that muga nanofibrous mat support higher growth of fibroblast cells (p<0.05) as compared to muga cast film (MCF). Muga nanofibrous mat and cast film are loaded with gentamycin sulphate. The release rate and antimicrobial efficiency of gentamycin sulphate loaded muga nanofibrous mat are found to be significantly higher (p<0.05) as compared to muga cast film. All these results indicate that muga nanofibrous mat would be a promising material for skin tissue engineering. PMID:27524022

  5. 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

  6. Modeling and Simulation of Coupled Cell Proliferation and Regulation in Heterogeneous Tissue.

    PubMed

    Zohdi, T I

    2015-07-01

    The primary objective of this work is to develop a computational framework that efficiently simulates the time-transient proliferation of cellular tissue, with heterogeneous microstructure, utilizing two strongly-coupled conservation laws: Conservation Law 1: comprises (a) rate of change of cells, (b) cellular migration, (c) cellular proliferation controlled by a cell mitosis regulating chemical, (d) cell apoptosis and Conservation Law 2: comprises (a) rate of change of the cell mitosis chemical regulator, (b) regulator diffusion, (c) regulator production by cells and (d) regulator decay. Specifically, a straightforward approach is developed that researchers in the field can easily implement and use as a computationally-efficient tool to study such biological systems. Because multifield coupling is present, a recursive, staggered, temporally-adaptive, Finite Difference Time Domain scheme is developed to resolve the interacting fields. The time-step adaptation allows the numerical scheme to iteratively resolve the changing physical fields by reducing the time-steps during phases of the process when the system is undergoing changes on relatively small time-scales or enlarging the time-steps when the processes are relatively slow. The spatial discretization grids are uniform and dense, and the heterogeneous microstructure, is embedded into the spatial discretization. The regular grid allows one to generate a matrix-free iterative formulation which is amenable to rapid computation and minimal memory requirements, making it ideal for laptop computation. Numerical examples are provided to illustrate the approach. PMID:25476161

  7. The influence of stromal cells on the pigmentation of tissue-engineered dermo-epidermal skin grafts.

    PubMed

    Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Klar, Agnieszka S; Widmer, Daniel S; Pontiggia, Luca; Weber, Andreas D; Weber, Daniel M; Schiestl, Clemens; Meuli, Martin; Reichmann, Ernst

    2015-03-01

    It has been shown in vitro that melanocyte proliferation and function in palmoplantar skin is regulated by mesenchymal factors derived from fibroblasts. In this study, we investigated in vivo the influence of mesenchymal-epithelial interactions in human tissue-engineered skin substitutes reconstructed from palmar- and nonpalmoplantar-derived fibroblasts. Tissue-engineered dermo-epidermal analogs based on collagen type I hydrogels were populated with either human palmar or nonpalmoplantar fibroblasts and seeded with human nonpalmoplantar-derived melanocytes and keratinocytes. These skin substitutes were transplanted onto full-thickness skin wounds of immunoincompetent rats. Four weeks after transplantation the development of skin color was measured and grafts were excised and analyzed with regard to epidermal characteristics, in particular melanocyte number and function. Skin substitutes containing palmar-derived fibroblasts in comparison to nonpalmoplantar-derived fibroblasts showed (a) a significantly lighter pigmentation; (b) a reduced amount of epidermal melanin granules; and (c) a distinct melanosome expression. However, the number of melanocytes in the basal layer remained similar in both transplantation groups. These findings demonstrate that human palmar fibroblasts regulate the function of melanocytes in human pigmented dermo-epidermal skin substitutes after transplantation, whereas the number of melanocytes remains constant. This underscores the influence of site-specific stromal cells and their importance when constructing skin substitutes for clinical application. PMID:25300246

  8. The Influence of Stromal Cells on the Pigmentation of Tissue-Engineered Dermo-Epidermal Skin Grafts

    PubMed Central

    Biedermann, Thomas; Böttcher-Haberzeth, Sophie; Klar, Agnieszka S.; Widmer, Daniel S.; Pontiggia, Luca; Weber, Andreas D.; Weber, Daniel M.; Schiestl, Clemens; Meuli, Martin

    2015-01-01

    It has been shown in vitro that melanocyte proliferation and function in palmoplantar skin is regulated by mesenchymal factors derived from fibroblasts. In this study, we investigated in vivo the influence of mesenchymal–epithelial interactions in human tissue-engineered skin substitutes reconstructed from palmar- and nonpalmoplantar-derived fibroblasts. Tissue-engineered dermo-epidermal analogs based on collagen type I hydrogels were populated with either human palmar or nonpalmoplantar fibroblasts and seeded with human nonpalmoplantar-derived melanocytes and keratinocytes. These skin substitutes were transplanted onto full-thickness skin wounds of immunoincompetent rats. Four weeks after transplantation the development of skin color was measured and grafts were excised and analyzed with regard to epidermal characteristics, in particular melanocyte number and function. Skin substitutes containing palmar-derived fibroblasts in comparison to nonpalmoplantar-derived fibroblasts showed (a) a significantly lighter pigmentation; (b) a reduced amount of epidermal melanin granules; and (c) a distinct melanosome expression. However, the number of melanocytes in the basal layer remained similar in both transplantation groups. These findings demonstrate that human palmar fibroblasts regulate the function of melanocytes in human pigmented dermo-epidermal skin substitutes after transplantation, whereas the number of melanocytes remains constant. This underscores the influence of site-specific stromal cells and their importance when constructing skin substitutes for clinical application. PMID:25300246

  9. 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.

  10. 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. PMID:27015452

  11. A practical guide to the treatment of complicated skin and soft tissue infections.

    PubMed

    Fung, Horatio B; Chang, Joanne Y; Kuczynski, Stephen

    2003-01-01

    Complicated skin and soft tissue infections (SSTIs) remain a common reason for hospitalisation. Optimal management of complicated SSTIs begins with a physical examination, and obtaining the complete social and medical history of the patient. Empirical intravenous antibacterial therapy is guided by expected pathogens, patient factors and diagnostic procedure reports, such as the Gram-stained smear of discharge or exudates. The majority of community-acquired SSTIs are caused by Staphylococcus aureus and beta-haemolytic streptococci. On the basis of recent surveillance data, 80-90% of these pathogens remain susceptible to cefazolin or oxacillin. Consequently, a first generation cephalosporin or an antistaphylococcal penicillin remains the first line empirical therapy for community-acquired skin and soft tissue infections. Vancomycin may be an appropriate alternative when vancomycin-resistant S. aureus is highly suspected on the basis of patient history and co-morbid conditions. With the global emergence and spread of macrolide-resistant S. aureus and beta-haemolytic streptococci, clindamycin rather than a macrolide is the recommended agent for empirical antibacterial therapy of community-acquired SSTIs in penicillin-allergic patients. Nosocomial complicated SSTIs are predominantly caused by S. aureus, Pseudomonas aeruginosa, Enterococcus spp., Escherichia coli and other Enterobacteriaceae. Piperacillin/tazobactam with or without vancomycin is the preferred agent for empirical treatment depending on local resistance statistics. The newer fluoroquinolones may have a role in the treatment of complicated SSTIs, especially in penicillin-allergic patients. More clinical studies are needed before a formal recommendation can be made. Many of the newer antimicrobial agents such as the carbapenems, oxazolidinones and streptogramins have been shown to be effective for the treatment of complicated SSTIs. However, because of their proven activity against highly resistant organisms

  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. Hyaluronan and Fibrin Biomaterial as Scaffolds for Neuronal Differentiation of Adult Stem Cells Derived from Adipose Tissue and Skin

    PubMed Central

    Gardin, Chiara; Vindigni, Vincenzo; Bressan, Eriberto; Ferroni, Letizia; Nalesso, Elisa; Puppa, Alessandro Della; D’Avella, Domenico; Lops, Diego; Pinton, Paolo; Zavan, Barbara

    2011-01-01

    Recently, we have described a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. Due to their possible application in neuronal tissue regeneration, here we tested two kinds of scaffold well known in tissue engineering application: hyaluronan based membranes and fibrin-glue meshes. Neurospheres from skin and adipose tissue were seeded onto two scaffold types: hyaluronan based membrane and fibrin-glue meshes. Neurospheres were then induced to acquire a glial and neuronal-like phenotype. Gene expression, morphological feature and chromosomal imbalance (kariotype) were analyzed and compared. Adipose and skin derived neurospheres are able to grow well and to differentiate into glial/neuron cells without any chromosomal imbalance in both scaffolds. Adult cells are able to express typical cell surface markers such as S100; GFAP; nestin; βIII tubulin; CNPase. In summary, we have demonstrated that neurospheres isolated from skin and adipose tissues are able to differentiate in glial/neuron-like cells, without any chromosomal imbalance in two scaffold types, useful for tissue engineering application: hyaluronan based membrane and fibrin-glue meshes. PMID:22072917

  14. 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

  15. 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

  16. Remote Skin Tissue Diagnostics In Vivo By Fiber Optic Evanescent Wave Fourier Transform Infrared (FEW-FTIR) Spectroscopy

    NASA Astrophysics Data System (ADS)

    Kolyakov, Sergei; Afanasyeva, Natalia; Bruch, Reinhard; Afanasyeva, Natalia

    1998-05-01

    The new method of fiber optical evanescent wave Fourier transform infrared (FEW-FTIR) spectroscopy has been applied to the diagnostics of normal skin 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 infrared (MIR) region is relatively inexpensive and can be adapted easily to any commercially available tabletop FTIR spectrometers. This method of diagnostics is fast (several seconds), 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 of 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.

  17. Heterogeneity of Borrelia burgdorferi Sensu Stricto Population and Its Involvement in Borrelia Pathogenicity: Study on Murine Model with Specific Emphasis on the Skin Interface

    PubMed Central

    Kern, Aurélie; Schnell, Gilles; Bernard, Quentin; Bœuf, Amandine; Jaulhac, Benoît; Collin, Elody; Barthel, Cathy

    2015-01-01

    Lyme disease is a multisystemic disorder caused by B. burgdorferi sl. The molecular basis for specific organ involvement is poorly understood. The skin plays a central role in the development of Lyme disease as the entry site of B. burgdorferi in which specific clones are selected before dissemination. We compared the skin inflammatory response (antimicrobial peptides, cytokines and chemokines) elicited by spirochete populations recovered from patients presenting different clinical manifestations. Remarkably, these spirochete populations induced different inflammatory profiles in the skin of C3H/HeN mice. As spirochete population transmitted into the host skin is heterogeneous, we isolated one bacterial clone from a population recovered from a patient with neuroborreliosis and compared its virulence to the parental population. This clone elicited a strong cutaneous inflammatory response characterized by MCP-1, IL-6 and antimicrobial peptides induction. Mass spectrometry of this clone revealed 110 overexpressed proteins when compared with the parental population. We further focused on the expression of nine bacterial surface proteins. bb0347 coding for a protein that interacts with host fibronectin, allowing bacterial adhesion to vascular endothelium and extracellular matrix, was found to be induced in host skin with another gene bb0213 coding for a hypothetical protein. These findings demonstrate the heterogeneity of the B. burgdorferi ss population and the complexity of the interaction involved early in the skin. PMID:26197047

  18. 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.

  19. 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. PMID:26335157

  20. Monte Carlo simulation of radiation transport in human skin with rigorous treatment of curved tissue boundaries

    NASA Astrophysics Data System (ADS)

    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.

  1. Mapping tissue shear modulus on Thiel soft-embalmed mouse skin with shear wave optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Song, Shaozhen; Joy, Joyce; Wang, Ruikang K.; Huang, Zhihong

    2015-03-01

    A quantitative measurement of the mechanical properties of biological tissue is a useful assessment of its physiologic conditions, which may aid medical diagnosis and treatment of, e.g., scleroderma and skin cancer. Traditional elastography techniques such as magnetic resonance elastography and ultrasound elastography have limited scope of application on skin due to insufficient spatial resolution. Recently, dynamic / transient elastography are attracting more applications with the advantage of non-destructive measurements, and revealing the absolute moduli values of tissue mechanical properties. Shear wave optical coherence elastography (SW-OCE) is a novel transient elastography method, which lays emphasis on the propagation of dynamic mechanical waves. In this study, high speed shear wave imaging technique was applied to a range of soft-embalmed mouse skin, where 3 kHz shear waves were launched with a piezoelectric actuator as an external excitation. The shear wave velocity was estimated from the shear wave images, and used to recover a shear modulus map in the same OCT imaging range. Results revealed significant difference in shear modulus and structure in compliance with gender, and images on fresh mouse skin are also compared. Thiel embalming technique is also proven to present the ability to furthest preserve the mechanical property of biological tissue. The experiment results suggest that SW-OCE is an effective technique for quantitative estimation of skin tissue biomechanical status.

  2. 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.

  3. In vitro bioartificial skin culture model of tissue rejection and inflammatory/immune mechanisms.

    PubMed

    Strande, L F; Foley, S T; Doolin, E J; Hewitt, C W

    1997-06-01

    We hypothesized that an in vitro bioartificial skin rejection model using living LSEs grown in tissue culture could be developed for the study of autologous, allogenic, and/or xenogeneic inflammatory/immune mechanisms and topical immunosuppressive drugs. Human fibroblasts were mixed with type 1 rat-tail collagen to form a matrix (4 to 5 days), on which human keratinocytes were seeded. After a keratinocyte monolayer formed, CT cultures were raised to the air-liquid interface for continued growth. In the REJ LSE model, immunocytes isolated from human blood were seeded on top of the NHEK monolayer at the time of air-lifting. Thickness measurements of the acellular keratin and keratinocyte layers, and nuclear/cytoplasmic ratios, in both CT and REJ were made using digital image analysis. Immunostaining with anticytokeratin demonstrated a viable, keratin-producing epidermal layer; staining with anti-TGF-beta suggested a role for this cytokine in the rejection or wound-healing process. The LSE appeared histologically similar to normal human epidermis. Immunocytes added to the REJ cultures caused an obvious rejection response and were clearly identifiable in the gels as CD45+ staining cells. The LSE model appears promising for the study of immune/inflammatory mechanisms, thermal injury, screening antirejection agents that might be applied topically and as an in vitro replacement for skin graft studies in animals. PMID:9193551

  4. 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. PMID:25420652

  5. Pseudomonas oryzihabitans: an unusual cause of skin and soft tissue infection.

    PubMed

    Tena, Daniel; Fernández, Cristina

    2015-01-01

    Skin and soft tissue infections (SSTIs) due to Pseudomonas oryzihabitans are very rare. The aim of the present study was to investigate the clinical and microbiological characteristics of this infection. We performed a retrospective review of six cases that occurred in our area over a period of 6 years, and six cases previously reported in the literature. Predisposing factors were recognized in 76.9% of patients, including previous surgery, immunosuppression, diabetes mellitus, trauma, bites and lactation. The source of infection was probably environmental in most cases. Our study shows that P. oryzihabitans should be considered a potential pathogen, especially in patients with surgical site infections, mastitis and wound infections after bites or trauma. Clinical outcome is usually favourable and treatment is not difficult due to the low level of resistance to commonly used antibiotics. PMID:26179756

  6. Management of Skin and Soft Tissue Infections in a County Correctional Center: A Quality Improvement Project.

    PubMed

    Mullen, Lisa A; O'Keefe, Catherine

    2015-10-01

    The number of antibiotic-resistant infections continues to increase. In 2005, there were nearly 11,406 deaths from methicillin-resistant Staphylococcus aureus (MRSA) infection in the United States. Since 1980, the United States has seen a 300% increase in the rate of incarceration. This is noteworthy because individuals who enter correctional facilities have an increased risk for MRSA skin and soft tissue infections (SSTIs) and the risk of colonization proportional to the length of stay. Correctional institutions have a vested interest in improving the screening and treatment of MRSA SSTIs, as it is a costly and potentially preventable problem. This article describes the process of implementing an MRSA screening and treatment policy in a county correctional center. PMID:26276136

  7. 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. PMID:26704998

  8. 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.

  9. 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. PMID:27390042

  10. 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

  11. The wound/burn guidelines - 4: Guidelines for the management of skin ulcers associated with connective tissue disease/vasculitis.

    PubMed

    Fujimoto, Manabu; Asano, Yoshihide; Ishii, Takayuki; Ogawa, Fumihide; Kawakami, Tamihiro; Kodera, Masanari; Abe, Masatoshi; Isei, Taiki; Ito, Takaaki; Inoue, Yuji; Imafuku, Shinichi; Irisawa, Ryokichi; Ohtsuka, Masaki; Ohtsuka, Mikio; Kadono, Takafumi; Kawaguchi, Masakazu; Kukino, Ryuichi; Kono, Takeshi; Sakai, Keisuke; Takahara, Masakazu; Tanioka, Miki; Nakanishi, Takeshi; Nakamura, Yasuhiro; Hashimoto, Akira; Hasegawa, Minoru; Hayashi, Masahiro; Fujiwara, Hiroshi; Maekawa, Takeo; Matsuo, Koma; Madokoro, Naoki; Yamasaki, Osamu; Yoshino, Yuichiro; Le Pavoux, Andres; Tachibana, Takao; Ihn, Hironobu

    2016-07-01

    The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS. PMID:26972733

  12. 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

  13. Epidermal stem cells and skin tissue engineering in hair follicle regeneration.

    PubMed

    Balañá, María Eugenia; Charreau, Hernán Eduardo; Leirós, Gustavo José

    2015-05-26

    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

  14. Influence of tissue parameters on visual reflectance spectra of port wine stains and normal skin

    NASA Astrophysics Data System (ADS)

    Norvang Nilsen, Lill T.; Fiskerstrand, Elisanne J.; Bakken, B.; Grini, D.; Standahl, O.; Milner, Thomas E.; Berns, Michael W.; Nelson, J. Stuart; Svaasand, Lars O.

    1996-01-01

    The visual appearance of port-wine stain lesions is often a red to purple color due to an enlarged blood volume in the upper dermis. The purpose of the treatment is to re-establish normal skin coloration. Visual reflectance spectra should therefore, in principle, contain all relevant information about the lesion. The influence on the spectra from the different tissue parameters, such as melanin, blood content and scattering, is rather composite. However, a simple mathematical model can give a good understanding of the relevance of the different components. This knowledge can be used to optimize the laser treatment of port-wine stain. In vivo reflectance spectra were obtained using an integrating sphere spectrophotometer. A simple mathematical model based on the diffusion approximation was used to simulate port- wine stain and normal skin reflectance spectra. The absorption coefficients of epidermis and dermis are mainly due to melanin and blood. These parameters were measured in separate in vivo experiments and obtained from skin biopsies. The scattering coefficients were based on reported values. Simulated reflectance spectra show good agreement with the measured ones. Even though the diffusion model has limited validity for wavelengths shorter than 600 nm, the simulated spectra from 450 to 600 nm give a qualitative understanding of the influence of the tissue parameters. The results show that dark red to almost dark grey port-wine stains contain enlarged blood fraction in the entire upper dermis. The red port-wine stains appear when the abnormal density of blood is confined to a thin layer. High amount of epidermal melanin results in reduced reflectance throughout the visible spectrum. The characteristic spectrum due to the blood is suppressed. The reflectance spectra are strongly dependent on the dermal and epidermal scattering coefficient; even minor changes as naturally occurring with age, might have a significant impact. A permanently reduced scattering

  15. Use of Clotted Human Plasma and Aprotinin in Skin Tissue Engineering: A Novel Approach to Engineering Composite Skin on a Porous Scaffold.

    PubMed

    Paul, Michelle; Kaur, Pritinder; Herson, Marisa; Cheshire, Perdita; Cleland, Heather; Akbarzadeh, Shiva

    2015-10-01

    Tissue-engineered composite skin is a promising therapy for the treatment of chronic and acute wounds, including burns. Providing the wound bed with a dermal scaffold populated by autologous dermal and epidermal cellular components can further entice host cell infiltration and vascularization to achieve permanent wound closure in a single stage. However, the high porosity and the lack of a supportive basement membrane in most commercially available dermal scaffolds hinders organized keratinocyte proliferation and stratification in vitro and may delay re-epithelization in vivo. The objective of this study was to develop a method to enable the in vitro production of a human skin equivalent (HSE) that included a porous scaffold and dermal and epidermal cells expanded ex vivo, with the potential to be used for definitive treatment of skin defects in a single procedure. A collagen-glycosaminoglycan dermal scaffold (Integra(®)) was populated with adult fibroblasts. A near-normal skin architecture was achieved by the addition of coagulated human plasma to the fibroblast-populated scaffold before seeding cultured keratinocytes. This resulted in reducing scaffold pore size and improving contact surfaces. Skin architecture and basement membrane formation was further improved by the addition of aprotinin (a serine protease inhibitor) to the culture media to inhibit premature clot digestion. Histological assessment of the novel HSE revealed expression of keratin 14 and keratin 10 similar to native skin, with a multilayered neoepidermis morphologically comparable to human skin. Furthermore, deposition of collagen IV and laminin-511 were detected by immunofluorescence, indicating the formation of a continuous basement membrane at the dermal-epidermal junction. The proposed method was efficient in producing an in vitro near native HSE using the chosen off-the-shelf porous scaffold (Integra). The same principles and promising outcomes should be applicable to other biodegradable

  16. 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

  17. In vivo measurement of skin surface strain and sub-surface layer deformation induced by natural tissue stretching.

    PubMed

    Maiti, Raman; Gerhardt, Lutz-Christian; Lee, Zing S; Byers, Robert A; Woods, Daniel; Sanz-Herrera, José A; Franklin, Steve E; Lewis, Roger; Matcher, Stephen J; Carré, Matthew J

    2016-09-01

    Stratum corneum and epidermal layers change in terms of thickness and roughness with gender, age and anatomical site. Knowledge of the mechanical and tribological properties of skin associated with these structural changes are needed to aid in the design of exoskeletons, prostheses, orthotics, body mounted sensors used for kinematics measurements and in optimum use of wearable on-body devices. In this case study, optical coherence tomography (OCT) and digital image correlation (DIC) were combined to determine skin surface strain and sub-surface deformation behaviour of the volar forearm due to natural tissue stretching. The thickness of the epidermis together with geometry changes of the dermal-epidermal junction boundary were calculated during change in the arm angle, from flexion (90°) to full extension (180°). This posture change caused an increase in skin surface Lagrange strain, typically by 25% which induced considerable morphological changes in the upper skin layers evidenced by reduction of epidermal layer thickness (20%), flattening of the dermal-epidermal junction undulation (45-50% reduction of flatness being expressed as Ra and Rz roughness profile height change) and reduction of skin surface roughness Ra and Rz (40-50%). The newly developed method, DIC combined with OCT imaging, is a powerful, fast and non-invasive methodology to study structural skin changes in real time and the tissue response provoked by mechanical loading or stretching. PMID:27310571

  18. 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.

  19. 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

  20. The dosimetric effects of tissue heterogeneities in intensity-modulated radiation therapy (IMRT) of the head and neck.

    PubMed

    Al-Hallaq, H A; Reft, C S; Roeske, J C

    2006-03-01

    The dosimetric effects of bone and air heterogeneities in head and neck IMRT treatments were quantified. An anthropomorphic RANDO phantom was CT-scanned with 16 thermoluminescent dosimeter (TLD) chips placed in and around the target volume. A standard IMRT plan generated with CORVUS was used to irradiate the phantom five times. On average, measured dose was 5.1% higher than calculated dose. Measurements were higher by 7.1% near the heterogeneities and by 2.6% in tissue. The dose difference between measurement and calculation was outside the 95% measurement confidence interval for six TLDs. Using CORVUS' heterogeneity correction algorithm, the average difference between measured and calculated doses decreased by 1.8% near the heterogeneities and by 0.7% in tissue. Furthermore, dose differences lying outside the 95% confidence interval were eliminated for five of the six TLDs. TLD doses recalculated by Pinnacle3's convolution/superposition algorithm were consistently higher than CORVUS doses, a trend that matched our measured results. These results indicate that the dosimetric effects of air cavities are larger than those of bone heterogeneities, thereby leading to a higher delivered dose compared to CORVUS calculations. More sophisticated algorithms such as convolution/superposition or Monte Carlo should be used for accurate tailoring of IMRT dose in head and neck tumours. PMID:16481684

  1. The dosimetric effects of tissue heterogeneities in intensity-modulated radiation therapy (IMRT) of the head and neck

    NASA Astrophysics Data System (ADS)

    Al-Hallaq, H. A.; Reft, C. S.; Roeske, J. C.

    2006-03-01

    The dosimetric effects of bone and air heterogeneities in head and neck IMRT treatments were quantified. An anthropomorphic RANDO phantom was CT-scanned with 16 thermoluminescent dosimeter (TLD) chips placed in and around the target volume. A standard IMRT plan generated with CORVUS was used to irradiate the phantom five times. On average, measured dose was 5.1% higher than calculated dose. Measurements were higher by 7.1% near the heterogeneities and by 2.6% in tissue. The dose difference between measurement and calculation was outside the 95% measurement confidence interval for six TLDs. Using CORVUS' heterogeneity correction algorithm, the average difference between measured and calculated doses decreased by 1.8% near the heterogeneities and by 0.7% in tissue. Furthermore, dose differences lying outside the 95% confidence interval were eliminated for five of the six TLDs. TLD doses recalculated by Pinnacle3's convolution/superposition algorithm were consistently higher than CORVUS doses, a trend that matched our measured results. These results indicate that the dosimetric effects of air cavities are larger than those of bone heterogeneities, thereby leading to a higher delivered dose compared to CORVUS calculations. More sophisticated algorithms such as convolution/superposition or Monte Carlo should be used for accurate tailoring of IMRT dose in head and neck tumours.

  2. 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. PMID:26441024

  3. 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 transmission. Of…

  4. Coagulation and ablation patterns of high-intensity focused ultrasound on a tissue-mimicking phantom and cadaveric skin.

    PubMed

    Kim, Hee-Jin; Kim, Han Gu; Zheng, Zhenlong; Park, Hyoun Jun; Yoon, Jeung Hyun; Oh, Wook; Lee, Cheol Woo; Cho, Sung Bin

    2015-12-01

    High-intensity focused ultrasound (HIFU) can be applied noninvasively to create focused zones of tissue coagulation on various skin layers. We performed a comparative study of HIFU, evaluating patterns of focused tissue coagulation and ablation upon application thereof. A tissue-mimicking (TM) phantom was prepared with bovine serum albumin and polyacrylamide hydrogel to evaluate the geometric patterns of HIFU-induced thermal injury zones (TIZs) for five different HIFU devices. Additionally, for each device, we investigated histologic patterns of HIFU-induced coagulation and ablation in serial sections of cadaveric skin of the face and neck. All HIFU devices generated remarkable TIZs in the TM phantom, with different geometric values of coagulation for each device. Most of the TIZs seemed to be separated into two or more tiny parts. In cadaveric skin, characteristic patterns of HIFU-induced ablation and coagulation were noted along the mid to lower dermis at the focal penetration depth of 3 mm and along subcutaneous fat to the superficial musculoaponeurotic system or the platysma muscle of the neck at 4.5 mm. Additionally, remarkable pre-focal areas of tissue coagulation were observed in the upper and mid dermis at the focal penetration depth of 3 mm and mid to lower dermis at 4.5 mm. For five HIFU devices, we outlined various patterns of HIFU-induced TIZ formation along pre-focal, focal, and post-focal areas of TM phantom and cadaveric skin of the face and neck. PMID:26341380

  5. Hypoxia induces expression of connective tissue growth factor in scleroderma skin fibroblasts

    PubMed Central

    Hong, K-H; Yoo, S-A; Kang, S-S; Choi, J-J; Kim, W-U; Cho, C-S

    2006-01-01

    Connective tissue growth factor (CTGF) plays a role in the fibrotic process of systemic sclerosis (SSc). Because hypoxia is associated with fibrosis in several profibrogenic conditions, we investigated whether CTGF expression in SSc fibroblasts is regulated by hypoxia. Dermal fibroblasts from patients with SSc and healthy controls were cultured in the presence of hypoxia or cobalt chloride (CoCl2), a chemical inducer of hypoxia-inducible factor (HIF)-1α. Expression of CTGF was evaluated by Northern and Western blot analyses. Dermal fibroblasts exposed to hypoxia (1% O2) or CoCl2 (1–100 µM) enhanced expression of CTGF mRNA. Skin fibroblasts transfected with HIF-1α showed the increased levels of CTGF protein and mRNA, as well as nuclear staining of HIF-1α, which was enhanced further by treatment of CoCl2. Simultaneous treatment of CoCl2 and transforming growth factor (TGF)-β additively increased CTGF mRNA in dermal fibroblasts. Interferon-γ inhibited the TGF-β-induced CTGF mRNA expression dose-dependently in dermal fibroblasts, but they failed to hamper the CoCl2-induced CTGF mRNA expression. In addition, CoCl2 treatment increased nuclear factor (NF)-κB binding activity for CTGF mRNA, while decreasing IκBα expression in dermal fibroblasts. Our data suggest that hypoxia, caused possibly by microvascular alterations, up-regulates CTGF expression through the activation of HIF-1α in dermal fibroblasts of SSc patients, and thereby contributes to the progression of skin fibrosis. PMID:17034590

  6. Chromium Is Elevated in Fin Whale (Balaenoptera physalus) Skin Tissue and Is Genotoxic to Fin Whale Skin Cells

    PubMed Central

    Wise, Catherine F.; Wise, Sandra S.; Thompson, W. Douglas; Perkins, Christopher; Wise, John Pierce

    2015-01-01

    Hexavalent chromium (Cr(VI)) is present in the marine environment and is a known carcinogen and reproductive toxicant. Cr(VI) is the form of chromium that is well absorbed through the cell membrane. It is also the most prevalent form in seawater. We measured the total Cr levels in skin biopsies obtained from healthy free-ranging fin whales from the Gulf of Maine and found elevated levels relative to marine mammals in other parts of the world. The levels in fin whale biopsies ranged from 1.71 ug/g to 19.6 ug/g with an average level of 10.07 ug/g. We also measured the cytotoxicity and genotoxicity of Cr(VI) in fin whale skin cells. We found that particulate and soluble Cr(VI) are both cytotoxic and genotoxic to fin whale skin cells in a concentration-dependent manner. The concentration range used in our cell culture studies used environmentally relevant concentrations based on the biopsy measurements. These data suggest that Cr(VI) may be a concern for whales in the Gulf of Maine. PMID:25805270

  7. Characterizing the beam steering and distortion of Gaussian and Bessel beams focused in tissues with microscopic heterogeneities

    PubMed Central

    Chen, Ye; Liu, Jonathan T.C.

    2015-01-01

    Bessel beams have recently been investigated as a means of improving deep-tissue microscopy in highly scattering and heterogeneous media. It has been suggested that the long depth-of-field and self-reconstructing property of a Bessel beam enables an increased penetration depth of the focused beam in tissues compared to a conventional Gaussian beam. However, a study is needed to better quantify the magnitude of the beam steering as well as the distortion of focused Gaussian and Bessel beams in tissues with microscopic heterogeneities. Here, we have developed an imaging method and quantitative metrics to evaluate the motion and distortion of low-numerical-aperture (NA) Gaussian and Bessel beams focused in water, heterogeneous phantoms, and fresh mouse esophagus tissues. Our results indicate that low-NA Bessel beams exhibit reduced beam-steering artifacts and distortions compared to Gaussian beams, and are therefore potentially useful for microscopy applications in which pointing accuracy and beam quality are critical, such as dual-axis confocal (DAC) microscopy. PMID:25909015

  8. 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.

  9. A Nth-order linear algorithm for extracting diffuse correlation spectroscopy blood flow indices in heterogeneous tissues

    NASA Astrophysics Data System (ADS)

    Shang, Yu; Yu, Guoqiang

    2014-09-01

    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.

  10. PLLA-collagen and PLLA-gelatin hybrid scaffolds with funnel-like porous structure for skin tissue engineering

    NASA Astrophysics Data System (ADS)

    Lu, Hongxu; Oh, Hwan Hee; Kawazoe, Naoki; Yamagishi, Kozo; Chen, Guoping

    2012-12-01

    In skin tissue engineering, a three-dimensional porous scaffold is necessary to support cell adhesion and proliferation and to guide cells moving into the repair area in the wound healing process. Structurally, the porous scaffold should have an open and interconnected porous architecture to facilitate homogenous cell distribution. Moreover, the scaffolds should be mechanically strong to protect deformation during the formation of new skin. In this study, the hybrid scaffolds were prepared by forming funnel-like collagen or gelatin sponge on a woven poly(l-lactic acid) (PLLA) mesh. The hybrid scaffolds combined the advantages of both collagen or gelatin (good cell-interactions) and PLLA mesh (high mechanical strength). The hybrid scaffolds were used to culture dermal fibroblasts for dermal tissue engineering. The funnel-like porous structure promoted homogeneous cell distribution and extracellular matrix production. The PLLA mesh reinforced the scaffold to avoid deformation. Subcutaneous implantation showed that the PLLA-collagen and PLLA-gelatin scaffolds promoted the regeneration of dermal tissue and epidermis and reduced contraction during the formation of new tissue. These results indicate that funnel-like hybrid scaffolds can be used for skin tissue regeneration.

  11. The clinical availability of oleic acid as an enhancer in optical clearing of skin tissue in vitro

    NASA Astrophysics Data System (ADS)

    Jiang, Jingying; Wang, Ruikang K.

    2005-03-01

    Currently, tissue optical clearing technique has shown a great potential in enhancing the capabilities of non-invasive light-based diagnostic and imaging techniques due to the increased light penetration into tissue. In order to facilitate the clinical availability of tissue optical clearing technique by the use of hyperosmotic agents, this study introduces oleic acid, a mono-unsaturated fatty acid which is generally believed to be safe, as enhancer and investigates the synergistic effect of oleic acid and propylene glycol (PG) on optical clearing of skin tissue in vitro. Experimental results from near infrared spectroscopy, mass loss measurement and transdermal skin resistance (TSR) assessment showed that, compared with dimethyl sulfoxide (DMSO) as enhancer, oleic acid obtained the similar clearing effect. However, due to its potential toxicity, DMSO has been controversial in clinical application. Therefore, in terms of optical application and clinic safety, the results presented revealed that oleic acid could be an optimum choice as enhancer for optical clearing of skin tissue.

  12. Quantification of the impact of MLC modeling and tissue heterogeneities on dynamic IMRT dose calculations

    SciTech Connect

    Mihaylov, I. B.; Lerma, F. A.; Fatyga, M.; Siebers, J. V.

    2007-04-15

    This study quantifies the dose prediction errors (DPEs) in dynamic IMRT dose calculations resulting from (a) use of an intensity matrix to estimate the multi-leaf collimator (MLC) modulated photon fluence (DPE{sub IGfluence}) instead of an explicit MLC particle transport, and (b) handling of tissue heterogeneities (DPE{sub hetero}) by superposition/convolution (SC) and pencil beam (PB) dose calculation algorithms. Monte Carlo (MC) computed doses are used as reference standards. Eighteen head-and-neck dynamic MLC IMRT treatment plans are investigated. DPEs are evaluated via comparing the dose received by 98% of the GTV (GTV D{sub 98%}), the CTV D{sub 95%}, the nodal D{sub 90%}, the cord and the brainstem D{sub 02%}, the parotid D{sub 50%}, the parotid mean dose (D{sub Mean}), and generalized equivalent uniform doses (gEUDs) for the above structures. For the MC-generated intensity grids, DPE{sub IGfluence} is within {+-}2.1% for all targets and critical structures. The SC algorithm DPE{sub hetero} is within {+-}3% for 98.3% of the indices tallied, and within {+-}3.4% for all of the tallied indices. The PB algorithm DPE{sub hetero} is within {+-}3% for 92% of the tallied indices. Statistical equivalence tests indicate that PB DPE{sub hetero} requires a {+-}3.6% interval to state equivalence with the MC standard, while the intervals are <1.5% for SC DPE{sub hetero} and DPE{sub IGfluence}. Overall, these results indicate that SC and MC IMRT dose calculations which use MC-derived intensity matrices for fluence prediction do not introduce significant dose errors compared with full Monte Carlo dose computations; however, PB algorithms may result in clinically significant dose deviations.

  13. 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.

  14. Skin-sparing mastectomy and immediate tissue expander breast reconstruction in patients with macromastia using the Passot breast reduction pattern.

    PubMed

    Rinker, Brian; Thornton, Brian P

    2014-01-01

    Skin-sparing mastectomy (SSM) with immediate tissue expander reconstruction poses a challenge in the patient with macromastia or excessive ptosis. Skin reduction via the Wise pattern has been described but is associated with high rates of skin necrosis. The study group consisted of 43 women with grade 2 or 3 ptosis who underwent SSM and immediate reconstruction with tissue expanders, using the Passot (horizontal) skin reduction pattern. Age ranged from 31 to 67 years (mean, 51 years). The endpoints measured were time to final expansion, mastectomy skin flap necrosis, infectious complications, and total complications. Thirty reconstructions were bilateral and 13 were unilateral (73 breasts total). Follow-up ranged from 6 to 55 months (mean, 20). Common comorbid conditions included hypertension (n = 16), obesity (n = 22), and smoking (n = 9). The mean body mass index was 30.6 (range, 19.4-58.6). Twenty-one patients underwent chemotherapy; 12 received radiation. The mean initial fill was 196 mL (range, 0-420 mL), and the mean time to final expansion was 84 days (range, 28-225 days). Five patients did not complete the reconstruction, 2 because of cancer recurrence and 3 because of infection. There were 3 cases of mastectomy flap necrosis occurring after tissue expander placement (7%). There were 7 infectious complications (16%). The use of a horizontal breast reduction pattern at the time of expander placement produces consistently good esthetic outcomes and a low rate of skin necrosis, and it should be considered as an option in patients with macromastia or ptosis undergoing SSM and immediate reconstruction. PMID:24835873

  15. Purification and characterization of pepsin-solubilized collagen from skin and connective tissue of giant red sea cucumber (Parastichopus californicus).

    PubMed

    Liu, Zunying; Oliveira, Alexandra C M; Su, Yi-Cheng

    2010-01-27

    Pepsin-solubilized collagen (PSC) was extracted from giant red sea cucumbers ( Parastichopus californicus ) and characterized for denaturation temperature (T(d)), maximum transition temperature (T(m)), enzyme-digested peptide maps, and gel-forming capability. SDS-PAGE showed that PSCs from giant red sea cucumber skin and connective tissue were both type I collagens, consisting of three alpha(1) chains of approximately 138 kDa each. The amino acid composition and peptide maps of PSCs digested by V8 protease were different from those of calf skin type I collagen. The T(d) and T(m) are 18.5 and 33.2 degrees C, respectively, for skin PSC and are 17.9 and 32.7 degrees C, respectively, for connective tissue PSC. Both skin and connective tissue PSCs exhibited good gel-forming capability at pH 6.5 and at an ionic strength of 300 mM salt (NaCl). Collagen isolated from giant red sea cucumbers might be used as an alternative to mammalian collagen in the food and pharmaceutical industries. PMID:20085374

  16. Variability of antibiotic susceptibility and toxin production of Staphylococcus aureus strains isolated from skin, soft tissue, and bone related infections

    PubMed Central

    2013-01-01

    Background Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. Results A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). Conclusions This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin. PMID:23924370

  17. Acinetobacter baumannii-Associated Skin and Soft Tissue Infections: Recognizing a Broadening Spectrum of Disease*

    PubMed Central

    Guerrero, Dubert M.; Perez, Federico; Conger, Nicholas G.; Solomkin, Joseph S.; Adams, Mark D.; Rather, Philip N.

    2010-01-01

    Abstract Background Acinetobacter baumannii is gaining importance as a cause of nosocomial infections, but its role in skin and soft tissue infection (SSTI) is not well defined. As a result of the outbreak of A. baumannii occurring in military personnel in Iraq and Afghanistan, reports of severe wound infections and SSTI caused by this pathogen are increasing in frequency. Methods We describe four cases of monomicrobial and polymicrobial A. baumannii–associated necrotizing SSTI accompanied by A. baumannii bacteremia and offer a review of similar experiences published in the literature. Results Our comparative analysis reveals four unique features associated with necrotizing SSTI associated with A. baumannii: i) Occurs in hosts with underlying comorbidities (e.g., trauma, cirrhosis); ii) is often accompanied by bacteremia; iii) multiple drug resistance and the presence of co-pathogens frequently complicated treatment (64% of cases); iv) the cases reported here and in our review required surgical debridement (84% of cases) and led to substantial mortality (∼30%). Conclusions As the prevalence of A. baumannii continues to increase in our health care system, SSTIs caused by this organism may become more common. Clinicians must be aware that the spectrum of disease caused by A. baumannii could include severe necrotizing SSTI and that vigilance for potential complications is necessary. PMID:19788383

  18. Meropenem in the treatment of complicated skin and soft tissue infections

    PubMed Central

    Fish, Douglas N

    2006-01-01

    Meropenem is a broad-spectrum carbapenem antibiotic with excellent activity against many pathogens associated with complicated skin and soft tissue infections (cSSTIs). At least three studies have shown meropenem to have good clinical efficacy and to be well tolerated in the treatment of cSSTIs. Two open-label studies compared meropenem 500 mg every 8 hours (total evaluable n=146) with imipenem/cilastatin 500mg every 6 hours (n=147). Clinical efficacy rates in evaluable patients 7–14 days after end of treatment were similar, 92% and 100% in meropenem-treated groups versus 89% and 100% in groups receiving imipenem/cilastatin. An additional prospective, randomized, double-blind study evaluated meropenem 500mg every 8 hours (261 evaluable patients) versus imipenem/cilastatin 500 mg every 8 hours (287 patients). Clinical efficacy rates of meropenem and imipenem/cilastatin 7–28 days after end of treatment were 86.2% and 82.9%, respectively. Meropenem was well tolerated in all studies. Carbapenems are currently recommended as appropriate for initial treatment of certain cSSTIs such as those likely to involve mixed and/or multidrug-resistant pathogens. Meropenem is an effective and safe alternative for monotherapy when used for appropriate types of cSSTIs. Higher doses (ie, 1 g every 8 hours) should be considered for treatment of cSSTIs in higher-risk patients where Pseudomonas aeruginosa is a suspected or documented pathogen. PMID:18360652

  19. Correlation between Nasal Microbiome Composition and Remote Purulent Skin and Soft Tissue Infections

    PubMed Central

    Johnson, Ryan C.; Ellis, Michael W.; Lanier, Jeffrey B.; Schlett, Carey D.; Cui, Tianyuan

    2014-01-01

    The incidence of skin and soft tissue infections (SSTIs) has increased dramatically over the past decade, resulting in significant morbidity in millions of otherwise healthy individuals worldwide. Certain groups, like military personnel, are at increased risk for SSTI development. Although nasal colonization with Staphylococcus aureus is an important risk factor for the development of SSTIs, it is not clear why some colonized individuals develop disease while others do not. Recent studies have revealed the importance of microbial diversity in human health. Therefore, we hypothesized that the nasal microbiome may provide valuable insight into SSTI development. To examine this hypothesis, we obtained anterior-naris samples from military trainees with cutaneous abscesses and from asymptomatic (non-SSTI) participants. We also obtained samples from within abscess cavities. Specimens were analyzed by culture, and the microbial community within each sample was characterized using a 16S sequencing-based approach. We collected specimens from 46 non-SSTI participants and from 40 participants with abscesses. We observed a significantly higher abundance of Proteobacteria in the anterior nares in non-SSTI participants (P < 0.0001) than in participants with abscesses. Additionally, we noted a significant inverse correlation between Corynebacterium spp. and S. aureus (P = 0.0001). The sensitivity of standard microbiological culture for abscesses was 71.4%. These data expand our knowledge of the complexity of the nasal and abscess microbiomes and potentially pave the way for novel therapeutic and prophylactic countermeasures against SSTI. PMID:25486991

  20. Metabolomic Response of Human Skin Tissue to Low Dose Ionizing Radiation

    SciTech Connect

    Hu, Zeping; Kim, Young-Mo; Sowa, Marianne B.; Robinson, Robert J.; Gao, Xiaoli; Metz, Thomas O.; Morgan, William F.; Zhang, Qibin

    2012-05-18

    Understanding how human organs respond to ionizing radiation (IR) at a systems biology level and identifying biomarkers for IR exposure at low doses can help provide a scientific basis for establishing radiation protection standards. Little is known regarding the physiological responses to low dose IR at the metabolite level, which represents the end-point of biochemical processes inside cells. Using a full thickness human skin tissue model and GC-MS-based metabolomics analysis, we examined the metabolic perturbations at three time points (3, 24 and 48 hr) after exposure to 3, 10 and 200 cGy of X-rays. PLS-DA score plots revealed dose- and time-dependent clustering between sham and irradiated groups. Importantly, a comparable number of metabolites were detected to have significant change 48 hr after exposure to 3 and 10 cGy of irradiation, when compared with the high dose of 200 cGy. Biochemical pathway analysis showed perturbations to DNA/RNA damage and repair, lipid and energy metabolisms, even at low doses of IR.

  1. Teicoplanin in the treatment of skin and soft tissue infections: results of a multicentre study.

    PubMed

    Lang, E; Földes, M; Marghescu, S

    1991-01-01

    The clinical efficacy and safety of teicoplanin was studied in hospitalized patients with skin and soft tissue infections. In an open multicentre study 64 patients were treated with teicoplanin i.v. and/or i.m. Predisposing or complicating factors for infection were present in almost 80% of the patients. Teicoplanin was usually given as an initial loading dose of 400 mg (87.1%), or 800 mg (6.5%) or various doses (6.5%). During the course of the study, the mean daily dose of teicoplanin was 261.3 mg. Sixty of the 62 evaluable patients responded to treatment. 58 gram-positive pathogens were isolated, consisting of Staphylococcus aureus (n = 41), coagulase-negative staphylococci (n = 6) and streptococci (n = 11). Elimination of pathogens was seen in 37/47 of all microbiologically evaluable cases. Persistence, recurrence or reinfection occurred in 7/47, 2/47 and 1/47, respectively. Adverse reactions were reported in only three patients with allergic reaction, local reaction and rise in transaminases in one case each. Therapy failed only in two patients. PMID:1832418

  2. Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas.

    PubMed

    Cho, Eun Yoon; Park, Kyeongmee; Do, Ingu; Cho, Junhun; Kim, Jiyun; Lee, Jeeyun; Kim, Seonwoo; Kim, Kyoung-Mee; Sohn, Tae Sung; Kang, Won Ki; Kim, Sung

    2013-05-01

    Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be

  3. 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

  4. Bi-layer scaffold of chitosan/PCL-nanofibrous mat and PLLA-microporous disc for skin tissue engineering.

    PubMed

    Lou, Tao; Leung, Matthew; Wang, Xuejun; Chang, Julia Yu Fong; Tsao, Ching Ting; Sham, Jonathan Ghing Chi; Edmondson, Dennis; Zhang, Miqin

    2014-06-01

    Current treatments for severe skin damage involve the grafting of extremely limited autogenic skin or the use of synthetic skin grafts that do not fully recapitulate the biological properties of native skin. In this study we developed a novel bi-layer scaffold that provides the microenvironmental cues favorable to promoting skin healing and regeneration. The scaffold is composed of a superficial chitosan/PCL nanofibrous mat (CP-nano mat) and an underlying PLLA microporous disc (PLLA-micro disc). The porous structure of the scaffold permits the interaction of biomolecules released from two types of cells distributed, respectively, throughout the two layers of the scaffold, but the nanofibers prevent the direct intermingling of the cell types. The CP-nano mat and PLLA-micro disc were fabricated by electrospinning and thermally induced phase separation, respectively, and host keratinoctyes as an epidermal equivalent and fibroblasts as a dermal equivalent, respectively, present in the native skin. The potential of this bi-layer scaffold to serve as a skin equivalent was evaluated by co-culture of keratinocytes and fibroblasts and subsequent assessment of cell proliferation, cell morphology, gene transcription, and protein expression. The cell proliferation was found to be greatest in co-culture on bi-layer scaffolds. The gene and protein expression analyses further confirmed that the bi-layer scaffold provided a micro-environment similar to those present in the native extracellular matrix during initial wound healing. Our study suggested that the bi-layer scaffold has great potential to serve as a skin equivalent in tissue engineering. PMID:24749404

  5. Polarimetry based partial least square classification of ex vivo healthy and basal cell carcinoma human skin tissues.

    PubMed

    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ikram, Masroor

    2016-06-01

    Optical polarimetry was employed for assessment of ex vivo healthy and basal cell carcinoma (BCC) tissue samples from human skin. Polarimetric analyses revealed that depolarization and retardance for healthy tissue group were significantly higher (p<0.001) compared to BCC tissue group. Histopathology indicated that these differences partially arise from BCC-related characteristic changes in tissue morphology. Wilks lambda statistics demonstrated the potential of all investigated polarimetric properties for computer assisted classification of the two tissue groups. Based on differences in polarimetric properties, partial least square (PLS) regression classified the samples with 100% accuracy, sensitivity and specificity. These findings indicate that optical polarimetry together with PLS statistics hold promise for automated pathology classification. PMID:27083851

  6. Combination effects of tissue heterogeneity and geometric targeting error in stereotactic body radiotherapy for lung cancer using CyberKnife.

    PubMed

    Kang, Ki Mun; Jeong, Bae Kwon; Choi, Hoon-Sik; Yoo, Seung Hoon; Hwang, Ui-Jung; Lim, Young Kyung; Jeong, Hojin

    2015-01-01

    We have investigated the combined effect of tissue heterogeneity and its variation associated with geometric error in stereotactic body radiotherapy (SBRT) for lung cancer. The treatment plans for eight lung cancer patients were calculated using effective path length (EPL) correction and Monte Carlo (MC) algorithms, with both having the same beam configuration for each patient. These two kinds of plans for individual patients were then subsequently recalculated with adding systematic and random geometric errors. In the ordinary treatment plans calculated with no geometric offset, the EPL calculations, compared with the MC calculations, largely overestimated the doses to PTV by ~ 21%, whereas the overestimation were markedly lower in GTV by ~ 12% due to relatively higher density of GTV than of PTV. When recalculating the plans for individual patients with assigning the systematic and random geometric errors, no significant changes in the relative dose distribution, except for overall shift, were observed in the EPL calculations, whereas largely altered in the MC calculations with a consistent increase in dose to GTV. Considering the better accuracy of MC than EPL algorithms, the present results demonstrated the strong coupling of tissue heterogeneity and geometric error, thereby emphasizing the essential need for simultaneous correction for tissue heterogeneity and geometric targeting error in SBRT of lung cancer. PMID:26699300

  7. 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

  8. 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.

  9. 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. PMID:22033085

  10. 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

  11. Effect of atmospheric fine particles on epidermal growth factor receptor mRNA expression in mouse skin tissue.

    PubMed

    Han, X; Liang, W L; Zhang, Y; Sun, L D; Liang, W Y

    2016-01-01

    We investigated the effect of atmospheric fine particles on epidermal growth factor receptor (Egfr) mRNA expression in mouse skin tissue and explored the effect of atmospheric fine particles on skin aging. Forty female BALB/c mice were randomly divided into four groups (each comprising 10 mice) as follows: a saline control group and low-, medium-, and high-dose atmospheric fine particle groups (1.6, 8.0, and 40.0 mg/kg, respectively) (fine particles were defined as those with a diameter of £2.5 mm, i.e., PM2.5). Each dose group was exposed to intratracheal instillation for 3 days. Twenty-four hours after the last exposure, real-time quantitative polymerase chain reaction was used to detect the expression of Egfr mRNA in the skin tissue of each mouse. The expression levels of Egfr mRNA in the medium- and high-dose PM2.5 groups were significantly higher (P < 0.05) than that in the control group, and were positively correlated with the dose. Medium and high concentrations of PM2.5 can induce the expression of Egfr mRNA and promote skin aging. PMID:27050971

  12. Pilot study to visualise and measure skin tissue oxygenation, erythema, total haemoglobin and melanin content using index maps in healthy controls

    NASA Astrophysics Data System (ADS)

    Poxon, Ian; Wilkinson, Jack; Herrick, Ariane; Dickinson, Mark; Murray, Andrea

    2014-02-01

    We report on a method for analysing multispectral images of skin in vivo for the measurement and visualisation of skin characteristics. Four different indices were used to characterise skin tissue oxygenation, erythema, total haemoglobin and melanin content. Index values were calculated pixel-wise and combined to create index maps to visualise skin properties. Quantitative measurement of tissue oxygenation saturation was possible by calibrating the oxygenation index using a commercial, calibrated oximeter. Index maps were tested by arterial occlusion of the index finger with multispectral images taken before, during and after occlusion in a pilot study with 10 healthy controls.

  13. Use of skin and blubber tissues of small cetaceans to assess the trace element content of internal organs.

    PubMed

    Aubail, A; Méndez-Fernandez, P; Bustamante, P; Churlaud, C; Ferreira, M; Vingada, J V; Caurant, F

    2013-11-15

    In order to evaluate the use of biopsy samples as non-destructive tool for assessing trace element concentrations in small cetaceans, the concentrations of 14 trace elements were determined in skin, blubber, liver and kidneys of four species of small cetaceans (i.e. common dolphin Delphinus delphis, harbour porpoise Phocoena phocoena, bottlenose dolphin Tursiops truncatus and striped dolphin Stenella coeruleolba), stranded and/or by-caught along the NE Atlantic Ocean coast between 2001 and 2008. Only Cu, Fe, Hg, Mn, Ni and Zn were above the detection limit of the instruments and showed recoveries satisfactory enough to be interpreted. Among these trace elements, Hg was the only one showing a significant correlation between concentrations in and those in liver and kidneys. In consequence skin and blubber can only be used as non-invasive monitoring tissues to investigate Hg bioaccumulation in internal tissues for cetacean populations. PMID:24064373

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

    PubMed

    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

  15. 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

  16. 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

  17. ‘Expansion in-situ’ concept as a new technique for expanding skin and soft tissue

    PubMed Central

    FANG, LIN; ZHOU, CHUANDE; YANG, MINGYONG

    2013-01-01

    Techniques for expanding skin and soft tissue are widely used to repair damaged areas since they facilitate the provision of new, additional skin tissue with similar quality, texture and color to that surrounding the defective area. Conventional expansion techniques involve placing expanders under the normal skin adjacent to a lesion. However, these techniques may involve additional incisions, complications with blood supply and ‘dog-ear’ deformities and may result in a low utilization rate of the expanded tissue. When reconstructing small defects that may not be sutured directly, these shortcomings, particularly the requirement to make additional incisions, limit the application of conventional techniques. The current study presents a novel approach to expansion called the ‘expansion in-situ’ technique. In this technique, the lesion is used as the center for expansion and expanders of optimal size are implanted under the lesion and surrounding normal soft tissue. Following expansion, the damaged area is excised directly. In order to avoid poor healing of the incision made during expander implantation, the overlapping suturing of both cut sides is conducted. This enlarges the contact area of both sides of the incision, thereby avoiding incision dehiscence and increasing wound healing during the expansion process. Between August 2006 and July 2011, the expansion in-situ technique was applied in 10 cases involving either nevus excision or scar removal. All 10 cases were treated successfully. Five of the cases were followed up over 1–3 years. The ‘expansion in-situ’ technique is likely to be useful for avoiding additional incisions and improving the utilization rate of expanded skin flaps. PMID:24223661

  18. Monitoring the process of tissue healing of rat skin in vivo after laser irradiation based on optical coherence tomography

    NASA Astrophysics Data System (ADS)

    He, Youwu; Wu, Shulian; Li, Zhifang; Cai, Shoudong; Li, Hui

    2010-11-01

    It is imperative to evaluate the tissue wound healing response after laser irradiation so as to develop effective devices for this clinical indication, and evaluate the thermal damage degree to take appropriate treatment. In our research, we prepare 6 white rat (approximately 2 months old, weight :28+/-2g). Each rat was injected intraperitoneally a single dose of 2% pentobarbital sodium. After the rat was anesthetized, the two side of the rats' back were denuded and antisepsised a standardized. An Er:YAG laser (2940nm, 2.5J/cm2, single spot, 4 times) was irradiated on rat skin in vivo, and the skin which before irradiated and the process of renovating scathe that irradiated after Er:YAG laser were observed by an Optical coherence tomography (OCT). The tissue recovery is about a twelve -day period. The results indicate that the scattering coefficient of post- tissue has changed distinctly. The and flexibility fiber is the chief component of rat dermis and the collagen is the main scattering material. The normal tissue has a large scattering coefficient, after laser irradiated, the collagen became concreting and putrescence and caused the structure change. It became more uniform density distribution, which results in a reduced scattering coefficient. In a word, OCT can noninvasively monitor changes in collagen structure and the recover process in thermal damage through monitor the tissue scattering coefficient.

  19. Spectra from 2.5-15 microm of tissue phantom materials, optical clearing agents and ex vivo human skin: implications for depth profiling of human skin.

    PubMed

    Viator, John A; Choi, Bernard; Peavy, George M; Kimel, Sol; Nelson, J Stuart

    2003-01-21

    Infrared measurements have been used to profile or image biological tissue, including human skin. Usually, analysis of such measurements has assumed that infrared absorption is due to water and collagen. Such an assumption may be reasonable for soft tissue, but introduction of exogenous agents into skin or the measurement of tissue phantoms has raised the question of their infrared absorption spectrum. We used Fourier transform infrared spectroscopy in attenuated total reflection mode to measure the infrared absorption spectra, in the range of 2-15 microm, of water, polyacrylamide, Intralipid, collagen gels, four hyperosmotic clearing agents (glycerol, 1,3-butylene glycol, trimethylolpropane, Topicare), and ex vivo human stratum corneum and dermis. The absorption spectra of the phantom materials were similar to that of water, although additional structure was noted in the range of 6-10 microm. The absorption spectra of the clearing agents were more complex, with molecular absorption bands dominating between 6 and 12 microm. Dermis was similar to water, with collagen structure evident in the 6-10 microm range. Stratum corneum had a significantly lower absorption than dermis due to a lower content of water. These results suggest that the assumption of water-dominated absorption in the 2.5-6 microm range is valid. At longer wavelengths, clearing agent absorption spectra differ significantly from the water spectrum. This spectral information can be used in pulsed photothermal radiometry or utilized in the interpretation of reconstructions in which a constant mu(ir) is used. In such cases, overestimating mu(ir) will underestimate chromophore depth and vice versa, although the effect is dependent on actual chromophore depth. PMID:12587910

  20. Development of tissue-targeting hemagglutinating virus of Japan envelope vector for successful delivery of therapeutic gene to mouse skin.

    PubMed

    Kawachi, Masako; Tamai, Katsuto; Saga, Kotaro; Yamazaki, Takehiko; Fujita, Hiroshi; Shimbo, Takashi; Kikuchi, Yasushi; Nimura, Keisuke; Nishifuji, Koji; Amagai, Masayuki; Uitto, Jouni; Kaneda, Yasufumi

    2007-10-01

    We report a novel strategy for constructing a tissue-targeting hemagglutinating virus of Japan (HVJ; Sendai virus) envelope vector (HVJ-E), and its application in gene therapy of a mouse model of genetic skin disease. Chimeric genes encoding viral F protein and green fluorescent protein (GFP) were constructed on the basis of various deletion mutants. The product of one chimeric gene, containing signal peptide, transmembrane domain, and the cytoplasmic tail of F protein, was transported to the cell surface and incorporated into new viruses released from HVJ-infected LLC-MK2 cells. For tissue targeting, in the preceding construct GFP was replaced with single-chain antibody (scFv) against mouse desmoglein 3 (mDsg3), a desmosomal cadherin found in basal layer keratinocytes of the skin. HVJ encoding scFv-F chimeric protein bound to mDsg3-coated plates much more efficiently than did wild-type HVJ. When chimeric HVJ was injected into a skin blister of a mouse model of epidermolysis bullosa, in which defective expression of type VII collagen results in a failure to secure epidermis to the underlying dermis, viral F protein expression was detected in most of the basal keratinocytes. Furthermore, chimeric HVJ-E introduced type VII collagen expression more efficiently compared with wild-type HVJ in basal keratinocytes of type VII collagen-deficient mouse skin, resulting in efficient amelioration of the genetic defect. Thus, a novel tissue-targeting HVJ-E could be used to successfully target epidermal keratinocytes both in vitro and in vivo. PMID:17892442

  1. Oxidative Damage and Nuclear Factor Erythroid 2-Related Factor 2 Protein Expression in Normal Skin and Keloid Tissue

    PubMed Central

    Lee, Yoon Jin; Kwon, Sun Bum; Kim, Chul Han; Cho, Hyun Deuk; Nam, Hae Seon; Lee, Sang Han; Lee, Mi Woo; Nam, Doo Hyun; Choi, Chang Yong

    2015-01-01

    Background Reactive oxygen species (ROS) play an important role in the induction of apoptosis under pathological conditions. Recently, a significant increase in ROS production and disrupted apoptosis mechanisms in keloids have been reported. Nuclear factor erythroid 2-related factor 2 (Nrf2) represents one of the most important cellular defense mechanisms against oxidative stress and is implicated in the regulation of apoptosis. Recently, it has been reported that Nrf2 upregulates Bcl-2, an anti-apoptotic protein. Objective To compare Nrf2 protein expression in normal skin tissues to keloid tissues. Methods ROS generation in keloid tissues was evaluated with OxyBlot analysis. Western blotting and/or immunohistochemical staining approaches were used to study expression of Nrf2 or Bcl-2 in keloid and normal skin tissues. Cellular fractionation was performed to examine subcellular distribution of Nrf2. Transfection of fibroblasts with Nrf2-specific small interfering RNA (siRNA) was conducted to understand the relationship between Nrf2 expression and apoptosis induction. Results Protein oxidation, a marker of oxidative stress, is increased in keloid tissues. Western blot analysis clearly showed that Nrf2 and Bcl-2 are downregulated in keloid tissues. Immunohistochemical staining of Nrf2 confirmed the results of the western blot analysis. Transfection of fibroblasts with the Nrf2-specific siRNA results in increased apoptosis and decreased cell viability. Conclusion Collectively, our data indicate that Nrf2 expression is downregulated in keloid tissues, and that Nrf2 is involved in the development of apoptosis in Nrf2 siRNA-transfected fibroblasts. We propose that a defective antioxidant system and apoptotic dysregulation may participate in keloid pathogenesis. PMID:26512164

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

    NASA Astrophysics Data System (ADS)

    Schmid, Gernot; Cecil, Stefan; Überbacher, Richard

    2013-07-01

    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.

  3. 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

    2013-07-01

    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. PMID:23774744

  4. Factors Associated with Decision to Hospitalize Emergency Department Patients with Skin and Soft Tissue Infection

    PubMed Central

    Talan, David A.; Salhi, Bisan A.; Moran, Gregory J.; Mower, William R.; Hsieh, Yu-Hsiang; Krishnadasan, Anusha; Rothman, Richard E.

    2015-01-01

    Introduction Emergency department (ED) hospitalizations for skin and soft tissue infection (SSTI) have increased, while concern for costs has grown and outpatient parenteral antibiotic options have expanded. To identify opportunities to reduce admissions, we explored factors that influence the decision to hospitalize an ED patient with a SSTI. Methods We conducted a prospective study of adults presenting to 12 U.S. EDs with a SSTI in which physicians were surveyed as to reason(s) for admission, and clinical characteristics were correlated with disposition. We employed chi-square binary recursive partitioning to assess independent predictors of admission. Serious adverse events were recorded. Results Among 619 patients, median age was 38.7 years. The median duration of symptoms was 4.0 days, 96 (15.5%) had a history of fever, and 46 (7.5%) had failed treatment. Median maximal length of erythema was 4.0cm (IQR, 2.0–7.0). Upon presentation, 39 (6.3%) had temperature >38°C, 81 (13.1%) tachycardia, 35 (5.7%), tachypnea, and 5 (0.8%) hypotension; at the time of the ED disposition decision, these findings were present in 9 (1.5%), 11 (1.8%), 7 (1.1%), and 3 (0.5%) patients, respectively. Ninety-four patients (15.2%) were admitted, 3 (0.5%) to the intensive care unit (ICU). Common reasons for admission were need for intravenous antibiotics in 80 (85.1%; the only reason in 41.5%), surgery in 23 (24.5%), and underlying disease in 11 (11.7%). Hospitalization was significantly associated with the following factors in decreasing order of importance: history of fever (present in 43.6% of those admitted, and 10.5% discharged; maximal length of erythema >10cm (43.6%, 11.3%); history of failed treatment (16.1%, 6.0%); any co-morbidity (61.7%, 27.2%); and age >65 years (5.4%, 1.3%). Two patients required amputation and none had ICU transfer or died. Conclusion ED SSTI patients with fever, larger lesions, and co-morbidities tend to be hospitalized, almost all to non-critical areas

  5. Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

    PubMed

    Hoffmann, Aswin L; Nahum, Alan E

    2013-10-01

    The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes. PMID:24029492

  6. Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects

    NASA Astrophysics Data System (ADS)

    Hoffmann, Aswin L.; Nahum, Alan E.

    2013-10-01

    The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, (\\alpha /\\beta )_{eff}^{NT}, which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for (\\alpha /\\beta )_{eff}^{NT} ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for (\\alpha /\\beta )_{eff}^{NT} exhibits a weak dependence on the number of fractions. As n is increased, (\\alpha /\\beta )_{eff}^{NT} increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of (\\alpha /\\beta )_{eff}^{NT} corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

  7. 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

  8. The expression of histamine H4 receptor mRNA in the skin and other tissues of normal dogs.

    PubMed

    Eisenschenk, Melissa N C; Torres, Sheila M F; Oliveira, Simone; Been, Clint S

    2011-10-01

    The histamine 4 (H(4)) receptor was first cloned and characterized in 2000 using the human H(3) receptor DNA sequence. The H(4) receptor has been shown to participate in various aspects of inflammation, such as chemotaxis, upregulation of adhesion molecule expression and modulation of cytokine secretion. The primary goal of this study was to determine whether H(4) receptor mRNA is expressed in normal canine skin by performing an RT-PCR. An additional goal was to determine the expression of this receptor in the colon, liver, spleen and kidney. Tissues were collected from five healthy, young-adult pit bull dogs. Samples were immediately placed in RNAlater(®) solution and stored at -20°C until processed. The amplified products in all skin samples in addition to the colon, liver, spleen and kidney (variable expression) had the expected size of 400-500 bp. The sequenced amplicons matched the National Center for Biotechnology Information published sequence for the canine H(4) receptor. The study results showed that canine normal skin expresses the H(4) receptor mRNA. Further studies using immunohistochemistry should be conducted to demonstrate the expression of the H(4) receptor at the protein level and to localize the expression of this receptor in the skin. PMID:21392139

  9. [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. PMID:15259980

  10. Vascular function and tissue injury in murine skin following hyperthermia and photodynamic therapy, alone and in combination.

    PubMed Central

    Moore, J. V.; West, C. M.; Haylett, A. K.

    1992-01-01

    The murine tail has been used as a model for injury to skin when hyperthermia (HT) and photodynamic therapy (PDT) using haematoporphyrin derivative, are used in combination. Skin injury by either agent alone was quantitated by the probability of tail necrosis as a function of dose of agent. 'Tolerance' doses of each modality were given and changes in skin vascular function were measured by the rate of clearance of 133Xenon. This was promptly inhibited but restored to normal by 7 days. The absolute numbers of hypodermal vessels of different sizes were measured in tail cross-sections and capillary numbers were found to be greatly reduced between 1 and 7 days, and restored to normal by 21-28 days. When a tolerance dose of PDT was followed at 1, 7, 21 and 28 days by test doses of HT, or vice versa, marked enhancements in probability of necrosis were observed when the interval was 1 or 7 days (Enhancement ratio (ER)PDT-HT = 1.5 and ERHT-PDT = 1.8). Prolonging the interval between modalities to 21-28 days spared the tissue (ERHT-PDT/21 DAYS = 1.1; ERPDT-HT/28 DAYS = 1.0). Close temporal apposition of PDT and HT, such as has been advocated to improve tumour control, may also increase injury to normal tissue through vascular effects common to both. PMID:1457342

  11. Bacterial skin and soft tissue infections in adults: A review of their epidemiology, pathogenesis, diagnosis, treatment and site of care

    PubMed Central

    Ki, Vincent; Rotstein, Coleman

    2008-01-01

    Skin and soft tissue infections (SSTIs) involve microbial invasion of the skin and underlying soft tissues. They have variable presentations, etiologies and severities. The challenge of SSTIs is to efficiently differentiate those cases that require immediate attention and intervention, whether medical or surgical, from those that are less severe. Approximately 7% to 10% of hospitalized patients are affected by SSTIs, and they are very common in the emergency care setting. The skin has an extremely diverse ecology of organisms that may produce infection. The clinical manifestations of SSTIs are the culmination of a two-step process involving invasion and the interaction of bacteria with host defences. The cardinal signs of SSTIs involve the features of inflammatory response, with other manifestations such as fever, rapid progression of lesions and bullae. The diagnosis of SSTIs is difficult because they may commonly masquerade as other clinical syndromes. To improve the management of SSTIs, the development of a severity stratification approach to determine site of care and appropriate empirical treatment is advantageous. The selection of antimicrobial therapy is predicated on knowledge of the potential pathogens, the instrument of entry, disease severity and clinical complications. For uncomplicated mild to moderate infections, the oral route suffices, whereas for complicated severe infections, intravenous administration of antibiotics is warranted. Recognition of the potential for resistant pathogens causing SSTIs can assist in guiding appropriate selection of antibiotic therapy. PMID:19352449

  12. 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.

  13. Skin microbiota-associated inflammation precedes autoantibody induced tissue damage in experimental epidermolysis bullosa acquisita.

    PubMed

    Ellebrecht, Christoph T; Srinivas, Girish; Bieber, Katja; Banczyk, David; Kalies, Kathrin; Künzel, Sven; Hammers, Christoph M; Baines, John F; Zillikens, Detlef; Ludwig, Ralf J; Westermann, Jürgen

    2016-04-01

    Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune blistering skin disease characterized by autoantibodies against type VII collagen (COL7). Immunization of SJL/J mice with recombinant murine COL7 results in break of tolerance and skin blisters. Strikingly, despite circulating autoantibodies, the same genetic background and identical environmental conditions, 20% of mice remain healthy. To elucidate the regulation of the transition from the presence of autoantibodies to overt autoimmune disease, we characterized the innate and adaptive immune response of mice that remain healthy after immunization and compared it to mice that developed skin disease. Both clinically healthy and diseased SJL/J mice showed circulating autoantibodies and deposition of complement-fixing IgG2c autoantibodies and C3 at the dermal-epidermal junction. However, only in diseased animals significant neutrophil infiltration and increase in FcgRIV expression were observed in the skin. In contrast, the expression of T cell signature cytokines in the T cell zone of the draining lymph node was comparable between clinically healthy and diseased animals after immunization. Surprisingly, health was associated with a decreased expression of CD11c, TNFA and KC (CXCL1) in the skin prior to immunization and could be predicted with a negative predictive value of >80%. Furthermore, mice that did not develop clinical disease showed a significantly higher richness and distinctly clustered diversity of their skin microbiota before immunization. Our data indicate that the decision whether blisters develop in the presence of autoantibodies is governed in the skin rather than in the lymph node, and that a greater richness of cutaneous bacterial species appears to be protective. PMID:26341384

  14. 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. PMID:27326543

  15. dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration.

    PubMed

    Nelson, Amanda M; Reddy, Sashank K; Ratliff, Tabetha S; Hossain, M Zulfiquer; Katseff, Adiya S; Zhu, Amadeus S; Chang, Emily; Resnik, Sydney R; Page, Carly; Kim, Dongwon; Whittam, Alexander J; Miller, Lloyd S; Garza, Luis A

    2015-08-01

    Regeneration of skin and hair follicles after wounding--a process known as wound-induced hair neogenesis (WIHN)--is a rare example of adult organogenesis in mammals. As such, WIHN provides a unique model system for deciphering mechanisms underlying mammalian regeneration. Here, we show that dsRNA, which is released from damaged skin, activates Toll-Like Receptor 3 (TLR3) and its downstream effectors IL-6 and STAT3 to promote hair follicle regeneration. Conversely, TLR3-deficient animals fail to initiate WIHN. TLR3 activation promotes expression of hair follicle stem cell markers and induces elements of the core hair morphogenetic program, including ectodysplasin A receptor (EDAR) and the Wnt and Shh pathways. Our results therefore show that dsRNA and TLR3 link the earliest events of mammalian skin wounding to regeneration and suggest potential therapeutic approaches for promoting hair neogenesis. PMID:26253200

  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. 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

  18. 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. PMID:27111016

  19. Bone-demineralization diagnosis in a bone-tissue-skin matrix using the pulsed-chirped photothermal radar

    NASA Astrophysics Data System (ADS)

    Kaiplavil, Sreekumar; Mandelis, Andreas

    2012-02-01

    A chirped pulsed photothermal radiometric radar is introduced for the diagnosis of biological samples, especially bones with tissue and skin overlayers. The constraints imposed by the laser safety (maximum permissible exposure, MPE) ceiling on pump laser energy and the strong attenuation of thermal-wave signals in tissues significantly limit the photothermally active depth in most biological specimens to a level which is normally insufficient for practical applications (approx. 1 mm below the skin surface). A theoretical approach for improvement of signal-to-noise ratio (SNR), minimizing the static (dc) component of the photothermal signal and making use of the photothermal radiometric nonlinearity has been introduced and verified by comparing the SNR of four distinct excitation wave forms (sine-wave, square-wave, constant- width and constant duty-cycle pulses) for chirping the pump laser, under constant exposure energy. At low frequencies fixed-pulsewidth chirps of large peak power were found to be superior to all other equal-energy modalities, with an SNR improvement up to two orders of magnitude. Distinct thickness-dependent characteristic delay times in a goat bone were obtained, establishing an active depth resolution range of ca. 2.8 mm in a layered skin-fat- bone structure, a favorable result compared to the maximum reported pulsed photothermal radiometric depth resolution < 1 mm in turbid biological media. Compared to radar peak delay and amplitude, the long-delayed radar output amplitude is found to be more sensitive to subsurface conditions. Two-dimensional spatial plots of this parameter depicting the back surface conditions of bones with and without fat-tissue overlayers are presented.

  20. Preparation and Characterization of Electrospun PLCL/Poloxamer Nanofibers and Dextran/Gelatin Hydrogels for Skin Tissue Engineering

    PubMed Central

    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. PMID:25405611

  1. Telavancin, a new lipoglycopeptide antimicrobial, in complicated skin and soft tissue infections.

    PubMed

    Jafari Saraf, Lida; Wilson, Samuel Eric

    2011-01-01

    Telavancin, a novel lipoglycopeptide with rapid concentration-dependent bactericidal effects, is a semisynthetic derivative of the glycopeptide, vancomycin. Telavancin has a dual mechanism of action, ie, inhibition of peptidoglycan polymerization and disruption of the bacterial membrane. It has linear pharmacokinetics, rapid bactericidal killing, and broad spectrum activity against Gram positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus. Phase II and III clinical trials for complicated skin and skin structure infections have shown telavancin to have similar efficacy and tolerability to that of vancomycin and standard anti-staphylococcal β-lactams plus vancomycin. In Phase II trials, there was a significant difference in eradication of MRSA between groups, ie, telavancin therapy 92% and standard therapy (vancomycin, nafcillin, oxacillin, or cloxacillin) 68% (P < 0.05). In Phase III trials, among clinically evaluable patients who had MRSA isolated at baseline, the overall therapeutic response was higher in patients treated with telavancin than in patients treated with vancomycin (89.9% versus 84.7%; 95% CI -0.3, 10.5). Also, the efficacy of telavancin was not inferior to that of vancomycin for the treatment of complicated skin and skin structure infections in the clinical trials. PMID:21694912

  2. 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. PMID:23634479

  3. 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. PMID:26781044

  4. 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.

  5. Discrimination of Basal Cell Carcinoma from Normal Skin Tissue Using High-Resolution Magic Angle Spinning 1H NMR Spectroscopy

    PubMed Central

    Mun, Je-Ho; Lee, Heonho; Yoon, Dahye; Kim, Byung-Soo; Kim, Moon-Bum; Kim, Shukmann

    2016-01-01

    High-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy is a useful tool for investigating the metabolism of various cancers. Basal cell carcinoma (BCC) is the most common skin cancer. However, to our knowledge, data on metabolic profiling of BCC have not been reported in the literature. The objective of the present study was to investigate the metabolic profiling of cutaneous BCC using HR-MAS 1H NMR spectroscopy. HR-MAS 1H NMR spectroscopy was used to analyze the metabolite profile and metabolite intensity of histopathologically confirmed BCC tissues and normal skin tissue (NST) samples. The metabolic intensity normalized to the total spectral intensities in BCC and NST was compared, and multivariate analysis was performed with orthogonal partial least-squares discriminant analysis (OPLS-DA). P values < 0.05 were considered statistically significant. Univariate analysis revealed 9 metabolites that showed statistically significant difference between BCC and NST. In multivariate analysis, the OPLS-DA models built with the HR-MAS NMR metabolic profiles revealed a clear separation of BCC from NST. The receiver operating characteristic curve generated from the results revealed an excellent discrimination of BCC from NST with an area under the curve (AUC) value of 0.961. The present study demonstrated that the metabolite profile and metabolite intensity differ between BCC and NST, and that HR-MAS 1H NMR spectroscopy can be a valuable tool in the diagnosis of BCC. PMID:26934749

  6. Characterization and in vitro evaluation of electrospun chitosan/polycaprolactone blend fibrous mat for skin tissue engineering.

    PubMed

    Prasad, Tilak; Shabeena, E A; Vinod, D; Kumary, T V; Anil Kumar, P R

    2015-01-01

    The electrospinning technique allows engineering biomimetic scaffolds within micro to nanoscale range mimicking natural extracellular matrix (ECM). Chitosan (CS) and polycaprolactone (PCL) were dissolved in a modified solvent mixture consisting of formic acid and acetone (3:7) and mixed in different weight ratios to get chitosan-polycaprolactone [CS-PCL] blend solutions. The CS-PCL blend polymer was electrospun in the same solvent system and compared with PCL. The physicochemical characterization of the electrospun fibrous mats was done using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), tensile test, swelling properties, water contact angle (WCA) analysis, surface profilometry and thermo gravimetric analysis (TGA). The CS-PCL fibrous mat showed decreased hydrophobicity. The CS-PCL mats also showed improved swelling property, tensile strength, thermal stability and surface roughness. The cytocompatibility of the CS-PCL and PCL fibrous mats were examined using mouse fibroblast (L-929) cell line by direct contact and cellular activity with extract of materials confirmed non-cytotoxic nature. The potential of CS-PCL and PCL fibrous mats as skin tissue engineering scaffolds were assessed by cell adhesion, viability, proliferation and actin distribution using human keratinocytes (HaCaT) and L-929 cell lines. Results indicate that CS-PCL is a better scaffold for attachment and proliferation of keratinocytes and is a potential material for skin tissue engineering. PMID:25578706

  7. Topical Nicotinamide Improves Tissue Regeneration in Excisional Full-Thickness Skin Wounds: A Stereological and Pathological Study

    PubMed Central

    Ashkani Esfahani, Soheil; Khoshneviszadeh, Mahsima; Namazi, Mohammad Reza; Noorafshan, Ali; Geramizadeh, Bita; Nadimi, Elham; Razavipour, Seyedeh Tahereh

    2015-01-01

    Background: Nicotinamide (NA), the active form of vitamin-B3, is hypothesized to have positive effects on the process of wound healing; it has anti-inflammatory, antioxidant, and immunomodulatory properties, as well as an epithelization inducing action. Objectives: In the present study, we aimed to determine the effects of topical administration of NA on skin wounds, based on histomorphometrical and pathological criteria. Materials and Methods: In this study, 36 male Sprague-Dawley rats (220 ± 20 g each), with 1 cm2 circular full-thickness wounds on their backs were divided into three groups (n = 12): NA group, was treated daily with a Nicotinamide 2% gel , untreated group (control), and base group, which were treated with the vehicle (base) of the gel (carboxymethylcellulose). Skin biopsies were prepared for microscopic analyses. Inflammation, granulation tissue formation, ulceration, epithelization, wound closure rate, fibroblast proliferation, collagen synthesis, and vascularization were studied criteria. Results: The results revealed that besides improving the wound healing by its anti-inflammatory, antioxidant, and epithelization inducing effects, NA also improved tissue regeneration through the increment of fibroblast proliferation, collagen synthesis, and vascularization. Conclusions: In spite of the few reported side effects, NA can be introduced as an effective agent on the wound healing process, an adjuvant therapy and possibly a treatment by itself. However, its chemical characteristics, as well as possible adverse effects warrants further research. PMID:26839851

  8. 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.

  9. Evaluation of changes in the haemoglobin of skin and muscle tissue of the calf, as induced by topical application of a nonivamide/nicoboxil cream.

    PubMed

    Warnecke, Jan M; Wendt, Thomas; Winkler, Stefan; Schak, Matthias; Schiffer, Thorsten; Kohl-Bareis, Matthias

    2014-02-01

    Topical agents like nonivamide and nicoboxil induce hyperaemisation and increase cutaneous blood flow and temperature. This study aimed to determine the effects of a nonivamide-nicoboxil cream on haemodynamics in the skin and calf muscle, via optical spectroscopy, discriminating between the changes for skin and muscle. Optical spectroscopy was applied in the visible (VIS) and near-infrared (NIR) wavelength range. The study determined the effect of the cream on changes in oxygenated (ΔoxyHb) and deoxygenated (ΔdeoxyHb) haemoglobin in skin and muscle, as well as on tissue oxygen saturation (SO2) in the skin of 14 healthy subjects. The left and right calves of the subjects were either treated with nonivamide-nicoboxil cream or were sham-administered. NIR spectroscopy allows noninvasive in-vivo examination of the oxygenation of human skeletal muscle. Topical administration of the nonivamide-nicoboxil cream significantly increased the concentration of oxygenated haemoglobin and tissue oxygen saturation in the skin, as well as the concentration of oxygenated haemoglobin in the muscle of the treated legs after 15 min, but with stronger and faster effects in the skin. The topical application of the nonivamide-nicoboxil cream increased blood flow in (smaller vessels of) the skin and muscle tissues. PMID:24502638

  10. 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

  11. Understanding Intratumoral Heterogeneity: Lessons from the Analysis of At-Risk Tissue and Premalignant Lesions in the Colon.

    PubMed

    Sievers, Chelsie K; Leystra, Alyssa A; Clipson, Linda; Dove, William F; Halberg, Richard B

    2016-08-01

    Advances in DNA sequencing have created new opportunities to better understand the biology of cancers. Attention is currently focused on precision medicine: does a cancer carry a mutation that is targetable with already available drugs? But, the timing at which multiple, targetable mutations arise during the adenoma to carcinoma sequence remains unresolved. Borras and colleagues identified mutations and allelic imbalance in at-risk mucosa and early polyps in the human colon. Their analyses indicate that mutations in key genes can arise quite early during tumorigenesis and that polyps are often multiclonal with at least two clones. These results are consistent with the "Big Bang" model of tumorigenesis, which postulates that intratumoral heterogeneity is a consequence of a mutational burst in the first few cell divisions following initiation that drives divergence from a single founder with unique but related clones coevolving. Emerging questions center around the ancestry of the tumor and impact of early intratumoral heterogeneity on tumor establishment, growth, progression, and most importantly, response to therapeutic intervention. Additional sequencing studies in which samples, especially at-risk tissue and premalignant neoplasms, are analyzed from animal models and humans will further our understanding of tumorigenesis and lead to more effective strategies for prevention and treatment. Cancer Prev Res; 9(8); 638-41. ©2016 AACRSee related article by Borras, et al., Cancer Prev Res 2016;9(6):417-427. PMID:27199343

  12. 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

  13. Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast

    PubMed Central

    2010-01-01

    Introduction Residual cancer following breast conserving surgery increases the risk of local recurrence and mortality. Margin assessment presents an unmet clinical need. Breast tissue is markedly heterogeneous, which makes distinguishing small foci of cancer within the spectrum of normal tissue potentially challenging. This is further complicated by the heterogeneity as a function of menopausal status. Optical spectroscopy can provide surgeons with intra-operative diagnostic tools. Here, we evaluate ex-vivo breast tissue and determine which sources of optical contrast have the potential to detect malignancy at the margins in women of differing breast composition. Methods Diffuse reflectance spectra were measured from 595 normal and 38 malignant sites from the margins of 104 partial mastectomy patients. All statistical tests were performed using Wilcoxon Rank-Sum tests. Normal and malignant sites were compared before stratifying the data by tissue type and depth and computing statistical differences. The frequencies of the normal tissue types were separated by menopausal status and compared to the corresponding optical properties. Results The mean reduced scattering coefficient, < μs' >, and concentration of total hemoglobin, [THb]), showed statistical differences between malignant (< μs' > : 8.96 cm-1 ± 2.24MAD, [THb]: 42.70 μM ± 29.31MAD) compared to normal sites (< μs' > : 7.29 cm-1 ± 2.15MAD, [THb]: 32.09 μM ± 16.73MAD) (P < 0.05). The sites stratified according to normal tissue type (fibro-glandular (FG), fibro-adipose (FA), and adipose (A)) or disease type (invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS)) showed that FG exhibited increased < μs' > and A showed increased [β-carotene] within normal tissues. Scattering differentiated between most malignant sites, DCIS (9.46 cm-1 ± 1.06MAD) and IDC (8.00 cm-1 ± 1.81MAD), versus A (6.50 cm-1 ± 1.95MAD). [β-carotene] showed marginal differences between DCIS (19.00 μM ± 6.93MAD

  14. Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs Using Low-Viscosity Bioink.

    PubMed

    Colosi, Cristina; Shin, Su Ryon; Manoharan, Vijayan; Massa, Solange; Costantini, Marco; Barbetta, Andrea; Dokmeci, Mehmet Remzi; Dentini, Mariella; Khademhosseini, Ali

    2016-01-27

    A novel bioink and a dispensing technique for 3D tissue-engineering applications are presented. The technique incorporates a coaxial extrusion needle using a low-viscosity cell-laden bioink to produce highly defined 3D biostructures. The extrusion system is then coupled to a microfluidic device to control the bioink arrangement deposition, demonstrating the versatility of the bioprinting technique. This low-viscosity cell-responsive bioink promotes cell migration and alignment within each fiber organizing the encapsulated cells. PMID:26606883

  15. 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.

  16. Stiff skin syndrome.

    PubMed

    Geng, S; Lei, X; Toyohara, J P; Zhan, P; Wang, J; Tan, S

    2006-07-01

    Stiff skin syndrome is a rare disorder characterized by pronounced skin induration, mild hypertrichosis and limited joint mobility, predominantly on the buttocks and thighs. Many heterogeneous cases have been reported under the name of stiff skin syndrome. We present a case of stiff skin syndrome from China, the diagnosis based on the patient's typical clinical and histopathological features. PMID:16836505

  17. Computational fluid dynamics modeling of airflow inside lungs using heterogenous anisotropic lung tissue elastic properties.

    PubMed

    Ilegbusi, Olusegun; Li, Ziang; Min, Yugang; Meeks, Sanford; Kupelian, Patrick; Santhanam, Anand P

    2012-01-01

    The aim of this paper is to model the airflow inside lungs during breathing and its fluid-structure interaction with the lung tissues and the lung tumor using subject-specific elastic properties. The fluid-structure interaction technique simultaneously simulates flow within the airway and anisotropic deformation of the lung lobes. The three-dimensional (3D) lung geometry is reconstructed from the end-expiration 3D CT scan datasets of humans with lung cancer. The lung is modeled as a poro-elastic medium with anisotropic elastic property (non-linear Young's modulus) obtained from inverse lung elastography of 4D CT scans for the same patients. The predicted results include the 3D anisotropic lung deformation along with the airflow pattern inside the lungs. The effect is also presented of anisotropic elasticity on both the spatio-temporal volumetric lung displacement and the regional lung hysteresis. PMID:22356987

  18. 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.

  19. Phenotypical heterogeneity linked to adipose tissue dysfunction in patients with Type 2 diabetes.

    PubMed

    Barchetta, Ilaria; Angelico, Francesco; Del Ben, Maria; Di Martino, Michele; Cimini, Flavia Agata; Bertoccini, Laura; Polimeni, Licia; Catalano, Carlo; Fraioli, Antonio; Del Vescovo, Riccardo; Morini, Sergio; Baroni, Marco Giorgio; Cavallo, Maria Gisella

    2016-10-01

    Adipose tissue (AT) inflammation leads to increased free fatty acid (FFA) efflux and ectopic fat deposition, but whether AT dysfunction drives selective fat accumulation in specific sites remains unknown. The aim of the present study was to investigate the correlation between AT dysfunction, hepatic/pancreatic fat fraction (HFF, PFF) and the associated metabolic phenotype in patients with Type 2 diabetes (T2D). Sixty-five consecutive T2D patients were recruited at the Diabetes Centre of Sapienza University, Rome, Italy. The study population underwent clinical examination and blood sampling for routine biochemistry and calculation of insulin secretion [homoeostasis model assessment of insulin secretion (HOMA-β%)] and insulin-resistance [homoeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance (ADIPO-IR)] indexes. Subcutaneous (SAT) and visceral (VAT) AT area, HFF and PFF were determined by magnetic resonance. Some 55.4% of T2D patients had non-alcoholic fatty liver disease (NAFLD); they were significantly younger and more insulin-resistant than non-NAFLD subjects. ADIPO-IR was the main determinant of HFF independently of age, sex, HOMA-IR, VAT, SAT and predicted severe NAFLD with the area under the receiver operating characteristic curve (AUROC)=0.796 (95% confidence interval: 0.65-0.94, P=0.001). PFF was independently associated with increased total adiposity but did not correlate with AT dysfunction, insulin resistance and secretion or NAFLD. The ADIPO-IR index was capable of predicting NAFLD independently of all confounders, whereas it did not seem to be related to intrapancreatic fat deposition; unlike HFF, higher PFF was not associated with relevant alterations in the metabolic profile. In conclusion, the presence and severity of AT dysfunction may drive ectopic fat accumulation towards specific targets, such as VAT and liver, therefore evaluation of AT dysfunction may contribute to the identification of different

  20. 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.

  1. 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.

  2. Microporous dermal-mimetic electrospun scaffolds pre-seeded with fibroblasts promote tissue regeneration in full-thickness skin wounds.

    PubMed

    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

  3. 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

  4. 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. PMID:27406581

  5. 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

    2015-01-01

    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. PMID:26132812

  6. Marine recruit adherence in a skin and soft tissue infection prevention trial: implications for recruit research and public health application.

    PubMed

    Schlett, Carey D; Grandits, Greg A; Millar, Eugene V; Whitman, Timothy J; Tribble, David R

    2012-11-01

    A cluster-randomized trial evaluating the effectiveness of chlorhexidine gluconate-impregnated wipes against skin and soft tissue infections (SSTIs) and colonization with methicillin-resistant Staphylococcus aureus (MRSA) was conducted among military recruits attending Officer Candidate School at Marine Corps Base Quantico, Virginia. Participants were instructed to use the wipes thrice weekly and were monitored daily for SSTI. Surveys assessed frequency of wipe use as well as knowledge and attitudes regarding MRSA SSTI. Use of chlorhexidine gluconate-impregnated wipes failed to prevent SSTI; however, study adherence was moderate. Adherence with the study regimen (defined as use of > or = 50% of the wipes) was 65% at week 2 and declined to 49% by week 6. Adherence was approximately 59% in the first two classes and declined in later classes. One-third felt that use of the wipes was disruptive. Participants were knowledgeable about MRSA SSTI prevention measures. However, only 53% agreed that MRSA commonly causes skin infections in military training facilities. Understanding adherence and its determinants is needed to optimize prevention strategies that require self-administration. Future efforts should address barriers to adherence with prevention strategies in recruit training settings. PMID:23198510

  7. Effect of low-level laser treatment of tissue-engineered skin substitutes: contraction of collagen lattices

    NASA Astrophysics Data System (ADS)

    Ho, Gideon; Barbenel, Joseph; Grant, M. Helen

    2009-05-01

    Fibroblast-populated collagen lattices (FPCL) are widely used in tissue-engineered artificial skin substitutes, but their main drawback is that interaction of fibroblasts and matrix causes contraction of the lattice, reducing it to about 20% of its original area. The effect of low-level laser treatment (LLLT) on the behavior of 3T3 fibroblasts seeded in collagen lattices containing 20% chondroitin-6-sulphate was investigated to determine whether LLLT could control the contraction of FPCL. A He-Ne laser was used at 632.8 nm to deliver a 5-mW continuous wave with fluences from 1 to 4 J/cm2. Laser treatment at 3 J/cm2 increased contraction of collagen lattices in the absence of cells but decreased contraction of cell seeded lattices over a 7-day period. The effect was energy dependent and was not observed at 1, 2, or 4 J/cm2. There was no alteration in fibroblast viability, morphology, or mitochondrial membrane potential after any laser treatments, but the distribution of actin fibers within the cells and collagen fibers in the matrices was disturbed at 3 J/cm2. These effects contribute to the decrease in contraction observed. LLLT may offer a means to control contraction of FPCL used as artificial skin substitutes.

  8. Heterogeneity among white adipose tissue depots in male C57BL/6J mice.

    PubMed

    Sackmann-Sala, Lucila; Berryman, Darlene E; Munn, Rachel D; Lubbers, Ellen R; Kopchick, John J

    2012-01-01

    The widespread prevalence of obesity has lead to extensive research on white adipose tissue (WAT), which frequently uses the C57BL/6J mouse strain as a model. In many studies, results obtained in one WAT depot are often extrapolated to all WAT. However, functional differences among WAT depots are now becoming apparent. Thus, to identify the molecular mechanisms responsible for WAT depot-specific differences under "normal" conditions, four C57BL/6J mouse WAT depots (inguinal, mesenteric, epididymal, and retroperitoneal) were analyzed. Depot proteomic profiles, along with weights, protein contents, adipocyte sizes and oxidative stress were determined. Mesenteric WAT had almost twice the protein content of the other depots analyzed. Mean adipocyte size was highest in epididymal and lowest in mesenteric and inguinal depots. The proteome of inguinal WAT displayed low levels of enzymes involved in ATP generation, glucose and lipid metabolism, and antioxidant proteins. Higher levels of these proteins were observed in mesenteric and epididymal WAT, with variable levels in the retroperitoneal depot. Some of these proteins showed depot-specific correlations with plasma levels of insulin, leptin, and adiponectin. In agreement with the proteomic data, levels of the antioxidant protein heat shock protein β1 (HSPβ1) also were lower in inguinal WAT when analyzed by western blotting and immunohistochemistry. Also, lipid peroxidation products showed similar trends. Our results are consistent with lower triglyceride turnover and lower oxidative stress in inguinal than mesenteric and epididymal WAT. The observed WAT depot-specific differences provide clues as to the mechanisms leading to these depots' respective diverse functions. PMID:21779095

  9. Cellular heterogeneity in superficial and deep subcutaneous adipose tissues in overweight patients.

    PubMed

    Boulet, Nathalie; Estève, David; Bouloumié, Anne; Galitzky, Jean

    2013-09-01

    Human abdominal adipose tissue (AAT) can be divided into two compartments according to anatomical location to dermis layer, i.e. superficial and deep compartments (sAAT and dAAT). In morbidly obese patients, dAAT mass has been linked to obesity-associated pathologies. In the present study, we characterized in overweight healthy individuals human sAAT and dAAT cellular composition and adipogenic potential. Twelve paired sAAT and dAAT samples were collected. sAAT compared to dAAT adipocytes are larger. In agreement with increased size, real-time PCR analyses performed on isolated adipocytes showed that sAAT adipocytes exhibited higher leptin transcript levels but also higher expression of genes involved in metabolism including hormone-sensitive lipase compared to dAAT adipocytes. Flow cytometry analyses performed on stroma-vascular fraction (SVF) showed no difference in the numbers of progenitor cells, endothelial cells and macrophages between sAAT and dAAT. Macrophage phenotypes were not distinct between both AAT compartments. However, CD3+ T lymphocyte number was higher in dAAT than in sAAT. Adipogenic potential of dAAT SVF was lower than sAAT SVF whereas the one of isolated progenitor cells was not distinct whatever the AAT compartments. Therefore, in overweight patients, both sAAT and dAAT compartments exhibit differences in terms of adipocytes and T lymphocyte accumulation. dAAT is characterized by higher T lymphocyte accumulation together with smaller less metabolically active adipocytes. The lower adipogenic potential of dAAT SVF is not due to intrinsic progenitor cell properties but more likely to the increased T lymphocyte accumulation. PMID:23184733

  10. Usefulness of liquid-crystal oral formulations to enhance the bioavailability and skin tissue targeting of p-amino benzoic acid as a model compound.

    PubMed

    Kadhum, Wesam R; Oshizaka, Takeshi; Ichiro, Hijikuro; Todo, Hiroaki; Sugibayashi, Kenji

    2016-06-10

    Topical formulations are not always suitable to deliver active ingredients to large areas of skin. Thus, in this study, we aimed to develop an oral formulation for skin tissue targeting with a high bioavailability using liquid crystal (LC) dispersions comprising cubosomes of a mal-absorptive model compound, p-amino benzoic acid (PABA), which is an active element in cosmeceuticals, dietary supplements and skin disorder medicines. The bioavailability and skin concentration of PABA were investigated after oral administration in rats. The effect of the remaining amount of the LC formulation in the stomach on the pharmacokinetic profiles of orally administered PABA was evaluated. The skin permeation and concentration of PABA were also investigated using an in vitro permeation experiment. As a result, the bioavailability of PABA was significantly improved by administration of PABA-LC formulations compared with PABA solution alone, although the effect was greatly influenced by the type of LC-forming lipids. The in vitro skin permeation study showed that the PABA concentration in the skin when applied from the dermis side was higher than when applied from the epidermis side. These findings suggested that oral administration advantageously supports skin targeting, and oral LC formulations could be a promising material in cosmeceutical, dietary and clinical fields. PMID:27072433

  11. Characterization of human skin cells for tissue engineering applications by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Pudlas, Marieke; Koch, Steffen; Bolwien, Carsten; Walles, Heike

    2010-02-01

    In the field of cell culture and tissue engineering is an increasing need for non-invasive methods to analyze living cells in vitro. One important application is the cell characterization in tissue engineering products. Raman spectroscopy is a method which analyzes cells without lysis, fixation or the use of any chemicals and do not affect cell vitality adversely if suitable laser powers and wavelength are used. This purely optical technique is based on inelastic scattering of laser photons by molecular vibrations of biopolymers. Basically Raman spectra of cells contain typical fingerprint regions and information about cellular properties. Characteristic peaks in Raman spectra could be assigned to biochemical molecules like proteins, nucleic acid or lipids. The distinction of cell types by a multivariate analysis of Raman spectra is possible due to their biochemical differences. As this method allows a characterization of cells without any cell damage it is a promising technology for the quality control of cells in tissue engineering or cell culture applications.

  12. Skin Cancer

    MedlinePlus

    ... early. If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments ... and a type of laser light to kill cancer cells. Biologic therapy boosts your body's own ability to ...

  13. 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 ...

  14. TAT-Mediated Acidic Fibroblast Growth Factor Delivery to the Dermis Improves Wound Healing of Deep Skin Tissue in Rat

    PubMed Central

    Tang, Lu; Zheng, Lulu; Jin, Zi; Yu, Bingjie; Wang, Zhitao; Lin, Peng; Yu, Weidan; Li, Haiyan; Li, Xiaokun; Wang, Xiaojie

    2015-01-01

    Background The definition of deep tissue injury was derived from multiple clinical cases as “A purple or maroon localized area of discolored intact skin or blood-filled blister due to damage of underlying soft tissue from pressure and/or shear”. Acidic fibroblast growth factor (aFGF) significantly improves wound healing under diabetic conditions. However, to date, the therapeutic application of aFGF has been limited, due to its low delivery efficiency and short half-life. Methodology/Principal Findings Using an animal model of magnet-induced pressure ulcers, transactivator of transcription protein (TAT)-aFGF was evaluated for transdermal delivery and wound healing. Immunohistochemistry and Western blotting were also performed to determine the expression of transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA), CD68, proliferating cell nuclear antigen (PCNA) and TGF-β-receptor II (TGF- βRII) in cultured human dermal fibroblasts. We found that that mice treated with TAT-aFGF had higher accumulation of aFGF in both dermis and subcutaneous tissues compared with mice treated with aFGF alone. In the remodeling phase, TAT-aFGF treatment decreased the expression of α-SMA to normal levels, thereby facilitating normal wound healing processes and abrogating hypertrophic scarring. In human dermal fibroblasts, TAT-aFGF reversed the suppressive effect of TNF-α on α-SMA expression and restored TGF-βRII and TGF-β1 expression. Conclusions/Significance Our results demonstrate that TAT-aFGF has a favorable therapeutic effect on the healing of subcutaneous deep tissue injury. PMID:26271041

  15. Tissue types (image)

    MedlinePlus

    ... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

  16. 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

  17. 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

  18. 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

    2016-01-01

    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 heterogene-ity 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

  19. 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.

  20. 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. PMID:20357814

  1. Skin and soft-tissue infections: a critical review and the role of telavancin in their treatment.

    PubMed

    Cardona, Amilcar F; Wilson, Samuel E

    2015-09-15

    Skin and soft-tissue infections (SSTIs) are an important cause of morbidity and mortality among hospitalized patients and a major therapeutic challenge for clinicians. Although uncomplicated SSTIs are managed successfully on an outpatient basis, more serious infections extending to the subcutaneous tissue, fascia, or muscle require complex management. Early diagnosis, selection of appropriate antimicrobials, and timely surgical intervention are key to successful treatment. Surgical-site infections, an important category of SSTI, occur in approximately half a million patients in North America annually. SSTIs are also a potential source for life-threatening bacteremia and metastatic abscesses. Gram-positive organisms, such as Staphylococcus aureus and Streptococcus pyogenes, are the dominant organisms isolated early in the infectious process, whereas gram-negative organisms are found in chronic wounds. Methicillin-resistant S. aureus (MRSA) is a potential bloodstream invader that requires aggressive antimicrobial treatment and surgery. Recent concerns regarding vancomycin activity include heteroresistance in MRSA and increase in the minimum inhibitory concentrations (>1 or 2 µg/mL); however, alternative agents, such as telavancin, daptomycin, linezolid, ceftaroline, dalbavancin, oritavancin, and tedizolid, are now available for the treatment of severe MRSA infections. Here, we present a review of the epidemiology, etiology, and available treatment options for the management of SSTIs. PMID:26316560

  2. 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.

  3. Influence of Skin and Subcutaneous Tissue on High-Intensity Focused Ultrasound Beam: Experimental Quantification and Numerical Modeling.

    PubMed

    Grisey, Anthony; Heidmann, Marc; Letort, Veronique; Lafitte, Pauline; Yon, Sylvain

    2016-10-01

    High-intensity focused ultrasound (HIFU) enables the non-invasive thermal ablation of tumors. However, numerical simulations of the treatment remain complex and difficult to validate in clinically relevant situations. In this context, needle hydrophone measurements of the acoustic field downstream of seven rabbit tissue layers comprising skin, subcutaneous fat and muscle were performed in different geometrical configurations. Increasing curvature and thickness of the sample were found to decrease the focusing of the beam: typically, a curvature of 0.05 mm(-1) decreased the maximum pressure by 45% and doubled the focal area. A numerical model based on k-Wave Toolbox was found to be in very good agreement with the reported measurements. It was used to extrapolate the effect of the superficial tissues on peak positive and peak negative pressure at focus, which affects both cavitation and target heating. The shape of the interface was found to have a strong influence on the values, and it is therefore an important parameter to monitor or to control in the clinical practice. This also highlights the importance of modeling realistic configurations when designing treatment procedures. PMID:27471120

  4. 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

  5. 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

  6. Optically-tracked handheld fluorescence imaging platform for monitoring skin response in the management of soft tissue sarcoma

    NASA Astrophysics Data System (ADS)

    Chamma, Emilie; Qiu, Jimmy; Lindvere-Teene, Liis; Blackmore, Kristina M.; Majeed, Safa; Weersink, Robert; Dickie, Colleen I.; Griffin, Anthony M.; Wunder, Jay S.; Ferguson, Peter C.; DaCosta, Ralph S.

    2015-07-01

    Standard clinical management of extremity soft tissue sarcomas includes surgery with radiation therapy. Wound complications (WCs) arising from treatment may occur due to bacterial infection and tissue breakdown. The ability to detect changes in these parameters during treatment may lead to earlier interventions that mitigate WCs. We describe the use of a new system composed of an autofluorescence imaging device and an optical three-dimensional tracking system to detect and coregister the presence of bacteria with radiation doses. The imaging device visualized erythema using white light and detected bacterial autofluorescence using 405-nm excitation light. Its position was tracked relative to the patient using IR reflective spheres and registration to the computed tomography coordinates. Image coregistration software was developed to spatially overlay radiation treatment plans and dose distributions on the white light and autofluorescence images of the surgical site. We describe the technology, its use in the operating room, and standard operating procedures, as well as demonstrate technical feasibility and safety intraoperatively. This new clinical tool may help identify patients at greater risk of developing WCs and investigate correlations between radiation dose, skin response, and changes in bacterial load as biomarkers associated with WCs.

  7. Total gadolinium tissue deposition and skin structural findings following the administration of structurally different gadolinium chelates in healthy and ovariectomized female rats

    PubMed Central

    Schroeder, Joseph; Siegmund, Heiko; Idée, Jean-Marc; Fretellier, Nathalie; Jestin-Mayer, Gaëlle; Factor, Cecile; Deng, Min; Kang, Wei; Morcos, Sameh K.

    2015-01-01

    Objective To assess the retention of gadolinium (Gd) in skin, liver, and bone following gadodiamide or gadoteric acid administration. Methods Gd was measured in skin, liver and femur bone in female rats 10 weeks after administration of 17.5 mmol Gd/kg over 5 days of Gd agents. Rat skin microscopy, energy filtering transmission electron microscopy and elemental analysis were performed, and repeated after receiving the same dosage of gadodiamide in rats with osteoporosis induced with bilateral ovariectomy (OVX). The OVX was performed 60 days after the last injection of gadodiamide and animals sacrificed 3 weeks later. Results Gd concentration was 180-fold higher in the skin, 25-fold higher in the femur, and 30-fold higher in the liver in rats received gadodiamide than rats received gadoteric acid. The retention of Gd in the skin with gadodiamide was associated with an increase in dermal cellularity, and Gd encrustation of collagen fibers and deposition inside the fibroblasts and other cells. No differences in Gd concentration in liver, skin, and femur were observed between rats receiving gadodiamide with or without OVX. Conclusions Gd tissue retention with gadodiamide was higher than gadoteric acid. Tissues Gd deposition did not alter following gadodiamide administration to ovariectomized rats. PMID:26435917

  8. Effects of copper vapor laser (CVL) on mice skin: histologic evaluation of damage and tissue stimulation

    NASA Astrophysics Data System (ADS)

    Nunes, Syllene; Moreno, E.; Oliveira, H.; Osaka, J.; Salvador, G.; Michalany, N.; Tolosa, E.

    2002-10-01

    This study was to evaluate the effects of the CVL with low energy and short pulse widths. 18 female mice, C57BL/6 (9-11 weeks old) were distributed into four groups. The control group (CG) wasn't exposed to laser beam . Group L1 had 2 laser expositions with 24 hours gap between them (0.5W). Group L2 had 3 expositions (0.5W and 0.25W) and group L3 had 4 expositions (0.25 W). It was used a CVL prototype (5lOnm, 13 Khz, pulse width of 20 ms and spot size of 0.8cm). 7 days after last laser pulse no groups presented actinic keratosis, tumors or collagen changes. CVL had effective action on pilosebaceous units. High energy with few short pulses induced hair follicles proliferation while low energy with many repetitive short pulses showed increased and specific tissue damage besides hair plugging.

  9. Noninvasive in-vivo near-infrared vibrational spectroscopic study of lipid and aqueous phases of skin and near-surface tissues

    NASA Astrophysics Data System (ADS)

    Chaiken, Joseph; Finney, William F.; Peterson, Karen P.; Peterson, Charles M.; Knudson, Paul E.; Weinstock, Ruth S.; Lein, Paul

    2000-05-01

    We report the use of near infrared vibrational spectroscopy to noninvasively probe the in-vivo lipid and aqueous phases of skin and near surface tissues under conditions of thermal and chemical modulation. We demonstrate thermally induced order- disorder transitions in lipids that can be directly compared to well known behavior of in-vitro samples of phospholipid bilayers and bulk fatty acids. We show reversible chemical modification of aqueous phase proteins which are also directly comparable to well known phenomena involving in-vitro proteins. The results of these studies demonstrate the capacity for noninvasively probing live human tissues on the molecular level using near infrared vibrational spectroscopy. This capacity suggests numerous potential applications ranging from assessing the efficacy of cosmetics, skin care treatments and transdermal therapeutic agents/treatments to serving as a diagnostic of various skin ailments, e.g. melanoma.

  10. 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.

  11. Effects of the tissue-air interface in calculations of beta-particle skin dose at a depth of 70 microns.

    PubMed

    Crawford, O H; Turner, J E; Hamm, R N; Ashley, J C

    1991-11-01

    The effects that the tissue-air interface has on the basal-layer dose at a depth of 70 microns from beta emitters on the skin surface are studied using Monte Carlo calculations. The dose is decreased at small lateral distances from a point source but is increased at large distances. PMID:1752748

  12. Examining the Relationships Between Bone Tissue Composition, Compositional Heterogeneity, and Fragility Fracture: A Matched Case-Controlled FTIRI Study.

    PubMed

    Boskey, Adele L; Donnelly, Eve; Boskey, Elizabeth; Spevak, Lyudmila; Ma, Yan; Zhang, Wei; Lappe, Joan; Recker, Robert R

    2016-05-01

    Fourier transform infrared imaging (FTIRI) provides information on spatial distribution of the chemical composition of thin tissue specimens at ∼7 µm spatial resolution. This study of 120 age- and bone mineral density (BMD)-matched patients was designed to investigate the association of FTIRI variables, measured in iliac crest biopsies, with fragility fractures at any site. An earlier study of 54 women found hip BMD to be a significant explanatory variable of fracture risk for cortical bone but not for cancellous bone. In the current study, where age and BMD were controlled through matching, no such association was observed, validating the pairing scheme. Our first study of unmatched iliac crest biopsies found increases in collagen maturity (cancellous and cortical bone) and mineral crystal size (cortical bone only) to be a significant explanatory variable of fracture when combined with other covariates. The ratio for collagen maturity has been correlated to the amount of enzymatic collagen cross-links. To assess the impact of other FTIRI variables (acid phosphate substitution, carbonate-to-phosphate ratio, and the pixel distribution [heterogeneity] of all relevant FTIRI variables), we examined biopsies from a matched case-controlled study, in which 60 women with fractures were each paired with an age- and BMD-matched female control. With the matched data set of 120 women, conditional logistic regression analyses revealed that significant explanatory variables of fracture were decreased carbonate-to-phosphate ratio in both cancellous (odds ratio [OR] = 0.580, 95% confidence interval [CI] 0.37-0.909, p = 0.0176) and cortical bone (OR = 0.519, 95% CI 0.325-0.829, p = 0.0061), and increased heterogeneity (broadened pixel distribution) of collagen maturity for cancellous bone (OR = 1.549, 95% CI 1.002-2.396, p = 0.0491). The observation that collagen maturity was no longer linked to fracture in age- and BMD-matched samples suggests that age

  13. Expression of Endothelial Nitric Oxide Synthase and Endothelin-1 in Skin Tissue from Amputated Limbs of Patients with Complex Regional Pain Syndrome

    PubMed Central

    Groeneweg, J. George; Antonissen, Claudia Heijmans; Huygen, Frank J. P. M.; Zijlstra, Freek J.

    2008-01-01

    Background and Objectives. Impaired microcirculation during the chronic stage of complex regional pain syndrome (CRPS) is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Endothelial dysfunction is suggested to be the main cause of diminished blood flow. The aim of this study was to examine the distribution of endothelial nitric oxide synthase (eNOS) and endothelin-1(ET-1) relative to vascular density represented by the endothelial marker CD31-immunoreactivity in the skin tissue of patients with chronic CRPS. Methods. We performed immunohistochemical staining on sections of skin specimens obtained from the amputated limbs (one arm and one leg) of two patients with CRPS. Results. In comparison to proximal specimens we found an increased number of migrated endothelial cells as well as an increase of eNOS activity in distal dermis specimens. Conclusions. We found indications that endothelial dysfunction plays a role in chronic CRPS. PMID:18663383

  14. 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. PMID:26099836

  15. 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.

  16. 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. PMID:26796702

  17. Clinical response and mortality in tigecycline complicated intra-abdominal infection and complicated skin and soft-tissue infection trials.

    PubMed

    Bassetti, Matteo; McGovern, Paul C; Wenisch, Christoph; Meyer, R Daniel; Yan, Jean Li; Wible, Michele; Rottinghaus, Scott T; Quintana, Alvaro

    2015-09-01

    An imbalance in all-cause mortality was noted in tigecycline phase 3 and 4 comparative clinical trials across all studied indications. We investigated clinical failure and mortality in phase 3 and 4 complicated skin and soft-tissue infection (cSSTI) and complicated intra-abdominal infection (cIAI) tigecycline trials using descriptive analyses of a blinded adjudication of mortality and multivariate regression analyses. Attributable mortality analyses of cSSTI revealed death due to infection in 0.1% of each treatment group (P=1.000). In cIAI, there were no significant differences between tigecycline (1.2%) and comparator (0.7%) subjects who died due to infection (P=0.243). For cIAI clinical failure, treatment interaction with organ dysfunction was observed with no difference observed between clinical cure for tigecycline (85.4%) and comparator (76.7%) treatment groups (odds ratio=0.58, 95% confidence interval 0.28-1.19). Tigecycline-treated subjects had more adverse events of secondary pneumonias (2.1% vs. 1.2%) and more adverse events of secondary pneumonias with an outcome of death (0.5% vs. 0.1%). These analyses do not suggest that tigecycline is a factor either for failure (cSSTI and cIAI studies) or for death (cIAI studies). PMID:26155003

  18. Treatment of complicated skin and soft-tissue infections caused by resistant bacteria: value of linezolid, tigecycline, daptomycin and vancomycin

    PubMed Central

    2010-01-01

    Antibiotic-resistant organisms causing both hospital-and community-acquired complicated skin and soft-tissue infections (cSSTI) are increasingly reported. A substantial medical and economical burden associated with MRSA colonisation or infection has been documented. The number of currently available appropriate antimicrobial agents is limited. Good quality randomised, controlled clinical trial data on antibiotic efficacy and safety is available for cSSTI caused by MRSA. Linezolid, tigecycline, daptomycin and vancomycin showed efficacy and safety in MRSA-caused cSSTI. None of these drugs showed significant superiority in terms of clinical cure and eradication rates. To date, linezolid offers by far the greatest number of patients included in controlled trials with a strong tendency of superiority over vancomycin in terms of eradication and clinical success. Tigecycline is an alternative in polymicrobial infections except by diabetic foot infections. Daptomycin might be a treatment option for cases of cSSTI with MRSA bacteremia. cSSTI caused by resistant Gram-negative bacteria are a matter of great concern. The development of new antibiotics in this area is an urgent priority to avoid the risk of a postantibiotic era with no antimicrobial treatment options. An individual approach for every single patient is mandatory to evaluate the optimal antimicrobial treatment regimen. PMID:21163730

  19. 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. PMID:25867210

  20. 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. PMID:27262852

  1. 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

  2. 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

  3. 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. PMID:19617720

  4. Local skin burn causes systemic (lung and kidney) endothelial cell injury reflected by increased circulating and decreased tissue factor VIII-related antigen.

    PubMed

    Gross, M A; Viders, D E; Brown, J M; Mulvin, D W; Miles, R H; Brentlinger, E R; Velasco, S E; Crawford, T S; Burton, L K; Repine, J E

    1989-08-01

    Inasmuch as xanthine oxidase (XO)-derived O2* metabolites may contribute to vascular endothelial injury and Factor VIII antigen (F8Ag) is a component of endothelial cells, we hypothesized that XO-derived O2* might damage and cause distant organ endothelial cells to release F8Ag in rats subjected to skin burn. We found that serum F8Ag (ELISA) increased in the blood of rats subjected to skin burn (70 degrees C water to shaved dorsal skin for 30 seconds) but not in sham control rats (30 degrees C water). Coincidentally, F8Ag levels also decreased in lung and kidney tissue sections (immunofluorescent staining) of burned rats but not sham rats. Increases in circulating F8Ag levels and decreases in tissue F8Ag levels appeared to result from XO-derived O2* metabolites: F8Ag levels did not increase in the blood and did not decrease in the tissues of rats pretreated with allopurinol (a specific XO inhibitor, 50 mg/kg) or dimethylthiourea (DMTU) (a permeable O2* metabolite scavenger, 250 mg/kg). Lung injury as assessed by permeability studies (I125-albumin leak) paralleled changes in blood F8Ag levels in sham, burn, allopurinol-, and DMTU-treated groups. We conclude that skin burn causes a systemic vascular injury that can be inhibited by allopurinol or DMTU and is reflected by increased circulating and tissue decreased Factor VIII antigen levels. Release of Factor VIII antigen may serve as a valuable marker of distant organ injury in patients with skin burn. PMID:2503901

  5. Tumor Necrosis Factor-α-induced Proteolytic Activation of Pro-matrix Metalloproteinase-9 by Human Skin Is Controlled by Down-regulating Tissue Inhibitor of Metalloproteinase-1 and Mediated by Tissue-associated Chymotrypsin-like Proteinase*

    PubMed Central

    Han, Yuan-Ping; Nien, Yih-Dar; Garner, Warren L.

    2008-01-01

    The proteolytic activation of pro-matrix metalloproteinase (MMP)-9 by conversion of the 92-kDa precursor into an 82-kDa active form has been observed in chronic wounds, tumor metastasis, and many inflammation-associated diseases, yet the mechanistic pathway to control this process has not been identified. In this report, we show that the massive expression and activation of MMP-9 in skin tissue from patients with chronically unhealed wounds could be reconstituted in vitro with cultured normal human skin by stimulation with transforming growth factor-β and tumor necrosis factor (TNF)-α. We dissected the mechanistic pathway for TNF-α induced activation of pro-MMP-9 in human skin. We found that proteolytic activation of pro-MMP-9 was mediated by a tissue-associated chymotrypsin-like proteinase, designated here as pro-MMP-9 activator (pM9A). This unidentified activator specifically converted pro-MMP-9 but not pro-MMP-2, another member of the gelatinase family. The tissue-bound pM9A was steadily expressed and not regulated by TNF-α, which indicated that the cytokine-mediated activation of pro-MMP-9 might be regulated at the inhibitor level. Indeed, the skin constantly secreted tissue inhibitor of metalloproteinase-1 at the basal state. TNF-α, but not transforming growth factor-β, down-regulated this inhibitor. The TNF-α-mediated activation of pro-MMP-9 was tightly associated with down-regulation of tissue inhibitor of metalloproteinase-1 in a dose-dependent manner. To establish this linkage, we demonstrate that the recombinant tissue inhibitor of metalloproteinase-1 could block the activation of pro-MMP-9 by either the intact skin or skin fractions. Thus, these studies suggest a novel regulation for the proteolytic activation of MMP-9 in human tissue, which is mediated by tissue-bound activator and controlled by down-regulation of a specific inhibitor. PMID:12004062

  6. Expression and vitamin D-mediated regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in healthy skin and in diabetic foot ulcers.

    PubMed

    López-López, Nallely; González-Curiel, Irma; Treviño-Santa Cruz, Marcela Beatriz; Rivas-Santiago, Bruno; Trujillo-Paez, Valentín; Enciso-Moreno, José Antonio; Serrano, Carmen J

    2014-11-01

    Diabetic foot ulcers (DFUs) are chronic wounds with high matrix metalloproteinase (MMP) activity, and are a frequent complication on diabetics. This work studied the expression of selected MMP and tissue inhibitor of metalloproteinases (TIMP) gene family members in DFU and normal skin biopsies, and in vitamin D-treated keratinocytes cultured from those biopsies. We report for the first time the expression of some of these genes in healthy skin. Our results suggest that vitamin D may modulate the expression of some MMP gene family members in keratinocytes. Gene expression in DFU and in non-diabetic healthy skin (control) biopsies was evaluated by RT-qPCR for MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-19, TIMP-1 and TIMP-2, and also by immunohistochemistry for MMP-1 and MMP-9. Primary keratinocytes cultured from DFU and healthy skin biopsies were used for gene expression analyses of selected MMPs and TIMPs by RT-qPCR, both in the presence and absence of calcitriol. The expression of MMP-1, MMP-8, MMP-9, MMP-10, and TIMP-2 in healthy skin is reported here for the first time. DFUs showed increased MMP-1, MMP-9 and TIMP-1 expression, compared to healthy skin. Calcitriol down-regulated MMP-1 and MMP-10 expression in DFU-derived keratinocytes but not in those derived from healthy skin. Our data demonstrate the expression of certain MMPs that had not been previously described in healthy skin, and further support previous reports of MMP and TIMP up-regulation in DFUs. Our results point to calcitriol as a potential modulator for the expression of certain MMP members in DFUs. PMID:25168880

  7. 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.

  8. Hydrocellular foam dressings promote wound healing associated with decrease in inflammation in rat periwound skin and granulation tissue, compared with hydrocolloid dressings.

    PubMed

    Yamane, Takumi; Nakagami, Gojiro; Yoshino, Sawako; Shimura, Mari; Kitamura, Aya; Kobayashi-Hattori, Kazuo; Oishi, Yuichi; Nishijima, Yoshimi; Minematsu, Takeo; Sanada, Hiromi

    2015-01-01

    The effects of modern dressings on inflammation, which represent the earliest phase of wound healing, are poorly understood. We investigated the effects of modern hydrocellular foam dressings (HCFs) on wound healing and on the gene expression levels of the inflammatory markers--interleukin (IL)-1β, IL-6, and IL-10--in rat periwound skin and granulation tissue by quantitative reverse transcription-polymerase chain reaction. HCF absorbed significantly higher volume of water than hydrocolloid dressing (HCD) and increased the contraction of wounds. Polymorphonuclear neutrophils were massively infiltrated to the wound edge and boarded between granulation and dermis in the HCD group. IL-1β, IL-6, and IL-10 mRNA levels were significantly decreased in the periwound skin around the wounds and granulation tissue covered with HCF. These findings suggest that HCF may promote wound healing along with decrease in inflammation by reducing gene expression levels of IL-1β, IL-6, and IL-10. PMID:25420023

  9. Comparative Exoproteomics and Host Inflammatory Response in Staphylococcus aureus Skin and Soft Tissue Infections, Bacteremia, and Subclinical Colonization

    PubMed Central

    Liew, Yun Khoon; Awang Hamat, Rukman; van Belkum, Alex; Chong, Pei Pei

    2015-01-01

    The exoproteome of Staphylococcus aureus contains enzymes and virulence factors that are important for host adaptation. We investigated the exoprotein profiles and cytokine/chemokine responses obtained in three different S. aureus-host interaction scenarios by using two-dimensional gel electrophoresis (2-DGE) and two-dimensional immunoblotting (2D-IB) combined with tandem mass spectrometry (MS/MS) and cytometric bead array techniques. The scenarios included S. aureus bacteremia, skin and soft tissue infections (SSTIs), and healthy carriage. By the 2-DGE approach, 12 exoproteins (the chaperone protein DnaK, a phosphoglycerate kinase [Pgk], the chaperone GroEL, a multisensor hybrid histidine kinase, a 3-methyl-2-oxobutanoate hydroxymethyltransferase [PanB], cysteine synthase A, an N-acetyltransferase, four isoforms of elongation factor Tu [EF-Tu], and one signature protein spot that could not be reliably identified by MS/MS) were found to be consistently present in more than 50% of the bacteremia isolates, while none of the SSTI or healthy-carrier isolates showed any of these proteins. By the 2D-IB approach, we also identified five antigens (methionine aminopeptidase [MetAPs], exotoxin 15 [Set15], a peptidoglycan hydrolase [LytM], an alkyl hydroperoxide reductase [AhpC], and a haptoglobin-binding heme uptake protein [HarA]) specific for SSTI cases. Cytokine and chemokine production varied during the course of different infection types and carriage. Monokine induced by gamma interferon (MIG) was more highly stimulated in bacteremia patients than in SSTI patients and healthy carriers, especially during the acute phase of infection. MIG could therefore be further explored as a potential biomarker of bacteremia. In conclusion, 12 exoproteins from bacteremia isolates, MIG production, and five antigenic proteins identified during SSTIs should be further investigated for potential use as diagnostic markers. PMID:25809633

  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. Epidemiology and Outcomes of Complicated Skin and Soft Tissue Infections among Inpatients in Southern China from 2008 to 2013

    PubMed Central

    Gao, Weiguo; Ouyang, Wenwei; Wei, Jia; Wen, Zehuai

    2016-01-01

    Complicated skin and soft tissue infections (cSSTI) are some of the most commonly treated infections in hospitals, and place heavy economic burdens on patients and society. Here we report the findings from an analysis of cSSTI based on a retrospective study which was conducted within the Chinese inpatient population. We focused our research on the analysis of the patient population, antibiotic treatment, clinical outcome and economic burden. The study population comprised 527 selected patients hospitalized between 2008 and 2013. Among the hospitalizations with microbiological diagnoses, 61.41% (n = 113) were diagnosed as infected with Gram-positive bacteria, while 46.20% (n = 85) were infected with Gram-negative bacteria. The most commonly found Gram-positive bacteria was Staphylococcus aureus (40.76%, n = 75), and the most common Gram-negative bacteria was Escherichia coli (14.13%, n = 26). About 20% of the Staphylococcus aureus were methicillin-resistant. The resistance rate of isolated Staphylococcus aureus or Escherichia coli to penicillin was around 90%; in contrast, the resistance rate to vancomycin, linezolid or imipenem was low (<20%). A large percentage of patients were treated with cephalosporins and fluoroquinolones, while vancomycin and imipenem were also included to treat drug-resistant pathogens. Over half of the hospitalizations (58.43%, n = 336) experienced treatment modifications. The cost to patients with antibiotic modifications was relatively higher than to those without. In conclusion, our study offers an analysis of the disease characteristics, microbiological diagnoses, treatment patterns and clinical outcomes of cSSTI in four hospitals in Guangdong Province, and sheds lights on the current clinical management of cSSTI in China. PMID:26918456

  12. Distribution of Fatal Vibrio Vulnificus Necrotizing Skin and Soft-Tissue Infections: A Systematic Review and Meta-Analysis.

    PubMed

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

    2016-02-01

    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

  13. 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

  14. Biaxial mechanical characterization of bat wing skin.

    PubMed

    Skulborstad, A J; Swartz, S M; Goulbourne, N C

    2015-06-01

    The highly flexible and stretchable wing skin of bats, together with the skeletal structure and musculature, enables large changes in wing shape during flight. Such compliance distinguishes bat wings from those of all other flying animals. Although several studies have investigated the aerodynamics and kinematics of bats, few have examined the complex histology and mechanical response of the wing skin. This work presents the first biaxial characterization of the local deformation, mechanical properties, and fiber kinematics of bat wing skin. Analysis of these data has provided insight into the relationships among the structural morphology, mechanical properties, and functionality of wing skin. Large spatial variations in tissue deformation and non-negligible fiber strains in the cross-fiber direction for both chordwise and spanwise fibers indicate fibers should be modeled as two-dimensional elements. The macroscopic constitutive behavior was anisotropic and nonlinear, with very low spanwise and chordwise stiffness (hundreds of kilopascals) in the toe region of the stress-strain curve. The structural arrangement of the fibers and matrix facilitates a low energy mechanism for wing deployment and extension, and we fabricate examples of skins capturing this mechanism. We propose a comprehensive deformation map for the entire loading regime. The results of this work underscore the importance of biaxial field approaches for soft heterogeneous tissue, and provide a foundation for development of bio-inspired skins to probe the effects of the wing skin properties on aerodynamic performance. PMID:25895436

  15. A Novel Method for Single Sample Multi-Axial Nanoindentation of Hydrated Heterogeneous Tissues Based on Testing Great White Shark Jaws

    PubMed Central

    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

  16. 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

  17. 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

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

    PubMed

    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

  19. 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

  20. Percutaneous absorption of steroids: determination of in vitro permeability and tissue reservoir characteristics in human skin layers.

    PubMed

    Magnusson, B M; Cross, S E; Winckle, G; Roberts, M S

    2006-01-01

    The skin localization of steroids following topical application is largely unknown. We determined the distribution of five steroids in human skin using excised epidermal, dermal, and full-thickness membranes in vitro. There was no significant difference in steroid maximum flux through epidermal and full-thickness membranes, other than significantly lower fluxes for the most polar steroid, aldosterone. Hydrocortisone had the highest dermal diffusivity and dermal penetration, and the accumulation of hydrocortisone and corticosterone was higher than that of the other steroids. Slower penetration and higher accumulation in the viable epidermis of progesterone in full-thickness skin were consistent with dermal penetration limitation effects associated with high lipophilicity. PMID:16931901

  1. 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

  2. Use of a Tissue Engineered Human Skin Model to Investigate the Effects of Wounding and of an Anti-Inflammatory on Melanoma Cell Invasion

    PubMed Central

    Marques, Claudia Mirian de Godoy; MacNeil, Sheila

    2016-01-01

    An increasing number of studies suggest inflammation stimulates tumour invasion. In melanoma, despite recent advances in targeted therapy and immunomodulatory therapies, this cancer remains difficult to treat. Our previous studies show melanoma cells interact with skin cells in their invasion into tissue engineered skin and suggest inflammation stimulates invasion. The aim of this study was to investigate the use of an anti-inflammatory on melanoma invasion. To do this we developed a wounded and inflamed in vitro 3D melanoma model in which to investigate the use of an anti-inflammatory on melanoma invasion. The tissue engineered skin model was based on human de-epidermised acellular dermis to which keratinocytes, fibroblasts and three different melanoma cell lines were added in various combinations. A simple incisional wound was made in the model and TNF-α and fibrin were added to simulate conditions of inflammation. Topical ibuprofen in a hydrogel was added and the extent of melanoma invasion into the dermis was assessed under the various conditions. The results showed that penetration of two of the cell lines (HBL and A375SM) into the tissue engineered skin was exacerbated by wounding and ibuprofen significantly decreased invasion of A375SM cells and slightly reduced invasion of HBL cells. A third cell line, C8161, was aggressively invasive under all conditions to an extent that was not influenced by wounding, TNF-α or the addition of ibuprofen. In summary, the results for one these cell lines (and a trend for a second cell line) support the hypothesis that a wound environment is conducive to melanoma invasion but the local addition of an anti-inflammatory drug such as ibuprofen may attenuate invasion. PMID:27270229

  3. Characterization of Staphylococcus aureus Isolated from Non-Native Patients with Skin and Soft Tissue Infections in Shanghai

    PubMed Central

    Yang, Hai-Hui; Zhu, Yue-Qiu; Guo, Xiao-Kui; Ni, Yu-Xing; Han, Li-Zhong

    2015-01-01

    Background Staphylococcus aureus is one predominant cause of skin and soft-tissue infections (SSTIs), but little information exists regarding the characterization of S. aureus from non-native patients with SSTIs in China. Methods In this study, we enrolled 52 non-native patients with S. aureus SSTIs, and 65 native control patients with S. aureus SSTIs in Shanghai. 52 and 65 S. aureus isolates were collected from both groups, respectively. S. aureus isolates were characterized by antimicrobial susceptibility testing, toxin gene detection, and molecular typing with sequence type, spa type, agr group and SCCmec type. Results Methicillin-resistant S. aureus (MRSA) was detected in 8 non-native patients and 14 native patients with SSTIs. Overall, antimicrobial susceptibilities of S. aureus isolated from non-native patients were found higher than those from native patients. CC59 (ST338 and ST59) was found in a total of 14 isolates (4 from non-native patients; 10 from native patients), 9 of which were carrying lukS/F-PV (3 from non-native patients; 6 from native patients). ST7 was found in 12 isolates and all 12 isolates were found in native patients. The livestock-associated clone ST398 was found in 11 isolates (6 from non-native patients; 5 from native patients), and 5 ST398 lukS/F-PV-positive methicillin-susceptible S. aureus (MSSA) were all discovered among non-native patients. The molecular epidemiology of S. aureus isolated from non-native patients was quite different from those from native patients. lukS/F-PV was more frequent in isolates originating from non-native patients with SSTIs compared to native patients (31 vs. 7, P <0.0001). Conclusions CC59 was the most common clonal complex among patients with SSTIs in Shanghai. The other most common sequence types were ST7 and Livestock ST398. The molecular epidemiology of S. aureus isolated from non-native patients was quite different from those from native patients. S. aureus isolated from non-native patients was

  4. A Multimodality Imaging and Software System for Combining an Anatomical and Physiological Assessment of Skin and Underlying Tissue Conditions

    PubMed Central

    Langemo, Diane; Spahn, James G.

    2016-01-01

    ABSTRACT OBJECTIVE: The timely and accurate assessment of skin and underlying tissue is crucial for making informed decisions relating to wound development and existing wounds. The study objective was to determine within- and between-reader agreement of Scout Visual-to-Thermal Overlay (WoundVision LLC, Indianapolis, Indiana) placement (moving the wound edge trace from the visual image onto the wound edge signature of the infrared image). MATERIALS AND METHODS: For establishing within- and between-reader agreement of the Scout Visual-to-Thermal Overlay feature, 5 different readers overlaid a wound edge trace from the visual image and placed it onto the congruent thermal representation of the wound on a thermal image 3 independent times. Forty different wound image pairs were evaluated by each reader. All readers were trained by the same trainer on the operation of the Scout prior to using the software features. The Scout Visual-to-Thermal Overlay feature allows clinicians to use an anatomical measurement of the wound on the visual image (area and perimeter) to extract a congruent physiological measurement of the wound on the thermal image (thermal intensity variation data) by taking the wound edge trace from the visual image and overlaying it onto the corresponding thermal signature of the same wound edge. RESULTS: The results are very similar both within- and between-readers. The coefficient of variation (CV) for the mean PV both within- and between-readers averages less than 1%, 0.89 and 0.77 respectively. When converted into degrees Celsius across all 5 readers and all 3 wound replicates, the average temperature differential is 0.28° C (Table 2). The largest difference observed was 0.63° C and the smallest difference observed was 0.04° C. CONCLUSIONS: The Scout software’s Visual-to-Thermal Overlay procedure, as implemented in this study, is very precise. This study demonstrates that the thermal signature of wounds may be delineated repeatedly by the same

  5. 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. PMID:26380335

  6. [Susceptibilities of multidrug-resistant pathogens responsible for complicated skin and soft tissue infections to standard bacteriophage cocktails].

    PubMed

    Gündoğdu, Aycan; Kılıç, Hüseyin; Ulu Kılıç, Ayşegül; Kutateladze, Mzia

    2016-04-01

    Skin and soft tissue infections (SSTIs) may represent a wide clinical spectrum from cellulitis to high-mortality associated necrotizing fasciitis. Limitations in therapy due to the multiple drug resistance, leads to increase in the morbidity and mortality rates, especially in complicated SSTIs such as diabetic foot, decubitus, and surgical wound infections. Therefore, alternative treatment strategies other than antibiotics are needed in appropriate clinical conditions. "Bacteriophage therapy", which is an old method and has been used as part of standard treatment in some countries such as Georgia and Russia, has again become popular worldwide. The aim of this study was to investigate the in vitro susceptibilities of multidrug-resistant (MDR) pathogens isolated from patients with complicated SSTIs, against standard bacteriophage (phage) cocktails. Six different ready-made phage preparations [Pyophage, Intestiphage, ENKO, SES, Fersisi and Staphylococcal Bacteriophage (Sb)] used in this study have been provided by G. Eliava Institute, Georgia. Because of the absence of ready-made phage preparations for Acinetobacter baumannii and Klebsiella pneumoniae, Φ1-Φ7 and ΦKL1- ΦKL3 phages were used provided from the same institute's phage library, respectively. Isolation and identification of the pathogens from abscess and wound samples of patients with SSTIs were performed by conventional methods and automatized VITEK®-2 (bioMerieux, ABD) system. Antimicrobial susceptibility testing was conducted complying CLSI standards' and the bacteria that were resistant to at least two different antibiotic groups were considered as MDR. Accordingly, a total of 33 isolates, nine of them were E.coli (8 ESBL and 1 ESBL + carbapenemase positive); nine were MDR P.aeruginosa; nine were MDR A.baumannii; three were methicillin-resistant Staphylococcus aureus (MRSA) and three were K.pneumoniae (1 ESBL, 1 carbapenemase and 1 ESBL + carbapenemase positive) were included in the study. The phage

  7. Skin turgor

    MedlinePlus

    Doughy skin; Poor skin turgor; Good skin turgor; Decreased skin turgor ... Call your health care provider if: Poor skin turgor occurs with vomiting, diarrhea, or fever. The skin is very slow to return to normal, or the skin "tents" up ...

  8. Evaluation of haemoglobin changes of skin and muscle tissue of the calf induced by topical application of a nonivamide / nicoboxil cream

    NASA Astrophysics Data System (ADS)

    Warnecke, Jan; Wendt, Thomas; Schak, Matthias; Schiffer, Thorsten; Bloch, Wilhelm; Kohl-Bareis, Matthias

    2011-07-01

    Topical agents inducing hyperaemisation like nonivamide or nicoboxil increase cutaneous blood flow and temperature and induce erythema. It is not proven up to now whether there is also a hyperaemisation effect in skeletal muscle. This study has the objective to determine the effects of a nonivamide / nicoboxil cream on haemodynamics in skin and calf muscle via optical spectroscopy in the visible and near-infrared with a separation of changes for skin and muscle. Left and right calves of 14 healthy subjects were treated with a nonivamide / nicoboxil cream or mock administration, and cutaneous and muscle haemoglobin were measured using a combined NIRS / VIS sensor. The topical application of the cream increased the concentration of oxygenated haemoglobin and tissue oxygen saturation significantly in skin as well as in muscle of the treated legs already after 15 minutes, with stronger and faster effects in skin. In contrast, the change in deoxygenated haemoglobin was found to be small. The kinetic of all changes varied widely between the subjects. The found haemoglobin changes might explain the beneficial effect of hyperaemisation creams for the treatment of minor injuries.

  9. Penile reconstruction with dermal template and vacuum therapy in severe skin and soft tissue defects caused by Fournier's gangrene and hidradenitis suppurativa.

    PubMed

    Ludolph, Ingo; Titel, Torsten; Beier, Justus P; Dragu, Adrian; Schmitz, Marweh; Wullich, Bernd; Horch, Raymund E

    2016-02-01

    The aim of this article is to improve the treatment of patients with complete skin loss of the penile shaft after Fournier's gangrene or hidradenitis suppurativa using modern biomatrices and topical negative pressure therapy. From January 2010 to December 2011, three patients with Fournier's gangrene or hidradenitis suppurativa were treated. After initial radical debridements, topical negative pressure therapy was applied for wound stabilisation. After that dermal templates (acellular dermal matrix) were used to achieve early healing and topical negative pressure-dressing in a special setting or a special foam compression bandage was used together with a urinary catheter. After integration of the dermal template, a split-thickness skin graft is used for coverage and again secured with a circular total negative pressure-dressing. In all cases, the split-thickness skin grafts healed very well applying this therapy concept. The patients were very satisfied with the functional as well as with the aesthetic outcome. We suggest a new method of staged reconstruction to successfully preserve the functionality of the penis after complete loss of the skin and soft tissue of the penile shaft using modern biomatrices and topical negative pressure therapy. PMID:24618357

  10. Expression and Distribution of the Guanine Nucleotide-binding Protein Subunit Alpha-s in Mice Skin Tissues and Its Association with White and Black Coat Colors.

    PubMed

    Yin, Zhihong; Zhao, Xin; Wang, Zhun; Li, Zhen; Bai, Rui; Yang, Shanshan; Zhao, Min; Pang, Quanhai

    2016-10-01

    Guanine nucleotide-binding protein subunit alpha-s (Gnαs) is a small subunit of the G protein-couple signaling pathway, which is involved in the formation of coat color. The expression level and distribution of Gnαs were detected by quantitative real-time-polymerase chain reaction (qPCR), western blot, and immunohistochemistry to investigate the underlying mechanisms of coat color in white and black skin tissues of mice. qPCR and western blot results suggested that Gnαs was expressed at significantly higher levels in black mice compared with that of white mice, and transcripts and protein possessed the same expression in both colors. Immunohistochemistry demonstrated Gnαs staining in the root sheath and dermal papilla in hair follicle of mice skins. The results indicated that the Gnαs gene was expressed in both white and black skin tissues, and the expression level of Gnαs in the two types of color was different. Therefore, Gnαs may be involved in the coat color formation in mice. PMID:26954226

  11. Soft Tissue Artefacts of the Human Back: Comparison of the Sagittal Curvature of the Spine Measured Using Skin Markers and an Open Upright MRI

    PubMed Central

    Zemp, Roland; List, Renate; Gülay, Turgut; Elsig, Jean Pierre; Naxera, Jaroslav; Taylor, William R.; Lorenzetti, Silvio

    2014-01-01

    Soft tissue artefact affects the determination of skeletal kinematics. Thus, it is important to know the accuracy and limitations of kinematic parameters determined and modelled based on skin marker data. Here, the curvature angles, as well as the rotations of the lumbar and thoracic segments, of seven healthy subjects were determined in the sagittal plane using a skin marker set and compared to measurements taken in an open upright MRI scanner in order to understand the influence of soft tissue artefact at the back. The mean STA in the flexed compared to the extended positions were 10.2±6.1 mm (lumbar)/9.3±4.2 mm (thoracic) and 10.7±4.8 mm (lumbar)/9.2±4.9 mm (thoracic) respectively. A linear regression of the lumbar and thoracic curvatures between the marker-based measurements and MRI-based measurements resulted in coefficients of determination, R2, of 0.552 and 0.385 respectively. Skin marker measurements therefore allow for the assessment of changes in the lumbar and thoracic curvature angles, but the absolute values suffer from uncertainty. Nevertheless, this marker set appears to be suitable for quantifying lumbar and thoracic spinal changes between quasi-static whole body postural changes. PMID:24748013

  12. Soft tissue artefacts of the human back: comparison of the sagittal curvature of the spine measured using skin markers and an open upright MRI.

    PubMed

    Zemp, Roland; List, Renate; Gülay, Turgut; Elsig, Jean Pierre; Naxera, Jaroslav; Taylor, William R; Lorenzetti, Silvio

    2014-01-01

    Soft tissue artefact affects the determination of skeletal kinematics. Thus, it is important to know the accuracy and limitations of kinematic parameters determined and modelled based on skin marker data. Here, the curvature angles, as well as the rotations of the lumbar and thoracic segments, of seven healthy subjects were determined in the sagittal plane using a skin marker set and compared to measurements taken in an open upright MRI scanner in order to understand the influence of soft tissue artefact at the back. The mean STA in the flexed compared to the extended positions were 10.2±6.1 mm (lumbar)/9.3±4.2 mm (thoracic) and 10.7±4.8 mm (lumbar)/9.2±4.9 mm (thoracic) respectively. A linear regression of the lumbar and thoracic curvatures between the marker-based measurements and MRI-based measurements resulted in coefficients of determination, R2, of 0.552 and 0.385 respectively. Skin marker measurements therefore allow for the assessment of changes in the lumbar and thoracic curvature angles, but the absolute values suffer from uncertainty. Nevertheless, this marker set appears to be suitable for quantifying lumbar and thoracic spinal changes between quasi-static whole body postural changes. PMID:24748013

  13. In-to-Out Body Antenna-Independent Path Loss Model for Multilayered Tissues and Heterogeneous Medium

    PubMed Central

    Kurup, Divya; Vermeeren, Günter; Tanghe, Emmeric; Joseph, Wout; Martens, Luc

    2015-01-01

    In this paper, we investigate multilayered lossy and heterogeneous media for wireless body area networks (WBAN) to develop a simple, fast and efficient analytical in-to-out body path loss (PL) model at 2.45 GHz and, thus, avoid time-consuming simulations. The PL model is an antenna-independent model and is validated with simulations in layered medium, as well as in a 3D human model using electromagnetic solvers. PMID:25551483

  14. In-to-out body antenna-independent path loss model for multilayered tissues and heterogeneous medium.

    PubMed

    Kurup, Divya; Vermeeren, Günter; Tanghe, Emmeric; Joseph, Wout; Martens, Luc

    2015-01-01

    In this paper, we investigate multilayered lossy and heterogeneous media for wireless body area networks (WBAN) to develop a simple, fast and efficient analytical in-to-out body path loss (PL) model at 2.45 GHz and, thus, avoid time-consuming simulations. The PL model is an antenna-independent model and is validated with simulations in layered medium, as well as in a 3D human model using electromagnetic solvers. PMID:25551483

  15. 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.

  16. Development and evaluation of a regression equation of prediction for fat-free soft tissue in heterogenous populations of cattle.

    PubMed

    Jenkins, T G; Leymaster, K A; MacNeil, M D

    1995-12-01

    Regression equations to predict kilograms of fat-free soft tissue (the sum of water and protein from chemical analyses) were developed from data collected on 526 steers and heifers. Straightbred animals representing Angus, Braunvieh, Charolais, Gelbvieh, Hereford, Limousin, Pinzgauer, Red Poll, and Simmental breeds of cattle contributed to the data set. Cattle ranged in slaughter weight and age from approximately 350 to 575 kg and from 13 to 23 mo, respectively. Diets (100% ground alfalfa, 67% ground alfalfa and 33% ground corn or 33% ground alfalfa and 67% ground corn) were cross-classified with breed and sex. Estimative traits included in the equation were warm carcass weight, fat depth at the 12th rib, and body impedance. Carcass soft-tissue samples were taken for determination of chemical constituents. The prediction equation accounted for 94% of the variation in fat-free soft tissue of the carcass. Adjusting for breed-sex-diet contemporary groups increased the R2 value by 2% units. The prediction model was evaluated using data collected on 65 steers sired by Charolais or by Hereford bulls at the Ft Keogh Livestock and Range Research Laboratory (Miles City, MT). Postweaning feeding strategies and slaughter ages varied among these animals. Carcass weight, back fat depth, and resistive impedance measures were recorded. Carcass soft-tissue samples were taken for determination of chemical constituents. Values of estimator variables recorded at Ft. Keogh were used in the regression equation to predict fat-free soft tissue for each animal. The values for kilogram of fat-free soft tissue determined from chemical analysis were regressed on predicted fat-free soft tissue. the results indicate that fat-free soft tissue of carcasses can be accurately predicted using estimative traits that do not diminish carcass value. PMID:8655437

  17. Bathysa cuspidata extract modulates the morphological reorganization of the scar tissue and accelerates skin wound healing in rats: a time-dependent study.

    PubMed

    Gonçalves, Reggiani V; Novaes, Rômulo D; Cupertino, Marli C; Araújo, Bruna M; Vilela, Emerson F; Machado, Aline T; Leite, João P V; Matta, Sérgio L P

    2014-01-01

    The technological development of pharmaceutical products based on plant extracts is currently responsible for a large number of recent innovations in healthcare. The objective of this study was to develop and investigate the effect and potential applicability of an ointment-based Bathysa cuspidata extract (BCE) for the management of skin wounds in rats. Three skin wounds of 12 mm in diameter were made on the backs of the animals, which were randomized into 4 groups according to the application received, i.e. the SAL group: 0.9% saline solution, the LAN group: lanolin, the BCE 2.5% group: 2.5% BCE emulsified in lanolin and the BCE 5% group: 5% BCE emulsified in lanolin. The applications were made daily over 21 days, and every 7 days tissue from different wounds was removed. On days 7, 14 and 21, the BCE 2.5% and BCE 5% groups showed the best results in relation to wound closure, and a higher proportion (in length, density and volume) of blood vessels and fibroblasts compared to the other groups. On days 7 and 14, there was a significant increase in the number of mast cells in these 2 groups when compared to the SAL and LAN groups. On day 21, they also had a higher proportion of collagen I than collagen III. B. cuspidata in an ointment base was effective in stimulating tissue cellularity, mast cell recruitment, neoangiogenesis, synthesis and maturation of collagen, epidermal thickness and surface area in scar tissue. These events were potentially related to the best quality and speed for skin regeneration in the rats treated with the BCE ointment. PMID:25300223

  18. 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.

  19. Microbial colonization of an in vitro model of a tissue engineered human skin equivalent--a novel approach.

    PubMed

    Holland, Diana B; Bojar, Richard A; Jeremy, Anthony H T; Ingham, Eileen; Holland, Keith T

    2008-02-01

    This was a preliminary investigation to define the conditions of colonization of a human skin equivalent (SE) model with cutaneous microorganisms. SEs of 24 mm diameter were constructed with a dermal matrix of fibrin containing fibroblasts and a stratified epidermis. Microbial colonization of the SEs was carried out in a dry environment, comparable to 'in vivo' skin, using a blotting technique to remove inoculation fluid. The microbial communities were sampled by scrub washing and viable cells enumerated on selective growth medium. Staphylococcus epidermidis, Propionibacterium acnes and Malassezia furfur (human skin commensals) and Staphylococcus aureus (transient pathogen) were colonized at inoculum densities of 10(2)-10(6) CFU SE(-1) on the surface of replicate SEs. Growth of all species was supported for upto 72-120 h, with recovery densities of between 10(4)-10(9) CFU SE(-1). A novel, real-time growth monitoring method was also developed, using S. aureus containing a lux cassette. Light output increased from 20 to 95 h, and colonization increased from 10(2) to 10(8) CFU SE(-1), as confirmed by conventional recovery. Thus, the SE model has potential to investigate interactions between resident and transient microbial communities with themselves and their habitat, and for testing treatments to control pathogen colonization of human skin. PMID:18081841

  20. Psoriatic arthritis: embracing pathogenetic and clinical heterogeneity?

    PubMed

    McInnes, Iain B

    2016-01-01

    Psoriatic arthritis (PsA) is a clinically heterogeneous condition of skin, joint, enthesis and bone that provides considerable unmet therapeutic need. Recent treatment advances have offered new opportunities to improve quality of life and long term well being for afflicted patients. It is timely therefore, to consider the underlying heterogeneity inherent in the disease from a pathologic aspect so as to best optimise the choice and order of therapeutic application over time. Herein I will discuss the various contributions made by immune pathways to discrete tissue compartments that in turn might allow a more targeted approach to the management of PsA in which different tissues express variable severity of involvement. PMID:27586796

  1. 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 ...

  2. Skin graft

    MedlinePlus

    Skin transplant; Skin autografting; FTSG; STSG; Split thickness skin graft; Full thickness skin graft ... site. Most people who are having a skin graft have a split-thickness skin graft. This takes ...

  3. 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.

  4. Tigecycline: an evidence-based review of its antibacterial activity and effectiveness in complicated skin and soft tissue and intraabdominal infections

    PubMed Central

    Dunn, Christopher J.

    2006-01-01

    Introduction: There is an urgent need for novel agents to manage serious bacterial infections, particularly those contracted in healthcare facilities. Tigecycline is a novel broad-spectrum glycylcycline with good activity against Gram-positive, many Gram-negative, anaerobic, and some atypical pathogens that has been developed to address this need. Aims: To review the evidence for the use of tigecycline in serious and complicated skin and soft tissue and intraabdominal infections. Evidence review: There is substantial evidence that tigecycline is as effective as vancomycin plus aztreonam in complicated skin and skin structure infections (SSSIs) and as effective as imipenem plus cilastatin in intraabdominal infections. Limited evidence shows effectiveness in patients with resistant Acinetobacter infection in an intensive care unit, and the possibility that the use of tigecycline may reduce length of hospital stay. The drug is well tolerated, with nausea and vomiting as the major adverse effects. Outcomes summary: The introduction of tigecycline should be beneficial at a time of increasing problems with bacterial resistance, and evidence to date has been sufficient for regulatory approval for complicated SSSIs and intraabdominal infections. Research into tigecycline’s efficacy in other infectious diseases (notably pneumonia and bacteremia) is ongoing. Further good quality studies and ongoing surveillance for any emerging bacterial resistance will be needed to determine outcomes with tigecycline relative to other novel antibacterial agents, and to explore the economic implications of its adoption. PMID:22500153

  5. 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. PMID:27411949

  6. Resveratrol-Enriched Rice Down-Regulates Melanin Synthesis in UVB-Induced Guinea Pigs Epidermal Skin Tissue.

    PubMed

    Lee, Taek Hwan; Seo, Jae Ok; Do, Moon Ho; Ji, Eunhee; Baek, So-Hyeon; Kim, Sun Yeou

    2014-09-01

    Synthetic compounds that are used in the clinic to regulate skin hyperpigmentation, such as arbutin, hydroquinone, and kojic acid, are only moderately effective. But, their use is limited by side effects. As part of an effort to overcome the limitations, we developed resveratrol-enriched rice (RR) using genetic engineering technique. Each of resveratrol and rice has been reported to produce anti-melanogenic effects. Therefore, we hypothesized that RR would show more anti-melanogenic effects than those of resveratrol or rice alone. Anti-melanogenic effect of RR was done by using melan-a mouse melanocytes. The depigmenting efficacy was then observed following topical application of the RR to UVB-stimulated hyperpigmented dorsal skin of guinea pigs. Treatment with RR extract resulted a 21.4 ± 0.7% decrease in tyrosinase expression at melan-a cells. Colorimetric analysis showed a significantly lower depigmenting value by day 9 following treatment with RR in UVB-irradiated guinea pigs the dorsal skin (p<0.01), indicating that RR produced a depigmentation effect. By staining with Fontana-Masson stain, we found that the RR-treated group had more effect histopathologically in epidermal melanin production than resveratrol or rice alone-treated group. RR was associated with reduction in the levels of microphthalmia-associated transcription factor (MITF), and downregulation of tyrosinase and tyrosinase-related protein (TRP-2) expression, leading to inhibit epidermal melanin production by western blot analysis. This study suggests that the resveratrol-enriched rice may be a promising candidate in regulating skin pigmentation with UVB exposure. PMID:25414774

  7. 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

  8. Differential Expression of microRNAs and their Regulatory Networks in Skin Tissue of Liaoning Cashmere Goat during Hair Follicle Cycles.

    PubMed

    Bai, Wen L; Dang, Yun L; Yin, Rong H; Jiang, Wu Q; Wang, Ze Y; Zhu, Yu B; Wang, Shi Q; Zhao, Ying Y; Deng, Liang; Luo, Guang B; Yang, Shu H

    2016-01-01

    MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules that negatively regulate gene expression. Herein, we investigated a selective number of miRNAs for their expression in skin tissue of Liaoning Cashmere goat during hair follicle cycles, and their intracellular regulatory networks were constructed based on bioinformatics analysis. The relative expression of six miRNAs (mir-103-3p, -15b-5p, 17-5p, -200b, -25-3p, and -30c-5p) at anagen phase is significantly higher than that at catagen and/or telogen phases. In comparison to anagen, the relative expression of seven miRNAs (mir-148a-3p, -199a-3p, -199a-5p, -24-3p, -30a-5p, -30e-5p, and -29a-3p) was revealed to be significantly up-regulated at catagen and/or telogen stages. The network analyses of miRNAs indicated those miRNAs investigated might be directly or indirectly involved in several signaling pathways through their target genes. These results provided a foundation for further insight into the roles of these miRNAs in skin tissue of Liaoning Cashmere goat during hair follicle cycles. PMID:26913551

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

    PubMed

    Liu, H; Gisquet, H; Blondel, W; Guillemin, F

    2012-12-01

    This study aims at investigating the efficiency of bimodal spectroscopy in detection of hypertrophic scar tissue on a preclinical model. Fluorescence and Diffuse Reflectance spectra were collected from 55 scars deliberately created on ears of 20 rabbits, amongst which some received tacrolimus injection to provide non-hypertrophic scar tissue. The spectroscopic data measured on hypertrophic and non-hypertrophic scar tissues were used for developing our classification algorithm. Spectral features were extracted from corrected data and analyzed to classify the scar tissues into hypertrophic or non-hypertrophic. The Algorithm was developed using k-NN classifier and validated by comparing to histological classification result with Leave-One-Out cross validation. Bimodal spectroscopy showed promising results in detecting hypertrophic tissue (sensibility 90.5%, specificity 94.4%). The features used for classification were extracted from the autofluorescence spectra collected at 4 CEFS with excitations at 360, 410, and 420 nm. This indicates the hypertrophic process may involve change in concentration of several fluorophores (collagen, elastin and NADH) excited in this range, or modification in volume of explored tissue layers (epidermis and dermis) due to tissue thickening. PMID:23243577

  10. A new measuring device for non-invasive determination of oxygen partial pressure and oxygen conductance of the skin and other tissues.

    PubMed

    Niehoff, K; Barnikol, W K

    1999-01-01

    .2.10(-5) ml O2 (STPD)/(atm.s.cm2) at 42 degrees C skin surface temperature; the intracutaneous partial pressure obtained was 5.5 kPa (41 mmHg) (STPD: "standard temperature pressure dry" conditions of the gas). At 42 degrees C skin temperature no burning occurs. The determined O2-conductance is in the same range as estimated formerly (see above). The intracutaneous oxygen partial pressure determined seems to be a realistic value of the tissue at 42 degrees C. By in vitro measurements with technical membranes the new device and procedure was validated giving precise values of the oxygen conductance. Hence the new method may be used for calibration of the oxygen flux optode (Holst et al., 1993). The O2-permeation coefficient (P) could be an important parameter for evaluating dermatological applications (which attempt to increase P) in the treatment of local dermal oxygen deficiency. The intracutaneous oxygen partial pressure found is a reasonable value for a surface temperature of 42 degrees. Because of the independence of the O2-partial pressure determined and the O2-consumption the new device exhibits no stirring effect and it provides more insight into the limitations of conventional transcutaneous oxygen measurement. PMID:10659205

  11. Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers.

    PubMed

    Cross, Sheree E; Magnusson, Beatrice M; Winckle, Gareth; Anissimov, Yuri; Roberts, Michael S

    2003-05-01

    In order to establish the relationship between solute lipophilicity and skin penetration (including flux and concentration behavior), we examined the in vitro penetration and membrane concentration of a series of homologous alcohols (C2-C10) applied topically in aqueous solutions to human epidermal, full-thickness, and dermal membranes. The partitioning/distribution of each alcohol between the donor solution, stratum corneum, viable epidermis, dermis, and receptor phase compartments was determined during the penetration process and separately to isolated samples of each tissue type. Maximum flux and permeability coefficients are compared for each membrane and estimates of alcohol diffusivity are made based on flux/concentration data and also the related tissue resistance (the reciprocal of permeability coefficient) for each membrane type. The permeability coefficient increased with increasing lipophilicity to alcohol C8 (octanol) with no further increase for C10 (decanol). Log vehicle:stratum corneum partition coefficients were related to logP, and the concentration of alcohols in each of the tissue layers appeared to increase with lipophilicity. No difference was measured in the diffusivity of smaller more polar alcohols in the three membranes; however, the larger more lipophilic solutes showed slower diffusivity values. The study showed that the dermis may be a much more lipophilic environment than originally believed and that distribution of smaller nonionized solutes into local tissues below a site of topical application may be estimated based on knowledge of their lipophilicity alone. PMID:12713577

  12. 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. PMID:26649556

  13. Sagging Skin

    MedlinePlus

    ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ... Non-ablative Laser Rejuvenation Non-invasive Body Contouring Treatments Skin Cancer Skin Cancer Information Free Skin Cancer Screenings Skin ...

  14. Skin Diseases: Skin Health and Skin Diseases

    MedlinePlus

    ... the sun. Photo: PhotoDisc Care for conditions from acne to wrinkles Did you know that your skin ... other skin conditions. Many skin problems, such as acne, also affect your appearance. Your skin can also ...

  15. Bacterial Skin Infections.

    PubMed

    Ibrahim, Fadi; Khan, Tariq; Pujalte, George G A

    2015-12-01

    Skin and soft tissue infections account for 0.5% of outpatient visits to primary care. Skin and soft tissue infections can usually be managed in an outpatient setting. However, there are certain circumstances as discussed in this article that require more urgent care or inpatient management. Primary care providers should be able to diagnose, manage, and provide appropriate follow-up care for these frequently seen skin infections. This article provides family physicians with a comprehensive review of the assessment and management of common bacterial skin infections. PMID:26612370

  16. 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

  17. 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 Central

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

    2015-01-01

    Generalized arterial calcification of infancy (GACI) is an intractable ectopic mineralization disorder caused by mutations in the ENPP1 gene resulting in reduced plasma inorganic pyrophosphate levels. We previously characterized the Enpp1asj mutant mouse as a model of GACI, and we have now explored the potential efficacy of bisphosphonates, non-hydrolyzable PPi analogs, in preventing ectopic mineralization in these mice. These 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 bymicrocomputed 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 GACI caused by ENPP1 mutations. PMID:26763447

  18. Hyaluronic acid/poly(lactic-co-glycolic acid) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate as skin tissue engineering scaffolds.

    PubMed

    Lee, Eun Ji; Lee, Jong Ho; Jin, Linhua; Jin, Oh Seong; Shin, Yong Cheol; Sang, Jin Oh; Lee, Jaebeom; Hyon, Suong-Hyu; Han, Dong-Wook

    2014-11-01

    In this study, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) for application to tissue engineering scaffolds for skin regeneration were prepared via coaxial electrospinning. Physicochemical properties of HA/PLGA-E core/shell fiber meshes were characterized by SEM, Raman spectroscopy, contact angle, EGCG release profiling and in vitro degradation. Biomechanical properties of HA/PLGA-E meshes were also investigated by a tensile strength test. SEM images showed that HA/PLGA-E fiber meshes had a three-dimensional interconnected pore structure with an average fiber diameter of about 1270 nm. Raman spectra revealed that EGCG was uniformly dispersed in the PLGA shell of meshes. HA/PLGA-E meshes showed sustained EGCG release patterns by controlled diffusion and PLGA degradation over 4 weeks. EGCG loading did not adversely affect the tensile strength and elastic modulus of HA/PLGA meshes, while increased their hydrophilicity and surface energy. Attachment of human dermal fibroblasts on HA/PLGA-E meshes was appreciably increased and their proliferation was steadily retained during the culture period. These results suggest that HA/PLGA-E core/shell fiber meshes can be potentially used as scaffolds supporting skin regeneration. PMID:25958546

  19. Contribution of Staphylococcus aureus Coagulases and Clumping Factor A to Abscess Formation in a Rabbit Model of Skin and Soft Tissue Infection

    PubMed Central

    Malachowa, Natalia; Kobayashi, Scott D.; Porter, Adeline R.; Braughton, Kevin R.; Scott, Dana P.; Gardner, Donald J.; Missiakas, Dominique M.; Schneewind, Olaf; DeLeo, Frank R.

    2016-01-01

    Staphylococcus aureus produces numerous factors that facilitate survival in the human host. S. aureus coagulase (Coa) and von Willebrand factor-binding protein (vWbp) are known to clot plasma through activation of prothrombin and conversion of fibrinogen to fibrin. In addition, S. aureus clumping factor A (ClfA) binds fibrinogen and contributes to platelet aggregation via a fibrinogen- or complement-dependent mechanism. Here, we evaluated the contribution of Coa, vWbp and ClfA to S. aureus pathogenesis in a rabbit model of skin and soft tissue infection. Compared to skin abscesses caused by the Newman wild-type strain, those caused by isogenic coa, vwb, or clfA deletion strains, or a strain deficient in coa and vwb, were significantly smaller following subcutaneous inoculation in rabbits. Unexpectedly, we found that fibrin deposition and abscess capsule formation appear to be independent of S. aureus coagulase activity in the rabbit infection model. Similarities notwithstanding, S. aureus strains deficient in coa and vwb elicited reduced levels of several proinflammatory molecules in human blood in vitro. Although a specific mechanism remains to be determined, we conclude that S. aureus Coa, vWbp and ClfA contribute to abscess formation in rabbits. PMID:27336691

  20. 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. PMID:26763447

  1. 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. PMID:26198368

  2. Epidemiology, clinical manifestations, and treatment options for skin and soft tissue infection caused by community-acquired methicillin-resistant Staphylococcus aureus

    PubMed Central

    Farley, Jason E.

    2009-01-01

    Purpose: This article reviews the evolving epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and the appropriate outpatient management of CA-MRSA skin and soft tissue infection. Further, the paper will provide the basis upon which an individualized patient educational plan may be developed. Data Sources: To complete this review, a search of English language publications was conducted through Medline and CINAHL databases (1966–2006). Conclusions: The epidemiology of CA-MRSA is becoming increasingly complex. Research that addresses the impact of this organism in high-risk populations and within families is urgently needed. Implications for Practice: Nurse practitioners must remain informed of the epidemiology of common and emerging drug-resistant organisms in their patient populations. PMID:18271763

  3. 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.

  4. 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

    2015-01-01

    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

  5. 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

  6. Proximal placement of lateral thigh skin markers reduces soft tissue artefact during normal gait using the Conventional Gait Model.

    PubMed

    Cockcroft, John; Louw, Quinette; Baker, Richard

    2016-11-01

    A primary source of measurement error in gait analysis is soft-tissue artefact. Hip and knee angle measurements, regularly used in clinical decision-making, are particularly prone to pervasive soft tissue on the femur. However, despite several studies of thigh marker artefact it remains unclear how lateral thigh marker height affects results using variants of the Conventional Gait Model. We compared Vicon Plug-in Gait hip and knee angle estimates during gait using a proximal and distal thigh marker placement for ten healthy subjects. Knee axes were estimated by optimizing thigh rotation offsets to minimize knee varus-valgus range during gait. Relative to the distal marker, the proximal marker produced 37% less varus-valgus range and 50% less hip rotation range (p < 0.001), suggesting that it produced less soft-tissue artefact in knee axis estimates. The thigh markers also produced different secondary effects on the knee centre estimate. Using whole gait cycle optimization, the distal marker showed greater minimum and maximum knee flexion (by 6° and 2° respectively) resulting in a 4° reduction in range. Mid-stance optimization reduced distal marker knee flexion by 5° throughout, but proximal marker results were negligibly affected. Based on an analysis of the Plug-in Gait knee axis definition, we show that the proximal marker reduced sensitivity to soft-tissue artefact by decreasing collinearity between the points defining the femoral frontal plane and reducing anteroposterior movement between the knee and thigh markers. This study suggests that a proximal thigh marker may be preferable when performing gait analysis using the Plug-in Gait model. PMID:26929983

  7. 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

  8. 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).

  9. Clinical applications of skin substitutes.

    PubMed

    Nyame, Theodore T; Chiang, H Abraham; Orgill, Dennis P

    2014-08-01

    A unique understanding of the components of mammalian skin has led to the development of numerous skin substitutes. These skin substitutes attempt to compensate for functional and physiologic deficits present in damaged tissue. Skin substitutes, when appropriately applied in optimized settings, offer a promising solution to difficult wound management. The body of literature on skin substitutes increases as the understanding of tissue engineering and molecular biology expands. Given the high cost of these products, future randomized large prospective studies are needed to guide the clinical applications of skin substitutes. PMID:25085091

  10. Staphylococcus aureus skin and soft tissue infections in primary healthcare in Denmark: a 12-year population-based study.

    PubMed

    Dalager-Pedersen, M; Søgaard, M; Schønheyder, H C

    2011-08-01

    A rise in community-onset Staphylococcus aureus infections has been observed in European countries. To ascertain secular trends of S. aureus infections in primary healthcare in Denmark, we conducted this register-based study in the North Denmark region, during the period 1997-2008. We identified all skin and mucosa specimens obtained by general practitioners and all prescriptions for the preferred oral anti-staphylococcal antibiotic, dicloxacillin. Repeat observations within a 12-month period were excluded prior to the calculation of age and gender standardised incidence rates per 100,000 person-years. We included 108,758 specimens, of which 42,778 (39%) yielded S. aureus. The annual incidence rate of specimens doubled during the study period, reaching 2,399 in 2008. The overall rate of S. aureus isolates increased 2-fold to a stable rate at about 850, but for isolates from children and for impetigo specimens, the increase was steeper, with a peak in 2002. A total of 156,462 dicloxacillin prescriptions had been redeemed and the annual prescription rate increased 2.5-fold, peaking at 3,714 in 2007. In conclusion, the annual rates of specimens, S. aureus infections and dicloxacillin prescriptions more than doubled in primary healthcare during the 12-year study period. A major impetigo epidemic and calls for antibiotic stewardship with increased utilisation of specimens were contributing factors. PMID:21279531

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

    PubMed

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

    2016-05-01

    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

  12. 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

  13. 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.

  14. 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

  15. Accuracies of facial soft tissue depth means for estimating ground truth skin surfaces in forensic craniofacial identification.

    PubMed

    Stephan, Carl N

    2015-07-01

    Facial soft tissue thickness means have long been used as a proxy to estimate the soft tissue envelope, over the skull, in craniofacial identification. However, estimation errors of these statistics are not well understood, making casework selection of the best performing estimation models impossible and overarching method accuracies controversial. To redress this situation, residuals between predicted and ground truth values were calculated in two experiments: (1) for 27 suites of means drawn from 10 recently published studies, all examining the same 10 landmarks (N ≥ 3051), and tested against six independent raw datasets of contemporary living adults (N = 797); and (2) pairwise tests of the above six, and five other, raw datasets (N = 1063). In total, 380 out-of-sample tests of 416 arithmetic means were conducted across 11 independent samples. Experiment 1 produced an overarching mean absolute percentage error (MAE) of 29% and a standard error of the estimate (S(est)) of 2.7 mm. Experiment 2 yielded MAE of 32% and S(est) of 2.8 mm. In any instance, MAE was always ≥20% of the ground truth value. The overarching 95% limits of the error, for contemporary samples, was large (11.4 mm). CT-derived means from South Korean males and Black South African females routinely performed well across the test samples and produced the smallest errors of any tests (but did so for Black American male reference samples). Sample-specific statistics thereby performed poorly despite discipline esteem. These results—and the practice of publishing means without prior model validation—demand major reforms in the field. PMID:25394746

  16. Skin lesion removal

    MedlinePlus

    ... Hair Small blood vessels in the skin Tattoos CRYOTHERAPY Cryotherapy is a method of super-freezing tissue in ... warts, actinic keratoses, solar keratoses, and molluscum contagiosum. Cryotherapy is done using a cotton swab that has ...

  17. Bleeding into the skin

    MedlinePlus

    ... under the tissue in larger flat areas (called purpura ), or in a very large bruised area (called ... in the newborn) Aging skin (ecchymosis) Idiopathic thrombocytopenic purpura (petechiae and purpura) Henoch-Schonlein purpura (purpura) Leukemia ( ...

  18. Photochemical tissue bonding

    DOEpatents

    Redmond, Robert W.; Kochevar, Irene E.

    2012-01-10

    Photochemical tissue bonding methods include the application of a photosensitizer to a tissue and/or tissue graft, followed by irradiation with electromagnetic energy to produce a tissue seal. The methods are useful for tissue adhesion, such as in wound closure, tissue grafting, skin grafting, musculoskeletal tissue repair, ligament or tendon repair and corneal repair.

  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. Contrast media are incomplete secretagogues acting on human basophils and mast cells isolated from heart and lung, but not skin tissue.

    PubMed

    Genovese, A; Stellato, C; Patella, V; Lamparter-Schummert, B; de Crescenzo, G; Adt, M; Marone, G

    1996-01-01

    To investigate the mechanisms of anaphylactoid reactions to radiocontrast media, in vitro mediator release induced by three iodinated contrast agents was examined using peripheral blood basophils and mast cells purified from human lung parenchyma, heart, and skin tissues. Three iodinated contrast agents, sodium and meglumine salts of ioxaglic acid, sodium and meglumine salts of ioxithalamic acid, and ioversol, were incubated with basophils purified from peripheral blood and human mast cells isolated and purified from different anatomical sites. Release of preformed (histamine and tryptase) and de novo synthesized mediators (prostaglandin D2 and leukotriene C4) into the supernatans was determined at various contrast medium concentrations after incubation for 60 min. Ioxaglate (0.2-0.3 M), ioxithalamate (0.3-0.5 M), and to a lesser extent ioversol (0.3-0.5 M) induced histamine release from basophils in a concentration-dependent manner. All three induced the release of preformed mediators (histamine and tryptase) from human lung, but not from skin mast cells. They also induced histamine and tryptase release from human heart mast cells. However, they did not induce the de novo synthesis of leukotriene C1 or prostaglandin D2 from human basophils or any type of mast cell examined. Cross-linking of IgE by anti-IgE induced the release of leukotriene C4 or prostaglandin D2 from human basophils or mast cells. Mannitol, an osmotic stimulus, induced the release of histamine from human basophils, but to a lesser extent from mast cells. These results show that different contrast media can differ in their ability to release mediators from enriched preparations of human basophils and mast cells. The three contrast agents examined act on basophils and mast cells as incomplete secretagogues, causing the release of preformed mediators, but not these novo synthesis of chemical mediators. It may be useful to measure plasma tryptase levels to detect adverse reactions caused by iodinated

  1. Monte Carlo study of skin optical clearing to enhance light penetration in the tissue: implications for photodynamic therapy of acne vulgaris

    NASA Astrophysics Data System (ADS)

    Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, Valery V.; Altshuler, Gregory B.; Yaroslavsky, Ilya V.

    2008-06-01

    Result of Monte Carlo simulations of skin optical clearing is presented. The model calculations were carried out with the aim of studying of spectral response of skin under immersion liquids action and calculation of enhancement of light penetration depth. In summary, we have shown that: 1) application of glucose, propylene glycol and glycerol produced significant decrease of light scattering in different skin layers; 2) maximal clearing effect will be obtained in case of optical clearing of skin dermis, however, absorbed light fraction in skin dermis changed insignificantly, independently on clearing agent and place it administration; 3) in contrast to it, the light absorbed fraction in skin adipose layer increased significantly in case of optical clearing of skin dermis. It is very important because it can be used for development of optical methods of obesity treatment; 4) optical clearing of superficial skin layers can be used for decreasing of power of light radiation used for treatm