Predicting Disease Progression in Scleroderma with Skin and Blood Biomarkers

DTIC Science & Technology

2014-10-01

AWARD NUMBER: W81XWH-13-1-0452 TITLE: Predicting Disease Progression in Scleroderma with Skin...Annual 3. DATES COVERED 23Sep 2013 – 22 Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Predicting Disease Progression in...Scleroderma (Systemic Sclerosis, SSc) is a chronic, incurable autoimmune disease associated with high morbidity and mortality primarily due to SSc-lung

Black hair follicular dysplasia in Large Münsterländer dogs: clinical, histological and ultrastructural features

PubMed Central

von Bomhard, Wolf; Mauldin, Elizabeth A.; Schmutz, Sheila M.; Leeb, Tosso; Casal, Margret L.

2012-01-01

Four Large Münsterländer cross-bred dogs affected with black hair follicular dysplasia (BHFD) and one unaffected control littermate were observed, and skin was sampled weekly over the first 19 weeks of life. Affected dogs were born with silvery grey hair, a consequence of melanin clumping in the hair shafts. Hair bulb melanocytes were densely pigmented, and contained abundant stage IV melanosomes but adjacent matrix keratinocytes lacked melanosomes. Melanin clumping was not prominent in epidermal melanocytes in the haired skin but occurred in the foot pads. Follicular changes progressed from bulbar clumping, clumping in the isthmus/ infundibulum and finally to dysplastic hair shafts. Alopecia developed progressively in pigmented areas. Silver-grey hair, melanin clumping, accumulation of stage IV melanosomes within melanocytes and insufficient melanin transfer to adjacent keratinocytes are also classic features of human Griscelli syndrome. The underlying cause in Griscelli syndrome is a defect of melanocytic intracellular transport proteins leading to inadequate and disorganized melanosome transfer to keratinocytes with resultant melanin clumping. In view of the correlation in the phenotype, histology and ultrastructure between both disorders, a defect in intracellular melanosome transport is postulated as the pathogenic mechanism in BHFD. PMID:16674733

The promise of advanced technology for future air transports

NASA Technical Reports Server (NTRS)

Bower, R. E.

1978-01-01

Progress in all weather 4-D navigation and wake vortex attenuation research is discussed and the concept of time based metering of aircraft is recommended for increased emphasis. The far term advances in aircraft efficiency were shown to be skin friction reduction and advanced configuration types. The promise of very large aircraft, possibly all wing aircraft is discussed, as is an advanced concept for an aerial relay transportation system. Very significant technological developments were identified that can improve supersonic transport performance and reduce noise. The hypersonic transport was proposed as the ultimate step in air transportation in the atmosphere. Progress in the key technology areas of propulsion and structures was reviewed. Finally, the impact of alternate fuels on future air transports was considered and shown not to be a growth constraint.

Repeat tuberculin skin testing leads to desensitisation in naturally infected tuberculous cattle which is associated with elevated interleukin-10 and decreased interleukin-1 beta responses.

PubMed

Coad, Michael; Clifford, Derek; Rhodes, Shelley G; Hewinson, R Glyn; Vordermeier, H Martin; Whelan, Adam O

2010-01-01

The principal surveillance tool used to control bovine tuberculosis in cattle is the removal of animals that provide a positive response to the tuberculin skin-test. In this study we performed a longitudinal investigation of the immunological and diagnostic consequences of repeated short-interval skin-tests in cattle naturally infected with Mycobacterium bovis. Tuberculin skin-test positive cattle were subjected to up to four further intradermal comparative cervical skin-tests at approximately 60-day intervals. A significant progressive reduction in the strength of the skin-test was observed after successive tests. In contrast, the magnitude of interferon-gamma (IFN-gamma) responses was not influenced by repeat skin-testing either transiently around the time of each skin-test or longitudinally following repeated tests. A significant boost in blood interleukin-10 (IL-10) production was observed within 3 days following each skin-test although the magnitude of this boosted response returned to lower levels by day 10 post-test. The application of a novel multiplex assay to simultaneously measure seven cytokines and chemokines also identified that skin-testing resulted in a significant and progressive reduction in antigen specific interleukin-1beta (IL-1beta) whilst confirming stable IFN-gamma and elevated IL-10 responses in the blood. Therefore, we have demonstrated that in cattle naturally infected with M. bovis, repeat short-interval skin-testing can lead to a progressive reduction in skin-test responsiveness which has potential negative consequences for the detection of infected animals with marginal or inconclusive skin-test responses. The desensitising effect is associated with decreased IL-1beta and elevated IL-10 responses, but importantly, does not influence antigen specific IFN-gamma responses. INRA, EDP Sciences, 2009

Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome.

PubMed

Piekutowska-Abramczuk, Dorota; Mierzewska, Hanna; Bekiesińska-Figatowska, Monika; Ciara, Elżbieta; Trubicka, Joanna; Pronicki, Maciej; Rokicki, Dariusz; Rydzanicz, Małgorzata; Płoski, Rafał; Pronicka, Ewa

2016-01-01

Pathogenic molecular variants in the ADAR gene are a known cause of rare diseases, autosomal recessive Aicardi- Goutières syndrome type 6, severe infantile encephalopathy with intracranial calcifications and dominant dyschromatosis symmetrica hereditaria, demonstrated mainly in Asian adults. Recently, they have been also found in patients with nonsyndromic bilateral striatal necrosis accompanied by skin changes of the freckles-like type. Here, we present Polish siblings with acute onset and slowly progressive extrapyramidal syndrome with preserved intellectual abilities and basal ganglia changes found in MRI. A Leigh syndrome was considered for a long time as the most frequent cause of such lesions in children. Finally, two molecular variants in non-mitochondria-related ADAR gene c.3202+1G>A (p.?) and c.577C>G (p.Pro193Ala) were revealed by whole exome sequencing. We suggest that bilateral striatal necrosis should be always differentiated from LS to prevent the diagnosis delay. The striatal involvement accompanied by the presence of freckles-like skin changes should direct differential diagnosis to the ADAR gene mutations screening.

Neurodegeneration as the presenting symptom in 2 adults with xeroderma pigmentosum complementation group F

PubMed Central

Shanbhag, Niraj M.; Geschwind, Michael D.; DiGiovanna, John J.; Groden, Catherine; Godfrey, Rena; Yousefzadeh, Matthew J.; Wade, Erin A.; Niedernhofer, Laura J.; Malicdan, May Christine V.; Kraemer, Kenneth H.; Gahl, William A.

2018-01-01

Objective To describe the features of 2 unrelated adults with xeroderma pigmentosum complementation group F (XP-F) ascertained in a neurology care setting. Methods We report the clinical, imaging, molecular, and nucleotide excision repair (NER) capacity of 2 middle-aged women with progressive neurodegeneration ultimately diagnosed with XP-F. Results Both patients presented with adult-onset progressive neurologic deterioration involving chorea, ataxia, hearing loss, cognitive deficits, profound brain atrophy, and a history of skin photosensitivity, skin freckling, and/or skin neoplasms. We identified compound heterozygous pathogenic mutations in ERCC4 and confirmed deficient NER capacity in skin fibroblasts from both patients. Conclusions These cases illustrate the role of NER dysfunction in neurodegeneration and how adult-onset neurodegeneration could be the major symptom bringing XP-F patients to clinical attention. XP-F should be considered by neurologists in the differential diagnosis of patients with adult-onset progressive neurodegeneration accompanied by global brain atrophy and a history of heightened sun sensitivity, excessive freckling, and skin malignancies. PMID:29892709

Time-dependent progression from the acute to chronic phases in atopic dermatitis induced by epicutaneous allergen stimulation in NC/Nga mice.

PubMed

Kim, Ji-Yun; Jeong, Mi Sook; Park, Mi Kyung; Lee, Mi-Kyung; Seo, Seong Jun

2014-01-01

Atopic dermatitis (AD) is a complicated skin condition influenced by genetic background and environmental factors. In this study, we applied Dermatophagoides farinae body extract (DfE) to the barrier-disrupted skin of NC/Nga mice twice a week for 8 weeks to identify the clinical and immunological factors in AD progression. Repeated application of the DfE to the skin of NC/Nga mice showed the similar consequences for the natural course of progression in human AD, histologically and immunologically. We confirmed that the AD-like skin lesions in NC/Nga mice did not last for the whole period of our experiment in spite of repeated topical applications of DfE twice a week. Topical DfE stimulation increased the skin mRNA expressions of Th1-, Th2- and Th17-related cytokines in the acute phase. The expression patterns of IL-4 and IL-13 in splenic T cells and skin lesions were consistent with the time course alterations of clinical features of AD-like skin symptoms. We also showed that there was a remission phase either just before or right after the chronic phase in this experimental model. Interestingly, splenic T-cell-derived IL-5 expression began to increase in the chronic phase, while skin-derived IL-5 mRNA expression increased in the acute phase. In conclusion, our results suggest that we should pay attention to the characteristics of each stage of AD progression and choose a suitable corresponding stage of animal model not only to elucidate the pathogenesis of AD but also to develop and evaluate therapeutic drugs for AD. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Skin rash in the intensive care unit: Stevens-Johnson syndrome, toxic epidermal necrolysis, or a rare manifestation of a hidden cutaneous malignancy: A case report.

PubMed

Al-Saffar, Farah; Ibrahim, Saif; Patel, Pujan; Jacob, Rafik; Palacio, Carlos; Cury, James

2016-03-01

Skin rashes are infrequently encountered in the intensive care units, either as a result or as a cause of admission. The entities of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of desquamating skin diseases that have multiple etiologies, the most common being drug-related reactions; very rarely, the cause may be cutaneous malignancies. We herein present a unique case of a 54-year-old male patient with psoriasis treated with methotrexate, who presented with a cellulitis-like clinical picture, then developed a severe progressive systemic inflammatory response syndrome, and progressed clinically to SJS, then TEN even after discontinuing the antibiotics and methotrexate. A skin biopsy demonstrated an aggressive and rapidly-progressing T-cell lymphoma. The present case highlights the necessity of skin biopsy when encountering SJS and TEN in the ICU in order to identify potentially treatable/controllable causes. Although it appeared reasonable to correlate TEN solely to medications, the skin biopsies clearly demonstrated an aggressive T-cell skin lymphoma. In a patient with a better general condition it may have been helpful to treat this malignancy. TEN is a life-threatening condition and skin biopsy is the cornerstone of diagnosis, despite the presence of multiple risk factors and the typical physical findings of a drug-induced reaction.

Precancerous Skin Lesions.

PubMed

Ferrándiz, C; Malvehy, J; Guillén, C; Ferrándiz-Pulido, C; Fernández-Figueras, M

Certain clinically and histologically recognizable skin lesions with a degree of risk of progression to squamous cell carcinoma have been traditionally grouped as precancerous skin conditions but now tend to be classified as in situ carcinomas. This consensus statement discusses various aspects of these lesions: their evaluation by means of clinical and histopathologic features, the initial evaluation of the patient, the identification of risk factors for progression, and the diagnostic and treatment strategies available today. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Progress in Malassezia Research in Korea

PubMed Central

Kim, Soo Young; Lee, Yang Won; Choe, Yong Beom

2015-01-01

Yeasts of the genus Malassezia are part of the normal flora of human skin. However, they are also associated with various skin diseases. Since the introduction of Malassezia to the Korean Dermatologic Society two decades ago, remarkable progress has been made in our knowledge of this genus. In this paper, we review recent developments in Malassezia research, including taxonomy and methods for species identification, recent genome analyses, Malassezia species distribution in healthy conditions and in specific skin diseases, trials investigating the mechanisms underlying Malassezia-related diseases, as well as therapeutic options. This review will enhance our understanding of Malassezia yeasts and related skin diseases in Korea. PMID:26719632

Progress in Malassezia Research in Korea.

PubMed

Kim, Soo Young; Lee, Yang Won; Choe, Yong Beom; Ahn, Kyu Joong

2015-12-01

Yeasts of the genus Malassezia are part of the normal flora of human skin. However, they are also associated with various skin diseases. Since the introduction of Malassezia to the Korean Dermatologic Society two decades ago, remarkable progress has been made in our knowledge of this genus. In this paper, we review recent developments in Malassezia research, including taxonomy and methods for species identification, recent genome analyses, Malassezia species distribution in healthy conditions and in specific skin diseases, trials investigating the mechanisms underlying Malassezia-related diseases, as well as therapeutic options. This review will enhance our understanding of Malassezia yeasts and related skin diseases in Korea.

New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms.

PubMed

Singh, Madhulika; Suman, Shankar; Shukla, Yogeshwer

2014-01-01

Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer.

Psychological interventions in the management of common skin conditions

PubMed Central

Shenefelt, Philip D

2010-01-01

The nervous system and the skin develop next to each other in the embryo and remain intimately interconnected and interactive throughout life. The nervous system can influence skin conditions through psychoneuroimmunoendocrine mechanisms and through behaviors. Understanding the pathophysiology aids in selection of treatment plans for correcting the negative effects of the psyche on specific skin conditions. Medication options include standard psychotropic medications and alternative herbs and supplements. Other options include biofeedback, cognitive-behavioral methods, hypnosis, meditation, progressive relaxation, the placebo effect, and suggestion. When simple measures fail, combining medications with other therapeutic options may produce better results. Skin conditions that have strong psychophysiologic aspects may respond well to techniques such as biofeedback, cognitive-behavioral methods, hypnosis, meditation, or progressive relaxation that help to counteract stress. Treatment of primary psychiatric disorders that negatively influence skin conditions often results in improvement of those skin conditions. Abnormal conditions of the skin, hair, and nails can also influence the psyche negatively. Treatment of secondary psychiatric disorders such as anxiety or depression that are triggered or exacerbated by the appearance of these skin conditions or the associated discomfort may also be required. PMID:22110329

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

PubMed Central

Herrick, Ariane L; Peytrignet, Sebastien; Lunt, Mark; Pan, Xiaoyan; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan J; Dinsdale, Graham; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon C; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jobanputra, Paresh; Jordan, Alison C; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja S; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susanna M; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

2018-01-01

Objectives Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). Methods The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. ‘Progressors’ were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). Results 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Conclusions Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. Trial registration number NCT02339441. PMID:29306872

Arterial hypertension and skin allergy are risk factors for progression from dengue to dengue hemorrhagic fever: a case control study.

PubMed

Teixeira, Maria Glória; Paixão, Enny S; Costa, Maria da Conceição N; Cunha, Rivaldo V; Pamplona, Luciano; Dias, Juarez P; Figueiredo, Camila A; Figueiredo, Maria Aparecida A; Blanton, Ronald; Morato, Vanessa; Barreto, Maurício L; Rodrigues, Laura C

2015-05-01

Currently, knowledge does not allow early prediction of which cases of dengue fever (DF) will progress to dengue hemorrhagic fever (DHF), to allow early intervention to prevent progression or to limit severity. The objective of this study is to investigate the hypothesis that some specific comorbidities increase the likelihood of a DF case progressing to DHF. A concurrent case-control study, conducted during dengue epidemics, from 2009 to 2012. Cases were patients with dengue fever that progressed to DHF, and controls were patients of dengue fever who did not progress to DHF. Logistic regression was used to estimate the association between DHF and comorbidities. There were 490 cases of DHF and 1,316 controls. Among adults, progression to DHF was associated with self-reported hypertension (OR = 1.6; 95% CI 1.1-2.1) and skin allergy (OR = 1.8; 95% CI 1.1-3.2) with DHF after adjusting for ethnicity and socio-economic variables. There was no statistically significant association between any chronic disease and progression to DHF in those younger than 15 years. Physicians attending patients with dengue fever should keep those with hypertension or skin allergies in health units to monitor progression for early intervention. This would reduce mortality by dengue.

Claudins 1, 2, 3, 4, 5 and 7 in solar keratosis and squamocellular carcinoma of the skin

PubMed Central

Hintsala, Hanna-Riikka; Siponen, Maria; Haapasaari, Kirsi-Maria; Karihtala, Peeter; Soini, Ylermi

2013-01-01

Claudins are tight junction proteins regulating the paracellular permeability of cell layers. We investigated the expression of claudins 1, 2, 3, 4, 5 and 7 in a sample set consisting of a total of 93 cases representing normal skin, actinic keratoses and squamous cell carcinomas of the skin. There were several changes found in claudin expression. Claudin 1 appeared to be progressively decreased in solar keratosis and skin squamous cell carcinomas compared to normal skin while expression of claudin 2 was increased. With claudins 3 and 5 occasional immunoreactivity was found in squamous cell carcinomas. Claudins 4 and 7 were variably expressed in skin neoplasia compared to normal skin. According to the results expression of claudins 1 and 2 change in parallel with the severity of the epidermal preneoplastic and neoplastic lesions thus probably influencing the disturbed epithelial polarity characteristic of these lesions. Claudin 1 under- and claudin 2 overexpression also lead to a leakier epithelial barrier function of the skin with a resulting damage to skin epithelial resistance. Other claudins investigated in this study did not show progressive changes even though occasional overexpression of them was found in skin squamous cell carcinoma. PMID:24294371

High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

PubMed

de Masson, Adele; O'Malley, John T; Elco, Christopher P; Garcia, Sarah S; Divito, Sherrie J; Lowry, Elizabeth L; Tawa, Marianne; Fisher, David C; Devlin, Phillip M; Teague, Jessica E; Leboeuf, Nicole R; Kirsch, Ilan R; Robins, Harlan; Clark, Rachael A; Kupper, Thomas S

2018-05-09

Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Studying skin tumourigenesis and progression in immunocompetent hairless SKH1-hr mice using chronic 7,12-dimethylbenz(a)anthracene topical applications to develop a useful experimental skin cancer model.

PubMed

Thomas, Giju; Tuk, Bastiaan; Song, Ji-Ying; Truong, Hoa; Gerritsen, Hans C; de Gruijl, Frank R; Sterenborg, Henricus J C M

2017-02-01

Previous studies have established that 7,12-dimethylbenz(a)anthracene (DMBA) can initiate skin tumourigenesis in conventional furred mouse models by acting on hair follicle stem cells. However, further cancer progression depends on repeated applications of tumour promoter agents. This study evaluated the timeline involved in skin tumourigenesis and progression in immunocompetent hairless SKH1-hr mice with dysfunctional hair follicles using only DMBA with no additional tumour promoter agents. The results showed that topical application of 30 µg (117 nmol) of DMBA over the back and flank regions of the mouse once a week and 15 µg (58.5 nmol) twice a week produced skin tumours after 7-8 weeks. However, by week 14 a heavy benign tumour load required the mice to be euthanized. Lowering the DMBA dose to 15 µg (58.5 nmol) once a week produced tumours more slowly and allowed the mice to be studied for a longer period to week 23. This low-dose DMBA regimen yielded a high percentage of malignant tumours (58.8%) after 23 weekly applications. Additionally DMBA-treated skin showed an increase in mean epidermal thickness in comparison to untreated and acetone-treated skin. Despite the aberrant hair follicles in SKH1-hr mice, this chemically driven skin cancer model in hairless mice can serve as a suitable alternative to the ultraviolet-induced skin cancer models and can be reliably replicated as demonstrated by both the pilot and main experiments.

Bilateral asymmetry of skin temperature is not related to bilateral asymmetry of crank torque during an incremental cycling exercise to exhaustion

PubMed Central

Formenti, Damiano; Ludwig, Nicola; Gargano, Marco; Bosio, Andrea; Rampinini, Ermanno; Alberti, Giampietro

2018-01-01

Although moderate relationships (|r| ∼ 0.5) were reported between skin temperature and performance-related variables (e.g., kinetic), it remains unclear whether skin temperature asymmetry reflects muscle force imbalance in cycling. Therefore, the aim of this study was to assess whether a relationship exists between kinetic and thermal asymmetry during a fatiguing exercise. Ten elite cyclists were enrolled and tested on a maximal incremental cycling test. Peak crank torques of both legs were obtained at the initial and final workload. Likewise, bilateral skin temperatures were recorded before and after exercise. Asymmetric indexes were also calculated for kinetic (AIK) and skin temperature (AIT) outcomes. The bilateral peak crank torques showed a larger difference at the final compared to the initial workload (p < 0.05) of the incremental exercise. Conversely, the bilateral skin temperature did not show any differences at both initial and final workload (p > 0.05). Additionally, trivial relationships were reported between AIK and AIT (−0.3 < r < 0.2) at the initial and final workload. The obtained results showed that changes in bilateral kinetic values did not reflect concurrent changes in bilateral skin temperatures. This finding emphasizes the difficulty of associating the asymmetry of skin temperature with those of muscle effort in elite cyclists. Lastly, our study also provided further insights on thermal skin responses during exhaustive cycling exercise in very highly-trained athletes. PMID:29507831

Recent Progress in Electronic Skin

PubMed Central

Wang, Xiandi; Dong, Lin; Zhang, Hanlu; Yu, Ruomeng; Wang, Zhong Lin

2015-01-01

The skin is the largest organ of the human body and can sense pressure, temperature, and other complex environmental stimuli or conditions. The mimicry of human skin's sensory ability via electronics is a topic of innovative research that could find broad applications in robotics, artificial intelligence, and human–machine interfaces, all of which promote the development of electronic skin (e‐skin). To imitate tactile sensing via e‐skins, flexible and stretchable pressure sensor arrays are constructed based on different transduction mechanisms and structural designs. These arrays can map pressure with high resolution and rapid response beyond that of human perception. Multi‐modal force sensing, temperature, and humidity detection, as well as self‐healing abilities are also exploited for multi‐functional e‐skins. Other recent progress in this field includes the integration with high‐density flexible circuits for signal processing, the combination with wireless technology for convenient sensing and energy/data transfer, and the development of self‐powered e‐skins. Future opportunities lie in the fabrication of highly intelligent e‐skins that can sense and respond to variations in the external environment. The rapidly increasing innovations in this area will be important to the scientific community and to the future of human life. PMID:27980911

New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms

PubMed Central

Singh, Madhulika; Suman, Shankar; Shukla, Yogeshwer

2014-01-01

Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer. PMID:24757666

Effects of the Particulate Matter₂.₅ (PM₂.₅) on Lipoprotein Metabolism, Uptake and Degradation, and Embryo Toxicity.

PubMed

Kim, Jae-Yong; Lee, Eun-Young; Choi, Inho; Kim, Jihoe; Cho, Kyung-Hyun

2015-12-01

Particulate matter2.5 (PM2.5) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which PM2.5 aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous PM2.5 solution on lipoprotein metabolism. Collected PM2.5 from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. PM2.5 extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. PM2.5 treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by PM2.5 solution in a dose-dependent manner. Further, PM2.5 solution caused cellular senescence in human dermal fibroblast cells. Microinjection of PM2.5 solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of PM2.5 induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins.

Effects of the Particulate Matter2.5 (PM2.5) on Lipoprotein Metabolism, Uptake and Degradation, and Embryo Toxicity

PubMed Central

Kim, Jae-Yong; Lee, Eun-Young; Choi, Inho; Kim, Jihoe; Cho, Kyung-Hyun

2015-01-01

Particulate matter2.5 (PM2.5) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which PM2.5 aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous PM2.5 solution on lipoprotein metabolism. Collected PM2.5 from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. PM2.5 extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. PM2.5 treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by PM2.5 solution in a dose-dependent manner. Further, PM2.5 solution caused cellular senescence in human dermal fibroblast cells. Microinjection of PM2.5 solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of PM2.5 induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins. PMID:26615830

[Neurological evaluation of the leper king Baldwin IV of Jerusalem].

PubMed

Guerrero-Peral, A L

In the medieval period, physicians became more aware of leprosy symptoms and differentiated it from other similar diseases. Baldwin, the leper king of Jerusalem (1161-1185), probably contributed to an increasing interest and tolerance to this disease in medieval Christian states. We review historical descriptions of the neurological manifestations he developed. William of Tyre gives us a description of first symptoms experienced by the prince when aged nine. He notices that half of his right arm and hand were partially numb. No skin or nervous lesions are described. By his early twenties, muscle weakness makes him unable to walk. He gets blinded, probably due to keratopathy related to facial nerves involvement. Repeated attacks of fever lead to progressive worsening of his disease. He finally dies in Jerusalem, aged twenty-five, probably due to a septicaemia from infected sores. The earliest sign of Baldwin's disease is anaesthesia. Though skin lesions are not described, it is likely that at this point he had a tuberculoid form of leprosy. As his disease finally takes a lepromatous form, we suspect that it began as a borderline, immunologically unstable form. Leper king Baldwin biography gives us interesting descriptions of neurological clinical features of leprosy. Besides, it helps us to discover twelfth century medicine knowledge about this disease.

New discoveries in the pathogenesis and classification of vitiligo.

PubMed

Rodrigues, Michelle; Ezzedine, Khaled; Hamzavi, Iltefat; Pandya, Amit G; Harris, John E

2017-07-01

Vitiligo is a common autoimmune disease that progressively destroys melanocytes in the skin, resulting in the appearance of patchy depigmentation. This disfiguring condition frequently affects the face and other visible areas of the body, which can be psychologically devastating. The onset of vitiligo often occurs in younger individuals and progresses for life, resulting in a heavy burden of disease and decreased quality of life. Presentation patterns of vitiligo vary, and recognition of these patterns provides both diagnostic and prognostic clues. Recent insights into disease pathogenesis offer a better understanding of the natural history of the disease, its associations, and potential for future treatments. The first article in this continuing medical education series outlines typical and atypical presentations of vitiligo, how they reflect disease activity, prognosis, and response to treatment. Finally, we discuss disease associations, risk factors, and our current understanding of disease pathogenesis. Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.

Biofeedback-assisted relaxation training to decrease test anxiety in nursing students.

PubMed

Prato, Catherine A; Yucha, Carolyn B

2013-01-01

Nursing students experiencing debilitating test anxiety may be unable to demonstrate their knowledge and have potential for poor academic performance. A biofeedback-assisted relaxation training program was created to reduce test anxiety. Anxiety was measured using Spielberger's Test Anxiety Inventory and monitoring peripheral skin temperature, pulse, and respiration rates during the training. Participants were introduced to diaphragmatic breathing, progressive muscle relaxation, and autogenic training. Statistically significant changes occurred in respiratory rates and skin temperatures during the diaphragmatic breathing session; respiratory rates and peripheral skin temperatures during progressive muscle relaxation session; respiratory and pulse rates, and peripheral skin temperatures during the autogenic sessions. No statistically significant difference was noted between the first and second TAI. Subjective test anxiety scores of the students did not decrease by the end of training. Autogenic training session was most effective in showing a statistically significant change in decreased respiratory and pulse rates and increased peripheral skin temperature.

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study.

PubMed

Herrick, Ariane L; Peytrignet, Sebastien; Lunt, Mark; Pan, Xiaoyan; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan J; Dinsdale, Graham; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon C; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jobanputra, Paresh; Jordan, Alison C; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja S; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susanna M; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

2018-04-01

Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. NCT02339441. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pancreatic Extraskeletal Osteosarcoma Metastasizing to the Scalp.

PubMed

Kim, Young Jae; Kim, Hak Tae; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Lee, Woo Jin

2018-06-01

Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal soft-tissue neoplasm that accounts for approximately 1% of all soft-tissue sarcomas. Over 70% of these malignant tumor progress to local recurrence and metastasis. It commonly metastasizes to the lungs, lymph nodes, bone, and skin and has a poor survival outcome. Cutaneous metastasis is exceedingly rare and known to be a sign of widespread metastases. We present a 57-year-old woman who presented with a rapidly growing protuberant mass on the scalp that was finally diagnosed as metastatic ESOS from a primary pancreatic ESOS. To our knowledge, there has been no reported case of pancreatic ESOS metastasizing to the scalp.

In vivo SILAC-based proteomics reveals phosphoproteome changes during mouse skin carcinogenesis.

PubMed

Zanivan, Sara; Meves, Alexander; Behrendt, Kristina; Schoof, Erwin M; Neilson, Lisa J; Cox, Jürgen; Tang, Hao R; Kalna, Gabriela; van Ree, Janine H; van Deursen, Jan M; Trempus, Carol S; Machesky, Laura M; Linding, Rune; Wickström, Sara A; Fässler, Reinhard; Mann, Matthias

2013-02-21

Cancer progresses through distinct stages, and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological, and pharmacological aspects of tumor development. To complement genomic investigations of this process, we here quantify phosphoproteomic changes in skin cancer development using the SILAC mouse technology coupled to high-resolution mass spectrometry. We distill protein expression signatures from our data that distinguish between skin cancer stages. A distinct phosphoproteome of the two stages of cancer progression is identified that correlates with perturbed cell growth and implicates cell adhesion as a major driver of malignancy. Importantly, integrated analysis of phosphoproteomic data and prediction of kinase activity revealed PAK4-PKC/SRC network to be highly deregulated in SCC but not in papilloma. This detailed molecular picture, both at the proteome and phosphoproteome level, will prove useful for the study of mechanisms of tumor progression. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Human papillomavirus 16 E5 oncogene contributes to two stages of skin carcinogenesis.

PubMed

Maufort, John P; Williams, Sybil M Genther; Pitot, Henry C; Lambert, Paul F

2007-07-01

High-risk human papillomaviruses (HPVs), which cause the vast majority of cervical cancer, other anogenital cancers, and a subset of head and neck squamous cell carcinomas, encode three oncogenes: E5, E6, and E7. To determine the oncogenic properties of HPV16 E5 in vivo, we previously generated K14E5 transgenic mice, in which expression of E5 was directed to the basal compartment of stratified squamous epithelia. In these mice, E5 induced epidermal hyperplasia and spontaneous skin tumors. In the current study, we determined how E5 contributes to tumor formation in the skin using a multistage model for skin carcinogenesis that specifies the role of genes in three stages: initiation, promotion, and malignant progression. Both initiation and promotion are required steps for papilloma formation. K14E5 mice treated with the initiating agent 7,12-dimethylbenz(a)anthracene (DMBA) developed more papillomas than like-treated nontransgenic mice, whereas neither K14E5 nor nontransgenic mice treated with the promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) developed papillomas. K14E5 mice treated with both DMBA and TPA to induce large numbers of papillomas had a higher incidence and earlier onset of carcinoma progression compared with like-treated nontransgenic mice. Thus, HPV16 E5 contributes to two stages of skin carcinogenesis: promotion and progression. The progressive neoplastic disease in K14E5 mice differed from that in nontransgenic mice in that benign tumors converted from exophytic to endophytic papillomas before progressing to carcinomas. Initial genetic and immunohistopathologic analyses did not determine the underlying basis for this distinct morphology, which correlates with a highly penetrant neoplastic phenotype.

Transcriptional regulation of ataxia-telangiectasia and Rad3-related protein by activated p21-activated kinase-1 protects keratinocytes in UV-B-induced premalignant skin lesions.

PubMed

Beesetti, S; Mavuluri, J; Surabhi, R P; Oberyszyn, T M; Tober, K; Pitani, R S; Joseph, L D; Venkatraman, G; Rayala, S K

2017-11-02

Sun-induced skin lesions, in particular actinic keratosis, are generally considered as premalignant skin lesions that can progress into squamous cell carcinoma (SCC) and invasive SCC if left untreated. Therefore, understanding the molecular mechanisms by which the ultraviolet-B (UV-B)-exposed cells are being protected and the signaling pathways that promote the progression of certain premalignant skin lesions to malignant lesions will permit us to prevent or cure skin cancers. In the current study, we found that phospho-p21-activated kinase-1 (Pak1) and Pak1 expression was high in clinical samples of sunlight-induced premalignant skin lesions assessed by immunohistochemistry. Further, we observed that phospho-Pak1 and Pak1 levels are high in UV-B-exposed hairless SKH mouse model skin samples as compared with unexposed skin tissue. Our results from cell line and animal models showed that Pak1 is activated in response to UV-B radiation, and this activated Pak1 translocates from the cytoplasm to the nucleus. Inside the nucleus, Pak1 via C-Fos binds to a specific promoter region of DNA repair kinase ATR (ataxia-telangiectasia and Rad3-related protein) and acts as a transcriptional regulator of ATR. Results from our analysis showed that Pak1 overexpression, knockdown and Pak1 knockout cell line models showed that Pak1 confers protection to keratinocytes from UV-B-induced apoptosis and DNA damage via ATR. To our knowledge, this is the first study that evaluates the functional and clinical significance of a signaling molecule, Pak1, in sun-induced premalignant skin lesions and indicates that increased Pak1 activation and expression could serve as an early warning sign of progression toward non-melanoma skin cancer, if ignored.

Skin autofluorescence is associated with the progression of chronic kidney disease: a prospective observational study.

PubMed

Tanaka, Kenichi; Nakayama, Masaaki; Kanno, Makoto; Kimura, Hiroshi; Watanabe, Kimio; Tani, Yoshihiro; Kusano, Yuki; Suzuki, Hodaka; Hayashi, Yoshimitsu; Asahi, Koichi; Sato, Keiji; Miyata, Toshio; Watanabe, Tsuyoshi

2013-01-01

Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD). Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis. Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004). Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD.

Skin Autofluorescence Is Associated with the Progression of Chronic Kidney Disease: A Prospective Observational Study

PubMed Central

Tanaka, Kenichi; Nakayama, Masaaki; Kanno, Makoto; Kimura, Hiroshi; Watanabe, Kimio; Tani, Yoshihiro; Kusano, Yuki; Suzuki, Hodaka; Hayashi, Yoshimitsu; Asahi, Koichi; Sato, Keiji; Miyata, Toshio; Watanabe, Tsuyoshi

2013-01-01

Background Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD). Methods Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis. Results Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004). Conclusions Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD. PMID:24349550

Skin immune sentinels in health and disease

PubMed Central

Nestle, Frank O.; Di Meglio, Paola; Qin, Jian-Zhong; Nickoloff, Brian J.

2010-01-01

Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103+ dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease. PMID:19763149

Skin immune sentinels in health and disease.

PubMed

Nestle, Frank O; Di Meglio, Paola; Qin, Jian-Zhong; Nickoloff, Brian J

2009-10-01

Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

PubMed

Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

2015-03-01

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

Use of skin temperature to predict tolerance to thermal environments.

DOT National Transportation Integrated Search

1971-01-01

Skin temperature is a sensitive index of the effect of the thermal environment on the seminude man. Skin temperatures and tolerance times from several studies have been utilized in an attempt to establish a relationship between (1) final skin tempera...

Imaging inflammatory acne: lesion detection and tracking

NASA Astrophysics Data System (ADS)

Cula, Gabriela O.; Bargo, Paulo R.; Kollias, Nikiforos

2010-02-01

It is known that effectiveness of acne treatment increases when the lesions are detected earlier, before they could progress into mature wound-like lesions, which lead to scarring and discoloration. However, little is known about the evolution of acne from early signs until after the lesion heals. In this work we computationally characterize the evolution of inflammatory acne lesions, based on analyzing cross-polarized images that document acne-prone facial skin over time. Taking skin images over time, and being able to follow skin features in these images present serious challenges, due to change in the appearance of skin, difficulty in repositioning the subject, involuntary movement such as breathing. A computational technique for automatic detection of lesions by separating the background normal skin from the acne lesions, based on fitting Gaussian distributions to the intensity histograms, is presented. In order to track and quantify the evolution of lesions, in terms of the degree of progress or regress, we designed a study to capture facial skin images from an acne-prone young individual, followed over the course of 3 different time points. Based on the behavior of the lesions between two consecutive time points, the automatically detected lesions are classified in four categories: new lesions, resolved lesions (i.e. lesions that disappear completely), lesions that are progressing, and lesions that are regressing (i.e. lesions in the process of healing). The classification our methods achieve correlates well with visual inspection of a trained human grader.

Protein Kinases and Transcription Factors Activation in Response to UV-Radiation of Skin: Implications for Carcinogenesis

PubMed Central

López-Camarillo, César; Ocampo, Elena Aréchaga; Casamichana, Mavil López; Pérez-Plasencia, Carlos; Álvarez-Sánchez, Elizbeth; Marchat, Laurence A.

2012-01-01

Solar ultraviolet (UV) radiation is an important environmental factor that leads to immune suppression, inflammation, photoaging, and skin carcinogenesis. Here, we reviewed the specific signal transduction pathways and transcription factors involved in the cellular response to UV-irradiation. Increasing experimental data supporting a role for p38, MAPK, JNK, ERK1/2, and ATM kinases in the response network to UV exposure is discussed. We also reviewed the participation of NF-κB, AP-1, and NRF2 transcription factors in the control of gene expression after UV-irradiation. In addition, we discussed the promising chemotherapeutic intervention of transcription factors signaling by natural compounds. Finally, we focused on the review of data emerging from the use of DNA microarray technology to determine changes in global gene expression in keratinocytes and melanocytes in response to UV treatment. Efforts to obtain a comprehensive portrait of the transcriptional events regulating photodamage of intact human epidermis after UV exposure reveals the existence of novel factors participating in UV-induced cell death. Progress in understanding the multitude of mechanisms induced by UV-irradiation could lead to the potential use of protein kinases and novel proteins as specific targets for the prevention and control of skin cancer. PMID:22312244

Assessment of Augmented Immune Surveillance and Tumor Cell Death by Cytoplasmic Stabilization of p53 as a Chemopreventive Strategy of 3 Promising Medicinal Herbs in Murine 2-Stage Skin Carcinogenesis.

PubMed

Ali, Farrah; Khan, Rehan; Khan, Abdul Quaiyoom; Lateef, Md Abdul; Maqbool, Tahir; Sultana, Sarwat

2014-07-01

Cancer is the final outcome of a plethora of events. Targeting the proliferation or inducing programmed cell death in a proliferating population is a major standpoint in the cancer therapy. However, proliferation is regulated by several cellular and immunologic processes. This study reports the inhibition of proliferation by augmenting immune surveillance, silencing acute inflammation, and inducing p53-mediated apoptosis of skin cancer by 3 promising medicinal extracts. We used the well-characterized model for experimental skin carcinogenesis in mice for 32 weeks to study the chemopreventive effect of the methanolic extracts of Trigonella foenumgraecum, Eclipta alba, and Calendula officinalis. All 3 extracts reduced the number, incidence, and multiplicity of tumors, which was confirmed by the pathologic studies that showed regressed tumors. There was a significant reduction in the PCNA+ nuclei in all treatment groups 32 weeks after the initiation. Mechanistic studies revealed that proliferative population in tumors is diminished by the restoration of the endogenous antioxidant defense, inhibition of the stress-related signal-transducing element NFκB, reduction of inflammation, enhancement of immunosurveillance of the genetically mutated cells, along with silencing of the cell cycle progression signals. Finally, all 3 medicinal extracts induced stable expression of p53 within the tumors, confirmed by the CFDA-Cy3 apoptosis assay. Results of our study confirm that these extracts not only limit the rate of proliferation by inhibition of the processes integral to cancer development but also induce stable cytoplasmic expression of p53-mediated apoptosis, leading to fewer and regressed tumors in mice. © The Author(s) 2013.

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.

Burn Wound Healing and Tissue Engineering.

PubMed

Singer, Adam J; Boyce, Steven T

In 2016 the American Burn Association held a State of the Science conference to help identify burn research priorities for the next decade. The current paper summarizes the work of the sub-committee on Burn Wound Healing and Tissue Engineering. We first present the priorities in wound healing research over the next 10 years. We then summarize the current state of the science related to burn wound healing and tissue engineering including determination of burn depth, limiting burn injury progression, eschar removal, management of microbial contamination and wound infection, measuring wound closure, accelerating wound healing and durable wound closure, and skin substitutes and tissue engineering. Finally, a summary of the round table discussion is presented.

A young child with fever, alopecia, and skin nodules: a clinicopathological conference.

PubMed

Vignesh, Pandiarajan; Gupta, Aman; Suri, Deepti; Chatterjee, Debajyoti; Saikia, Uma Nahar; Trehan, Amita; Singh, Surjit

2017-11-21

The illness started as a continuous high-grade fever noted up to 103°F.. Subsequently, he also developed red painful skin nodules that initially appeared over shins and later progressed to involve thighs, trunks, upper extremities, and face. The nodules also appeared over scalp and there was a was a progressive loss of scalp hair. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

New imaging-based biomarkers for melanoma diagnosis using coherent Raman Scattering microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wang, Hequn; Osseiran, Sam; Roider, Elisabeth; Fisher, David E.; Evans, Conor L.

2016-02-01

Recently, pheomelanin has been found to play a critical role in melanoma progression given its pro-oxidant chemical properties as well as its marked presence in pre-cancerous and malignant melanoma lesions, even in the absence of ultraviolet radiation. In addition, epidemiological evidence indicates a strong correlation between melanoma incidence and skin type, with the highest incidence occurring in individuals of the red-haired/fair-skinned phenotype. Interestingly, nevus count correlates well with melanoma incidence and skin type, except in the population most prone to developing melanoma, where nevus count strikingly drops. As such, a current hypothesis proposes that fair-skinned red-haired individuals, who are unable to stimulate production of eumelanin due to a mutation in MC1R in melanocytes, may actually harbor numerous "invisible", pheomelanin-rich nevi that evade clinical detection, supporting the high incidence of melanoma in that population. Here, we show for the very first time that melanocytes extracted from genetically modified MC1R-mutant, red-haired mice displayed bright perinuclear distributions of signal within the cells under coherent anti-Stokes Raman scattering (CARS) microscopy. Changes in pheomelanin production in siRNA knockdowns of cultured human melanoma cells were also sensed. We then successfully imaged pheomelanin distributions in both ex vivo and in vivo mouse ear skin. Finally, melanosomes within amelanotic melanoma patient tissue sections were found to show bright pheomelanin signals. This is the first time, to our knowledge, that pheomelanin has been found spatially localized in a human amelanotic melanoma sample. These pheomelanotic CARS features may be used as potential biomarkers for melanoma detection, especially for amelanotic melanomas.

Substance P induced preprotachykinin-a mRNA, neutral endopeptidase mRNA and substance P in cultured normal fibroblasts.

PubMed

Bae, Sang-Jae; Matsunaga, Yoshitaka; Takenaka, Motoi; Tanaka, Yoichi; Hamazaki, Yoichiro; Shimizu, Kazuhiro; Katayama, Ichiro

2002-04-01

In certain skin diseases, stress can modulate the induction and/or progression of cutaneous manifestations. However, little is known about the circuit in neuroendocrine and in the immune systems of the skin. To address this question, we have analyzed the regulatory mechanisms of autocrine induction of substance P (SP) by cultured normal human fibroblasts that compose the major population of the skin and might augment stress-induced skin inflammatory responses. In nonstimulated conditions, normal fibroblasts express a moderate amount of preprotachykinin-A (PPT-A), a precursor of SP mRNA, and exogenous SP significantly upregulated PPT-A mRNA expression. Maximum response of SP peptide and SP mRNA in fibroblasts was observed 1-3 h after stimulation with SP. In contrast, the expression of neutral endopeptidase (NEP), a cell surface peptide with hydrolyzing activity of SP, was increased in fibroblasts stimulated with SP after 24 h. The administration of NEP inhibitor (phosphoramidon) to the fibroblasts induced higher SP production. In addition, the neurokinin (NK) receptor antagonists (spantide, FK224 and FK888) and protein synthesis inhibitor (cycloheximide) inhibited SP production by 30-40% of control response. In immunostaining study, specific cytoplasmic staining of SP was observed in fibroblasts stimulated with SP. Finally, we confirmed that the nucleotide sequence of the PPT-A expressed in fibroblasts perfectly corresponded to the gene bank human PPT-A cDNA. This is the first report that SP mRNA, NEP mRNA and SP peptide can be induced by normal human skin fibroblasts in response to exogenous SP, and that fibroblast-derived SP might play an important role in the induction and acceleration of certain cutaneous diseases. Copyright 2002 S. Karger AG, Basel

Skin resurfacing procedures: new and emerging options

PubMed Central

Loesch, Mathew M; Somani, Ally-Khan; Kingsley, Melanie M; Travers, Jeffrey B; Spandau, Dan F

2014-01-01

The demand for skin resurfacing and rejuvenating procedures has progressively increased in the last decade and has sparked several advances within the skin resurfacing field that promote faster healing while minimizing downtime and side effects for patients. Several technological and procedural skin resurfacing developments are being integrated into clinical practices today allowing clinicians to treat a broader range of patients’ skin types and pathologies than in years past, with noteworthy outcomes. This article will discuss some emerging and developing resurfacing therapies and treatments that are present today and soon to be available. PMID:25210469

Skin resurfacing procedures: new and emerging options.

PubMed

Loesch, Mathew M; Somani, Ally-Khan; Kingsley, Melanie M; Travers, Jeffrey B; Spandau, Dan F

2014-01-01

The demand for skin resurfacing and rejuvenating procedures has progressively increased in the last decade and has sparked several advances within the skin resurfacing field that promote faster healing while minimizing downtime and side effects for patients. Several technological and procedural skin resurfacing developments are being integrated into clinical practices today allowing clinicians to treat a broader range of patients' skin types and pathologies than in years past, with noteworthy outcomes. This article will discuss some emerging and developing resurfacing therapies and treatments that are present today and soon to be available.

Failure Analysis of Discrete Damaged Tailored Extension-Shear-Coupled Stiffened Composite Panels

NASA Technical Reports Server (NTRS)

Baker, Donald J.

2005-01-01

The results of an analytical and experimental investigation of the failure of composite is tiffener panels with extension-shear coupling are presented. This tailored concept, when used in the cover skins of a tiltrotor aircraft wing has the potential for increasing the aeroelastic stability margins and improving the aircraft productivity. The extension-shear coupling is achieved by using unbalanced 45 plies in the skin. The failure analysis of two tailored panel configurations that have the center stringer and adjacent skin severed is presented. Finite element analysis of the damaged panels was conducted using STAGS (STructural Analysis of General Shells) general purpose finite element program that includes a progressive failure capability for laminated composite structures that is based on point-stress analysis, traditional failure criteria, and ply discounting for material degradation. The progressive failure predicted the path of the failure and maximum load capability. There is less than 12 percent difference between the predicted failure load and experimental failure load. There is a good match of the panel stiffness and strength between the progressive failure analysis and the experimental results. The results indicate that the tailored concept would be feasible to use in the wing skin of a tiltrotor aircraft.

Skin tightening.

PubMed

Woolery-Lloyd, Heather; Kammer, Jenna N

2011-01-01

Skin tightening describes the treatment of skin laxity via radiofrequency (RF), ultrasound, or light-based devices. Skin laxity on the face is manifested by progressive loss of skin elasticity, loosening of the connective tissue framework, and deepening of skin folds. This results in prominence of submandibular and submental tissues. Genetic factors (chronological aging) and extrinsic factors (ultraviolet radiation) both contribute to skin laxity. There are many RF, ultrasound, and light-based devices directed at treating skin laxity. All of these devices target and heat the dermis to induce collagen contraction. Heating of the dermis causes collagen denaturation and immediate collagen contraction in addition to long-term collagen remodeling. Via RF, light, or ultrasound, these skin tightening devices deliver heat to the dermis to create new collagen and induce skin tightening. This chapter will provide an overview of the various skin tightening devices. Copyright © 2011 S. Karger AG, Basel.

Skin colour assessment of replanted fingers in digital images and its reliability for the incorporation of images in nursing progress notes.

PubMed

Terashima, Taiko; Yoshimura, Sadako

2018-03-01

To determine whether nurses can accurately assess the skin colour of replanted fingers displayed as digital images on a computer screen. Colour measurement and clinical diagnostic methods for medical digital images have been studied, but reproducing skin colour on a computer screen remains difficult. The inter-rater reliability of skin colour assessment scores was evaluated. In May 2014, 21 nurses who worked on a trauma ward in Japan participated in testing. Six digital images with different skin colours were used. Colours were scored from both digital images and direct patient's observation. The score from a digital image was defined as the test score, and its difference from the direct assessment score as the difference score. Intraclass correlation coefficients were calculated. Nurses' opinions were classified and summarised. The intraclass correlation coefficients for the test scores were fair. Although the intraclass correlation coefficients for the difference scores were poor, they improved to good when three images that might have contributed to poor reliability were excluded. Most nurses stated that it is difficult to assess skin colour in digital images; they did not think it could be a substitute for direct visual assessment. However, most nurses were in favour of including images in nursing progress notes. Although the inter-rater reliability was fairly high, the reliability of colour reproduction in digital images as indicated by the difference scores was poor. Nevertheless, nurses expect the incorporation of digital images in nursing progress notes to be useful. This gap between the reliability of digital colour reproduction and nurses' expectations towards it must be addressed. High inter-rater reliability for digital images in nursing progress notes was not observed. Assessments of future improvements in colour reproduction technologies are required. Further digitisation and visualisation of nursing records might pose challenges. © 2017 John Wiley & Sons Ltd.

The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials.

PubMed

Petrelli, F; Borgonovo, K; Barni, S

2013-09-01

Skin rash is an early and frequent phenomenon during treatment with anti-epidermal growth factor receptor monoclonal antibodies. The objective of this review is to assess the predictive value of skin rash in patients with advanced colorectal cancer treated with cetuximab and panitumumab. We searched PubMed and ASCO Meetings for publications reporting the correlation of skin rash with survival and/or response rate. Hazard ratios (HRs) with 95% confidence intervals for progression and/or survival, and/or risk ratios (RRs) for response rate in patients with rash were obtained from publications and pooled in a meta-analysis. Fourteen publications (for a total of 3,833 patients) were included in this meta-analysis. The occurrence of skin toxicity represents a predictive factor for survival (HR 0.51; p<0.00001) and progression (HR 0.58; p<0.00001). Similarly, patients who developed moderate or severe rash had an increased chance of response (35 vs 13%; RR 2.23, p<0.00001). The occurrence of skin rash during treatment with cetuximab and panitumumab represents a significant predictor of the efficacy of these drugs. The hypothesis that, in patients who lack substantial skin toxicity, this treatment is not beneficial and requires early discontinuation deserves further study.

Increased expression of enhancer of Zeste Homolog 2 (EZH2) differentiates squamous cell carcinoma from normal skin and actinic keratosis.

PubMed

Xie, Qiang; Wang, Hongbei; Heilman, Edward R; Walsh, Michael G; Haseeb, M A; Gupta, Raavi

2014-01-01

Enhancer of Zeste Homolog 2 (EZH2) is a polycomb group protein that has been shown to be involved in the progression of multiple human cancers including melanoma. The expression of EZH2 in normal skin and in pre-malignant and malignant cutaneous squamous cell carcinoma (SCC) has not been studied. We examined the expression of EZH2 in normal skin, actinic keratosis (AK), SCC in situ, well-differentiated (SCC-WD), moderately-differentiated (SCC-MD) and poorly-differentiated SCC (SCC-PD) to ascertain whether EZH2 expression differentiates these conditions. Immunohistochemical staining for EZH2 was performed on formalin-fixed paraffin-embedded biopsies and a tissue microarray containing normal skin, AK, SCC in situ, and SCC of different grades. In comparison to the normal skin, EZH2 expression in actinic keratosis was increased (p=0.03). Similarly, EZH2 expression in all of the neoplastic conditions studied (SCC in situ, SCC-WD, SCC-MD and SCC-PD) was greatly increased in comparison to both the normal skin and actinic keratosis (p≤0.001). EZH2 expression increases incrementally from normal skin to AK and further to SCC, suggesting a role for EZH2 in the progression and differentiation of SCC. EZH2 expression may be used as a diagnostic marker for differentiating SCC from AK or normal skin.

Cutaneous antigen-stimulating lymphokine production by lymphocytes of patients with progressive systemic sclerosis (scleroderma).

PubMed Central

Kondo, H; Rabin, B S; Rodnan, G P

1976-01-01

Cell-mediated immunity to skin extracts was studied by the macrophage migration inhibition test, lymphocyte transformation, and direct cytotoxicity to skin fibroblasts, in normal individuals and patients with progressive systemic sclerosis. The latter included 18 individuals with diffuse scleroderma and 12 with the CREST syndrome, a variant form of systemic sclerosis in which there is more limited involvement of the skin. Controls consisted of 13 patients with other connective tissue diseases and 16 normal individuals. Phosphate-buffered saline and 3 M KCl extracts of both normal and sclerodermatous skin were used as antigens. No evidence of lymphocyte reactivity was found by the lymphocyte transformation and direct cytotoxicity test procedures. However, the lymphocytes of patients with diffuse scleroderma did respond to extracts of both normal and sclerodermatous skin in the migration inhibition assay. 10 of 16 patients (62.5%) had migration indices below 2 SD of the normal range, 1 of 10 CREST patients and 1 of 13 patients with other connective tissue diseases showed similar reactivity. Antisera specific for immunoglobulin-bearing lymphocytes (B lymphocytes) and T lymphocytes were used to characterize the lymphocytes found in skin biopsies of patients with diffuse scleroderma. T lymphocytes made up the majority of lymphocytes in the skin infiltrates. These findings suggest that lymphocytes sensitized to skin extracts are present in patients with diffuse scleroderma. The cell-mediated immune reaction to skin antigens may be a factor in the pathogenesis of diffuse scleroderma. Images PMID:791970

Progress in the Development of Oxygen Reduction Reaction Catalysts for Low-Temperature Fuel Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Dongguo; Lv, Haifeng; Kang, Yijin

2016-04-06

In this paper, we present a brief summary on the most recent progress in the design of catalysts for electrochemical reduction of oxygen. The main challenge in the wide spread of fuel cell technology is to lower the content of, or even eliminate, Pt and other precious metals in catalysts without sacrificing their performance. Pt-based nanosized catalysts with novel and refined architectures continue to dominate in catalytic performance, and formation of Pt-skin-like surfaces is key to achieving the highest values in activity. Moreover, durability has also been improved in Pt-based systems with addition of Au, which plays an important rolemore » in stabilizing the Pt topmost layers against dissolution. However, various carbon-based materials without precious metal have shown improvement in activity and durability and have been explored to serve as catalyst supports. Finally, understanding how the doped elements interact with each other and/or carbon is challenging and necessary in the design of robust fuel cell catalysts.« less

The oncogenic action of ionizing radiation on rat skin. Final progress report, May 1, 1990--April 30, 1992

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burns, F.J.; Garte, S.J.

1992-12-31

The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/{mu}), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression formore » each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of {sup 14}C-thymidine. The return of these cells to S-phase a second time was detected by a second label ({sup 3}H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The {sup 14}C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with {sup 14}C increased after 42 hr and remained relatively constant thereafter.« less

Progression of leprosy neuropathy: a case series study

PubMed Central

Vital, Robson T; Illarramendi, Ximena; Nascimento, Osvaldo; Hacker, Mariana A; Sarno, Euzenir N; Jardim, Marcia R

2012-01-01

A need still exists to determine the clinical and neurophysiological characteristics of leprosy neuropathy at distinct times of the disease by different methods that measure the various nerve fiber functions. A prospective clinical study was performed with 10 paucibacillary (PB) and 12 multibacillary (MB) patients evaluated at diagnosis and one year after cessation of multidrug therapy (MDT). Peripheral nerve function was assessed clinically and by means of the sympathetic skin response, skin vasomotor reflex, and nerve conduction study (NCS). At diagnosis, 73% of the total 22 patients had nerve function impairment (NFI). Autonomic function (χ2= 5.5, P= 0.019) and NCS (χ2= 7.765, P= 0.01) were significantly more altered in MB than PB patients. At final evaluation, NFI of the MB patients had worsened, especially among the six who had leprosy reaction. As the NFI of PB patients showed improvement, a significant difference between the two groups (χ2= 12.320, P= 0.001) was observed. A high prevalence of neuropathy was observed in newly diagnosed patients. Associating different tests with a thorough clinical neurological evaluation increases detection rates. PMID:22741099

Quantification of loosely associated and tightly associated bacteria on broiler carcass skin using swabbing, stomaching, and grinding methods.

PubMed

Singh, P; Lee, H C; Chin, K B; Ha, S D; Kang, I

2015-12-01

This research was conducted to quantify bacterial populations after swabbing or stomaching, followed by grinding the swabbed or stomached broiler skins. For each of 3 replications, 3 eviscerated broilers were randomly taken from a processing line in a local broiler processing plant. Ten swabs and 10 stomachs per bird were conducted on the left- and the right-side skins (10×7 cm), respectively, which were then finally ground. Results indicated that mesophilic aerobic bacteria (MAB) in the first swabbed sample were significantly lower than those in the first stomached sample (P<0.05), with no difference seen for the remaining sampling times (P>0.05). During 10 swabbings followed by final grinding, 8, 9, and 83% of MAB were detected after the first swabbing, after the second through 10th swabbings, and after final grinding of the skin, respectively. During 10 stomachings followed by the final grinding, 17, 18, and 65% of MAB were detected after the first stomaching, after the second through 10th stomachings, and after final grinding of the skin, respectively. Escherichia coli (E. coli) and coliforms were significantly higher in the first stomaching than those in the first swabbing (P<0.05), with no difference seen between the 2 sampling methods for the rest sampling times (P>0.05). Populations of E. coli and coliforms decreased step-wisely from the highest after grinding to the intermediate after first and second sampling, and to the least after 10th sampling (P<0.05), regardless of swabbing or grinding. In this study, less than 35% of MAB seemed loosely associated in the skin of eviscerated broiler, whereas more than 65% of MAB looked tightly associated, which were not recovered by stomaching or swabbing even 10 times but were recovered by grinding the skin. © 2015 Poultry Science Association Inc.

Granulomatous slack skin syndrome: Report of a unique case.

PubMed

Maheswari, S Uma; Sampath, V; Ramesh, A

2018-01-01

Granulomatous slack skin syndrome is a rare variant of cutaneous T-cell lymphoma (mycosis fungoides). It is characterized clinically by redundant skin folds, which show a predilection towards flexural areas such as the axilla and the groin. Histologically, it shows a granulomatous T-cell infiltrate and loss of elastic tissue. It has an indolent but progressive course; and is usually refractory to treatment. We report a unique case of slack skin syndrome, sparing the classical sites with rapid and unusual involvement of non-intertriginous areas.

Intake of high-fat diet stimulates the risk of ultraviolet radiation-induced skin tumors and malignant progression of papillomas to carcinoma in SKH-1 hairless mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaid, Mudit; Singh, Tripti; Prasad, Ram

Previously, we showed that administration of a high-fat diet (HF-diet) to C57BL/6 mice exacerbates their response to short-term UVB radiation-induced inflammation in the skin. To explore the effects of an HF-diet on UVB-induced tumorigenesis, we have used the SKH-1 hairless mouse model in which the mice are exposed to UVB radiation (180 mJ/cm{sup 2}) three times a week for 24 weeks. The development of UVB-induced skin tumors was rapid and the tumor multiplicity and tumor size were significantly higher (P < 0.01–0.005) in the mice fed an HF-diet than the mice fed a control-diet (C-diet). Moreover, the malignant progression ofmore » UVB-induced papillomas to carcinomas was higher in HF-diet-fed mice. On analysis of tumors and tumor-uninvolved skin samples from the tumor-bearing mice, we found that administration of an HF-diet significantly enhanced the levels of UVB-induced expression of cyclooxygenase-2 (COX-2), prostaglandin E{sub 2} (P < 0.01), and PGE{sub 2} receptors, and activation of NF-κB in the UVB-exposed skin as well as in tumors. In addition the HF-diet enhanced the expression of proinflammatory cytokines, including tumor necrosis factor-α (P < 0.01), interleukin (IL)-1β (P < 0.01) and IL-6 (P < 0.05) in the UVB-exposed skin as well as in tumors. Western blot analysis revealed that HF-diet enhanced the levels of epidermal cell proliferation, phosphatidylinositol 3-kinase and phosphorylation of Akt at Ser{sup 473} in UVB-exposed skin and skin tumors. Collectively, these data demonstrate that the regular consumption of an HF-diet increases the risk of photocarcinogenesis in mice and that this is associated with enhanced expression of inflammatory mediators in the UVB-exposed skin and tumors. - Highlights: • Consumption of high-fat diet increases UVB-induced skin tumor development in mice. • Intake of high-fat diet stimulates progression of UV-induced papilloma to carcinoma. • Intake of high-fat diet enhances inflammation in UV-exposed skin • Regular consumption of low-fat diet may inhibit the risk of photocarcinogenesis.« less

Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways

PubMed Central

Slominski, Andrzej T.; Zmijewski, Michal A.; Semak, Igor; Zbytek, Blazej; Pisarchik, Alexander; Li, Wei; Zjawiony, Jordan; Tuckey, Robert C.

2013-01-01

Skin is the largest body organ forming a metabolically active barrier between external and internal environments. The metabolic barrier is composed of cytochromes P450 (CYPs) that regulate its homeostasis through activation or inactivation of biologically relevant molecules. In this review we focus our attention on local steroidogenic and secosteroidogenic systems in relation to skin cancer, e.g., prevention, attenuation of tumor progression and therapy. The local steroidogenic system is composed of locally expressed CYPs involved in local production of androgens, estrogens, gluco- and mineralo-corticosteroids from cholesterol (initiated by CYP11A1) or from steroid precursors delivered to the skin, and of their metabolism and/or inactivation. Cutaneous 7-hydroxylases (CYP7A1, CYP7B1 and CYP39) potentially can produce 7-hydroxy/oxy-steroids/sterols with modifying effects on local tumorigenesis. CYP11A1 also transforms 7-dehydrocholesterol (7DHC)→22(OH)7DHC→20,22(OH)2-7DHC→7-dehydropregnenolone, which can be further metabolized to other 5,7-steroidal dienes. These 5,7-dienal intermediates are converted by ultraviolet radiation B (UVB) into secosteroids which show pro-differentiation and anti-cancer properties. Finally, the skin is the site of activation of vitamin D3 through two alternative pathways. The classical one involves sequential hydroxylation at positions 25 and 1 to produce active 1,25(OH)2D3, which is further inactivated through hydroxylation at C24. The novel pathway is initiated by CYP11A1 with predominant production of 20(OH)D3 which is further metabolized to biologically active but non-calcemic D3-hydroxyderivatives. Classical and non-classical (novel) vitamin D analogs show pro-differentiation, anti-proliferative and anticancer properties. In addition, melatonin is metabolized by local CYPs. In conclusion cutaneously expressed CYPs have significant effects on skin physiology and pathology trough regulation of its chemical milieu. PMID:23869782

Intensive Care in a Patient with Toxic Epidermal Necrolysis

PubMed Central

Fischer, M.

2017-01-01

Toxic epidermal necrolysis (TEN) is a serious adverse drug reaction with high lethality, which usually requires intensive-medical care. A 44-year-old man developed generalized exanthema with increasing exfoliation and mucosal involvement after taking allopurinol, ibuprofen, and etoricoxib. The clinical diagnosis of TEN was histologically confirmed. Prednisolone therapy with 3 mg/kg body weight (BW) was not able to prevent further progress to finally 80% of the body surface, and infliximab 5 mg/kg BW was given as a single dose. This prevented further progression of the TEN. Despite marked improvement in skin findings, the ICU stay was prolonged by a complex analgosedation, transient kidney failure, volume management, positioning therapy, and vegetatively impeded weaning. Moreover, there was colonization with multiresistant bacteria (MRSA and VRE). Nonetheless, the patient could be restored to health and was released after four weeks. Infliximab seems to be effective in the treatment of TEN, especially in cases of rapid progression. Moreover, patients with TEN are difficult to handle in intensive-medical care, whereby attention should especially be paid to sufficient pain therapy, and the positioning of the patient is a particular challenge. PMID:29225976

Topical stabilized retinol treatment induces the expression of HAS genes and HA production in human skin in vitro and in vivo.

PubMed

Li, Wen-Hwa; Wong, Heng-Kuan; Serrano, José; Randhawa, Manpreet; Kaur, Simarna; Southall, Michael D; Parsa, Ramine

2017-05-01

Skin Aging manifests primarily with wrinkles, dyspigmentations, texture changes, and loss of elasticity. During the skin aging process, there is a loss of moisture and elasticity in skin resulting in loss of firmness finally leading to skin sagging. The key molecule involved in skin moisture is hyaluronic acid (HA), which has a significant water-binding capacity. HA levels in skin decline with age resulting in decrease in skin moisture, which may contribute to loss of firmness. Clinical trials have shown that topically applied ROL effectively reduces wrinkles and helps retain youthful appearance. In the current study, ROL was shown to induce HA production and stimulates the gene expression of all three forms of hyaluronic acid synthases (HAS) in normal human epidermal keratinocytes monolayer cultures. Moreover, in human skin equivalent tissues and in human skin explants, topical treatment of tissues with a stabilized-ROL formulation significantly induced the gene expression of HAS mRNA concomitant with an increased HA production. Finally, in a vehicle-controlled human clinical study, histochemical analysis confirmed increased HA accumulation in the epidermis in ROL-treated human skin as compared to vehicle. These results show that ROL increases skin expression of HA, a significant contributing factor responsible for wrinkle formation and skin moisture, which decrease during aging. Taken together with the activity to increase collagen, elastin, and cell proliferation, these studies establish that retinol provides multi-functional activity for photodamaged skin.

Recent advances in understanding vitiligo.

PubMed

Manga, Prashiela; Elbuluk, Nada; Orlow, Seth J

2016-01-01

Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.

Depigmentation therapy in vitiligo universalis with cryotherapy and 4-hydroxyanisole.

PubMed

Di Nuzzo, S; Masotti, A

2010-03-01

Vitiligo is a disease characterized by the loss of melanocytes, resulting in progressive depigmentation of skin, and areas of normally pigmented skin can be of cosmetic concern. Several options have been tried to remove the pigment and make the skin a more even colour. We present an easy and effective therapeutic procedure based on single-session cryotherapy followed by topical 4-hydroxyanisole (4-HA).

Failure of Ibuprofen to prevent progressive dermal ischemia after burning in guinea pigs.

PubMed

Tan, Qian; Lin, Zihao; Ma, Wenxi; Chen, Huairen; Wang, Lei; Ning, Guansen; Zhou, Xu

2002-08-01

It is controversial whether the use of prostaglandin inhibitors could prevent progressive dermal ischemia in the postburn stasis zone. This study evaluated the effect of Ibuprofen on preventing postburn dermal ischemia using an animal model of India ink perfusion and skin transparent preparation techniques. The closely clipped backs of the guinea pigs were bathed in 75 degrees C water for 10s. Ibuprofen-treated groups were fed intragastrically with Ibuprofen (12.5mg/kg) every 6h. All animals were perfused with 70% India ink via a cervical artery cannula at 16 kPa constant pressure at 0, 8, 16, 24h postburn. Skin transparent preparations were made, and 6-keto-PGF(1 alpha) and T x B(2) levels in skin tissue were assessed. India ink filling rates in skin capillary plexuses decreased gradually with postburn time elapsing (P<0.01). 6-keto-PGF(1 alpha) and T x B(2) levels in two groups increased. The increase of T x B(2) was dominant, which was related to postburn dermal ischemia (r=0.742, P<0.01). Though levels of 6-keto-PGF(1 alpha) and T x B(2) decreased in Ibuprofen-treated groups, India ink filling rates showed no significant difference between controls and experimental groups (P>0.05). The results were also confirmed by observation of skin transparent preparations. This study suggests that Ibuprofen has no preventive effect on progressive dermal ischemia after burning.

Cell Therapy in Dermatology

PubMed Central

Petrof, Gabriela; Abdul-Wahab, Alya; McGrath, John A.

2014-01-01

Harnessing the regenerative capacity of keratinocytes and fibroblasts from human skin has created new opportunities to develop cell-based therapies for patients. Cultured cells and bioengineered skin products are being used to treat patients with inherited and acquired skin disorders associated with defective skin, and further clinical trials of new products are in progress. The capacity of extracutaneous sources of cells such as bone marrow is also being investigated for its plasticity in regenerating skin, and new strategies, such as the derivation of inducible pluripotent stem cells, also hold great promise for future cell therapies in dermatology. This article reviews some of the preclinical and clinical studies and future directions relating to cell therapy in dermatology, particularly for inherited skin diseases associated with fragile skin and poor wound healing. PMID:24890834

Autophagy in human skin fibroblasts: Comparison between young and aged cells and evaluation of its cellular rhythm and response to Ultraviolet A radiation.

PubMed

Pernodet, Nadine; Dong, Kelly; Pelle, Edward

2016-01-01

Autophagic mechanisms play critical roles in cell maintenance. Damaged organelles that are not removed by autophagosomes, which act by engulfing and degrading these cellular components, have been linked to various pathologies. Recently, the progression of aging has also been correlated to a compromised autophagic response. Here, we report for the first time a significant reduction in autophagic levels in synchronized aged normal human skin fibroblasts as compared to young fibroblasts. We measured a 77.9% reduction in autophagy as determined by reverse transcription-polymerase chain reaction for LC3B expression, a microtubule-associated protein correlated to late stage autophagosome formation. In addition, we visualized these same changes by immunocytofluorescence with antibodies directed against LC3B. By harvesting synchronized, as well as unsynchronized cells over time, we were also able to measure for the first time a nighttime peak in autophagy that was present in young but absent in aged fibroblasts. Finally, since human skin is constantly subjected to environmentally induced oxidative stress from sunlight, we exposed fibroblasts to 10 J/cm2 ultraviolet A and found, in good agreement with current literature, not only that irradiation could partially reactivate autophagy in the aged cells, but also that this increase was phase shifted earlier from its endogenous temporal pattern because of its loss of synchronization with circadian rhythm.

Purification and characterization of novel antioxidant peptides from enzymatic hydrolysates of tilapia (Oreochromis niloticus) skin gelatin.

PubMed

Zhang, Yufeng; Duan, Xiu; Zhuang, Yongliang

2012-11-01

To obtain hydrolysates with high degree of hydrolysis (DH) and scavenging radical activity, tilapia skin gelatin (TSG) was hydrolyzed by properase E and multifect neutral. The optimum hydrolysis condition of each enzyme was determined using the orthogonal experiment, and double-enzyme hydrolysis was further applied. The results showed the tilapia skin gelatin hydrolysate (TSGH) obtained by progressive hydrolysis using multifect neutral and properase E had the highest DH and hydroxyl radical scavenging activity. The IC(50) values of TSGH on scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide anion radical (·O(2)) and hydroxyl radical (·OH) activities were also determined. TSGH was further purified using gel filtration chromatography, ion exchange chromatography, and RP-HPLC. The peptides were identified using nano-LC-ESI mass spectrometry. Finally, two antioxidant peptides were identified and the amino acid sequences were Glu-Gly-Leu (317.33 Da) and Tyr-Gly-Asp-Glu-Tyr (645.21 Da), respectively. The IC(50) values of two peptides on hydroxyl radical scavenging activities were 4.61 μg mL(-1)and 6.45 μg mL(-1), respectively. Therefore, the results demonstrated that the hydrolysates of TSG prepared by multifect neutral and properase E could serve as a source of peptides with high antioxidant activity. It provided a scientific basis for the preparation of antioxidant peptides. Copyright © 2012 Elsevier Inc. All rights reserved.

Warm hands, cold heart: progressive whole-body cooling increases warm thermosensitivity of human hands and feet in a dose-dependent fashion.

PubMed

Filingeri, Davide; Morris, Nathan B; Jay, Ollie

2017-01-01

What is the central question of this study? Investigations on inhibitory/facilitatory modulation of vision, touch and pain show that conditioning stimuli outside the receptive field of testing stimuli modulate the central processing of visual, touch and painful stimuli. We asked whether contextual modulation also exists in human temperature integration. What is the main finding and its importance? Progressive decreases in whole-body mean skin temperature (the conditioning stimulus) significantly increased local thermosensitivity to skin warming but not cooling (the testing stimuli) in a dose-dependent fashion. In resembling the central mechanisms underlying endogenous analgesia, our findings point to the existence of an endogenous thermosensory system in humans that could modulate local skin thermal sensitivity to facilitate thermal behaviour. Although inhibitory/facilitatory central modulation of vision and pain has been investigated, contextual modulation of skin temperature integration has not been explored. Hence, we tested whether progressive decreases in whole-body mean skin temperature (T sk ; a large conditioning stimulus) alter the magnitude estimation of local warming and cooling stimuli applied to hairy and glabrous skin. On four separate occasions, eight men (27 ± 5 years old) underwent a 30 min whole-body cooling protocol (water-perfused suit; temperature, 5°C), during which a quantitative thermosensory test, consisting of reporting the perceived magnitude of warming and cooling stimuli (±8°C from 30°C baseline) applied to the hand (palm/dorsum) and foot (sole/dorsum), was performed before cooling and every 10 min thereafter. The cooling protocol resulted in large progressive reductions in T sk [10 min, -3.36°C (95% confidence interval -2.62 to -4.10); 20 min, -5.21°C (-4.47 to -5.95); and 30 min, -6.32°C (-5.58 to -7.05); P < 0.001], with minimal changes (∼0.08°C) in rectal temperature. While thermosensitivity to local skin cooling remained unchanged (P = 0.831), sensitivity to skin warming increased significantly at each level of T sk for all skin regions [10 min, +4.9% (-1.1 to +11.0); 20 min, +6.1% (+0.1-12.2); and 30 min, +7.9% (+1.9-13.9); P = 0.009]. Linear regression indicated a 1.2% °C -1 increase in warm thermosensitivity with whole-body skin cooling. Overall, large decreases in T sk significantly facilitated warm but not cold sensory processing of local thermal stimuli, in a dose-dependent fashion. In highlighting a novel feature of human temperature integration, these findings point to the existence of an endogenous thermosensory system that could modulate local skin thermal sensitivity in relationship to whole-body thermal states. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Treatment of tissue extravasation by antitumor agents.

PubMed

Larson, D L

1982-05-01

Infiltration of antitumor agents into subcutaneous tissues may either result in a local area of self-resolving inflammation, or progress to full-thickness loss of skin and underlying vital structures. The immediate treatment of 50 extravasations occurring over a 20-month period resulted in our developing a protocol of appropriate care. Once extravasation is suspected, the intravenous line is removed, ice is applied intermittently for three days, and the wound is observed closely. No drugs are even given locally. If local pain persists or skin changes progress, the area of involvement is debrided and, a skin graft is applied two to three days later. As a result of this conservative approach, only 12 of 50 patients have required surgery. This method of treatment has minimized patient mortality, hospitalizations, and loss of synchronization of chemotherapy.

Successful oral desensitization against skin rash induced by alectinib in a patient with anaplastic lymphoma kinase-positive lung adenocarcinoma: A case report.

PubMed

Shirasawa, Masayuki; Kubotaa, Masaru; Harada, Shinya; Niwa, Hideyuki; Kusuhara, Seiichiro; Kasajima, Masashi; Hiyoshi, Yasuhiro; Ishihara, Mikiko; Igawa, Satoshi; Masuda, Noriyuki

2016-09-01

Alectinib has been approved for the treatment of patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive advanced non-small cell lung cancer. In terms of adverse effects, the occurrence of a severe skin rash induced by alectinib is reportedly rare, compared with the occurrence of skin rash induced by epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In the present case report, a 76-year-old woman with ALK-positive lung adenocarcinoma experienced disease progression after undergoing first-line chemotherapy. Subsequently, alectinib was administered as a second-line therapy. However, she discontinued alectinib therapy after 11days because of the occurrence of an alectinib-induced skin rash. Since the skin rash improved within one week, we attempted to perform oral desensitization to alectinib. The patient has not shown any recurrence of the rash or disease progression for 7 months since the successful oral desensitization to alectinib. Here, we describe the first case of successful oral desensitization against a skin rash induced by alectinib in a patient with ALK-positive lung adenocarcinoma. Desensitization to overcome adverse effects and to enable sustained treatment with alectinib should be considered in patients who develop alectinib sensitivities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Recent progress in tissue optical clearing for spectroscopic application

NASA Astrophysics Data System (ADS)

Sdobnov, A. Yu.; Darvin, M. E.; Genina, E. A.; Bashkatov, A. N.; Lademann, J.; Tuchin, V. V.

2018-05-01

This paper aims to review recent progress in optical clearing of the skin and over naturally turbid biological tissues and blood using this technique in vivo and in vitro with multiphoton microscopy, confocal Raman microscopy, confocal microscopy, NIR spectroscopy, optical coherence tomography, and laser speckle contrast imaging. Basic principles of the technique, its safety, advantages and limitations are discussed. The application of optical clearing agent on a tissue allows for controlling the optical properties of tissue. Optical clearing-induced reduction of tissue scattering significantly facilitates the observation of deep-located tissue regions, at the same time improving the resolution and image contrast for a variety of optical imaging methods suitable for clinical applications, such as diagnostics and laser treatment of skin diseases, mucosal tumor imaging, laser disruption of pathological abnormalities, etc. Structural images of different skin layers obtained ex vivo for porcine ear skin samples at application of Omnipaque™ and glycerol solutions during 60 min. Red color corresponds to TPEAF signal channel. Green color corresponds to SHG signal channel.

Kindler syndrome: extension of FERMT1 mutational spectrum and natural history.

PubMed

Has, Cristina; Castiglia, Daniele; del Rio, Marcela; Diez, Marta Garcia; Piccinni, Eugenia; Kiritsi, Dimitra; Kohlhase, Jürgen; Itin, Peter; Martin, Ludovic; Fischer, Judith; Zambruno, Giovanna; Bruckner-Tuderman, Leena

2011-11-01

Mutations in the FERMT1 gene (also known as KIND1), encoding the focal adhesion protein kindlin-1, underlie the Kindler syndrome (KS), an autosomal recessive skin disorder with an intriguing progressive phenotype comprising skin blistering, photosensitivity, progressive poikiloderma with extensive skin atrophy, and propensity to skin cancer. Herein we review the clinical and genetic data of 62 patients, and delineate the natural history of the disorder, for example, age at onset of symptoms, or risk of malignancy. Although most mutations are predicted to lead to premature termination of translation, and to loss of kindlin-1 function, significant clinical variability is observed among patients. There is an association of FERMT1 missense and in-frame deletion mutations with milder disease phenotypes, and later onset of complications. Nevertheless, the clinical variability is not fully explained by genotype-phenotype correlations. Environmental factors and yet unidentified modifiers may play a role. Better understanding of the molecular pathogenesis of KS should enable the development of prevention strategies for disease complications. © 2011 Wiley Periodicals, Inc.

TRPV3 in Drug Development

PubMed Central

Broad, Lisa M.; Mogg, Adrian J.; Eberle, Elizabeth; Tolley, Marcia; Li, Dominic L.; Knopp, Kelly L.

2016-01-01

Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP (Transient Receptor Potential) super-family. It is a relatively underexplored member of the thermo-TRP sub-family (Figure 1), however, genetic mutations and use of gene knock-outs and selective pharmacological tools are helping to provide insights into its role and therapeutic potential. TRPV3 is highly expressed in skin, where it is implicated in skin physiology and pathophysiology, thermo-sensing and nociception. Gain of function TRPV3 mutations in rodent and man have enabled the role of TRPV3 in skin health and disease to be particularly well defined. Pre-clinical studies provide some rationale to support development of TRPV3 antagonists for therapeutic application for the treatment of inflammatory skin conditions, itch and pain. However, to date, only one compound directed towards block of the TRPV3 receptor (GRC15300) has progressed into clinical trials. Currently, there are no known clinical trials in progress employing a TRPV3 antagonist. PMID:27618069

Vitamin D Levels and Related Genetic Polymorphisms, Sun Exposure, Skin Color, and Risk of Aggressive Prostate Cancer

DTIC Science & Technology

2011-07-01

sun exposure, and dietary calcium and vitamin D intake are ascertained. Finally, the melanin content of the skin is measured using a skin reflectance...meter called a Dermaspectrometer, to measure baseline skin melanin content, which is known to inhibit vitamin D synthesis from sunlight. This...three hospitals in Chicago, along with demographic and medical information, BMI, and skin melanin content using a portable narrow-band reflectometer

Novel Molecular Therapies for Heritable Skin Disorders

PubMed Central

Uitto, Jouni; Christiano, Angela M.; Irwin McLean, W. H.; McGrath, John A.

2013-01-01

Tremendous progress has been made in the past two decades in molecular genetics of heritable skin diseases, and pathogenic mutations have been identified in as many as 500 distinct human genes. This progress has resulted in improved diagnosis with prognostic implications, refined genetic counseling, and has formed the basis for prenatal and presymptomatic testing as well as preimplantation genetic diagnosis. However, there has been relatively little progress in developing effective and specific treatments for these often devastating diseases. Very recently, however, a number of novel molecular strategies, including gene therapy, cell-based approaches, and protein replacement therapy have been explored for treatment of these conditions. This overview will focus on the prototypic heritable blistering disorders, epidermolysis bullosa and related keratinopathies, in which significant progress has been recently made towards treatment, and illustrate how some of the translational research therapies have already entered the clinical arena. PMID:22158553

Necrotizing Fasciitis: How Reliable are the Cutaneous Signs?

PubMed Central

Kiat, Ho Jun; En Natalie, Yap Hui; Fatimah, Lateef

2017-01-01

Necrotizing fasciitis (NF) is a surgical emergency. It is often aggressive and characterized by the rapidly progressive inflammatory infection of the fascia that causes extensive necrosis of the subcutaneous tissue and fascia, relatively sparing the muscle and skin tissue. As the disease progresses, thrombosis of the affected cutaneous perforators subsequently devascularizes the overlying skin. The course indeed can be a fulminant one. The diagnosis of NF, especially in the early stages, is extremely challenging, and it can be very close in presentation to other skin and subcutaneous tissue infections. The primary site of the pathology is the deep fascia. Necrosis of the tissues and fascia may manifest as erythema without sharp margins, swelling, warmth, shiny, and exquisitely tender areas. Pain out of proportion to physical examination findings may be observed. The subcutaneous tissue may be firm and indurated such that the underlying muscle groups cannot be distinctly palpated. Eventually, as the overlying skin is stripped of its blood supply, skin necrosis ensues and hemorrhagic bullae form. Bacteremia and sepsis invariably develop when the infection is well established. This paper discusses some of issues related to the cutaneous signs found in NF and also provides a review the current, available literature on the subject matter. PMID:29097860

Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression.

PubMed

Richman, Erin L; Stampfer, Meir J; Paciorek, Alan; Broering, Jeanette M; Carroll, Peter R; Chan, June M

2010-03-01

Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004-2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.

Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression1234

PubMed Central

Richman, Erin L; Stampfer, Meir J; Paciorek, Alan; Broering, Jeanette M; Carroll, Peter R; Chan, June M

2010-01-01

Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk. PMID:20042525

An objective assessment of melanin in vitiligo skin treated with Balneo PUVA therapy.

PubMed

Hegyi, V; Petrovajová, M; Novotný, M

2014-02-01

Visual clinical methods of skin color evaluation for diagnostic purposes are so far mostly subjective and thus inaccurate. We present a modified method of melanin amount measurement based on diffuse reflectance spectroscopy (DRS). This method is non-invasive and objective, and allows easy quantification and comparison of melanin levels. Skin pigmentation was measured by DRS method in 0-18 year old patients at the Department of Pediatric Dermatovenerology, School of Medicine Comenius University Bratislava. Patients were treated for their vitiligo by Balneo PUVA treatment twice weekly. Each patient had measured his remittance spectra from the treated vitiliginous skin before the treatment was started, after 10 irradiations of Balneo PUVA and at the end of the treatment after 25 irradiations of Balneo PUVA. In our study as a reference skin for spectroscopic assessment of melanin in vivo was used the averaged remittance spectra (measured on the inner arm) from the sample of 10 albino patients. The remittance spectra obtained from the vitiligo patients were ratioed against the newly described remittance reference albino skin. We exploited the linear behavior of the spectral curve in the 620-720 nm interval (significant for melanin absorption) and used the slope of the regression line to compute the quantification index α. By clinical examination before the Balneo PUVA therapy, after the 10th dose of Balneo PUVA therapy as well as at the end of the complete course of Balneo PUVA therapy (after 25 irradiations) we recorded a marked increase of pigmentation in all treated patients for their vitiligo. In each patient the values of melanin quantification angle α were calculated. Statistically we found a significant difference between the melanin quantification angle α in vitiliginous skin before, during the 10th dose of treatment and after the treatment. Similar significant difference was also observed between treated and non-involved skin. We could confirm a clear association between clinical visual examination of treated vitiligo lesions, objective data collected by DRS and melanin quantification angle α. By using a new standard for the reference skin (albino skin) we could more exactly compare melanin levels in different subjects. Our proposed melanin quantification angle α expresses the extent of the difference in melanin levels between the examined skin lesions. We successfully used this index to quantify the variations of melanin (progress of repigmentation) throughout different stages of treatment of the same lesion and also to objectively evaluate the final effect of the therapy. In the present study, we showed that the diffuse reflectance spectroscopy (DRS) may be suitable method to measure skin colour and the content of human skin melanin in vivo. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Joint and tendon involvement predict disease progression in systemic sclerosis: a EUSTAR prospective study.

PubMed

Avouac, Jérôme; Walker, Ulrich A; Hachulla, Eric; Riemekasten, Gabriela; Cuomo, Giovanna; Carreira, Patricia E; Caramaschi, Paola; Ananieva, Lidia P; Matucci-Cerinic, Marco; Czirjak, Laszlo; Denton, Christopher; Ladner, Ulf Müller; Allanore, Yannick

2016-01-01

To determine whether joint synovitis and tendon friction rubs (TFRs) can predict the progression of systemic sclerosis (SSc) over time. We performed a prospective cohort study that included 1301 patients with SSc from the EUSTAR database with disease duration ≤3 years at inclusion and with a follow-up of at least 2 years. Presence or absence at clinical examination of synovitis and TFRs was extracted at baseline. Outcomes were skin, cardiovascular, renal and lung progression. Overall disease progression was defined according to the occurrence of at least one organ progression. Joint synovitis (HR: 1.26, 95% CI 1.01 to 1.59) and TFRs (HR: 1.32, 95% CI 1.03 to 1.70) were independently predictive of overall disease progression, as were also the diffuse cutaneous subset (HR: 1.30, 95% CI 1.05 to 1.61) and positive antitopoisomerase-I antibodies (HR: 1.25, 95% CI 1.02 to 1.53). Regarding skin progression, joint synovitis (HR: 1.67, 95% CI 1.06 to 2.64) and TFRs (HR: 1.69, 95% CI 1.02 to 2.77) were also independently predictive of worsening of the modified Rodnan skin score. For cardiovascular progression, joint synovitis was predictive of the occurrence of new digital ulcer(s) (HR: 1.45, 95% CI 1.08 to 1.96) and decreased left ventricular ejection fraction (HR: 2.20, 95% CI 1.06 to 4.57); TFRs were confirmed to be an independent predictor of scleroderma renal crisis (HR: 2.33, 95% CI 1.03 to 6.19). Joint synovitis and TFRs are independent predictive factors for disease progression in patients with early SSc. These easily detected clinical markers may be useful for the risk stratification of patients with SSc. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Association between serum ligands and the skin toxicity of anti-epidermal growth factor receptor antibody in metastatic colorectal cancer.

PubMed

Takahashi, Naoki; Yamada, Yasuhide; Furuta, Koh; Nagashima, Kengo; Kubo, Akiko; Sasaki, Yusuke; Shoji, Hirokazu; Honma, Yoshitaka; Iwasa, Satoru; Okita, Natsuko; Takashima, Atsuo; Kato, Ken; Hamaguchi, Tetsuya; Shimada, Yasuhiro

2015-05-01

Skin toxicity is a known clinical signature used to predict the prognosis of anti-epidermal growth factor receptor (EGFR) antibody treatment in metastatic colorectal cancer (mCRC). There are no biological markers to predict skin toxicity before anti-EGFR antibody treatment in mCRC patients. Between August 2008 and August 2011, pretreatment serum samples were obtained from KRAS wild-type (WT) patients who received anti-EGFR antibody treatment. Serum levels of ligands were measured by ELISA. A total of 103 KRAS WT patients were enrolled in the study. Progression-free survival and overall survival of patients with a high grade (grade 2-3) of skin toxicity were significantly longer than those with a low grade (grade 0-1) of skin toxicity (median progression-free survival, 6.4 months vs 2.4 months, P < 0.001; median overall survival, 14.6 months vs 7.1 months, P = 0.006). There were significant differences in distribution of serum levels of epiregulin (EREG), amphiregulin (AREG), and hepatocyte growth factor (HGF) between groups of low/high grade of skin toxicity (P < 0.048, P < 0.012, P < 0.012, respectively). In addition, serum levels of HGF, EREG, and AREG were inversely proportional to grades of skin toxicity as determined by the Cochran-Armitage test (P = 0.019, P = 0.047, P = 0.021, respectively). Our study indicated that serum levels such as HGF, EREG, and AREG may be significant markers to predict the grade of skin toxicity and the prognosis of anti-EGFR antibody treatment, which contribute to improvement of the management of skin toxicity and survival time in mCRC patients. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Progression of Mouse Skin Carcinogenesis Is Associated with Increased Erα Levels and Is Repressed by a Dominant Negative Form of Erα

PubMed Central

Michalopoulos, Ioannis; Sideridou, Maria; Tsimaratou, Katerina; Christodoulou, Ioannis; Pyrillou, Katerina; Gorgoulis, Vassilis; Vlahopoulos, Spiros; Zoumpourlis, Vassilis

2012-01-01

Estrogen receptors (ER), namely ERα and ERβ, are hormone-activated transcription factors with an important role in carcinogenesis. In the present study, we aimed at elucidating the implication of ERα in skin cancer, using chemically-induced mouse skin tumours, as well as cell lines representing distinct stages of mouse skin oncogenesis. First, using immunohistochemical staining we showed that ERα is markedly increased in aggressive mouse skin tumours in vivo as compared to the papilloma tumours, whereas ERβ levels are low and become even lower in the aggressive spindle tumours of carcinogen-treated mice. Then, using the multistage mouse skin carcinogenesis model, we showed that ERα gradually increases during promotion and progression stages of mouse skin carcinogenesis, peaking at the most aggressive stage, whereas ERβ levels only slightly change throughout skin carcinogenesis. Stable transfection of the aggressive, spindle CarB cells with a dominant negative form of ERα (dnERα) resulted in reduced ERα levels and reduced binding to estrogen responsive elements (ERE)-containing sequences. We characterized two highly conserved EREs on the mouse ERα promoter through which dnERα decreased endogenous ERα levels. The dnERα-transfected CarB cells presented altered protein levels of cytoskeletal and cell adhesion molecules, slower growth rate and impaired anchorage-independent growth in vitro, whereas they gave smaller tumours with extended latency period of tumour onset in vivo. Our findings suggest an implication of ERα in the aggressiveness of spindle mouse skin cancer cells, possibly through regulation of genes affecting cell shape and adhesion, and they also provide hints for the effective targeting of spindle cancer cells by dnERα. PMID:22870269

Progression of mouse skin carcinogenesis is associated with the orchestrated deregulation of mir-200 family members, mir-205 and their common targets.

PubMed

Skourti, Elena; Logotheti, Stella; Kontos, Christos K; Pavlopoulou, Athanasia; Dimoragka, Paraskevi T; Trougakos, Ioannis P; Gorgoulis, Vassilis; Scorilas, Andreas; Michalopoulos, Ioannis; Zoumpourlis, Vassilis

2016-08-01

MicroRNAs are small, non-coding RNAs which regulate post-transcriptionally hundreds of target mRNAs. Given that their expression is deregulated in several cancer types, they represent potential diagnostic, prognostic, and predictive biomarkers, as well as next-generation therapeutic targets. Nevertheless, the involvement of miRNAs in non-melanoma skin cancer, a cancer type with increasing prevalence, is not extensively studied, and their comprehensive characterization as regard to the initiation, promotion, and progression stages is missing. To this end, we exploited a well-established multistage mouse skin carcinogenesis model in order to identify miRNAs consistently implicated in different stages of skin carcinogenesis. The cell lines comprising this model were subjected to miRNA expression profiling using microarrays, followed by bioinformatics analysis and validation with Q-PCR, as well as treatment with miRNA modulators. We showed that among all deregulated miRNAs in our system, only a functionally coherent group consisting of the miR-200 family members and miR-205-5p displays a pattern of progressive co-downregulation from the early toward the most aggressive stages of carcinogenesis. Their overlapping, co-regulated putative targets are potentially inter-associated and, of these, the EMT-related Rap1a is overexpressed toward aggressive stages. Ectopic expression of miR-205-5p in spindle cancer cells reduces Rap1a, mitigates cell invasiveness, decreases proliferation, and delays tumor onset. We conclude that deregulation of this miRNA group is primarily associated with aggressive phenotypes of skin cancer cells. Restoration of the miR-205-5p member of this group in spindle cells reduces the expression of critical, co-regulated targets that favor cancer progression, thus reversing the EMT characteristics. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Natural infection of guinea pigs exposed to patients with highly drug-resistant tuberculosis

PubMed Central

Dharmadhikari, Ashwin S.; Basaraba, Randall J.; Van Der Walt, Martie L.; Weyer, Karin; Mphahlele, Matsie; Venter, Kobus; Jensen, Paul A.; First, Melvin W.; Parsons, Sydney; McMurray, David N.; Orme, Ian M.; Nardell, Edward A.

2012-01-01

A natural TB infection model using guinea pigs may provide useful information for investigating differences in transmission efficiency and establishment of active disease by clinical TB strains in a highly susceptible host under controlled environmental conditions. We sought to examine the capacity of naturally transmitted multidrug-resistant M. tuberculosis to establish infection and produce active disease in guinea pigs. Guinea pigs were continuously exposed for 4 months to the exhaust air of a 6-bed multidrug-resistant tuberculosis inpatient hospital ward in South Africa. Serial tuberculin skin test reactions were measured to determine infection. All animals were subsequently evaluated for histologic disease progression at necropsy. Although 75% of the 362 exposed guinea pigs had positive skin test reactions [≥6mm], only 12% had histopathologic evidence of active disease. Reversions (≥ 6 mm change) in skin test reactivity were seen in 22% of animals, exclusively among those with reactions of 6 to 13 mm. Only two of 86 guinea pigs with reversion had histological evidence of disease compared to 47% (31/66) of guinea pigs with large, non-reverting reactions. Immunosuppression of half the guinea pigs across all skin test categories did not significantly accelerate disease progression. In guinea pigs that reverted a skin test, a second positive reaction in 27 (33%) of them strongly suggested re-infection due to ongoing exposure. These results show that a large majority of guinea pigs naturally exposed to human-source strains of multidrug-resistant tuberculosis became infected, but that many resolved their infection and a large majority failed to progress to detectable disease. PMID:21478054

A case of rectal carcinoma with skin and bone marrow metastasis with concurrent extensive visceral involvement; unusual and dismal co-incidence.

PubMed

Arslan, Cagatay; Sen, Cenk Ahmet; Ortac, Ragip

2015-06-01

Novel systemic therapies and modern surgical and ablative approaches have improved the survival rates for the patients with metastatic colorectal cancer. However, there are still patients with poor prognosis and underlying mechanisms that could not be defined clearly. Metastatic colorectal cancer patients with skin metastasis have a poor prognosis. A 45-year-old man, who presented with large bowel obstruction, was diagnosed with metastatic rectal adenocarcinoma. Unresectable liver metastases were found at diagnosis. FOLFOX plus bevacizumab treatment was started, but the patient developed bowel obstruction after the third cycle. Therefore, ileostomy was performed. Multiple skin, lung, liver and bone metastases appeared during that time. Bone marrow biopsy demonstrated diffuse infiltration by adenocarcinoma cells. Even though partial remission was achieved after 4 cycles of FOLFIRI-cetuximab, the disease progressed after the 8th cycle. The patient lost his life due to disease progression 8 months after the diagnosis. Bone marrow and skin are unusual sites of metastasis for colorectal carcinoma. Metastases in bone marrow and skin develop at later stages of metastatic disease. This patient lived only 4 months after the development of skin and bone marrow metastases. Skin and bone marrow metastases may be the harbingers of short survival. Biopsy of metastatic sites is crucial for diagnosis and detailed molecular analysis. Molecular pathway alterations underlying worse disease course may be found, and hence probable targets for drug improvement may be indicated.

CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo

PubMed Central

Rashighi, Mehdi; Agarwal, Priti; Richmond, Jillian M; Harris, Tajie H; Dresser, Karen; Su, Mingwan; Zhou, Youwen; Deng, April; Hunter, Chris A; Luster, Andrew D; Harris, John E

2014-01-01

Vitiligo is an autoimmune disease of the skin that results in disfiguring white spots. There are no FDA-approved treatments for vitiligo, and most off-label treatments yield unsatisfactory results. Vitiligo patients have increased numbers of autoreactive, melanocyte-specific CD8+ T cells in the skin and blood, which are directly responsible for melanocyte destruction. Here we report that gene expression in lesional skin from vitiligo patients reveals an IFN-γ-specific signature, including the chemokine CXCL10. CXCL10 is elevated in both vitiligo patient skin and serum and CXCR3, its receptor, is expressed on pathogenic T cells. To address the function of CXCL10 in vitiligo, we employed a mouse model of disease that also exhibits an IFN-γ-specific gene signature, expression of CXCL10 in the skin, and upregulation of CXCR3 on antigen-specific T cells. Mice that receive Cxcr3−/− T cells develop minimal depigmentation, as do mice lacking Cxcl10 or treated with CXCL10 neutralizing antibody. CXCL9 promotes autoreactive T cell global recruitment to the skin but not effector function while, in contrast, CXCL10 is required for effector function and localization within the skin. Surprisingly, CXCL10 neutralization in mice with established, widespread depigmentation induces reversal of disease, evidenced by repigmentation. These data identify a critical role for CXCL10 in both the progression and maintenance of vitiligo, and thereby support inhibiting CXCL10 as a targeted treatment strategy. PMID:24523323

Potential skin involvement in ALS: revisiting Charcot's observation - a review of skin abnormalities in ALS.

PubMed

Paré, Bastien; Gros-Louis, François

2017-07-26

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons of the brain and spinal cord, leading to progressive paralysis and death. Interestingly, many skin changes have been reported in ALS patients, but never as yet fully explained. These observations could be due to the common embryonic origin of the skin and neural tissue known as the ectodermal germ layer. Following the first observation in ALS patients' skin by Dr Charcot in the 19th century, in the absence of bedsores unlike other bedridden patients, other morphological and molecular changes have been observed. Thus, the skin could be of interest in the study of ALS and other neurodegenerative diseases. This review summarizes skin changes reported in the literature over the years and discusses about a novel in vitro ALS tissue-engineered skin model, derived from patients, for the study of ALS.

A Single-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of the Effectiveness of ANT1 Soybean Extract Cream on Skin Recovery After Nd: YAG Laser Treatment.

PubMed

Hsieh, Meng-Chien; Wu, Yi-Chia; Huang, Shu-Hung; Kuo, Yur-Ren; Lee, Su-Shin

2018-02-01

Nd:YAG laser has been used extensively for its versatility in treating many common aesthetic problems, but numerous adverse effects are often complained by recipients of Nd:YAG laser. This study introduces the ANT1 soybean extract cream, which was formulated to alleviate adverse effects after laser therapy. This study explores whether ANT1 enhances the repair mechanism of the postlaser skin, decreases laser-induced complication, and shortens recovery time. The study also aims to pinpoint the ANT1 concentration that is most effective in improving the skin condition after Nd-YAG laser therapy. This study was a single-center, randomized, double-blind, placebo-controlled trial. Patients eligible for the study were Asian women, aged 25 to 40 years, who were free of dermatological diseases and allergic reaction. There were a total of 45 subjects. Each subject received a session of Nd-YAG laser therapy every 2 weeks, totaling 3 sessions. Facial skin assessment was achieved via VISIA complexion analysis. VISIA complexion analysis quantitatively assessed the skin condition and tracked the recovery progress of each subject at baseline, immediately after all 3 laser sessions, and a week after the final laser treatment. Skin condition was evaluated by VISIA complexion analysis. Skin condition was recorded in aspects of pigmented spots, wrinkles, texture, pores, and red area. After Nd-YAG laser therapy, postlaser inflammation was observed in all subjects. Throughout the laser sessions and the outpatient follow-up clinic, the adverse effects of laser therapy, such as redness, spots, wrinkles, pores, and textures, decreased with the use of ANT1 cream. There has been a marked effect in wrinkle reduction in the patients who received a higher concentration of ANT1 cream (P ≤ 0.05). Statistically significant improvement in spots and pores is also seen (P ≤ 0.05). Through this study, the results suggest that the application of ANT1 soybean extract cream ameliorates the complications and enhances the cosmetic effects of Nd-YAG laser therapy. A higher concentration of the ANT1 cream significantly reduces wrinkles and redness after laser. All in all, this study proves that the ANT1 soy extract cream may be a useful addition to postlaser care for an overall enhancement in skin condition and recovery.

Expression and function of macrophage migration inhibitory factor in the pathogenesis of UV-induced cutaneous nonmelanoma skin cancer.

PubMed

Heise, Ruth; Vetter-Kauczok, Claudia S; Skazik, Claudia; Czaja, Katharina; Marquardt, Yvonne; Lue, Hongqi; Merk, Hans F; Bernhagen, Jürgen; Baron, Jens M

2012-01-01

Chronic skin exposure to ultraviolet light stimulates the production of cytokines known to be involved in the initiation of skin cancer. Recent studies in mouse models suggested a role for macrophage migration inhibitory factor (MIF) in the UVB-induced pathogenesis of nonmelanoma skin cancer (NMSC). Our studies aimed at defining the pathophysiological function of MIF in cutaneous inflammatory reactions and in the development and progression of NMSC. Immunohistochemical analysis revealed a moderate expression of MIF in normal human skin samples but an enhanced expression of this cytokine in lesional skin of patients with actinic keratosis or cutaneous SCC. Enzyme-linked immunosorbent assay studies showed a time-dependent increase in MIF secretion after a moderate single-dose UVB irradiation in NHEKs and SCC tumor cells. MIF is known to interact with CXCR2, CXCR4 and CD74. These receptors are not constitutively expressed in keratinocytes and HaCaT cells and their expression is not induced by UVB irradiation either. However, stimulation with IFNγ upregulated CD74 surface expression in these cells. Affymetrix(®) Gene Chip analysis revealed that only keratinocytes prestimulated with IFNγ are responsive to MIF. These findings indicate that MIF may be an important factor in the pathogenesis of NMSC tumorigenesis and progression in an inflammatory environment. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

Progressive hemifacial atrophy (Parry-Romberg syndrome). Case report.

PubMed

Mazzeo, N; Fisher, J G; Mayer, M H; Mathieu, G P

1995-01-01

Progressive hemifacial atrophy (Parry-Romberg syndrome) is a slowly progressing facial atrophy of subcutaneous fat and the wasting of associated skin, cartilage, and bone. This disorder includes an active progressive phase (2 to 10 years) followed by a burning out of the atrophic process with subsequent stability. This article presents a review of the literature and a case report with unique dental involvement as a result of this disease process.

Accidental sulfur mustard exposure: A case report.

PubMed

Schmidt, Annette; Steinritz, Dirk; Rudolf, Klaus-Dieter; Thiermann, Horst; Striepling, Enno

2018-09-01

The clinical progression following a sulfur mustard-induced skin exposure is well documented in the literature. Upon skin contact and a characteristic latency period, sulfur mustard (SM) causes erythema, blister formation and ulceration, which is associated with wound healing disorders that may require surgical treatment. Here, we present a case report of accidental exposure to SM in a laboratory setting which required surgical treatment of the skin. The case was illustrated at close intervals over a period of two years and underlines that exposure to SM has to be taken into account when typical clinical symptoms occur. Moreover skin grafts appear to be effective in SM-induced non healing skin ulcerations. Copyright © 2017 Elsevier B.V. All rights reserved.

Both Predator and Prey

PubMed Central

Löw, Andreas; Lang, Peter J.; Smith, J. Carson; Bradley, Margaret M.

2013-01-01

This research examined the psychophysiology of emotional arousal anticipatory to potentially aversive and highly pleasant outcomes. Human brain reactions (event-related potentials) and body reactions (heart rate, skin conductance, the probe startle reflex) were assessed along motivational gradients determined by apparent distance from sites of potential punishment or reward. A predator-prey survival context was simulated using cues that signaled possible money rewards or possible losses; the cues appeared to loom progressively closer to the viewer, until a final step when a rapid key response could ensure reward or avoid a punishing loss. The observed anticipatory response patterns of heightened vigilance and physiological mobilization are consistent with the view that the physiology of emotion is founded on action dispositions that evolved in mammals to facilitate survival by dealing with threats or capturing life-sustaining rewards. PMID:18947351

The multitasking organ: recent insights into skin immune function.

PubMed

Di Meglio, Paola; Perera, Gayathri K; Nestle, Frank O

2011-12-23

The skin provides the first line defense of the human body against injury and infection. By integrating recent findings in cutaneous immunology with fundamental concepts of skin biology, we portray the skin as a multitasking organ ensuring body homeostasis. Crosstalk between the skin and its microbial environment is also highlighted as influencing the response to injury, infection, and autoimmunity. The importance of the skin immune network is emphasized by the identification of several skin-resident cell subsets, each with its unique functions. Lessons learned from targeted therapy in inflammatory skin conditions, such as psoriasis, provide further insights into skin immune function. Finally, we look at the skin as an interacting network of immune signaling pathways exemplified by the development of a disease interactome for psoriasis. Copyright © 2011 Elsevier Inc. All rights reserved.

Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma.

PubMed

Baba, Yuko; Funakoshi, T; Mori, M; Emoto, K; Masugi, Y; Ekmekcioglu, S; Amagai, M; Tanese, K

2017-12-01

Accumulating evidence suggests that the lipid lytic enzyme monoacylglycerol lipase (MAGL) promotes tumour invasion and metastasis through up-regulation of pro-tumorigenic signalling lipids in several tumour cell lines. However, the expression status of MAGL in clinical melanoma tissues and its clinicopathological significance remain unclear. To correlate the tumour expression status of MAGL with the clinicopathological information of patients with malignant melanoma. Polymerase chain reaction (PCR) array screening was performed, and the results were validated using immunocytochemical analysis of tumour and non-tumour melanocytic cell lines. Immunohistochemical staining for MAGL was performed for 74 melanoma samples, including 48 primary and 26 metastatic tumours, in which the expression of MAGL was determined by evaluating the percentage of MAGL-positive tumour cells and the MAGL staining intensity. Finally, we analysed the association of MAGL expression status with tumour progression, tumour thickness and vascular invasion of the primary lesion. Immunocytochemical analysis revealed that MAGL was expressed in all 12 melanoma cell lines, but not in normal human epidermal melanocytes. In the immunohistochemical analysis, positive staining for MAGL was noted in 32 of 48 (64.5%) primary lesions, 14 of 17 (82.4%) lymph node metastatic lesions and 7 of 9 (77.8%) skin metastatic lesions. Metastatic tumours had a significantly higher staining intensity (P = 0.033 for lymph node, P = 0.010 for skin). In the analysis of primary lesions, higher MAGL expression correlated with greater tumour thickness (P = 0.015) and the presence of vascular invasion (P = 0.017). On further evaluation of MAGL-positive primary lesions, staining intensity of MAGL tended to be higher in deeper areas of the tumour mass. The expression of MAGL in tumour cells reflects the aggressiveness of melanoma cells and may serve as a marker of tumour progression. © 2017 European Academy of Dermatology and Venereology.

Microbial ecology of the skin in the era of metagenomics and molecular microbiology.

PubMed

Hannigan, Geoffrey D; Grice, Elizabeth A

2013-12-01

The skin is the primary physical barrier between the body and the external environment and is also a substrate for the colonization of numerous microbes. Previously, dermatological microbiology research was dominated by culture-based techniques, but significant advances in genomic technologies have enabled the development of less-biased, culture-independent approaches to characterize skin microbial communities. These molecular microbiology approaches illustrate the great diversity of microbiota colonizing the skin and highlight unique features such as site specificity, temporal dynamics, and interpersonal variation. Disruptions in skin commensal microbiota are associated with the progression of many dermatological diseases. A greater understanding of how skin microbes interact with each other and with their host, and how we can therapeutically manipulate those interactions, will provide powerful tools for treating and preventing dermatological disease.

Overload of iron in the skin of patients with varicose ulcers. Possible contributing role of iron accumulation in progression of the disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ackerman, Z.; Seidenbaum, M.; Loewenthal, E.

1988-09-01

The brown pigmentation of the skin associated with venous ulceration is caused by increased local iron deposition. Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for the noninvasive determination of iron levels in the skin of patients with venous ulceration. The mean (+/- SEM) iron concentration in the skin around the venous ulcer was elevated, compared with control values of nonulcerated skin (250 +/- 54 vs 128 +/- 39 micrograms) and compared with normal skin from the forearm (250 +/- 54 vs 14 +/- 2.5 micrograms). These data suggest that dermal iron deposition may not bemore » an incidental by-product of increased venous pressure, but may actively perpetuate tissue damage in venous ulcerations.« less

Proteomic Analysis of Laser Microdissected Melanoma Cells from Skin Organ Cultures

PubMed Central

Hood, Brian L.; Grahovac, Jelena; Flint, Melanie S.; Sun, Mai; Charro, Nuno; Becker, Dorothea; Wells, Alan; Conrads, Thomas P

2010-01-01

Gaining insights into the molecular events that govern the progression from melanoma in situ to advanced melanoma, and understanding how the local microenvironment at the melanoma site influences this progression, are two clinically pivotal aspects that to date are largely unexplored. In an effort to identify key regulators of the crosstalk between melanoma cells and the melanoma-skin microenvironment, primary and metastatic human melanoma cells were seeded into skin organ cultures (SOCs), and grown for two weeks. Melanoma cells were recovered from SOCs by laser microdissection and whole-cell tryptic digests analyzed by nanoflow liquid chromatography-tandem mass spectrometry with an LTQ-Orbitrap. The differential protein abundances were calculated by spectral counting, the results of which provides evidence that cell-matrix and cell-adhesion molecules that are upregulated in the presence of these melanoma cells recapitulate proteomic data obtained from comparative analysis of human biopsies of invasive melanoma and a tissue sample of adjacent, non-involved skin. This concordance demonstrates the value of SOCs for conducting proteomic investigations of the melanoma microenvironment. PMID:20459140

In vitro assessment of eye irritancy using the Reconstructed Human Corneal Epithelial SkinEthic HCE model: application to 435 substances from consumer products industry.

PubMed

Cotovio, José; Grandidier, Marie-Hélène; Lelièvre, Damien; Bremond, Christelle; Amsellem, Carolle; Maloug, Saber; Ovigne, Jean-Marc; Loisel-Joubert, Sophie; Lee, Aline Van Der; Minondo, Anne-Marie; Capallere, Christophe; Bertino, Béatrice; Alépée, Nathalie; Tinois-Tessonneaud, Estelle; de Fraissinette, Anne De Brugerolle; Meunier, Jean-Roch; Leclaire, Jacques

2010-03-01

The 7th amendment of the EU Cosmetics Directive led to the ban of eye irritation testing for cosmetic ingredients in animals, effective from March 11th 2009. Over the last 20years, many efforts have been made to find reliable and relevant alternative methods. The SkinEthic HCE model was used to evaluate the in vitro eye irritancy potential of substances from a cosmetic industry portfolio. An optimized protocol based on a specific 1-h treatment and a 16-h post-treatment incubation period was first assessed on a set of 102 substances. The prediction model (PM) based on a 50% viability cut-off, allowed to draw up two classes (Irritants and Non-Irritants), with good associated sensitivity (86.2%) and specificity (83.5%). To check the robustness of the method, the evaluated set was expanded up to 435 substances. Final performances maintained a high level and were characterized by an overall accuracy value > 82% when using EU or GHS classification rules. Results showed that the SkinEthic HCE test method is a promising in vitro tool for the prediction of eye irritancy. Optimization datasets were shared with the COLIPA Eye Irritation Project Team and ECVAM experts, and reviewed as part of an ongoing progression to enter an ECVAM prospective validation study for eye irritation. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

[Study on objectively evaluating skin aging according to areas of skin texture].

PubMed

Shan, Gaixin; Gan, Ping; He, Ling; Sun, Lu; Li, Qiannan; Jiang, Zheng; He, Xiangqian

2015-02-01

Skin aging principles play important roles in skin disease diagnosis, the evaluation of skin cosmetic effect, forensic identification and age identification in sports competition, etc. This paper proposes a new method to evaluate the skin aging objectively and quantitatively by skin texture area. Firstly, the enlarged skin image was acquired. Then, the skin texture image was segmented by using the iterative threshold method, and the skin ridge image was extracted according to the watershed algorithm. Finally, the skin ridge areas of the skin texture were extracted. The experiment data showed that the average areas of skin ridges, of both men and women, had a good correlation with age (the correlation coefficient r of male was 0.938, and the correlation coefficient r of female was 0.922), and skin texture area and age regression curve showed that the skin texture area increased with age. Therefore, it is effective to evaluate skin aging objectively by the new method presented in this paper.

Carcinogen-induced squamous papillomas and oncogenic progression in the absence of the SSeCKS/AKAP12 metastasis suppressor correlates with FAK upregulation

PubMed Central

Akakura, Shin; Bouchard, Rene; Bshara, Wiam; Morrison, Carl; Gelman, Irwin H.

2011-01-01

The ability of SSeCKS/Gravin/AKAP12 (SSeCKS) to negatively regulate cell cycle progression is thought to relate to its spatiotemporal scaffolding activity for key signaling molecules such as protein kinase A and C, calmodulin, and cyclins. SSeCKS is downregulated upon progression to malignancy in many cancer types, including melanoma and non-melanoma skin cancer. The forced re-expression of SSeCKS is especially potent in suppressing metastasis through the inhibition of VEGF-mediated neovascularization. We have previously shown that SSeCKS-null (KO) mice exhibit hyperplasia and focal dysplasia in the prostate marked by activated Akt. To address whether KO-mice exhibit increased skin carcinogenesis, WT and KO C57BL/6 mice were treated topically with 12-O-tetradecanoylphorbol-13-acetate and 7,12-dimethylbenzanthracene. Compared to WT mice, KO mice developed squamous papillomas more rapidly and in greater numbers, and also exhibited significantly increased progression to squamous cell carcinoma. Untreated KO epidermal layers were thicker than those in age-matched WT mice, and exhibited significantly increased levels of FAK and phospho-ERK1/2, known mediators of carcinogen-induced squamous papilloma progression to carcinoma. Compared to protein levels in WT mouse embryo fibroblasts (MEF), SSeCKS levels were increased in FAK-null cells whereas FAK levels were increased in SSeCKS-null cells. RNAi studies in WT MEF cells suggest that SSeCKS and FAK attenuate each other’s expression. Our study implicates a role for SSeCKS in preventing of skin cancer progression possibly through negatively regulating FAK expression. PMID:21128249

F-111 Adhesive Bonded Repairs Assessment Program - Progress Report 2: Analysis of FM300-2K Repairs

DTIC Science & Technology

2015-01-01

primarily the effect of panel skin thickness The previous report found that while repair location on the aircraft structure may have had some effect...typically are manufactured by adhesively bonding an upper and lower aluminium skin to aluminium honeycomb-core. The structure provides added stiffness to...component, one of the typical repair techniques requires removal of the damaged skin and honeycomb core. New core is adhesively bonded back in place and an

Skin permeability enhancement by Bacillus subtilis alkaline protease: Application to transdermal drug delivery.

PubMed

Nounou, Mohamed I; Zaghloul, Taha I; Ahmed, Nehal A; Eid, Amira A; El-Khordagui, Labiba K

2017-08-30

Enzymes may offer great potentials in topical pharmaceutical applications provided that treatment conditions are controlled for efficacy and safety. In this study, the effect of alkaline protease produced by recombinant Bacillus subtilis cells on the ex-vivo permeability of rabbit ear skin was investigated under different conditions of enzyme activity (5-60 units) and exposure time (15-60min). Data for transepidermal water loss (TEWL) and permeation of a hydrophilic dye, rhodamine B (Rb), indicated biphasic activity-dependent and exposure time-dependent skin permeability. Maximum effects were obtained at 20 proteolytic units and 30min exposure. Findings proved consistent with histopathological changes indicating progressive stratum corneum (SC) loss and disruption of the dermo-epidermal junction at 20 units and up to 30min exposure time followed by dermal hyalinization at longer exposure. This was associated with progressive loss of skin hair. Applying the identified pretreatment conditions to transdermal delivery of vardenafil in a gel base across dorsal rat skin indicated a significant increase in plasma levels at 30 and 60min with minimal histopathological changes 5days post enzyme treatment. Accordingly, the recombinant B. subtilis alkaline protease offers promise as a pharmaceutical enzyme for transdermal drug delivery bioenhancement and dermatological applications. Copyright © 2017 Elsevier B.V. All rights reserved.

IL-22 is required for Th17 cell–mediated pathology in a mouse model of psoriasis-like skin inflammation

PubMed Central

Ma, Hak-Ling; Liang, Spencer; Li, Jing; Napierata, Lee; Brown, Tom; Benoit, Stephen; Senices, Mayra; Gill, Davinder; Dunussi-Joannopoulos, Kyriaki; Collins, Mary; Nickerson-Nutter, Cheryl; Fouser, Lynette A.; Young, Deborah A.

2008-01-01

Psoriasis is a chronic skin disease resulting from the dysregulated interplay between keratinocytes and infiltrating immune cells. We report on a psoriasis-like disease model, which is induced by the transfer of CD4+CD45RBhiCD25– cells to pathogen-free scid/scid mice. Psoriasis-like lesions had elevated levels of antimicrobial peptide and proinflammatory cytokine mRNA. Also, similar to psoriasis, disease progression in this model was dependent on the p40 common to IL-12 and IL-23. To investigate the role of IL-22, a Th17 cytokine, in disease progression, mice were treated with IL-22–neutralizing antibodies. Neutralization of IL-22 prevented the development of disease, reducing acanthosis (thickening of the skin), inflammatory infiltrates, and expression of Th17 cytokines. Direct administration of IL-22 into the skin of normal mice induced both antimicrobial peptide and proinflammatory cytokine gene expression. Our data suggest that IL-22, which acts on keratinocytes and other nonhematopoietic cells, is required for development of the autoreactive Th17 cell–dependent disease in this model of skin inflammation. We propose that IL-22 antagonism might be a promising therapy for the treatment of human psoriasis. PMID:18202747

IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation.

PubMed

Ma, Hak-Ling; Liang, Spencer; Li, Jing; Napierata, Lee; Brown, Tom; Benoit, Stephen; Senices, Mayra; Gill, Davinder; Dunussi-Joannopoulos, Kyriaki; Collins, Mary; Nickerson-Nutter, Cheryl; Fouser, Lynette A; Young, Deborah A

2008-02-01

Psoriasis is a chronic skin disease resulting from the dysregulated interplay between keratinocytes and infiltrating immune cells. We report on a psoriasis-like disease model, which is induced by the transfer of CD4(+)CD45RB(hi)CD25(-) cells to pathogen-free scid/scid mice. Psoriasis-like lesions had elevated levels of antimicrobial peptide and proinflammatory cytokine mRNA. Also, similar to psoriasis, disease progression in this model was dependent on the p40 common to IL-12 and IL-23. To investigate the role of IL-22, a Th17 cytokine, in disease progression, mice were treated with IL-22-neutralizing antibodies. Neutralization of IL-22 prevented the development of disease, reducing acanthosis (thickening of the skin), inflammatory infiltrates, and expression of Th17 cytokines. Direct administration of IL-22 into the skin of normal mice induced both antimicrobial peptide and proinflammatory cytokine gene expression. Our data suggest that IL-22, which acts on keratinocytes and other nonhematopoietic cells, is required for development of the autoreactive Th17 cell-dependent disease in this model of skin inflammation. We propose that IL-22 antagonism might be a promising therapy for the treatment of human psoriasis.

SIRT1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival

PubMed Central

Becatti, Matteo; Fiorillo, Claudia; Barygina, Victoria; Cecchi, Cristina; Lotti, Torello; Prignano, Francesca; Silvestro, Agrippino; Nassi, Paolo; Taddei, Niccolò

2014-01-01

Vitiligo is an acquired and progressive hypomelanotic disease that manifests as circumscribed depigmented patches on the skin. The aetiology of vitiligo remains unclear, but recent experimental data underline the interactions between melanocytes and other typical skin cells, particularly keratinocytes. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. Sirtuins (silent mating type information regulation 2 homolog) 1, well-known modulators of lifespan in many species, have a role in gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy ageing. In the literature there is no evidence for SIRT1 signalling in vitiligo and its possible involvement in disease progression. Here, biopsies were taken from the perilesional skin of 16 patients suffering from non-segmental vitiligo and SIRT1 signalling was investigated in these cells. For the first time, a new SIRT1/Akt, also known as Protein Kinase B (PKB)/mitogen-activated protein kinase (MAPK) signalling has been revealed in vitiligo. SIRT1 regulates MAPK pathway via Akt-apoptosis signal-regulating kinase-1 and down-regulates pro-apoptotic molecules, leading to decreased oxidative stress and apoptotic cell death in perilesional vitiligo keratinocytes. We therefore propose SIRT1 activation as a novel way of protecting perilesional vitiligo keratinocytes from damage. PMID:24410795

Polyamines and Nonmelanoma Skin Cancer

PubMed Central

Gilmour, Susan K.

2007-01-01

Elevated levels of polyamines have long been associated with skin tumorigenesis. Tightly regulated metabolism of polyamines is critical for cell survival and normal skin homeostasis, and these controls are dysregulated in skin tumorigenesis. A key enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC) is upregulated in skin tumors compared to normal skin. Use of transgenic mouse models has demonstrated that polyamines play an essential role in the early promotional phase of skin tumorigenesis. The formation of skin tumors in these transgenic mice is dependent upon polyamine biosynthesis, especially putrescine, since treatment with inhibitors of ODC activity blocks the formation of skin tumors and causes the rapid regression of existing tumors. Although the mechanism by which polyamines promote skin tumorigenesis are not well understood, elevated levels of polyamines have been shown to stimulate epidermal proliferation, alter keratinocyte differentiation status, increase neovascularization, and increase synthesis of extracellular matrix proteins in a manner similar to that seen in wound healing. It is becoming increasingly apparent that elevated polyamine levels activate not only epidermal cells but also underlying stromal cells in the skin to promote the development and progression of skin tumors. The inhibition of polyamine biosynthesis has potential to be an effective chemoprevention strategy for nonmelanoma skin cancer. PMID:17234230

Mathematical and computational modelling of skin biophysics: a review

PubMed Central

2017-01-01

The objective of this paper is to provide a review on some aspects of the mathematical and computational modelling of skin biophysics, with special focus on constitutive theories based on nonlinear continuum mechanics from elasticity, through anelasticity, including growth, to thermoelasticity. Microstructural and phenomenological approaches combining imaging techniques are also discussed. Finally, recent research applications on skin wrinkles will be presented to highlight the potential of physics-based modelling of skin in tackling global challenges such as ageing of the population and the associated skin degradation, diseases and traumas. PMID:28804267

Mathematical and computational modelling of skin biophysics: a review

NASA Astrophysics Data System (ADS)

Limbert, Georges

2017-07-01

The objective of this paper is to provide a review on some aspects of the mathematical and computational modelling of skin biophysics, with special focus on constitutive theories based on nonlinear continuum mechanics from elasticity, through anelasticity, including growth, to thermoelasticity. Microstructural and phenomenological approaches combining imaging techniques are also discussed. Finally, recent research applications on skin wrinkles will be presented to highlight the potential of physics-based modelling of skin in tackling global challenges such as ageing of the population and the associated skin degradation, diseases and traumas.

Ripening-induced changes in grape skin proanthocyanidins modify their interaction with cell walls.

PubMed

Bindon, Keren A; Kennedy, James A

2011-03-23

Proanthocyanidins were isolated from the skins of Cabernet Sauvignon grapes at different stages of grape development in order to study the effect of proanthocyanidin modification on the interaction with grape cell wall material. After veraison, the degree of proanthocyanidin polymerization increased, and thereafter was variable between 24 and 33 subunits as ripening progressed. Affinity of skin cell wall material for proanthocyanidin decreased with proanthocyanidin ripeness following veraison. A significant negative relationship (R2=0.93) was found for average proanthocyanidin molecular mass and the proportion of high molecular mass proanthocyanidin adsorbed by skin cell wall material. This indicated that as proanthocyanidin polymerization increased, the affinity of a component of high molecular mass proanthocyanidins for skin cell wall material declined. This phenomenon was only associated with skin proanthocyanidins from colored grapes, as high molecular mass proanthocyanidins of equivalent subunit composition from colorless mutant Cabernet Sauvignon grapes had a higher affinity for skin cell wall material.

Protective molecular mechanisms of resveratrol in UVR-induced Skin carcinogenesis.

PubMed

Aziz, Saba W; Aziz, Moammir H

2018-01-01

Skin cancer is a major health problem worldwide. It is the most common cancer in the United States and poses a significant healthcare burden. Excessive UVR exposure is the most common cause of skin cancer. Despite various precautionary measures to avoid direct UVR exposure, the incidence of skin cancer and mortality related to it remains high. Furthermore, the current treatment options are expensive and have side effects including toxicity to normal cells. Thus, a safe and effective approach is needed to prevent and treat skin cancer. Chemopreventive strategy using naturally occurring compounds, such as resveratrol, is a promising approach to reduce the incidence of UVR-induced skin cancer and delay its progression. This review highlights the current body of evidence related to chemopreventive role of resveratrol and its molecular mechanisms in UVR-induced skin carcinogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype

PubMed Central

Leal, Ermelindo C.; Carvalho, Eugénia; Tellechea, Ana; Kafanas, Antonios; Tecilazich, Francesco; Kearney, Cathal; Kuchibhotla, Sarada; Auster, Michael E.; Kokkotou, Efi; Mooney, David J.; LoGerfo, Frank W.; Pradhan-Nabzdyk, Leena; Veves, Aristidis

2016-01-01

Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear. We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds. We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models. SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process. SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing. In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. PMID:25871534

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

Scleroderma and dentistry: Two case reports.

PubMed

Dixit, Shantanu; Kalkur, Chaithra; Sattur, Atul P; Bornstein, Michael M; Melton, Fred

2016-10-24

Scleroderma is a chronic connective tissue disorder with unknown etiology. It is characterized by excessive deposition of extracellular matrix in the connective tissues causing vascular disturbances which can result in tissue hypoxia. These changes are manifested as atrophy of the skin and/or mucosa, subcutaneous tissue, muscles, and internal organs. Such changes can be classified into two types, namely, morphea (localized) and diffuse (systemic). Morphea can manifest itself as hemifacial atrophy (Parry-Romberg syndrome) although this remains debatable. Hence, we present a case of morphea, associated with Parry-Romberg syndrome, and a second case with the classical signs of progressive systemic sclerosis. Case one: A 20-year-old man of Dravidian origin presented to our out-patient department with a complaint of facial asymmetry, difficulty in speech, and loss of taste sensation over the last 2 years. There was no history of facial trauma. After physical and radiological investigations, we found gross asymmetry of the left side of his face, a scar on his chin, tongue atrophy, relative microdontia, thinning of the ramus/body of his mandible, and sclerotic lesions on his trunk. Serological investigations were positive for antinuclear antibody for double-stranded deoxyribonucleic acid and mitochondria. A biopsy was suggestive of morphea. Hence, our final diagnosis was mixed morphea with Parry-Romberg syndrome. Case two: A 53-year-old woman of Dravidian origin presented to our out-patient department with a complaint of gradually decreasing mouth opening over the past 7 years. Her medical history was noncontributory. On clinical examination, we found her perioral, neck, and hand skin to be sclerotic. Also, her fingers exhibited bilateral telangiectasia. An oral examination revealed completely edentulous arches as well as xerostomia and candidiasis. Her serological reports were positive for antinuclear antibodies against centromere B, Scl-70, and Ro-52. A hand and wrist radiograph revealed acro-osteolysis of the middle finger on her right hand. Hence, our final diagnosis was progressive systemic sclerosis. Through this article, we have tried to emphasize the importance of a general examination when diagnosing rare systemic diseases such as scleroderma and the role of the general dentist when caring for such patients, even though they can be quite rare in general practice.

Is the skin a sanctuary for breast cancer cells during treatment with anti-HER2 antibodies?

PubMed

Graziano, Vincenzo; Scognamiglio, Maria Teresa; Zilli, Marinella; Giampietro, Jamara; Vici, Patrizia; Natoli, Clara; Grassadonia, Antonino

2015-01-01

The occurrence of skin metastases is a common event in patients affected by advanced breast cancer, usually associated with systemic disease progression. Here we describe 2 cases of diffuse cutaneous metastases from HER2-overexpressing breast cancer occurring despite a dramatic response in liver and bone, respectively, during treatment with anti-HER2 antibodies Trastuzumab and Pertuzumab. We discuss the reasons for this discrepancy and suggest a possible implication of impaired immune response in the skin. Future research should provide strategies to overcome the induction of immune privilege in the skin in order to avoid discontinuation of effective treatments.

A Technique for the Growth of Epidermal Sheets Obtained from Patients Undergoing Reduction Mammoplasty.

DTIC Science & Technology

1991-03-06

flask with Dispase, a neutral protease and attached to petrolatum gauze. At this point the sheets could be used as skin grafts . Progress: 1...a composite in vitro skin graft . We believe that development of an artificial dermis as part of a composite in vitro graft is where our future

Progress on the development of skin friction sensors.

NASA Technical Reports Server (NTRS)

Mcvey, E. S.; Moore, J. W.

1972-01-01

A skin friction measuring system is described which will operate to 2000 F for short periods of time and continuously to 1300 F. A prototype system has been constructed and is being placed in operation. Information on alternative feasible systems is presented. Emphasis is placed on presenting research results in the form of useful design information and experimental data.

Automatic detection and segmentation of vascular structures in dermoscopy images using a novel vesselness measure based on pixel redness and tubularness

NASA Astrophysics Data System (ADS)

Kharazmi, Pegah; Lui, Harvey; Stoecker, William V.; Lee, Tim

2015-03-01

Vascular structures are one of the most important features in the diagnosis and assessment of skin disorders. The presence and clinical appearance of vascular structures in skin lesions is a discriminating factor among different skin diseases. In this paper, we address the problem of segmentation of vascular patterns in dermoscopy images. Our proposed method is composed of three parts. First, based on biological properties of human skin, we decompose the skin to melanin and hemoglobin component using independent component analysis of skin color images. The relative quantities and pure color densities of each component were then estimated. Subsequently, we obtain three reference vectors of the mean RGB values for normal skin, pigmented skin and blood vessels from the hemoglobin component by averaging over 100000 pixels of each group outlined by an expert. Based on the Euclidean distance thresholding, we generate a mask image that extracts the red regions of the skin. Finally, Frangi measure was applied to the extracted red areas to segment the tubular structures. Finally, Otsu's thresholding was applied to segment the vascular structures and get a binary vessel mask image. The algorithm was implemented on a set of 50 dermoscopy images. In order to evaluate the performance of our method, we have artificially extended some of the existing vessels in our dermoscopy data set and evaluated the performance of the algorithm to segment the newly added vessel pixels. A sensitivity of 95% and specificity of 87% were achieved.

Nutraceuticals: A Review.

PubMed

Souyoul, Skylar A; Saussy, Katharine P; Lupo, Mary P

2018-03-01

Skin aging is continuously influenced by various internal and external factors such as the biologic progression of cells, ultraviolet (UV) radiation, tobacco, nutritional deficiencies, and hormonal imbalances that lead to the degradation of skin cells. Through the degradation of skin cells, free radicals and inflammation weaken repair mechanisms and result in collagen and elastic fiber breakdown. The appearance of aging skin is highlighted by skin roughness, wrinkling, pigmentation change, telangiectasias, loss of elasticity, and decreased firmness, all of which are accelerated by these internal and external factors. Throughout the years, nutraceuticals have been studied to delay and fight against these internal and external factors, many of which are found in foods and byproducts consumed naturally. The aim of this review is to aid dermatologists in understanding the mechanism of action of popular nutraceuticals and their possible efficacy in antiaging and skin health.

Spectroscopic methods for the photodiagnosis of nonmelanoma skin cancer.

PubMed

Drakaki, Eleni; Vergou, Theognosia; Dessinioti, Clio; Stratigos, Alexander J; Salavastru, Carmen; Antoniou, Christina

2013-06-01

The importance of dermatological noninvasive imaging techniques has increased over the last decades, aiming at diagnosing nonmelanoma skin cancer (NMSC). Technological progress has led to the development of various analytical tools, enabling the in vivo/in vitro examination of lesional human skin with the aim to increase diagnostic accuracy and decrease morbidity and mortality. The structure of the skin layers, their chemical composition, and the distribution of their compounds permits the noninvasive photodiagnosis of skin diseases, such as skin cancers, especially for early stages of malignant tumors. An important role in the dermatological diagnosis and disease monitoring has been shown for promising spectroscopic and imaging techniques, such as fluorescence, diffuse reflectance, Raman and near-infrared spectroscopy, optical coherence tomography, and confocal laser-scanning microscopy. We review the use of these spectroscopic techniques as noninvasive tools for the photodiagnosis of NMSC.

Spectroscopic methods for the photodiagnosis of nonmelanoma skin cancer

NASA Astrophysics Data System (ADS)

Drakaki, Eleni; Vergou, Theognosia; Dessinioti, Clio; Stratigos, Alexander J.; Salavastru, Carmen; Antoniou, Christina

2013-06-01

The importance of dermatological noninvasive imaging techniques has increased over the last decades, aiming at diagnosing nonmelanoma skin cancer (NMSC). Technological progress has led to the development of various analytical tools, enabling the in vivo/in vitro examination of lesional human skin with the aim to increase diagnostic accuracy and decrease morbidity and mortality. The structure of the skin layers, their chemical composition, and the distribution of their compounds permits the noninvasive photodiagnosis of skin diseases, such as skin cancers, especially for early stages of malignant tumors. An important role in the dermatological diagnosis and disease monitoring has been shown for promising spectroscopic and imaging techniques, such as fluorescence, diffuse reflectance, Raman and near-infrared spectroscopy, optical coherence tomography, and confocal laser-scanning microscopy. We review the use of these spectroscopic techniques as noninvasive tools for the photodiagnosis of NMSC.

The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders

PubMed Central

Działo, Magdalena; Mierziak, Justyna; Korzun, Urszula; Preisner, Marta; Szopa, Jan; Kulma, Anna

2016-01-01

Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract. PMID:26901191

A pseudo-outbreak of skin disease in British troops.

PubMed Central

Croft, A; Smith, H; Creamer, I

1996-01-01

When a newspaper report claimed that a serious outbreak of skin disease had occurred in British Army troops stationed at the Bocac Dam, in western Bosnia, all troops at the Bocac Dam location (n = 96), followed by a matched control group of troops (n = 91) at a nearby location, were examined by two investigators. 14% of the study population and 21% of the control group were found to have skin disorders. Most were complaints that are commonly encountered in general medical practice. There was a striking absence of skin infestations. The historical consultation rate for skin disorders had not increased. It was concluded that an outbreak of skin disease had not occurred in British troops guarding the dam. This epidemiological study shows that, even under conditions of modern field hygiene, up to one in five soldiers will have skin disease. Skin infestations, however, have become progressively less common during military campaigns this century, probably because of better personal hygiene, good preventive medicine practices and better access to effective health care. PMID:8976888

The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders.

PubMed

Działo, Magdalena; Mierziak, Justyna; Korzun, Urszula; Preisner, Marta; Szopa, Jan; Kulma, Anna

2016-02-18

Phenolic compounds constitute a group of secondary metabolites which have important functions in plants. Besides the beneficial effects on the plant host, phenolic metabolites (polyphenols) exhibit a series of biological properties that influence the human in a health-promoting manner. Evidence suggests that people can benefit from plant phenolics obtained either by the diet or through skin application, because they can alleviate symptoms and inhibit the development of various skin disorders. Due to their natural origin and low toxicity, phenolic compounds are a promising tool in eliminating the causes and effects of skin aging, skin diseases, and skin damage, including wounds and burns. Polyphenols also act protectively and help prevent or attenuate the progression of certain skin disorders, both embarrassing minor problems (e.g., wrinkles, acne) or serious, potentially life-threatening diseases such as cancer. This paper reviews the latest reports on the potential therapy of skin disorders through treatment with phenolic compounds, considering mostly a single specific compound or a combination of compounds in a plant extract.

Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma.

PubMed

Demehri, Shadmehr; Morimoto, Mitsuru; Holtzman, Michael J; Kopan, Raphael

2009-05-19

Asthma is a common allergic lung disease frequently affecting individuals with a prior history of eczema/atopic dermatitis (AD); however, the mechanism underlying the progression from AD to asthma (the so-called "atopic march") is unclear. Here we show that, like humans with AD, mice with skin-barrier defects develop AD-like skin inflammation and are susceptible to allergic asthma. Furthermore, we show that thymic stromal lymphopoietin (TSLP), overexpressed by skin keratinocytes, is the systemic driver of this bronchial hyper-responsiveness. As an AD-like model, we used mice with keratinocyte-specific deletion of RBP-j that sustained high systemic levels of TSLP. Antigen-induced allergic challenge to the lung airways of RBP-j-deficient animals resulted in a severe asthmatic phenotype not seen in similarly treated wild-type littermates. Elimination of TSLP signaling in these animals blocked the atopic march, demonstrating that high serum TSLP levels were required to sensitize the lung to allergic inflammation. Furthermore, we analyzed outbred K14-TSLP(tg) mice that maintained high systemic levels of TSLP without developing any skin pathology. Importantly, epidermal-derived TSLP was sufficient to trigger the atopic march, sensitizing the lung airways to inhaled allergens in the absence of epicutaneous sensitization. Based on these findings, we propose that in addition to early treatment of the primary skin-barrier defects, selective inhibition of systemic TSLP may be the key to blocking the development of asthma in AD patients.

Medicine: The final frontier in cancer diagnosis

NASA Astrophysics Data System (ADS)

Leachman, Sancy A.; Merlino, Glenn

2017-01-01

A computer, trained to classify skin cancers using image analysis alone, can now identify certain cancers as successfully as can skin-cancer doctors. What are the implications for the future of medical diagnosis? See Letter p.115

Skin mechanical properties and modeling: A review.

PubMed

Joodaki, Hamed; Panzer, Matthew B

2018-04-01

The mechanical properties of the skin are important for various applications. Numerous tests have been conducted to characterize the mechanical behavior of this tissue, and this article presents a review on different experimental methods used. A discussion on the general mechanical behavior of the skin, including nonlinearity, viscoelasticity, anisotropy, loading history dependency, failure properties, and aging effects, is presented. Finally, commonly used constitutive models for simulating the mechanical response of skin are discussed in the context of representing the empirically observed behavior.

Characterization of atopic skin and the effect of a hyperforin-rich cream by laser scanning microscopy.

PubMed

Meinke, Martina C; Richter, Heike; Kleemann, Anke; Lademann, Juergen; Tscherch, Kathrin; Rohn, Sascha; Schempp, Christoph M

2015-05-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.

Characterization of atopic skin and the effect of a hyperforin-rich cream by laser scanning microscopy

NASA Astrophysics Data System (ADS)

Meinke, Martina C.; Richter, Heike; Kleemann, Anke; Lademann, Juergen; Tscherch, Kathrin; Rohn, Sascha; Schempp, Christoph M.

2015-05-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.

Skin bioprinting: a novel approach for creating artificial skin from synthetic and natural building blocks.

PubMed

Augustine, Robin

2018-05-12

Significant progress has been made over the past few decades in the development of in vitro-engineered substitutes that mimic human skin, either as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. Tissue engineering has been developing as a novel strategy by employing the recent advances in various fields such as polymer engineering, bioengineering, stem cell research and nanomedicine. Recently, an advancement of 3D printing technology referred as bioprinting was exploited to make cell loaded scaffolds to produce constructs which are more matching with the native tissue. Bioprinting facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissue-engineering approaches. Bioprinted skin substitutes or equivalents containing dermal and epidermal components offer a promising approach in skin bioengineering. Various materials including synthetic and natural biopolymers and cells with or without signalling molecules like growth factors are being utilized to produce functional skin constructs. This technology emerging as a novel strategy to overcome the current bottle-necks in skin tissue engineering such as poor vascularization, absence of hair follicles and sweat glands in the construct.

SkinChip, a new tool for investigating the skin surface in vivo.

PubMed

Lévêque, Jean Luc; Querleux, Bernard

2003-11-01

Non-invasive methods used for characterizing skin micro-relief and skin surface hydration were developed in the 1980s. Although they allowed some progress in the knowledge of skin properties, they are not completely satisfactory in many aspects. Today, new technologies are emerging that may address such issues. We adapted the technology produced by the ST Microelectronics Company for sensing fingerprint for the measurement of skin surface properties. Accordingly, we developed acquisition software for obtaining routinely the distribution of skin surface capacitance along different body sites. Image analysis softwares were also processed for collecting both the main orientations of the micro-relief lines and their density. The average value of skin capacitance is also obtained. The images allow a highly precise observation of the skin topography that can be easily quantified in terms of line density and line orientation. The mean gray levels of the images appear much closely correlated to the Corneometer values. This new device appears to be a very convenient way for characterizing the properties of the skin surface. With regard to hydration, it usefully provides both the average value and the hydration chart of the investigated skin zones.

Progressive Damage Analyses of Skin/Stringer Debonding

NASA Technical Reports Server (NTRS)

Daville, Carlos G.; Camanho, Pedro P.; deMoura, Marcelo F.

2004-01-01

The debonding of skin/stringer constructions is analyzed using a step-by-step simulation of material degradation based on strain softening decohesion elements and a ply degradation procedure. Decohesion elements with mixed-mode capability are placed at the interface between the skin and the flange to simulate the initiation and propagation of the delamination. In addition, the initiation and accumulation of fiber failure and matrix damage is modeled using Hashin-type failure criteria and their corresponding material degradation schedules. The debonding predictions using simplified three-dimensional models correlate well with test results.

Characterization of damaged skin by impedance spectroscopy: chemical damage by dimethyl sulfoxide.

PubMed

White, Erick A; Orazem, Mark E; Bunge, Annette L

2013-10-01

To relate changes in the electrochemical impedance spectra to the progression and mechanism of skin damage arising from exposure to dimethyl sulfoxide (DMSO). Electrochemical impedance spectra measured before and after human cadaver skin was treated with neat DMSO or phosphate buffered saline (control) for 1 h or less were compared with electrical circuit models representing two contrasting theories describing the progression of DMSO damage. Flux of a model lipophilic compound (p-chloronitrobenzene) was also measured. The impedance spectra collected before and after 1 h treatment with DMSO were consistent with a single circuit model; whereas, the spectra collected after DMSO exposure for 0.25 h were consistent with the model circuits observed before and after DMSO treatment for 1 h combined in series. DMSO treatments did not significantly change the flux of p-chloronitrobenzene compared to control. Impedance measurements of human skin exposed to DMSO for less than about 0.5 h were consistent with the presence of two layers: one damaged irreversibly and one unchanged. The thickness of the damaged layer increased proportional to the square-root of treatment time until about 0.5 h, when DMSO affected the entire stratum corneum. Irreversible DMSO damage altered the lipophilic permeation pathway minimally.

SHINING A LIGHT ON XERODERMA PIGMENTOSUM

PubMed Central

DiGiovanna, John J.; Kraemer, Kenneth H.

2012-01-01

Xeroderma pigmentosum (XP) is a rare, autosomal recessive disorder of DNA repair characterized by sun sensitivity and ultraviolet (UV) induced skin and mucous membrane cancers. Described in 1874 by Moriz Kaposi in Vienna, nearly 100 years later James Cleaver in San Francisco reported defective DNA repair in XP cells. This eventually provided the basis for a mechanistic link between sun exposure, DNA damage, somatic mutations and skin cancer. XP cells were found to have defects in 7 of the proteins of the nucleotide excision repair pathway and in DNA polymerase eta. XP cells are hypersensitive to killing by UV and XP cancers have characteristic “UV signature” mutations. Clinical studies at NIH found a nearly 10,000-fold increase in skin cancer in XP patients under age 20 years demonstrating the substantial importance of DNA repair in cancer prevention in the general population. About 25 % of XP patients have progressive neurological degeneration with progressive loss of neurons, probably from DNA damage induced by oxidative metabolism which kills non-dividing cells in the nervous system. Interestingly, patients with another disorder, trichothiodystrophy have defects in some of the same genes as XP but they have primary developmental abnormalities without an increase in skin cancer. PMID:22217736

Microneedles for intradermal and transdermal delivery

PubMed Central

Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

2014-01-01

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

Skin physiology in men and women: in vivo evaluation of 300 people including TEWL, SC hydration, sebum content and skin surface pH.

PubMed

Luebberding, S; Krueger, N; Kerscher, M

2013-10-01

Evidence is given that differences in skin physiological properties exist between men and women. However, despite an assessable number of available publications, the results are still inconsistent. Therefore, the aim of this clinical study is the first systematic assessment of gender-related differences in skin physiology in men and women, with a special focus on changes over lifetime. A total of 300 healthy male and female subjects (20-74 years) were selected following strict criteria including age, sun behaviour or smoking habits. TEWL, hydration level, sebum production and pH value were measured with worldwide-acknowledged biophysical measuring methods at forehead, cheek, neck, volar forearm and dorsum of hand. Until the age of 50 men's TEWL is significantly lower than the water loss of women of the same age, regardless of the location. With ageing gender-related differences in TEWL assimilate. Young men show higher SC hydration in comparison with women. But, whereas SC hydration is stable or even increasing in women over lifetime, the skin hydration in men is progressively decreasing, beginning at the age of 40. Sebum production in male skin is always higher and stays stable with increasing age, whereas sebum production in women progressively decreases over lifetime. Across all localizations and age groups, the pH value in men is below 5, the pH value of female subjects is, aside from limited expectations, higher than 5. Skin physiological distinctions between the sexes exist and are particularly remarkable with regard to sebum production and pH value. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Increased systemic and epidermal levels of IL-17A and IL-1β promotes progression of non-segmental vitiligo.

PubMed

Bhardwaj, Supriya; Rani, Seema; Srivastava, Niharika; Kumar, Ravinder; Parsad, Davinder

2017-03-01

Non-segmental vitiligo (NSV) results from autoimmune destruction of melanocytes. The altered levels of various cytokines have been proposed in the pathogenesis of vitiligo. However, the exact immune mechanisms have not yet been fully elucidated. To investigate the role of epidermal and systemic cytokines in active and stable NSV patients. Serum levels of inflammatory cytokines were checked in 42 active and 30 stable NSV patients with 30 controls. The lesional, perilesional and normal skin sections were subjected to H&E staining. The mRNA expression of inflammatory cytokines and their respective receptors were assessed by quantitative PCR in lesional skin of both active and stable NSV skin. The MITF and IL-17A were immunolocalized in lesional, perilesional and normal skin tissue. Significant increase in the expression of inflammatory cytokines, IL-17A, IL-1β and TGF-β was observed in active patients, whereas no change was observed in stable patients. A marked reduction in epidermal thickness was observed in lesional skin sections. Significant increase in IL-17A and significant decrease in microphthalmia associated transcription factor (MITF) expression was observed in lesional and perilesional skin sections. Moreover, qPCR analysis showed significant alterations in the mRNA levels of IL-17A, IL-1β, IFN-γ, TGF-β and their respective receptors in active and stable vitiligo patient samples. Increased levels of IL-17A and IL-1β cytokines and decreased expression of MITF suggested a possible role of these cytokines in dysregulation of melanocytic activity in the lesional skin and hence might be responsible for the progression of active vitiligo. Copyright © 2016 Elsevier Ltd. All rights reserved.

The application of skin metabolomics in the context of transdermal drug delivery.

PubMed

Li, Jinling; Xu, Weitong; Liang, Yibiao; Wang, Hui

2017-04-01

Metabolomics is a powerful emerging tool for the identification of biomarkers and the exploration of metabolic pathways in a high-throughput manner. As an administration site for percutaneous absorption, the skin has a variety of metabolic enzymes, except other than hepar. However, technologies to fully detect dermal metabolites remain lacking. Skin metabolomics studies have mainly focused on the regulation of dermal metabolites by drugs or on the metabolism of drugs themselves. Skin metabolomics techniques include collection and preparation of skin samples, data collection, data processing and analysis. Furthermore, studying dermal metabolic effects via metabolomics can provide novel explanations for the pathogenesis of some dermatoses and unique insights for designing targeted prodrugs, promoting drug absorption and controlling drug concentration. This paper reviews current progress in the field of skin metabolomics, with a specific focus on dermal drug delivery systems and dermatosis. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Parkinson disease and progressive supranuclear palsy: protein expression in skin.

PubMed

Rodríguez-Leyva, Ildefonso; Chi-Ahumada, Erika G; Carrizales, Juan; Rodríguez-Violante, Mayela; Velázquez-Osuna, Salvador; Medina-Mier, Verónica; Martel-Gallegos, María G; Zarazúa, Sergio; Enríquez-Macías, Lourdes; Castro, Adriana; Calderón-Garcidueñas, Ana Laura; Jiménez-Capdeville, María E

2016-03-01

This study characterizes the expression of tau (p-tau) and α-synuclein (α-syn) by immunohistochemistry in the skin of three different populations: healthy control (HC), Parkinson disease (PD), and progressive supranuclear paralysis (PSP) subjects, with the purpose of finding a biomarker that could differentiate between subjects with PD and PSP. We evaluated the presence of p-tau and α-syn in a pilot study in the skin of three distinct groups of patients: 17 healthy subjects, 17 patients with PD, and 10 patients with PSP. Four millimeters punch biopsies were obtained from the occipital area and analyzed by immunohistochemistry using antibodies against α-syn and phosphorylated species of tau. PHF (paired helical filaments) antibody identifies p-tau in both normal and pathological conditions and AT8 recognizes p-tau characteristic of pathological conditions. Differences between the three groups were assessed by quantification of immunopositive areas in the epidermis. The immunopositivity pattern of p-tau and α-syn was significantly different among the three groups. Healthy subjects showed minimal staining using AT8 and α-syn. The PD group showed significantly higher α-syn and AT8 immunopositivity, while the PSP group only expressed higher AT8 immunopositivity than HCs. These data suggest that the skin reflects brain pathology. Therefore, immunohistochemical analysis of p-tau and α-syn in the skin can be useful for further characterization of PD and PSP.

Iron deposition in skin of patients with haemochromatosis

NASA Astrophysics Data System (ADS)

Pinheiro, T.; Silva, J. N.; Alves, L. C.; Filipe, P.

2003-09-01

Haemochromatosis is the most common inherited liver disease in Caucasians and the most common autosomal recessive genetic disorder. It is characterized by inappropriately high iron absorption resulting in progressive iron overload in parenchymal organs such as liver, heart, pancreas, pituitary, joints, and skin. Upon early detection, haemochromatosis can be a manageable chronic disease but, if undetected, is potentially fatal. Skin biopsies were obtained from patients and from healthy donors. Images of the elemental distributions in skin were obtained using nuclear microscopy techniques (nuclear microprobe, NMP). Elemental profiles along skin, and intra-, and extra-cellular iron concentrations, were determined. Results for patients with haemochromatosis were cross-examined with morphologic features and with data obtained for healthy skin. Skin iron content is much increased in patients with haemochromatosis when compared with healthy subjects. Extensive iron deposits are observed at dermis, at the dermo-epidermal interface, at upper epidermis layers and at stratum corneum. Iron deposition was observed preferentially at cell boundaries or at the interstitial matrix.

Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis.

PubMed

Li, Jingting; Sen, George L

2015-12-14

Organotypic cultures allow the reconstitution of a 3D environment critical for cell-cell contact and cell-matrix interactions which mimics the function and physiology of their in vivo tissue counterparts. This is exemplified by organotypic skin cultures which faithfully recapitulates the epidermal differentiation and stratification program. Primary human epidermal keratinocytes are genetically manipulable through retroviruses where genes can be easily overexpressed or knocked down. These genetically modified keratinocytes can then be used to regenerate human epidermis in organotypic skin cultures providing a powerful model to study genetic pathways impacting epidermal growth, differentiation, and disease progression. The protocols presented here describe methods to prepare devitalized human dermis as well as to genetically manipulate primary human keratinocytes in order to generate organotypic skin cultures. Regenerated human skin can be used in downstream applications such as gene expression profiling, immunostaining, and chromatin immunoprecipitations followed by high throughput sequencing. Thus, generation of these genetically modified organotypic skin cultures will allow the determination of genes that are critical for maintaining skin homeostasis.

Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers.

PubMed

Fernandes, Ana R; Santos, Ana C; Sanchez-Lopez, Elena; Kovačević, Andjekla B; Espina, Marta; Calpena, Ana C; Veiga, Francisco J; Garcia, Maria L; Souto, Eliana B

2018-01-01

Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options. © 2017 S. Karger AG, Basel.

Progress against cancer in the Netherlands since the late 1980s: an epidemiological evaluation.

PubMed

Karim-Kos, Henrike E; Kiemeney, Lambertus A L M; Louwman, Marieke W J; Coebergh, Jan Willem W; de Vries, Esther

2012-06-15

Progress against cancer through prevention and treatment is often measured by survival statistics only instead of analyzing trends in incidence, survival and mortality simultaneously because of interactive influences. This study combines these parameters of major cancers to provide an overview of the progress achieved in the Netherlands since 1989 and to establish in which areas action is needed. The population-based Netherlands Cancer Registry and Statistics Netherlands provided incidence, 5-year relative survival and mortality of 23 major cancer types. Incidence, survival and mortality changes were calculated as the estimated annual percentage change. Optimal progress was defined as decreasing incidence and/or improving survival accompanied by declining mortality, and deterioration as increasing incidence and/or deteriorating survival accompanied by increasing mortality rates. Optimal progress was observed in 12 of 19 cancer types among males: laryngeal, lung, stomach, gallbladder, colon, rectal, bladder, prostate and thyroid cancer, leukemia, Hodgkin and non-Hodgkin lymphoma. Among females, optimal progress was observed in 12 of 21 cancers: stomach, gallbladder, colon, rectal, breast, cervical, uterus, ovarian and thyroid cancer, leukemia, Hodgkin and non-Hodgkin lymphoma. Deterioration occurred in three cancer types among males: skin melanoma, esophageal and kidney cancer, and among females six cancer types: skin melanoma, oral cavity, pharyngeal, esophageal, pancreatic and lung cancer. Our conceptual framework limits misinterpretations from separate trends and generates a more balanced discussion on progress. Copyright © 2011 UICC.

Chemically induced skin carcinogenesis: Updates in experimental models (Review)

PubMed Central

NEAGU, MONICA; CARUNTU, CONSTANTIN; CONSTANTIN, CAROLINA; BODA, DANIEL; ZURAC, SABINA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

2016-01-01

Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands-on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro-inflammatory cytokines, and simultaneous inflammation sustained by pro-inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

Biomarkers predict outcome in Charcot-Marie-Tooth disease 1A.

PubMed

Fledrich, Robert; Mannil, Manoj; Leha, Andreas; Ehbrecht, Caroline; Solari, Alessandra; Pelayo-Negro, Ana L; Berciano, José; Schlotter-Weigel, Beate; Schnizer, Tuuli J; Prukop, Thomas; Garcia-Angarita, Natalia; Czesnik, Dirk; Haberlová, Jana; Mazanec, Radim; Paulus, Walter; Beissbarth, Tim; Walter, Maggie C; Triaal, Cmt-; Hogrel, Jean-Yves; Dubourg, Odile; Schenone, Angelo; Baets, Jonathan; De Jonghe, Peter; Shy, Michael E; Horvath, Rita; Pareyson, Davide; Seeman, Pavel; Young, Peter; Sereda, Michael W

2017-11-01

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited neuropathy, a debilitating disease without known cure. Among patients with CMT1A, disease manifestation, progression and severity are strikingly variable, which poses major challenges for the development of new therapies. Hence, there is a strong need for sensitive outcome measures such as disease and progression biomarkers, which would add powerful tools to monitor therapeutic effects in CMT1A. We established a pan-European and American consortium comprising nine clinical centres including 311 patients with CMT1A in total. From all patients, the CMT neuropathy score and secondary outcome measures were obtained and a skin biopsy collected. In order to assess and validate disease severity and progression biomarkers, we performed qPCR on a set of 16 animal model-derived potential biomarkers in skin biopsy mRNA extracts. In 266 patients with CMT1A, a cluster of eight cutaneous transcripts differentiates disease severity with a sensitivity and specificity of 90% and 76.1%, respectively. In an additional cohort of 45 patients with CMT1A, from whom a second skin biopsy was taken after 2-3 years, the cutaneous mRNA expression of GSTT2, CTSA, PPARG, CDA, ENPP1 and NRG1-Iis changing over time and correlates with disease progression. In summary, we provide evidence that cutaneous transcripts in patients with CMT1A serve as disease severity and progression biomarkers and, if implemented into clinical trials, they could markedly accelerate the development of a therapy for CMT1A. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pediatric Scleroderma –Systemic and Localized Forms

PubMed Central

Torok, Kathryn S.

2012-01-01

Synopsis statement Pediatric scleroderma includes two major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, with an initial inflammatory phase associated with endothelial activation, and a later fibrotic phase evidenced by collagenization of tissue and appreciable skin thickness, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, and though not fatal like SSc, up to a quarter of the patients may have extracutaneous disease manifestations, such as arthritis and uveitis. While any organ may be affected in SSc, vascular (Raynaud’s phenomenon), cutaneous (skin thickening), GI, pulmonary and musculoskeletal involvement are most commonly seen in children. Auto-antibody profiles in childhood onset SSc can assist in predicting internal organ involvement. Treatment for both forms of scleroderma targets the active inflammatory stage and halts disease progression; however, progress still needs to be made towards the development of a more effective anti-fibrotic therapy to help reverse disease damage. PMID:22560576

Sun protection education for diverse audiences: need for skin cancer pictures.

PubMed

Guevara, Yanina; Gaber, Rikki; Clayman, Marla L; Gordon, Elisa J; Friedewald, John; Robinson, June K

2015-03-01

Sun protection education is needed for kidney transplant recipients, whose increased risk of skin cancer could be ameliorated with sun protection. Cognitive interviews with 24 participants equally stratified among non-Hispanic White, non-Hispanic Black, and Hispanic/Latino kidney transplant recipients were performed to evaluate a sun protection education workbook. Study participants were recruited over the phone using a registry of 700 kidney transplant recipients. Participants included 12 women and 12 men with a median age of 52. In 16 of the cognitive interviews with non-Hispanic Blacks and Hispanic/Latinos, pictures of skin cancer were requested by the participants in order to see the appearance of skin cancer. Kidney transplant recipients with skin of color did not consider themselves at risk to develop skin cancer and wanted to see examples of skin cancer occurring on people with skin of color. Based on these results, the workbook was modified to include pictures of squamous cell carcinoma on varying skin tones. Then, 8 participants evaluated the revised workbook in cognitive interviews and found the photographs acceptable and necessary to demonstrate the severity of skin cancer and personalize their risk of developing skin cancer. The participants progressed from having knowledge of skin cancer to believing that they could develop skin cancer because they observed skin cancers on people with their skin tone. Using pictures of skin cancers occurring on people with similar skin tone may heighten a kidney transplant recipients' sense of vulnerability and possibly improve the use of sun protection.

Substance P promotes wound healing in diabetes by modulating inflammation and macrophage phenotype.

PubMed

Leal, Ermelindo C; Carvalho, Eugénia; Tellechea, Ana; Kafanas, Antonios; Tecilazich, Francesco; Kearney, Cathal; Kuchibhotla, Sarada; Auster, Michael E; Kokkotou, Efi; Mooney, David J; LoGerfo, Frank W; Pradhan-Nabzdyk, Leena; Veves, Aristidis

2015-06-01

Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear. We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds. We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models. SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process. SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing. In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Towards universal Kangaroo Mother Care: recommendations and report from the First European conference and Seventh International Workshop on Kangaroo Mother Care.

PubMed

Nyqvist, K H; Anderson, G C; Bergman, N; Cattaneo, A; Charpak, N; Davanzo, R; Ewald, U; Ibe, O; Ludington-Hoe, S; Mendoza, S; Pallás-Allonso, C; Ruiz Peláez, J G; Sizun, J; Widström, A-M

2010-06-01

The hallmark of Kangaroo Mother Care (KMC) is the kangaroo position: the infant is cared for skin-to-skin vertically between the mother's breasts and below her clothes, 24 h/day, with father/substitute(s) participating as KMC providers. Intermittent KMC (for short periods once or a few times per day, for a variable number of days) is commonly employed in high-tech neonatal intensive care units. These two modalities should be regarded as a progressive adaptation of the mother-infant dyad, ideally towards continuous KMC, starting gradually and progressively with intermittent KMC. The other components in KMC are exclusive breastfeeding (ideally) and early discharge in kangaroo position with strict follow-up. Current evidence allows the following general statements about KMC in affluent and low-income settings: KMC enhances bonding and attachment; reduces maternal postpartum depression symptoms; enhances infant physiologic stability and reduces pain, increases parental sensitivity to infant cues; contributes to the establishment and longer duration of breastfeeding and has positive effects on infant development and infant/parent interaction. Therefore, intrapartum and postnatal care in all types of settings should adhere to a paradigm of nonseparation of infants and their mothers/families. Preterm/low-birth-weight infants should be regarded as extero-gestational foetuses needing skin-to-skin contact to promote maturation. Kangaroo Mother Care should begin as soon as possible after birth, be applied as continuous skin-to-skin contact to the extent that this is possible and appropriate and continue for as long as appropriate.

In vitro permeation of palladium powders through intact and damaged human skin.

PubMed

Crosera, Matteo; Mauro, Marcella; Bovenzi, Massimo; Adami, Gianpiero; Baracchini, Elena; Maina, Giovanni; Larese Filon, Francesca

2018-05-01

The use of palladium (Pd) has grown in the last decades, commonly used in automotive catalytic converters, jewellery and dental restorations sectors. Both general and working population can be exposed to this metal, which may act as skin sensitizer. This study investigated in vitro palladium powders permeation through excised intact and damaged human skin using the Franz diffusion cell method and the effect of rapid skin decontamination using sodium laureth-sulphate. 1 mL of a 10 min sonicated suspension made of 2.5 g of Pd powder in 50 mL synthetic sweat at pH 4.5 and room temperature was applied to the outer surface of the skin membranes for 24 h. Pd permeation, assessed by ICP-MS, was higher when damaged skin was used (p = 0.03). Final flux permeation values and lag times were 0.02 ± 0.01 μg cm -2  h -1 and 6.00 ± 3.95 h for intact, and 0.10 ± 0.02 μg cm -2  h -1 and 2.05 ± 1.49 h for damaged skin samples, respectively. Damaged skin protocol enhances Pd skin penetration inside dermal layer (p = 0.04), thus making the metal available for systemic uptake. Pd penetration (p = 0.02) and permeation (p = 0.012) through intact skin decreased significantly when a cleaning procedure was applied. This study demonstrates that after skin exposure to Pd powders a small permeation of the metal happen both through intact and damaged skin and that an early decontamination with a common cleanser can significantly decrease the final amount of metal available forsystemic uptake. Copyright © 2018 Elsevier B.V. All rights reserved.

A Framework for Measuring the Progress in Exoskeleton Skills in People with Complete Spinal Cord Injury

PubMed Central

van Dijsseldonk, Rosanne B.; Rijken, Hennie; van Nes, Ilse J. W.; van de Meent, Henk; Keijsers, Noel L. W.

2017-01-01

For safe application of exoskeletons in people with spinal cord injury at home or in the community, it is required to have completed an exoskeleton training in which users learn to perform basic and advanced skills. So far, a framework to test exoskeleton skills is lacking. The aim of this study was to develop and test the hierarchy and reliability of a framework for measuring the progress in the ability to perform basic and advanced skills. Twelve participants with paraplegia were given twenty-four training sessions in 8 weeks with the Rewalk-exoskeleton. During the 2nd, 4th, and 6th training week the Intermediate-skills-test was performed consisting of 27 skills, measured in an hierarchical order of difficulty, until two skills were not achieved. When participants could walk independently, the Final-skills-test, consisting of 20 skills, was performed in the last training session. Each skill was performed at least two times with a maximum of three attempts. As a reliability measure the consistency was used, which was the number of skills performed the same in the first two attempts relative to the total number. Ten participants completed the training program. Their number of achieved intermediate skills was significantly different between the measurements XF2(2) = 12.36, p = 0.001. Post-hoc analysis revealed a significant increase in the median achieved intermediate skills from 4 [1–7] at the first to 10.5 [5–26] at the third Intermediate-skills-test. The rate of participants who achieved the intermediate skills decreased and the coefficient of reproducibility was 0.98. Eight participants met the criteria to perform the Final-skills-test. Their median number of successfully performed final skills was 16.5 [13–20] and 17 [14–19] skills in the first and second time. The overall consistency of >70% was achieved in the Intermediate-skills-test (73%) and the Final-skills-test (81%). Eight out of twelve participants experienced skin damage during the training, in four participants this resulted in missed training sessions. The framework proposed in this study measured the progress in performing basic and advanced exoskeleton skills during a training program. The hierarchical ordered skills-test could discriminate across participants' skill-level and the overall consistency was considered acceptable. PMID:29311780

A Framework for Measuring the Progress in Exoskeleton Skills in People with Complete Spinal Cord Injury.

PubMed

van Dijsseldonk, Rosanne B; Rijken, Hennie; van Nes, Ilse J W; van de Meent, Henk; Keijsers, Noel L W

2017-01-01

For safe application of exoskeletons in people with spinal cord injury at home or in the community, it is required to have completed an exoskeleton training in which users learn to perform basic and advanced skills. So far, a framework to test exoskeleton skills is lacking. The aim of this study was to develop and test the hierarchy and reliability of a framework for measuring the progress in the ability to perform basic and advanced skills. Twelve participants with paraplegia were given twenty-four training sessions in 8 weeks with the Rewalk-exoskeleton. During the 2nd, 4th, and 6th training week the Intermediate-skills-test was performed consisting of 27 skills, measured in an hierarchical order of difficulty, until two skills were not achieved. When participants could walk independently, the Final-skills-test, consisting of 20 skills, was performed in the last training session. Each skill was performed at least two times with a maximum of three attempts. As a reliability measure the consistency was used, which was the number of skills performed the same in the first two attempts relative to the total number. Ten participants completed the training program. Their number of achieved intermediate skills was significantly different between the measurements X F 2 (2) = 12.36, p = 0.001. Post-hoc analysis revealed a significant increase in the median achieved intermediate skills from 4 [1-7] at the first to 10.5 [5-26] at the third Intermediate-skills-test. The rate of participants who achieved the intermediate skills decreased and the coefficient of reproducibility was 0.98. Eight participants met the criteria to perform the Final-skills-test. Their median number of successfully performed final skills was 16.5 [13-20] and 17 [14-19] skills in the first and second time. The overall consistency of >70% was achieved in the Intermediate-skills-test (73%) and the Final-skills-test (81%). Eight out of twelve participants experienced skin damage during the training, in four participants this resulted in missed training sessions. The framework proposed in this study measured the progress in performing basic and advanced exoskeleton skills during a training program. The hierarchical ordered skills-test could discriminate across participants' skill-level and the overall consistency was considered acceptable.

RACK1, a clue to the diagnosis of cutaneous melanomas in horses.

PubMed

Campagne, Cécile; Julé, Sophia; Bernex, Florence; Estrada, Mercedes; Aubin-Houzelstein, Geneviève; Panthier, Jean-Jacques; Egidy, Giorgia

2012-06-29

Melanocytic proliferations are common in horses but the diagnosis of malignancy is not always straightforward. To improve diagnosis and prognosis, markers of malignancy are needed. Receptor for activated C kinase 1 (RACK1) protein may be such a marker. RACK1 was originally found to characterize malignant melanocytic lesions in the Melanoblastoma-bearing Libechov minipig (MeLiM) and, later, in human patients. Our purpose was to investigate the value of RACK1 in the classification of cutaneous melanocytic proliferations in horses. Using immunofluorescence, we report here that both MITF (Microphthalmia-associated transcription factor) and PAX3 (Paired box 3) allow the identification of melanocytic cells in horse skin samples. Importantly, RACK1 was detected in melanocytic lesions but not in healthy skin melanocytes. Finally, we found that RACK1 labeling can be used in horses to distinguish benign melanocytic tumors from melanomas. Indeed, RACK1 labeling appeared more informative to assess malignancy than individual histomorphological features. This study confirms that horses provide an interesting model for melanoma genesis studies. It establishes MITF and PAX3 as markers of horse melanocytic cells. RACK1 emerges as an important marker of malignancy which may contribute to progress in the diagnosis of melanomas in both human and veterinary medicine.

RACK1, a clue to the diagnosis of cutaneous melanomas in horses

PubMed Central

2012-01-01

Background Melanocytic proliferations are common in horses but the diagnosis of malignancy is not always straightforward. To improve diagnosis and prognosis, markers of malignancy are needed. Receptor for activated C kinase 1 (RACK1) protein may be such a marker. RACK1 was originally found to characterize malignant melanocytic lesions in the Melanoblastoma-bearing Libechov minipig (MeLiM) and, later, in human patients. Our purpose was to investigate the value of RACK1 in the classification of cutaneous melanocytic proliferations in horses. Results Using immunofluorescence, we report here that both MITF (Microphthalmia-associated transcription factor) and PAX3 (Paired box 3) allow the identification of melanocytic cells in horse skin samples. Importantly, RACK1 was detected in melanocytic lesions but not in healthy skin melanocytes. Finally, we found that RACK1 labeling can be used in horses to distinguish benign melanocytic tumors from melanomas. Indeed, RACK1 labeling appeared more informative to assess malignancy than individual histomorphological features. Conclusions This study confirms that horses provide an interesting model for melanoma genesis studies. It establishes MITF and PAX3 as markers of horse melanocytic cells. RACK1 emerges as an important marker of malignancy which may contribute to progress in the diagnosis of melanomas in both human and veterinary medicine. PMID:22747534

Antibodies to elastin peptides in sera of Belgian Draught horses with chronic progressive lymphoedema.

PubMed

van Brantegem, L; de Cock, H E V; Affolter, V K; Duchateau, L; Hoogewijs, M K; Govaere, J; Ferraro, G L; Ducatelle, R

2007-09-01

Chronic progressive lymphoedema (CPL) is a recently recognised disease of the lymphatic system characterised by lesions in the skin of the lower legs in several draught horse breeds, including the Belgian Draught hourse. Clinical signs slowly progress and result in severe disfigurement of the limbs. Ideally, supportive treatment should be started early in the disease process. However early diagnosis and monitoring progression of CPL is still a challenge. Elastin changes, characterised by morphological alterations as well as increased desmosine levels, in the skin of the distal limbs of horses affected with CPL are probably associated with a marked release of elastin degradation products, which elicit production of circulating anti-elastin antibodies (AEAbs) in the serum. An enzyme-linked immunosorbent assay (ELISA) for detection of serum AEAbs may document elastin breakdown. An ELISA technique was used to evaluate levels of AEAbs in sera of 97 affected Belgian Draught horses that were clinically healthy except for possible skin lesions, associated with CPL in their distal limbs. The horses were divided into 5 groups according to the severity of these skin lesions: normal horses (Group 1, n = 36), horses with mild lesions (Group 2, n = 43), horses with moderate lesions (Group 3, n = 8), horses with severe lesions (Group 4, n = 10) and, as a control, healthy Warmblood horses, unaffected by the disease (Group 5, n = 83). Horses with clinical signs of CPL had significantly higher AEAb levels compared to clinically normal Belgian Draught horses and to healthy Warmblood horses. These levels correlated with severity of lesions. CPL in draught horses is associated with an increase of serum AEAbs. Evaluation of serum levels of AEAbs by ELISA might be a useful diagnostic aid for CPL. Pathological degradation of elastic fibres, resulting in deficient support of the distal lymphatics, is proposed as a contributing factor for CPL in Belgian Draught horses.

Dense deconvolution net: Multi path fusion and dense deconvolution for high resolution skin lesion segmentation.

PubMed

He, Xinzi; Yu, Zhen; Wang, Tianfu; Lei, Baiying; Shi, Yiyan

2018-01-01

Dermoscopy imaging has been a routine examination approach for skin lesion diagnosis. Accurate segmentation is the first step for automatic dermoscopy image assessment. The main challenges for skin lesion segmentation are numerous variations in viewpoint and scale of skin lesion region. To handle these challenges, we propose a novel skin lesion segmentation network via a very deep dense deconvolution network based on dermoscopic images. Specifically, the deep dense layer and generic multi-path Deep RefineNet are combined to improve the segmentation performance. The deep representation of all available layers is aggregated to form the global feature maps using skip connection. Also, the dense deconvolution layer is leveraged to capture diverse appearance features via the contextual information. Finally, we apply the dense deconvolution layer to smooth segmentation maps and obtain final high-resolution output. Our proposed method shows the superiority over the state-of-the-art approaches based on the public available 2016 and 2017 skin lesion challenge dataset and achieves the accuracy of 96.0% and 93.9%, which obtained a 6.0% and 1.2% increase over the traditional method, respectively. By utilizing Dense Deconvolution Net, the average time for processing one testing images with our proposed framework was 0.253 s.

[Effect of tobacco smoking on skin and mucosa appearance, ageing and pathological conditions].

PubMed

Czogała, Jan; Goniewicz, Maciej Ł; Czubek, Agnieszka; Gołabek, Karolina; Sobczak, Andrzej

2008-01-01

Tobacco smoking is considered to be one of the main factors that negatively affect the skin, mucous membranes and teeth, i.e. the body parts that decide on the so called 'healthy look' and 'attraction'. This paper is a review of literature on the subject of harmful and pathological influence of tobacco smoking on the skin and the immunological system. Furthermore, the paper described such smoking results as wrinkle development, skin elasticity and thickness loss, as well as a decreased ability of tissues to regenerate. Finally, the authors discussed various diseases connected with tobacco use: changes in the skin, teeth and mucous membranes, and cancerous lesions.

Inhibitory effects of B‑cell translocation gene 2 on skin cancer cells via the Wnt/β‑catenin signaling pathway.

PubMed

Gao, Shou-Song; Yang, Xiao-Hong; Wang, Meng

2016-10-01

B-cell translocation gene 2 (BTG2), a tumor suppressor gene, is downregulated in several types of human cancer cell. However, its function in skin cancer cells has not been fully elucidated. Therefore, the present study investigated the expression and function of BTG2 in skin cancer cells, and investigated the underlying molecular mechanism. The results indicated that BTG2 expression was downregulated in skin cancer cell lines. Overexpression of BTG2 significantly inhibited cell proliferation, cell cycle progression, and the invasion and migration of skin cancer cells. Furthermore, it was determined that overexpression of BTG2 significantly decreased the protein expression levels of β‑catenin, cyclin D1 and v‑myc avian myelocytomatosis viral oncogene homolog in skin cancer cells. This suggests that BTG2 may function as a tumor suppressor by interfering with the Wnt/β‑catenin signaling pathway in skin cancer cells. Thus, novel therapeutic strategies and agents targeting BTG2 may be potential treatments for skin cancer.

Hyperactivation of JAK1 tyrosine kinase induces stepwise, progressive pruritic dermatitis

PubMed Central

Yasuda, Takuwa; Fukada, Toshiyuki; Nishida, Keigo; Nakayama, Manabu; Matsuda, Masashi; Miura, Ikuo; Fukuda, Shinji; Kabashima, Kenji; Nakaoka, Shinji; Bin, Bum-Ho; Kubo, Masato; Hasegawa, Takanori; Ohara, Osamu; Koseki, Haruhiko; Wakana, Shigeharu

2016-01-01

Skin homeostasis is maintained by the continuous proliferation and differentiation of epidermal cells. The skin forms a strong but flexible barrier against microorganisms as well as physical and chemical insults; however, the physiological mechanisms that maintain this barrier are not fully understood. Here, we have described a mutant mouse that spontaneously develops pruritic dermatitis as the result of an initial defect in skin homeostasis that is followed by induction of a Th2-biased immune response. These mice harbor a mutation that results in a single aa substitution in the JAK1 tyrosine kinase that results in hyperactivation, thereby leading to skin serine protease overexpression and disruption of skin barrier function. Accordingly, treatment with an ointment to maintain normal skin barrier function protected mutant mice from dermatitis onset. Pharmacological inhibition of JAK1 also delayed disease onset. Together, these findings indicate that JAK1-mediated signaling cascades in skin regulate the expression of proteases associated with the maintenance of skin barrier function and demonstrate that perturbation of these pathways can lead to the development of spontaneous pruritic dermatitis. PMID:27111231

Hyperactivation of JAK1 tyrosine kinase induces stepwise, progressive pruritic dermatitis.

PubMed

Yasuda, Takuwa; Fukada, Toshiyuki; Nishida, Keigo; Nakayama, Manabu; Matsuda, Masashi; Miura, Ikuo; Dainichi, Teruki; Fukuda, Shinji; Kabashima, Kenji; Nakaoka, Shinji; Bin, Bum-Ho; Kubo, Masato; Ohno, Hiroshi; Hasegawa, Takanori; Ohara, Osamu; Koseki, Haruhiko; Wakana, Shigeharu; Yoshida, Hisahiro

2016-06-01

Skin homeostasis is maintained by the continuous proliferation and differentiation of epidermal cells. The skin forms a strong but flexible barrier against microorganisms as well as physical and chemical insults; however, the physiological mechanisms that maintain this barrier are not fully understood. Here, we have described a mutant mouse that spontaneously develops pruritic dermatitis as the result of an initial defect in skin homeostasis that is followed by induction of a Th2-biased immune response. These mice harbor a mutation that results in a single aa substitution in the JAK1 tyrosine kinase that results in hyperactivation, thereby leading to skin serine protease overexpression and disruption of skin barrier function. Accordingly, treatment with an ointment to maintain normal skin barrier function protected mutant mice from dermatitis onset. Pharmacological inhibition of JAK1 also delayed disease onset. Together, these findings indicate that JAK1-mediated signaling cascades in skin regulate the expression of proteases associated with the maintenance of skin barrier function and demonstrate that perturbation of these pathways can lead to the development of spontaneous pruritic dermatitis.

Burn Rehabilitation and Research: Proceedings of a Consensus Summit

DTIC Science & Technology

2009-08-01

to determine appropriate utilization of therapy services. As patients with burn in- juries progress through various stages of recovery, their...tissue align- ment of an associated joint or anatomic structure. Contractures can affect a skin crease, skin juncture, or margin and may secondarily...comprehensive burn rehabilitation data base Increase utilization of current web sites for global communication Journal of Burn Care & Research 548

Cell-type-specific roles for COX-2 in UVB-induced skin cancer

PubMed Central

Herschman, Harvey

2014-01-01

In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2 flox/flox mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2 flox/flox;K14Cre + mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2 flox/flox;K14Cre + papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2 flox/flox; LysMCre + myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer. PMID:24469308

Cell-type-specific roles for COX-2 in UVB-induced skin cancer.

PubMed

Jiao, Jing; Mikulec, Carol; Ishikawa, Tomo-o; Magyar, Clara; Dumlao, Darren S; Dennis, Edward A; Fischer, Susan M; Herschman, Harvey

2014-06-01

In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2(flox/flox) mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2(flox/flox);K14Cre(+) mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2(flox/flox);K14Cre(+) papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2(flox/flox); LysMCre(+) myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The management of skin toxicity during cetuximab treatment in advanced colorectal cancer: how much does it cost? A retrospecive economic assessment from a single-center experience.

PubMed

Giuliani, Jacopo; Indelli, Monica; Marzola, Marina; Raisi, Elena; Frassoldati, Antonio

2012-01-01

Skin rash is a predictable and manageable side effect of anti-EGFR therapy such as cetuximab. The aim of this study is to estimate the costs for the foreseeable management of skin toxicity in patients treated with cetuximab in our institute in order to assess the direct medical economic impact. We retrospectively analyzed all consecutive patients with advanced colorectal cancer treated with cetuximab at our institute from June 2006 to May 2011. We evaluated the severity and mean duration of skin rash for each grade and we identified the costs for the different therapeutic interventions. Patients were treated according to the general consensus management of skin toxicity associated with cetuximab treatment. We evaluated 31 patients. The median follow-up was 28.95 months (range, 1.84-75.49). At last follow-up 10 patients (32.3%) were alive with metastases, 18 patients (58.1%) had died, 1 patient (3.2%) was alive without evidence of disease, and 2 patients (6.5%) were lost to follow-up. The median progression-free survival was 8.26 months and the median overall survival 32.89 months. Nineteen patients (61.3%) developed skin toxicities: 7 patients (22.6%) grade 1, 9 patients (29.0%) grade 2, 3 patients (9.7%) grade 3; no grade 4 skin toxicity was observed. The median duration of grade 1 toxicity was 79 days (no specific treatments were started), of grade 2 toxicity 95 days (cost range, € 199.50-294.50) and of grade 3 toxicity 64 days (cost range, € 159.42-233.90). Our experience, through the analysis of nonselected cases, showed that the management of skin toxicities related to cetuximab is not so expensive. We recommend proper care of low-grade toxicities in order to reduce progression to high-grade toxicities and the resulting risk of hospitalization, which really impacts on costs.

Human Skin Cells Are More Sensitive than Human Lung Cells to the Cytotoxic and Cell Cycle Arresting Impacts of Particulate and Soluble Hexavalent Chromium

PubMed Central

Xie, Hong; Holmes, Amie L.; Wise, Sandra S.; Young, Jamie L.; Wise, James T. F.; Wise, John Pierce

2015-01-01

Hexavalent chromium Cr(VI) is a known human lung carcinogen, with solubility playing an important role in its carcinogenic potency. Dermal exposure to Cr(VI) is common and has been associated with skin damage; however, no link between chromate exposure and skin cancer has been found. In this study, we compared the cytotoxic and clastogenic effects of Cr(VI) and its impacts on cell cycle progression in human lung and skin fibroblasts. We found human skin cells arrested earlier in their cell cycle and exhibit more cytotoxicity than human lung cells, despite taking up similar amounts of Cr. These outcomes are consistent with a hypothesis that different cellular and molecular responses underlie the differences in carcinogenic outcome in these two tissues. PMID:25805272

Raman microspectroscopy as a diagnostic tool for the non-invasive analysis of fibrillin-1 deficiency in the skin and in the in vitro skin models.

PubMed

Brauchle, Eva; Bauer, Hannah; Fernes, Patrick; Zuk, Alexandra; Schenke-Layland, Katja; Sengle, Gerhard

2017-04-01

Fibrillin microfibrils and elastic fibers are critical determinants of elastic tissues where they define as tissue-specific architectures vital mechanical properties such as pliability and elastic recoil. Fibrillin microfibrils also facilitate elastic fiber formation and support the association of epithelial cells with the interstitial matrix. Mutations in fibrillin-1 (FBN1) are causative for the Marfan syndrome, a congenital multisystem disorder characterized by progressive deterioration of the fibrillin microfibril/ elastic fiber architecture in the cardiovascular, musculoskeletal, ocular, and dermal system. In this study, we utilized Raman microspectroscopy in combination with principal component analysis (PCA) to analyze the molecular consequences of fibrillin-1 deficiency in skin of a mouse model (GT8) of Marfan syndrome. In addition, full-thickness skin models incorporating murine wild-type and Fbn1 GT8/GT8 fibroblasts as well as human HaCaT keratinocytes were generated and analyzed. Skin models containing GT8 fibroblasts showed an altered epidermal morphology when compared to wild-type models indicating a new role for fibrillin-1 in dermal-epidermal crosstalk. Obtained Raman spectra together with PCA allowed to discriminate between healthy and deficient microfibrillar networks in murine dermis and skin models. Interestingly, results obtained from GT8 dermis and skin models showed similar alterations in molecular signatures triggered by fibrillin-1 deficiency such as amide III vibrations and decreased levels of glycan vibrations. Overall, this study indicates that Raman microspectroscopy has the potential to analyze subtle changes in fibrillin-1 microfibrils and elastic fiber networks. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. Mutations in building blocks of the fibrillin microfibril/ elastic fiber network manifest in disease conditions such as aneurysms, emphysema or lax skin. Understanding how structural changes induced by fibrillin-1 mutation impact the architecture of fibrillin microfibrils, which then translates into an altered activation state of targeted growth factors, represents a huge challenge in elucidating the genotype-phenotype correlations in connective tissue disorders such as Marfan syndrome. This study shows that Raman microspectroscopy is able to reveal structural changes in fibrillin-1 microfibrils and elastic fiber networks and to discriminate between normal and diseased networks in vivo and in vitro. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Modeling Delamination in Postbuckled Composite Structures Under Static and Fatigue Loads

NASA Technical Reports Server (NTRS)

Bisagni, Chiara; Brambilla, Pietro; Bavila, Carlos G.

2013-01-01

The ability of the Abaqus progressive Virtual Crack Closure Technique (VCCT) to model delamination in composite structures was investigated for static, postbuckling, and fatigue loads. Preliminary evaluations were performed using simple Double Cantilever Beam (DCB) and Mixed-Mode Bending (MMB) specimens. The nodal release sequences that describe the propagation of the delamination front were investigated. The effect of using a sudden or a gradual nodal release was evaluated by considering meshes aligned with the crack front as well as misaligned meshes. Fatigue simulations were then performed using the Direct Cyclic Fatigue (DCF) algorithm. It was found that in specimens such as the DCB, which are characterized by a nearly linear response and a pure fracture mode, the algorithm correctly predicts the Paris Law rate of propagation. However, the Abaqus DCF algorithm does not consider different fatigue propagation laws in different fracture modes. Finally, skin/stiffener debonding was studied in an aircraft fuselage subcomponent in which debonding occurs deep into post-buckling deformation. VCCT was shown to be a robust tool for estimating the onset propagation. However, difficulties were found with the ability of the current implementation of the Abaqus progressive VCCT to predict delamination propagation within structures subjected to postbuckling deformations or fatigue loads.

Multiple-reflection model of human skin and estimation of pigment concentrations

NASA Astrophysics Data System (ADS)

Ohtsuki, Rie; Tominaga, Shoji; Tanno, Osamu

2012-07-01

We describe a new method for estimating the concentrations of pigments in the human skin using surface spectral reflectance. We derive an equation that expresses the surface spectral reflectance of the human skin. First, we propose an optical model of the human skin that accounts for the stratum corneum. We also consider the difference between the scattering coefficient of the epidermis and that of the dermis. We then derive an equation by applying the Kubelka-Munk theory to an optical model of the human skin. Unlike a model developed in a recent study, the present equation considers pigments as well as multiple reflections and the thicknesses of the skin layers as factors that affect the color of the human skin. In two experiments, we estimate the pigment concentrations using the measured surface spectral reflectances. Finally, we confirm the feasibility of the concentrations estimated by the proposed method by evaluating the estimated pigment concentrations in the skin.

Photoprotective Potential of Penta-O-Galloyl-β-DGlucose by Targeting NF-κB and MAPK Signaling in UVB Radiation-Induced Human Dermal Fibroblasts and Mouse Skin.

PubMed

Kim, Byung-Hak; Choi, Mi Sun; Lee, Hyun Gyu; Lee, Song-Hee; Noh, Kum Hee; Kwon, Sunho; Jeong, Ae Jin; Lee, Haeri; Yi, Eun Hee; Park, Jung Youl; Lee, Jintae; Joo, Eun Young; Ye, Sang-Kyu

2015-11-01

Exposure of the skin to ultraviolet radiation can cause skin damage with various pathological changes including inflammation. In the present study, we identified the skin-protective activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (pentagalloyl glucose, PGG) in ultraviolet B (UVB) radiation-induced human dermal fibroblasts and mouse skin. PGG exhibited antioxidant activity with regard to intracellular reactive oxygen species (ROS) generation as well as ROS and reactive nitrogen species (RNS) scavenging. Furthermore, PGG exhibited anti-inflammatory activity, inhibiting the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, resulting in inhibition of the expression of pro-inflammatory mediators. Topical application of PGG followed by chronic exposure to UVB radiation in the dorsal skin of hairless mice resulted in a significant decrease in the progression of inflammatory skin damages, leading to inhibited activation of NF-κB signaling and expression of pro-inflammatory mediators. The present study demonstrated that PGG protected from skin damage induced by UVB radiation, and thus, may be a potential candidate for the prevention of environmental stimuli-induced inflammatory skin damage.

Using a Distant Abdominal Skin Flap to Treat Digital Constriction Bands: A Case Report for Vohwinkel Syndrome.

PubMed

Zhang, Mingzi; Song, Kexin; Ding, Ning; Shu, Chang; Wang, Youbin

2016-02-01

In this study, a Vohwinkel syndrome case is presented where in 5th digit constriction bands in the right hand were reconstructed using a distant abdominal skin flap. Vohwinkel syndrome, or keratoderma hereditarium mutilans, is a rare, autosomal dominant genetic skin condition that causes palmoplantar hyperkeratosis and constricts finger and/or toe bands. In a typical manifestation, the finger and toe constriction bands lead to progressive strangulation and autoamputation, which requires immediate clinical treatment. Topical keratolytics and systemic retinoids have been used to treat hyperkeratosis but without consistent results. Only 1 effective approach for autoamputation has been accepted, reconstructive surgery.Applying a distant abdominal skin flap produced satisfying postoperative effects at the 18-month follow-up.

State of the art in non-animal approaches for skin sensitization testing: from individual test methods towards testing strategies.

PubMed

Ezendam, Janine; Braakhuis, Hedwig M; Vandebriel, Rob J

2016-12-01

The hazard assessment of skin sensitizers relies mainly on animal testing, but much progress is made in the development, validation and regulatory acceptance and implementation of non-animal predictive approaches. In this review, we provide an update on the available computational tools and animal-free test methods for the prediction of skin sensitization hazard. These individual test methods address mostly one mechanistic step of the process of skin sensitization induction. The adverse outcome pathway (AOP) for skin sensitization describes the key events (KEs) that lead to skin sensitization. In our review, we have clustered the available test methods according to the KE they inform: the molecular initiating event (MIE/KE1)-protein binding, KE2-keratinocyte activation, KE3-dendritic cell activation and KE4-T cell activation and proliferation. In recent years, most progress has been made in the development and validation of in vitro assays that address KE2 and KE3. No standardized in vitro assays for T cell activation are available; thus, KE4 cannot be measured in vitro. Three non-animal test methods, addressing either the MIE, KE2 or KE3, are accepted as OECD test guidelines, and this has accelerated the development of integrated or defined approaches for testing and assessment (e.g. testing strategies). The majority of these approaches are mechanism-based, since they combine results from multiple test methods and/or computational tools that address different KEs of the AOP to estimate skin sensitization potential and sometimes potency. Other approaches are based on statistical tools. Until now, eleven different testing strategies have been published, the majority using the same individual information sources. Our review shows that some of the defined approaches to testing and assessment are able to accurately predict skin sensitization hazard, sometimes even more accurate than the currently used animal test. A few defined approaches are developed to provide an estimate of the potency sub-category of a skin sensitizer as well, but these approaches need further independent evaluation with a new dataset of chemicals. To conclude, this update shows that the field of non-animal approaches for skin sensitization has evolved greatly in recent years and that it is possible to predict skin sensitization hazard without animal testing.

Effective Skin Cancer Treatment by Topical Co-delivery of Curcumin and STAT3 siRNA Using Cationic Liposomes.

PubMed

Jose, Anup; Labala, Suman; Ninave, Kunal Manoj; Gade, Sudeep Kumar; Venuganti, Venkata Vamsi Krishna

2018-01-01

The aim of the present study was to evaluate the effectiveness of iontophoretic co-delivery of curcumin and anti-STAT3 siRNA using cationic liposomes against skin cancer. Curcumin was encapsulated in DOTAP-based cationic liposomes and then complexed with STAT3 siRNA. This nanocomplex was characterized for the average particle size, zeta-potential, and encapsulation efficiency. The cell viability studies in B16F10 mouse melanoma cells have shown that the co-delivery of curcumin and STAT3 siRNA significantly (p < 0.05) inhibited the cancer cell growth compared with either liposomal curcumin or STAT3 siRNA alone. The curcumin-loaded liposomes were able to penetrate up to a depth of 160 μm inside the skin after iontophoretic (0.47 mA/cm 2 ) application. The in vivo efficacy studies were performed in the mouse model of melanoma skin cancer. Co-administration of the curcumin and STAT3 siRNA using liposomes significantly (p < 0.05) inhibited the tumor progression as measured by tumor volume and tumor weight compared with either liposomal curcumin or STAT3 siRNA alone. Furthermore, the iontophoretic administration of curcumin-loaded liposome-siRNA complex showed similar effectiveness in inhibiting tumor progression and STAT3 protein suppression compared with intratumoral administration. Taken together, cationic liposomes can be utilized for topical iontophoretic co-delivery of small molecule and siRNA for effective treatment of skin diseases.

Letterman Army Institute of Research Annual Research Progress Report, FY 1981.

DTIC Science & Technology

1981-10-01

with physiology and mech- anisms of skin damage and repair. The mechanisms by which nerve agents and vesicants produce physiologic aberration and...enzyme vital for nerve function. Organophos- phates react rapidly and covalently with the enzyme to produce an in- active enzyme. Reactivation of the...warfare agents . These organic molecules may also alter the natural defense mechanism by activating or deactivating enzymes in the skin that destroy

Adenoid cystic carcinoma of submandibular gland metastatic to great toes: case report and literature review.

PubMed

Rafael, Oana C; Paul, Doru; Chen, Sheng; Kraus, Dennis

2016-08-01

Adenoid cystic carcinoma (ACC) is a rare malignant tumor of the salivary glands, with higher frequency in the submandibular gland, a prolonged clinical course, and poor long-term survival. It tends to metastasize to lungs, bone, liver, brain, and rarely to skin. Comprehensive skin examination and appropriate follow-up is recommended, since cutaneous metastasis represents disease progression, requiring management and prognosis adjustment.

Spontaneous Development of Cutaneous Squamous Cell Carcinoma in Mice with Cell-specific Deletion of Inhibitor of κB Kinase 2

PubMed Central

Kirkley, Kelly S; Walton, Kelly D; Duncan, Colleen; Tjalkens, Ronald B

2017-01-01

The deletion of NFκB in epithelial tissues by using skin-specific promoters can cause both tumor formation and severe inflammatory dermatitis, indicating that this signaling pathway is important for the maintenance of immune homeostasis in epithelial tissues. In the present study, we crossed mice transgenic for loxP-Ikbk2 and human Gfap-cre to selectively delete IKK2 in CNS astrocytes. Unexpectedly, a subset of mice developed severe and progressive skin lesions marked by hyperplasia, hyperkeratosis, dysplasia, inflammation, and neoplasia with a subset of lesions diagnosed as squamous cell carcinoma (SCC). The development of lesions was monitored over a 3.5-y period and over 4 filial generations. Average age of onset of was 4 mo of age with 19.5% of mice affected with frequency increasing in progressive generations. Lesion development appeared to correlate not only with unintended IKK2 deletion in GFAP expressing cells of the epidermis, but also with increased expression of TNF in lesioned skin. The skins changes described in these animals are similar to those in transgenic mice with an epidermis-specific deletion of NFκB and thus represents another genetic mouse model that can be used to study the role of NFκB signaling in regulating the development of SCC. PMID:28935002

Fault-related fold styles and progressions in fold-thrust belts: Insights from sandbox modeling

NASA Astrophysics Data System (ADS)

Yan, Dan-Ping; Xu, Yan-Bo; Dong, Zhou-Bin; Qiu, Liang; Zhang, Sen; Wells, Michael

2016-03-01

Fault-related folds of variable structural styles and assemblages commonly coexist in orogenic belts with competent-incompetent interlayered sequences. Despite their commonality, the kinematic evolution of these structural styles and assemblages are often loosely constrained because multiple solutions exist in their structural progression during tectonic restoration. We use a sandbox modeling instrument with a particle image velocimetry monitor to test four designed sandbox models with multilayer competent-incompetent materials. Test results reveal that decollement folds initiate along selected incompetent layers with decreasing velocity difference and constant vorticity difference between the hanging wall and footwall of the initial fault tips. The decollement folds are progressively converted to fault-propagation folds and fault-bend folds through development of fault ramps breaking across competent layers and are followed by propagation into fault flats within an upper incompetent layer. Thick-skinned thrust is produced by initiating a decollement fault within the metamorphic basement. Progressive thrusting and uplifting of the thick-skinned thrust trigger initiation of the uppermost incompetent decollement with formation of a decollement fold and subsequent converting to fault-propagation and fault-bend folds, which combine together to form imbricate thrust. Breakouts at the base of the early formed fault ramps along the lowest incompetent layers, which may correspond to basement-cover contacts, domes the upmost decollement and imbricate thrusts to form passive roof duplexes and constitute the thin-skinned thrust belt. Structural styles and assemblages in each of tectonic stages are similar to that in the representative orogenic belts in the South China, Southern Appalachians, and Alpine orogenic belts.

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma.

PubMed

Kramkimel, N; Thomas-Schoemann, A; Sakji, L; Golmard, Jl; Noe, G; Regnier-Rosencher, E; Chapuis, N; Maubec, E; Vidal, M; Avril, Mf; Goldwasser, F; Mortier, L; Dupin, N; Blanchet, B

2016-02-01

Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF (V600) -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine patients treated with single-agent vemurafenib were prospectively analyzed. Vemurafenib plasma concentration (n = 159) was measured at days 15, 30, 60, and 90 after treatment initiation. Clinical and biological determinants (including plasma vemurafenib concentration) for efficacy and safety were assessed using Cox's model and multivariate stepwise logistic regression. Median progression-free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 % CI] 2.0-6.0) and 11.0 (95% CI 7.0-16.0) months, respectively. Twenty-nine patients (49 %) experienced any grade ≥3 toxicity and the most frequent grade ≥2 toxicity was skin rash (37 %). Severe toxicities led to definitive discontinuation in seven patients (12 %). Grade ≥2 skin rash was not statistically associated with better objective response at day 60 (p = 0.06) and longer PFS (hazard ratio 0.47; 95 % CI 0.21-1.08; p = 0.075). Grade ≥2 skin rash was statistically increased in patients with ECOG  ≥ 1 (odds ratio 4.67; 95 % CI 1.39-15.70; p = 0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was significantly associated with a shorter PFS (1.5 [0.5-5.5] vs. 4.5 [2-undetermined] months, p = 0.029). Finally, vemurafenib concentration was significantly greater in patients developing grade ≥2 rash (61.7 ± 25.0 vs. 36.3 ± 17.9 mg/L, p < 0.0001). These results suggest that early plasma drug monitoring may help identify outpatients at high risk of non-response or grade ≥ 2 skin rash.

Proteomic analysis reveals the important roles of alpha-5-collagen and ATP5β during skin ulceration syndrome progression of sea cucumber Apostichopus japonicus.

PubMed

Zhao, Zelong; Jiang, Jingwei; Pan, Yongjia; Sun, Hongjuan; Guan, Xiaoyan; Gao, Shan; Chen, Zhong; Dong, Ying; Zhou, Zunchun

2018-03-20

Apostichopus japonicus is one of the most important aquaculture species in China. Skin ulceration syndrome (SUS) of sea cucumber is a common and serious disease affected the development of A. japonicus culture industry. To better understand the response mechanisms of A. japonicus during SUS progression, the protein variations in the body wall of A. japonicus at different stages of SUS were investigated by a comparative proteomic approach based on isobaric tags for relative and absolute quantification. A total of 1449 proteins were identified from the samples at different SUS stages. Among these proteins, 145 proteins were differentially expressed in the SUS-related samples compared to those of healthy A. japonicus. These differentially expressed proteins involved a wide range of functions. Among these differentially expressed proteins, only two proteins, alpha-5-collagen and an unknown function protein, were differentially expressed during the whole progression of SUS compared with healthy A. japonicus. In addition, ATP synthase subunit beta (ATP5β) interacted with a variety of proteins with different functions during the SUS progression. These results implied that alpha-5-collagen and ATP5β could play important roles during the SUS progression of A. japonicus. Our study provided a new sight to understand the molecular responses of sea cucumber during the SUS progression and accumulated data for the prevention of SUS in sea cucumber aquaculture. The current study aimed to reveal how the body wall of Apostichopus japonicus response to skin ulceration syndrome (SUS). To the best of our knowledge, this is the first proteomic study analyzing the differences in protein profile of sea cucumber during the whole SUS progression. By analyzing the expression differences of the proteome via isobaric labeling-based quantitative proteomic, we identified some proteins which may play important roles during the SUS progression. According to the enrichment analyses of these proteins based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, a draft view of how the sea cucumber affected by SUS has been drawn. The common and unique differentially expressed proteins by Venn analysis showed that alpha-5-collagen was down-regulated at all stages of SUS, which had the potential as a target component for the host-directed SUS therapy. In addition, ATP5β, a subunit of mitochondrial ATP synthase, interacting with a variety of proteins with different functions during the SUS progression. This result illustrated that energy production and metabolism could play an important role in the formation of skin ulceration and resistance to pathogens in sea cucumber. The results of this study will be helpful for researchers to gain insights into the complex molecular mechanism of SUS in sea cucumber. Copyright © 2018 Elsevier B.V. All rights reserved.

An experimental investigation of the flow physics of high-lift systems

NASA Technical Reports Server (NTRS)

Thomas, Flint O.; Nelson, R. C.

1995-01-01

This progress report is a series of overviews outlining experiments on the flow physics of confluent boundary layers for high-lift systems. The research objectives include establishing the role of confluent boundary layer flow physics in high-lift production; contrasting confluent boundary layer structures for optimum and non-optimum C(sub L) cases; forming a high quality, detailed archival data base for CFD/modelling; and examining the role of relaminarization and streamline curvature. Goals of this research include completing LDV study of an optimum C(sub L) case; performing detailed LDV confluent boundary layer surveys for multiple non-optimum C(sub L) cases; obtaining skin friction distributions for both optimum and non-optimum C(sub L) cases for scaling purposes; data analysis and inner and outer variable scaling; setting-up and performing relaminarization experiments; and a final report establishing the role of leading edge confluent boundary layer flow physics on high-lift performance.

Methodology for diagnosing of skin cancer on images of dermatologic spots by spectral analysis.

PubMed

Guerra-Rosas, Esperanza; Álvarez-Borrego, Josué

2015-10-01

In this paper a new methodology for the diagnosing of skin cancer on images of dermatologic spots using image processing is presented. Currently skin cancer is one of the most frequent diseases in humans. This methodology is based on Fourier spectral analysis by using filters such as the classic, inverse and k-law nonlinear. The sample images were obtained by a medical specialist and a new spectral technique is developed to obtain a quantitative measurement of the complex pattern found in cancerous skin spots. Finally a spectral index is calculated to obtain a range of spectral indices defined for skin cancer. Our results show a confidence level of 95.4%.

Methodology for diagnosing of skin cancer on images of dermatologic spots by spectral analysis

PubMed Central

Guerra-Rosas, Esperanza; Álvarez-Borrego, Josué

2015-01-01

In this paper a new methodology for the diagnosing of skin cancer on images of dermatologic spots using image processing is presented. Currently skin cancer is one of the most frequent diseases in humans. This methodology is based on Fourier spectral analysis by using filters such as the classic, inverse and k-law nonlinear. The sample images were obtained by a medical specialist and a new spectral technique is developed to obtain a quantitative measurement of the complex pattern found in cancerous skin spots. Finally a spectral index is calculated to obtain a range of spectral indices defined for skin cancer. Our results show a confidence level of 95.4%. PMID:26504638

Sweat Gland Progenitors in Development, Homeostasis, and Wound Repair

PubMed Central

Lu, Catherine; Fuchs, Elaine

2014-01-01

The human body is covered with several million sweat glands. These tiny coiled tubular skin appendages produce the sweat that is our primary source of cooling and hydration of the skin. Numerous studies have been published on their morphology and physiology. Until recently, however, little was known about how glandular skin maintains homeostasis and repairs itself after tissue injury. Here, we provide a brief overview of sweat gland biology, including newly identified reservoirs of stem cells in glandular skin and their activation in response to different types of injuries. Finally, we discuss how the genetics and biology of glandular skin has advanced our knowledge of human disorders associated with altered sweat gland activity. PMID:24492848

Skin appendage-derived stem cells: cell biology and potential for wound repair.

PubMed

Xie, Jiangfan; Yao, Bin; Han, Yutong; Huang, Sha; Fu, Xiaobing

2016-01-01

Stem cells residing in the epidermis and skin appendages are imperative for skin homeostasis and regeneration. These stem cells also participate in the repair of the epidermis after injuries, inducing restoration of tissue integrity and function of damaged tissue. Unlike epidermis-derived stem cells, comprehensive knowledge about skin appendage-derived stem cells remains limited. In this review, we summarize the current knowledge of skin appendage-derived stem cells, including their fundamental characteristics, their preferentially expressed biomarkers, and their potential contribution involved in wound repair. Finally, we will also discuss current strategies, future applications, and limitations of these stem cells, attempting to provide some perspectives on optimizing the available therapy in cutaneous repair and regeneration.

[Features of skin graft in pediatric plastic surgery].

PubMed

Depoortère, C; François, C; Belkhou, A; Duquennoy-Martinot, V; Guerreschi, P

2016-10-01

Skin graft is a skin tissue fragment transferred from a donor site to a receiving site with a spontaneous revascularization. Basic process of plastic surgery, skin graft known in children, specific, warnings and refinements. It finds its indication in many pediatric cases: integumental diseases (neavus, hamartoma), acute burns and scars, traumatic loss of substance or surgically induced, congenital malformations of the hands and feet, etc. Specific skin graft techniques in children are developed: donor sites, sampling technique and procedure, early postoperative care. Especially in children, the scalp is a perfect site for split skin graft and technique is actively developed. Refinements and special cases are discussed: use of dermal matrices, allografts, xenografts, negative pressure therapy, prior skin expansion of the donor site. Results of skin graft in children are exposed: taking of graft, growth and shrinkage, pigmentation. Skin graft sometimes allows to stay the complex movement and get the best final benefit, permanent or at least temporary, in a growing being. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Skin changes in streptozotocin-induced diabetic rats.

PubMed

Andrade, Thiago Antônio Moretti; Masson-Meyers, Daniela Santos; Caetano, Guilherme Ferreira; Terra, Vânia Aparecida; Ovidio, Paula Payão; Jordão-Júnior, Alceu Afonso; Frade, Marco Andrey Cipriani

2017-09-02

Diabetes can cause serious health complications, which can affect every organ of the body, including the skin. The molecular etiology has not yet been clarified for all diabetic skin conditions. Thus, this study aimed to investigate the changes of diabetes in skin compared to non-diabetic skin in rats. Fifteen days after establishing the diabetic status, skin samples from the dorsum-cervical region were harvested for subsequent analysis of alterations caused by diabetes. Our results demonstrate that diabetes stimulated higher inflammation and oxidative stress in skin, but antioxidant defense levels were lower compared to the non-diabetic group (p < 0.05). This could have been related to a decreased number of blood vessels and low expression of VEGF, eNOS and TGF-β1. Finally, insulin signaling proteins IRS, Akt, Shc and ERK showed a low expression in the diabetic group. Thus, our study shows that the pathology of diabetes induced immunohistopathological and biochemical skin changes compared to non-diabetic skin in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Interleukin-17 receptor A maintains and protects the skin barrier to prevent allergic skin inflammation1

PubMed Central

Floudas, Achilleas; Saunders, Sean P.; Moran, Tara; Schwartz, Christian; Hams, Emily; Fitzgerald, Denise C.; Johnston, James A.; Ogg, Graham S.; McKenzie, Andrew N.; Walsh, Patrick T.; Fallon, Padraic G.

2017-01-01

Atopic dermatitis (AD) is a common inflammatory skin disease affecting up to 20% of children and 3% of adults worldwide and is associated with dysregulation of the skin barrier. While type 2 responses are implicated in AD, emerging evidence indicates potential role for the IL-17A signalling axis in AD pathogenesis. In this study we show that in the filaggrin mutant mouse model of spontaneous AD, IL-17RA deficiency (Il17ra-/-) resulted in severe exacerbation of skin inflammation. Interestingly, Il17ra-/- mice without the filaggrin mutation also developed spontaneous progressive skin inflammation with eosinophilia, increased levels of thymic stromal lymphopoietin (TSLP) and IL-5 in the skin. Il17ra-/- mice have a defective skin barrier with altered filaggrin expression. The barrier dysregulation and spontaneous skin inflammation in Il17ra-/- mice was dependent on TSLP, but not the other alarmins IL-25 and IL-33. The associated skin inflammation was mediated by IL-5 expressing pathogenic effector (pe) Th2 cells and was independent of TCRγδ T cells and IL-22. An absence of IL-17RA in non-hematopoietic cells, but not in the hematopoietic cells, was required for the development of spontaneous skin inflammation. Skin microbiome dysbiosis developed in the absence of IL-17RA, with antibiotic intervention resulting in significant amelioration of skin inflammation and reductions in skin infiltrating peTh2 cells and TSLP. This study describes a previously unappreciated protective role for IL-17RA signalling in regulation of the skin barrier and maintenance of skin immune homeostasis. PMID:28615416

Human Herpesvirus-6 cytopathic inclusions: an exceptional and recognizable finding on skin biopsy during HHV6 reactivation after autologous stem-cell transplantation.

PubMed

Roux, Jennifer; Battistella, Maxime; Fornecker, Luc; Legoff, Jérôme; Deau, Bénédicte; Houhou, Nadira; Bouaziz, Jean-David; Thieblemont, Catherine; Janin, Anne

2012-08-01

Skin rash are common in immunocompromised patients, particularly after bone marrow transplantation. Human herpes virus 6 (HHV6) reactivation is often suspected, but its clinical presentation and the routine laboratory tests may be unspecific, thus leading to late diagnosis. In this case, we report specific intralymphocytic cytopathic inclusions on skin biopsy as a sign of systemic HHV6 reactivation. A 56-year-old patient presented progressive erythroderma and fever occurring after autologous hematopoietic stem-cell transplantation for mantle cell lymphoma. The skin biopsy showed a perivascular infiltrate of medium-to-large lymphocytes with irregular nuclei containing a large central basophilic inclusion surrounded by a clear halo. High levels of HHV-6 genomic in skin biopsy confirm HHV-6-induced cytopathic effect. The clinical course improved with intravenous foscavir. The specific histopathological findings encountered in this case are exceptional but recognizable, and along with HHV-6 DNA detection allow a prompt recognition of HHV6 skin rash.

Antimicrobial Active Clothes Display No Adverse Effects on the Ecological Balance of the Healthy Human Skin Microflora

PubMed Central

Hoefer, Dirk; Hammer, Timo R.

2011-01-01

The progressive public use of antimicrobial clothes has raised issues concerning skin health. A placebo-controlled side-to-side study was run with antimicrobial clothes versus fabrics of similar structure but minus the antimicrobial activity, to evaluate possible adverse effects on the healthy skin microflora. Sixty volunteers were enrolled. Each participant received a set of form-fitting T-shirts constructed in 2 halves: an antibacterial half, displaying activities of 3–5 log-step reductions due to silver-finishes or silver-loaded fibres and a nonantibacterial control side. The microflora of the scapular skin was analyzed weekly for opportunistic and pathogenic microorganisms over six weeks. The antibacterial halves did not disturb the microflora in number or composition, whereas a silver-containing deodorant displayed a short-term disturbance. Furthermore, parameters of skin morphology and function (TEWL, pH, moisture) did not show any significant shifts. In summary, antimicrobial clothes did not show adverse effects on the ecological balance of the healthy skin microflora. PMID:22363849

New perspectives on dandruff and seborrheic dermatitis: lessons we learned from bacterial and fungal skin microbiota.

PubMed

Paulino, Luciana Campos

2017-06-01

The human body is inhabited by complex microbial communities, which positively impact different aspects of our health, and might also be related to the development of diseases. Progress in technologies, particularly sequencing methods and bioinformatics tools, has been crucial for the advances in this field. Microbial communities from skin can modulate immune response and protect the host against pathogens, and there are also data supporting their association with several skin conditions; including dandruff and seborrheic dermatitis. For decades, they have been thought to be related to Malassezia yeasts; however, the microbial role has not been elucidated, and their etiology remains poorly understood. This review discusses the recent findings in dandruff and seborrheic dermatitis and their relation to the skin microbiota. Data provided new perceptions to aid in the understanding of these skin disorders, broadening our view of their etiology and the possible roles of microbial communities in symptom development.

Dermoscopy of keratinocyte skin cancer.

PubMed

Kupsa, Romana; Deinlein, Teresa; Woltsche, Nora; Hofmann-Wellenhof, Rainer; Zalaudek, Iris

2016-12-01

Keratinocyte skin cancer (KSC) refers to a broad class of tumors with a regrettably rising incidence worldwide. The term KSC stands for different stages of skin cancer including actinic keratosis (AK), Bowen's Disease (BD) and invasive squamous cell carcinoma (SCC). These tumors tend to grow slow, are unlikely to result in distant metastatic disease and death but they frequently destroy underlying tissues and should therefore be removed at the earliest possible stage. The fact that the cure rate is very high when KSC is detected in early stages emphasizes once more the applicability of dermoscopy as an integrative part of the clinical examination of skin tumors. In the first part of this review article, we summarize key points of the dermoscopic diagnosis of KSC including different stages of AK, BD and SCC. In the second part we want to focus on the progression model of KSC and the role of dermoscopy in the management of keratinocyte skin cancer.

Inter-Individual Variability in Human Response to Low-Dose Ionizing Radiation, Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rocke, David

2016-08-01

In order to investigate inter-individual variability in response to low-dose ionizing radiation, we are working with three models, 1) in-vivo irradiated human skin, for which we have a realistic model, but with few subjects, all from a previous project, 2) ex-vivo irradiated human skin, for which we also have a realistic model, though with the limitations involved in keeping skin pieces alive in media, and 3) MatTek EpiDermFT skin plugs, which provides a more realistic model than cell lines, which is more controllable than human samples.

Near infrared spectrum simulation applied to human skin for diagnosis

NASA Astrophysics Data System (ADS)

Tsai, Chen-Mu; Fang, Yi-Chin; Wang, Chih-Yu; Chiu, Pin-Chun; Wu, Guo-Ying; Zheng, Wei-Chi; Chemg, Shih-Hao

2007-11-01

This research proposes a new method for skin diagnose using near infrared as the light source (750nm~1300nm). Compared to UV and visible light, near infrared might penetrate relatively deep into biological soft tissue in some cases although NIR absorption property of tissue is not a constant for water, fat, and collagen etc. In the research, NIR absorption and scattering properties for skin are discussed firstly using the theory of molecule vibration from Quantum physics and Solid State Physics; secondly the practical model for various NIR absorption spectrum to skin tissue are done by optical simulation for human skin. Finally, experiments are done for further identification of proposed model for human skin and its reaction to near infrared. Results show success with identification from both theory and experiments.

Human Skin 3D Bioprinting Using Scaffold-Free Approach.

PubMed

Pourchet, Léa J; Thepot, Amélie; Albouy, Marion; Courtial, Edwin J; Boher, Aurélie; Blum, Loïc J; Marquette, Christophe A

2017-02-01

Organ in vitro synthesis is one of the last bottlenecks between tissue engineering and transplantation of synthetic organs. Bioprinting has proven its capacity to produce 3D objects composed of living cells but highly organized tissues such as full thickness skin (dermis + epidermis) are rarely attained. The focus of the present study is to demonstrate the capability of a newly developed ink formulation and the use of an open source printer, for the production of a really complete skin model. Proofs are given through immunostaining and electronic microscopy that the bioprinted skin presents all characteristics of human skin, both at the molecular and macromolecular level. Finally, the printability of large skin objects is demonstrated with the printing of an adult-size ear. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

77 FR 2910 - Schedule for Rating Disabilities; Evaluation of Scars; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-20

...; Evaluation of Scars; Correction AGENCY: Department of Veterans Affairs. ACTION: Final rule; correction... that addresses the Skin, so that it more clearly reflected VA's policies concerning the evaluation of... Rating Disabilities that addresses the Skin, 38 CFR 4.118, by revising the criteria for the evaluation of...

Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

PubMed Central

Colihueque, Nelson; Araneda, Cristian

2014-01-01

Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

An Overview of Ultraviolet B Radiation-Induced Skin Cancer Chemoprevention by Silibinin.

PubMed

Kumar, Rahul; Deep, Gagan; Agarwal, Rajesh

2015-06-01

Skin cancer incidences are rising worldwide, and one of the major causative factors is excessive exposure to solar ultraviolet radiation (UVR). Annually, ~5 million skin cancer patients are treated in United States, mostly with nonmelanoma skin cancer (NMSC), which is also frequent in other Western countries. As sunscreens do not provide adequate protection against deleterious effects of UVR, additional and alternative chemoprevention strategies are urgently needed to reduce skin cancer burden. Over the last couple of decades, extensive research has been conducted to understand the molecular basis of skin carcinogenesis, and to identifying novel agents which could be useful in the chemoprevention of skin cancer. In this regard, several natural non-toxic compounds have shown promising efficacy in preventing skin carcinogenesis at initiation, promotion and progression stages, and are considered important in better management of skin cancer. Consistent with this, we and others have studied and established the notable efficacy of natural flavonolignan silibinin against UVB-induced skin carcinogenesis. Extensive pre-clinical animal and cell culture studies report strong anti-inflammatory, anti-oxidant, DNA damage repair, immune-modulatory and anti-proliferative properties of silibinin. Molecular studies have identified that silibinin targets pleotropic signaling pathways including mitogenic, cell cycle, apoptosis, autophagy, p53, NF-κB, etc. Overall, the skin cancer chemopreventive potential of silibinin is well supported by comprehensive mechanistic studies, suggesting its greater use against UV-induced cellular damages and photocarcinogenesis.

An Overview of Ultraviolet B Radiation-Induced Skin Cancer Chemoprevention by Silibinin

PubMed Central

Kumar, Rahul; Deep, Gagan; Agarwal, Rajesh

2015-01-01

Skin cancer incidences are rising worldwide, and one of the major causative factors is excessive exposure to solar ultraviolet radiation (UVR). Annually, ~5 million skin cancer patients are treated in United States, mostly with nonmelanoma skin cancer (NMSC), which is also frequent in other Western countries. As sunscreens do not provide adequate protection against deleterious effects of UVR, additional and alternative chemoprevention strategies are urgently needed to reduce skin cancer burden. Over the last couple of decades, extensive research has been conducted to understand the molecular basis of skin carcinogenesis, and to identifying novel agents which could be useful in the chemoprevention of skin cancer. In this regard, several natural non-toxic compounds have shown promising efficacy in preventing skin carcinogenesis at initiation, promotion and progression stages, and are considered important in better management of skin cancer. Consistent with this, we and others have studied and established the notable efficacy of natural flavonolignan silibinin against UVB-induced skin carcinogenesis. Extensive pre-clinical animal and cell culture studies report strong anti-inflammatory, anti-oxidant, DNA damage repair, immune-modulatory and anti-proliferative properties of silibinin. Molecular studies have identified that silibinin targets pleotropic signaling pathways including mitogenic, cell cycle, apoptosis, autophagy, p53, NF-κB, etc. Overall, the skin cancer chemopreventive potential of silibinin is well supported by comprehensive mechanistic studies, suggesting its greater use against UV-induced cellular damages and photocarcinogenesis. PMID:26097804

Multiple rare opportunistic and pathogenic fungi in persistent foot skin infection.

PubMed

Chan, Giek Far; Sinniah, Sivaranjini; Idris, Tengku Idzzan Nadzirah Tengku; Puad, Mohamad Safwan Ahmad; Abd Rahman, Ahmad Zuhairi

2013-03-01

Persistent superficial skin infection caused by multiple fungi is rarely reported. Recently, a number of fungi, both opportunistic and persistent in nature were isolated from the foot skin of a 24-year old male in Malaysia. The fungi were identified as Candida parapsilosis, Rhodotorula mucilaginosa, Phoma spp., Debaryomyces hansenii, Acremonium spp., Aureobasidium pullulans and Aspergillus spp., This is the first report on these opportunistic strains were co-isolated from a healthy individual who suffered from persistent foot skin infection which was diagnosed as athlete's foot for more than 12 years. Among the isolated fungi, C. parapsilosis has been an increasingly common cause of skin infections. R. mucilaginosa and D. hansenii were rarely reported in cases of skin infection. A. pullulans, an emerging fungal pathogen was also being isolated in this case. Interestingly, it was noted that C. parapsilosis, R. mucilaginosa, D. hansenii and A. pullulans are among the common halophiles and this suggests the association of halotolerant fungi in causing persistent superficial skin infection. This discovery will shed light on future research to explore on effective treatment for inhibition of pathogenic halophiles as well as to understand the interaction of multiple fungi in the progress of skin infection.

Cytoprotective Polyphenols Against Chronological Skin Aging and Cutaneous Photodamage.

PubMed

Davinelli, Sergio; Bertoglio, Juan Carlos; Polimeni, Ascanio; Scapagnini, Giovanni

2018-01-01

Skin aging is a complex biological process influenced by a combination of intrinsic and extrinsic factors, leading to cumulative alterations of skin structure, function and appearance. Polyphenols, which are secondary plant metabolites, represent one of the largest classes of compounds used in dermatology and nutricosmetics to combat skin aging. The main objective is to provide an overview of the existing literature linking skin aging and the ability of polyphenols as regulatory elements able to maintain skin homeostasis. In this review, we discuss recent progress in understanding the molecular bases of skin aging, with specific emphasis on some well known and extensively studied polyphenols which have significant anti-aging influences and photoprotective effects. Although no relevant clinical data exist and standard delivery systems have not been established, promising results have been obtained in many in vitro and animal models. A wide variety of polyphenols may minimize mechanisms underlying the functional manifestations of photoaging and chronological skin aging. Polyphenols exert their influence mostly through their antioxidant and anti-inflammatory effects, thereby abrogating collagen degradation and/or increasing procollagen synthesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Clinical Test of Nano gold Cosmetic for Recovering Skin Damage Due to Chemicals: Special Case

NASA Astrophysics Data System (ADS)

Taufikurohmah, T.; Wardana, A. P.; Tjahjani, S.; Sanjaya, I. G. M.; Baktir, A.; Syahrani, A.

2018-01-01

Manufacturing of Nano gold cosmetics was done at PT. Gizi Indonesia. Clinical trials to cosmetics data supported that cosmetics are able to treat skin health which has been reported partially. For special cases, the recovery process of facial skin damage should also receive attention including cases of facial skin damage caused by chemicals such as phenol, HCl, aqua regia or other harsh chemicals. The problem determined whether the Nano gold is able to recover skin damage due to the harsh chemicals. This clinical trial data on the forms of early skin damage caused by phenol was delivered in the forms of facial photos patients. The recovery progress of facial skin condition was obtained every week for two months. The data included the forms of widespread wounds during the recovery process. This statement supported by anova statistical analysis of the widespread wound changing every week for 8 times. The conclusion is skin damage due to Phenol impregnation can be recovered with the use of Nano gold cosmetics for 8 weeks. This results support the manufacturing of Nano gold cosmetics for the needs of society. It also suggest that Nano gold material can be used for medicine manufacturing in the future.

Grant Closeout Requirements and Reports

Cancer.gov

Requirements and reports to comply with grant closeout, including Final Federal Financial Report (FFR, SF425); Final Research Performance Progress Report (FRPPR); Interim Research Performance Progress Report (IRPPR); Final Invention Statement (FIS, HHS

Origin and tectonic significance of a Mesozoic multi-layer over-thrust system within the Yangtze Block (South China)

NASA Astrophysics Data System (ADS)

Yan, Dan-Ping; Zhou, Mei-Fu; Song, Hong-Lin; Wang, Xin-Wen; Malpas, John

2003-01-01

In the Yangtze Block (South China), a well-developed Mesozoic thrust system extends through the Xuefeng and Wuling mountains in the southeast to the Sichuan basin in the northwest. The system comprises both thin- and thick-skinned thrust units separated by a boundary detachment fault, the Dayin fault. To the northwest, the thin-skinned belt is characterized by either chevron anticlines and box synclines to the northwest or chevron synclines to the southeast. The former structural style displays narrow exposures for the cores of anticlines and wider exposures for the cores of synclines. Thrust detachments occur along Silurian (Fs) and Lower Cambrian (Fc) strata and are dominantly associated with the anticlines. To the southeast, this style of deformation passes gradually into one characterized by chevron synclines with associated principal detachment faults along Silurian (Fs), Cambrian (Fc) and Lower Sinian (Fz) strata. There are, however, numerous secondary back thrusts. Therefore, the thin-skinned belt is like the Valley and Ridge Province of the North American Applachian Mountains. The thick-skinned belt structurally overlies the thin-skinned belt and is characterized by a number of klippen including the Xuefeng and Wuling nappes. It is thus comparable to the Blue Ridge Province of Appalachia. The structural pattern of this thrust system in South China can be explained by a model involving detachment faulting along various stratigraphic layers at different stages of its evolution. The system was developed through a northwest stepwise progression of deformation with the earliest delamination along Lower Sinian strata (Fz). Analyses of balanced geological cross-sections yield about 18.1-21% (total 88 km) shortening for the thin-skinned unit and at least this amount of shortening for the thick-skinned unit. The compressional deformation from southeast to northwest during Late Jurassic to Cretaceous time occurred after the westward progressive collision of the Yangtze Block with the North China Block and suggests that the orogenic event was intracontinental in nature.

Quantitative and qualitative evaluation of dermal elastin of draught horses with chronic progressive lymphoedema.

PubMed

De Cock, H E V; Van Brantegem, L; Affolter, V K; Oosterlinck, M; Ferraro, G L; Ducatelle, R

2009-01-01

Chronic progressive lymphoedema (CPL) in horses, a disease of certain draught breeds, is associated with altered elastin metabolism. The characteristic lesions are seen in the skin of the lower (distal) limbs. This study was based on horses of susceptible breeds, with and without CPL, and on horses of a non-susceptible breed. Skin samples were obtained for examination from the neck (considered a non-affected region) and from the distal limb. The skin lesions were characterized histologically and the dermal elastic fibres were evaluated morphologically and quantitatively. In all horses the mean elastin concentrations were highest in the superficial dermis, gradually decreasing in the mid-dermis and deep dermis. As compared with horses of a non-susceptible breed, affected horses had increased amounts of dermal elastin in both the distal limb and neck, while non-affected horses of a susceptible breed had decreased amounts. The findings support an earlier hypothesis that CPL of horses is a generalized disease. Reduced efficiency of the elastic network in supporting the dermal lymphatics may explain the development of CPL.

Skin infection caused by Scedosporium apiospermum in immunocompromised patients. Report of two cases.

PubMed

Valenzuela Salas, I; Martinez Peinado, C; Fernandez Miralbell, A; Soto Diaz, Augustin; Nogueras Morillas, P; Martin Castro, A; Tercedor Sanchez, J; Garcia Mellado, V

2013-10-16

Scedosporium apiospermum is a filamentous fungus that can cause cutaneous or extracutaneous disease. A large number of cases have been published over the last decades, mainly in patients immunocompromised as a result of their disease or treatment. These kinds of infections can progress rapidly and become disseminated, leading to very serious or even fatal complications. We report two new cases of skin infection by Scedosporium apiospermum from our hospital.

Spontaneous dermal abscesses and ulcers as a result of Serratia marcescens.

PubMed

Friedman, N Deborah; Peterson, Neeraja B; Sumner, William T; Alexander, Barbara D

2003-08-01

Serratia sp have only rarely been reported as isolates from leg ulcers. We describe the case of a middle-aged man with a medical history significant for alcohol-induced cirrhosis who presented with rapidly progressive skin ulcers initially starting as purple nodules. These skin ulcers and underlying dermal abscesses were found to be a result of S marcescens, with the presumed portal of entry being a toe-web infection.

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.

Role of the liver X receptors in skin physiology: Putative pharmacological targets in human diseases.

PubMed

Ouedraogo, Zangbéwendé Guy; Fouache, Allan; Trousson, Amalia; Baron, Silvère; Lobaccaro, Jean-Marc A

2017-10-01

Liver X receptors (LXRs) are members of the nuclear receptor superfamily that have been shown to regulate various physiological functions such as lipid metabolism and cholesterol homeostasis. Concordant reports have elicited the possibility to target them to cure many human diseases including arteriosclerosis, cancer, arthritis, and diabetes. The high relevance of modulating LXR activities to treat numerous skin diseases, mainly those with exacerbated inflammation processes, contrasts with the lack of approved therapeutic use. This review makes an assessment to sum up the findings regarding the physiological roles of LXRs in skin and help progress towards the therapeutic and safe management of their activities. It focuses on the possible pharmacological targeting of LXRs to cure or prevent selected skin diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Tissue expansion in the treatment of pressure ulcers.

PubMed

Esposito, G; Di Caprio, G; Ziccardi, P; Scuderi, N

1991-03-01

The authors report their experience using skin expanders in 11 patients with severe bed sores. The expanders, with different volumes, from 250 to 1000 cc, were generally overfilled using the cutaneous tonometer. In fact, with the information revealed by this apparatus on the skin in expansion, the authors were able to reduce the filling intervals without risking ulceration. In their experience, the results obtained were satisfactory: All patients treated achieved surgical recovery. The authors see a wide future for skin-expander use in pressure-ulcer treatment. They have a working hypothesis about using expanders to progressively advance sensitive skin in areas subject to ulceration. This hypothesis is based on the possibility of reexpanding the same flap several times, as has been seen in the treatment of other types of pathology.

Skin problems following septorhinoplasty.

PubMed

Koc, Eltaf A O; Buyuklu, Fuat; Koç, Bulent; Demirci, Gulsen T

2015-06-01

Septorhinoplasty is one of the most commonly performed plastic surgery procedures in the world. Studies on septorhinoplasty in the literature mainly focus on the surgical procedures and their outcomes, but the general appearance of the nose and nasal skin following surgery is also very important. Case-control study examining 30 septorhinoplasty patients and 20 septoplasty patients for postoperative skin conditions. There were significant differences identified between the septorhinoplasty group and the septoplasty group with respect to their mean preoperative Global Acne Grading System, Seborrheic Dermatitis Area Severity Index, and visual analog scores (acne, seborrhea, and ecchymosis). The aim of study was to identify and evaluate postoperative skin conditions among septorhinoplasty patients, as well as the progression and duration of treatment of these conditions. 3b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Novel Medical Strategies Combating Nonmelanoma Skin Cancer

PubMed Central

Bhandari, Prasan R; Pai, Varadraj V

2014-01-01

The incidence of nonmelanoma skin cancer (NMSC) continues to rise, partly because of aging, the frequency of early childhood sunburns, and sporadic extreme recreational sun exposure. A nonsurgical approach to selected cutaneous malignancy could possibly reduce the cost as well as morbidity of surgical treatment for NMSC. There has been growing interest in isolating compounds that could suppress or reverse the biochemical changes necessary for cutaneous malignancies to progress by pharmacologic intervention. By targeting diverse pathways recognized as important in the pathogenesis of nonmelanoma skin cancers, a combination approach with multiple agents or addition of chemopreventative agents to topical sunscreens may offer the potential for novel and synergistic therapies in treating nonmelanoma skin cancer. This preliminary information will expand to include more therapeutic options for NMSC in the future. PMID:25484380

POEMS syndrome with Guillan-Barre syndrome-like acute onset: a case report and review of neurological progression in 30 cases.

PubMed

Isose, S; Misawa, S; Kanai, K; Shibuya, K; Sekiguchi, Y; Nasu, S; Fujimaki, Y; Noto, Y; Nakaseko, C; Kuwabara, S

2011-06-01

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan-Barré syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5-51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.

Mechanisms of skin aging induced by EGFR inhibitors.

PubMed

Gerber, Peter Arne; Buhren, Bettina Alexandra; Schrumpf, Holger; Hevezi, Peter; Bölke, Edwin; Sohn, Dennis; Jänicke, Reiner U; Belum, Viswanath Reddy; Robert, Caroline; Lacouture, Mario E; Homey, Bernhard

2016-10-01

The mechanisms of skin aging have not been completely elucidated. Anecdotal data suggests that EGFR inhibition accelerates aging-like skin changes. The objective of the study was to evaluate the clinical characteristics and investigate the cellular and molecular mechanisms underlying skin changes associated with the use of EFGRIs. Patients during prolonged treatment with EGFRIs (>3 months) were analyzed for aging-like skin changes. Baseline EGFR expression was compared in young (<25 years old) vs. old (> 65 years old) skin. In addition, the regulation of extracellular matrix, senescence-associated genes, and cell cycle status was measured in primary human keratinocytes treated with erlotinib in vitro. There were progressive signs of skin aging, including xerosis cutis, atrophy, rhytide formation, and/or actinic purpura in 12 patients. Keratinocytes treated with erlotinib in vitro showed a significant down-modulation of hyaluronan synthases (HAS2 and HAS3), whereas senescence-associated genes (p21, p53, IL-6, maspin) were upregulated, along with a G1 cell cycle arrest and stronger SA β-Gal activity. There was significantly decreased baseline expression in EGFR density in aged skin, when compared to young controls. EGFR inhibition results in molecular alterations in keratinocytes that may contribute to the observed skin aging of patients treated with respective targeted agents.

Mechanisms of skin aging induced by EGFR inhibitors

PubMed Central

Gerber, Peter Arne; Buhren, Bettina Alexandra; Schrumpf, Holger; Hevezi, Peter; Bölke, Edwin; Sohn, Dennis; Jänicke, Reiner; Belum, Viswanath Reddy; Robert, Caroline; Lacouture, Mario E.; Homey, Bernhard

2017-01-01

BACKGROUND The mechanisms of skin aging have not been completely elucidated. Anecdotal data suggests that EGFR inhibition accelerates aging-like skin changes. OBJECTIVE To evaluate the clinical characteristics and investigate the cellular and molecular mechanisms underlying skin changes associated with the use of EFGRIs. PATIENTS AND METHODS Patients during prolonged treatment with EGFRIs (>3 months) were analyzed for aging-like skin changes. Baseline EGFR expression was compared in young (< 25 years old) vs. old (> 65 years old) skin. In addition, the regulation of extracellular matrix, senescence-associated genes, and cell cycle status was measured in primary human keratinocytes treated with erlotinib in vitro. RESULTS Progressive signs of skin aging, including xerosis cutis, atrophy, rhytide formation and/or actinic purpura in 12 patients. Keratinocytes treated with erlotinib in vitro showed a significant down-modulation of hyaluronan synthases (HAS2 and HAS3), whereas senescence-associated genes (p21, p53, IL-6, maspin) were upregulated, along with a G1 cell cycle arrest and stronger SA β-Gal activity. There was significantly decreased baseline expression in EGFR-density in aged skin, when compared to young controls. CONCLUSIONS EGFR inhibition results in molecular alterations in keratinocytes that may contribute to the observed skin aging of patients treated with respective targeted agents. PMID:27165055

Time-resolved fluorescence microscopy (FLIM) as an analytical tool in skin nanomedicine.

PubMed

Alexiev, Ulrike; Volz, Pierre; Boreham, Alexander; Brodwolf, Robert

2017-07-01

The emerging field of nanomedicine provides new approaches for the diagnosis and treatment of diseases, for symptom relief, and for monitoring of disease progression. Topical application of drug-loaded nanoparticles for the treatment of skin disorders is a promising strategy to overcome the stratum corneum, the upper layer of the skin, which represents an effective physical and biochemical barrier. The understanding of drug penetration into skin and enhanced penetration into skin facilitated by nanocarriers requires analytical tools that ideally allow to visualize the skin, its morphology, the drug carriers, drugs, their transport across the skin and possible interactions, as well as effects of the nanocarriers within the different skin layers. Here, we review some recent developments in the field of fluorescence microscopy, namely Fluorescence Lifetime Imaging Microscopy (FLIM)), for improved characterization of nanocarriers, their interactions and penetration into skin. In particular, FLIM allows for the discrimination of target molecules, e.g. fluorescently tagged nanocarriers, against the autofluorescent tissue background and, due to the environmental sensitivity of the fluorescence lifetime, also offers insights into the local environment of the nanoparticle and its interactions with other biomolecules. Thus, FLIM shows the potential to overcome several limits of intensity based microscopy. Copyright © 2017 Elsevier B.V. All rights reserved.

An unusual course after injection of industrial silicone for penile augmentation.

PubMed

Shin, Yu Seob; You, Jae Hyung; Choi, Hwang; Zhang, Li Tao; Zhao, Chen; Choi, In Sung; Park, Jong Kwan

2015-01-01

A 48-year-old male patient had an injection of industrial silicone under the penile skin for augmentation by non-medical practitioners a week before. There was complete necrosis of the dorsal part of the penile skin and soft tissue. In a penile magnetic resonance image, big masses of silicone under the penile skin were found and a part of the silicone was partially exposed. Debridement of the necrotic tissue was done. As the right side of the tunica albuginea was thin-walled, a silicone-induced infection developed. Because of this, the wet dressing was done daily without closing the wound for the next 23 days. Finally, both scrotal skins were drawn and sutured to the dorsal glandular skin after the total penile skin was completely removed and sutured with T-style anastomosis. The ventral flap was anastomosed to the ventral glandular skin with the end-to-end technique with inverted V incision at 1 cm proximal from the sutured margin. Flaps survived completely without skin necrosis or dehiscence.

Skin diseases in geriatric patients: our experience from a public skin outpatient clinic in Siena.

PubMed

Rubegni, P; Poggiali, S; Nami, N; Rubegni, M; Fimiani, M

2012-12-01

With the progressive aging of the Italian population, geriatric health care has become a major issue for health authorities. However, little data is available regarding geriatric skin diseases. In order to provide rapid access to specialist help, in 2003 we created a dermatology clinic dedicated only to geriatric patients age 65 and older. To determine the characteristic pattern and the prevalence of various skin disorders among the geriatric patients seen at the clinic, we performed a retrospective and descriptive study of all skin diseases in patients seen in our office from January 2003 to December 2009. We evaluated: age, proportion and gender for all skin disease categories. A total of 2100 geriatric patients were examined. The male to female ratio was 1.4 to 1. The most common disorder was pruritus "sine materia" (18.9%) followed by benign tumors (13.5%); 9.1% of our patients presented with actinic keratoses and 13.2% with malignant tumors. As reported by others, the quality of life in patients with skin cancer was better than patients with rashes as skin cancer patients tended to wait longer before seeking specialist care. To improve the assessment of skin diseases, we often worked closely with The prevalence of skin diseases in our patients emphasized the importance of educating the elderly about sun protection, the early detection of skin cancer, the use of emollients and proper skin care in general.

On the tear resistance of skin

DOE PAGES

Yang, Wen; Sherman, Vincent R.; Gludovatz, Bernd; ...

2015-03-27

Tear resistance is vitally important for the various functions of skin, especially protection from predatorial attack. Here, we mechanistically quantify the extreme tear resistance of skin and identify the underlying structural features, which lead to its sophisticated failure mechanisms. Here we explain why it is virtually impossible to propagate a tear in rabbit skin, chosen as a model material for the dermis of vertebrates. Finally, we express the deformation in terms of four mechanisms of collagen fibril activity in skin under tensile loading that virtually eliminate the possibility of tearing in pre-notched samples: fibril straightening, fibril reorientation towards the tensilemore » direction, elastic stretching and interfibrillar sliding, all of which contribute to the redistribution of the stresses at the notch tip.« less

Reversal of skin aging with topical retinoids.

PubMed

Hubbard, Bradley A; Unger, Jacob G; Rohrich, Rod J

2014-04-01

Topical skin care and its place in plastic surgery today are often overlooked by clinicians formulating a plan for facial rejuvenation. Not only is it important to consider topical skin care as part of comprehensive care, but clinicians should also be educated with the data available in today's literature. This review aims to familiarize the reader with the biological processes of skin aging and evidence-based clinical outcomes afforded by various topical therapies. Furthermore, this review will focus on solar damage, the value of retinoids, and how they can be used in conjunction with forms of treatment such as chemical peel, dermabrasion, and lasers. Finally, guidelines will be provided to help the physician administer appropriate skin care based on the data presented.

Facial skin color measurement based on camera colorimetric characterization

NASA Astrophysics Data System (ADS)

Yang, Boquan; Zhou, Changhe; Wang, Shaoqing; Fan, Xin; Li, Chao

2016-10-01

The objective measurement of facial skin color and its variance is of great significance as much information can be obtained from it. In this paper, we developed a new skin color measurement procedure which includes following parts: first, a new skin tone color checker made of pantone Skin Tone Color Checker was designed for camera colorimetric characterization; second, the chromaticity of light source was estimated via a new scene illumination estimation method considering several previous algorithms; third, chromatic adaption was used to convert the input facial image into output facial image which appears taken under canonical light; finally the validity and accuracy of our method was verified by comparing the results obtained by our procedure with these by spectrophotometer.

Optical perception for detection of cutaneous T-cell lymphoma by multi-spectral imaging

NASA Astrophysics Data System (ADS)

Hsiao, Yu-Ping; Wang, Hsiang-Chen; Chen, Shih-Hua; Tsai, Chung-Hung; Yang, Jen-Hung

2014-12-01

In this study, the spectrum of each picture element of the patient’s skin image was obtained by multi-spectral imaging technology. Spectra of normal or pathological skin were collected from 15 patients. Principal component analysis and principal component scores of skin spectra were employed to distinguish the spectral characteristics with different diseases. Finally, skin regions with suspected cutaneous T-cell lymphoma (CTCL) lesions were successfully predicted by evaluation and classification of the spectra of pathological skin. The sensitivity and specificity of this technique were 89.65% and 95.18% after the analysis of about 109 patients. The probability of atopic dermatitis and psoriasis patients misinterpreted as CTCL were 5.56% and 4.54%, respectively.

Surfactants have multi-fold effects on skin barrier function.

PubMed

Lemery, Emmanuelle; Briançon, Stéphanie; Chevalier, Yves; Oddos, Thierry; Gohier, Annie; Boyron, Olivier; Bolzinger, Marie-Alexandrine

2015-01-01

The stratum corneum (SC) is responsible for the barrier properties of the skin and the role of intercorneocyte skin lipids, particularly their structural organization, in controlling SC permeability is acknowledged. Upon contacting the skin, surfactants interact with the SC components leading to barrier damage. To improve knowledge of the effect of several classes of surfactant on skin barrier function at three different levels. The influence of treatments of human skin explants with six non-ionic and four ionic surfactant solutions on the physicochemical properties of skin was investigated. Skin surface wettability and polarity were assessed through contact angle measurements. Infrared spectroscopy allowed monitoring the SC lipid organization. The lipid extraction potency of surfactants was evaluated thanks to HPLC-ELSD assays. One anionic and one cationic surfactant increased the skin polarity by removing the sebaceous and epidermal lipids and by disturbing the organization of the lipid matrix. Another cationic surfactant displayed a detergency effect without disturbing the skin barrier. Several non-ionic surfactants disturbed the lipid matrix organization and modified the skin wettability without any extraction of the skin lipids. Finally two non-ionic surfactants did not show any effect on the investigated parameters or on the skin barrier. The polarity, the organization of the lipid matrix and the lipid composition of the skin allowed describing finely how surfactants can interact with the skin and disturb the skin barrier function.

An implementation algorithm to improve skin-to-skin practice in the first hour after birth.

PubMed

Brimdyr, Kajsa; Cadwell, Karin; Stevens, Jeni; Takahashi, Yuki

2018-04-01

Evidence supporting the practice of skin-to-skin contact and breastfeeding soon after birth points to physiologic, social, and psychological benefits for both mother and baby. The 2009 revision of Step 4 of the WHO/UNICEF "Ten Steps to Successful Breastfeeding" elaborated on the practice of skin-to-skin contact between the mother and her newly born baby indicating that the practice should be "immediate" and "without separation" unless documented medically justifiable reasons for delayed contact or interruption exist. While in immediate, continuous, uninterrupted skin-to-skin contact with mother in the first hour after birth, babies progress through 9 instinctive, complex, distinct, and observable stages including self-attachment and suckling. However, the most recent Cochrane review of early skin-to-skin contact cites inconsistencies in the practice; the authors found "inadequate evidence with respect to details … such as timing of initiation and dose." This paper introduces a novel algorithm to analyse the practice of skin to skin in the first hour using two data sets and suggests opportunities for practice improvement. The algorithm considers the mother's Robson criteria, skin-to-skin experience, and Widström's 9 Stages. Using data from vaginal births in Japan and caesarean births in Australia, the algorithm utilizes data in a new way to highlight challenges to best practice. The use of a tool to analyse the implementation of skin-to-skin care in the first hour after birth illuminates the successes, barriers, and opportunities for improvement to achieving the standard of care for babies. Future application should involve more diverse facilities and Robson's classifications. © 2017 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.

SMART SKINS - A Development Roadmap

NASA Astrophysics Data System (ADS)

Lochocki, Joseph M.

1990-02-01

The Air Force Project Forecast II identified a number of key technology initiatives for development. This paper addresses one such initiative, PT-16, Smart Skins. The concept of the Smart Skin is introduced by briefly highlighting its attributes and potential advantages over standard avionics packaging and maintenance, and then goes on to describe some of the key ingredients necessary for its development. Problem areas are brought out along with some of the required trades that must be made. Finally, a time phased development roadmap is introduced which shows Calspan's proposed sequence of technology development programs that can, in combination, lead to first functional Smart Skins implementations in narrowband form in the late 1990's and in wideband form in first decade of the twenty - first century. A Smart Skins implementation in integral aircraft skin structure form will take at least until 2010.

Photodamage: all signs lead to actinic keratosis and early squamous cell carcinoma.

PubMed

Wei, Jerry; Kok, Lai Fong; Byrne, Scott N; Halliday, Gary M

2015-01-01

Ultraviolet (UV) radiation is likely to drive the initiation and progression of skin cancer from actinic keratosis to squamous cell carcinoma. Signs of photodamage occur at multiple steps. UV radiation damages many cellular constituents, including lipids, proteins and DNA, all of which are likely to contribute to UV-induced skin cancer. Two biological events culminating from photodamage are mutations in the genes critical to the control of cell division, differentiation and invasion and immunosuppression. DNA photodamage, if unrepaired prior to cell division, can result in the incorporation of an incorrect nucleotide into newly synthesised DNA. Mutations in critical genes contribute to carcinogenesis. Photodamage to proteins such as those involved in DNA repair or proteins or lipids involved in cellular signalling can interfere with this repair process and contribute to mutagenesis. Mutations in key genes, including TP53, BRM, PTCH1, and HRAS, contribute to skin carcinogenesis. UV also damages immunity. Photodamage to DNA and signalling lipids as well as other molecular changes are detrimental to the key cells that regulate immunity. Photodamaged dendritic cells and altered responses by mast cells lead to the activation of T and B regulatory cells that suppress immunity to the protein products of UV-mutated genes. This stops the immune response from its protective function of destroying mutated cells, enabling the transformed cells to progress to skin cancer. UV appears to play a pivotal role at each of these steps, and therefore, signs of photodamage point to the development of skin cancer. © 2015 S. Karger AG, Basel.

[Dermatophytic disease: exuberant hyperkeratosis with cutaneous horns].

PubMed

Boudghène-Stambouli, O; Mérad-Boudia, A

1998-10-01

Dermatophytic disease is a chronic dermatophytosis involving the skin and viscera and caused by benign dermatophytes which cross the skin barrier. We present a case presenting previously unreported giant cutaneous horns. A male Algerian patient aged 29 years consulted for chronic skin disease which had progressed for 2 years. Manifestations included warts, papulonodules, eczematiform lesions, lichenifications, alopecia, onyxis, multiple node enlargement and giant cutaneous horns on the plantar aspect of the feet making walking difficult. The patient's kinhood included 10 members and the patient's parents were first cousins; no other family member had a similar disease state. Laboratory findings included eosinophilia (11%, 550 cells/mm3), an inflammatory syndrome, and normal phosphorus and calcium levels despite demineralization of the hands and feet. The tuberculin interdermal reaction was positive but the trichophytine interdermal reaction was negative. Trichophyton violaceum was found in all mycological samples from skin and nails. The histology examination of skin biopsies revealed acanthosis, considerable hyperkeratosis, and myceleal filaments invading the horny layer, the sweat glands and hair follicles. Abscesses and granulomas were also seen in the superficial dermis. Oral griseofulvin 1 g per day and topical applications with ketoconazole gave clear improvement. Dermatophytic disease is a chronic dermatophytosis observed mainly in North Africa. The locally high rate of consanguinous marriages would suggest autosomal recessive inheritance of a genetic anomaly possibly associated with deficient cellular immunity. The lesions are polymorphous and develop progressively, probably due to diminished cellular immunity. This case with giant cutaneous horns would be a new variant. Antifungals can provide definitive cure. The pathogenesis of this severe dermatophytosis remains to be established.

VEGF-C and VEGF-D blockade inhibits inflammatory skin carcinogenesis.

PubMed

Alitalo, Annamari K; Proulx, Steven T; Karaman, Sinem; Aebischer, David; Martino, Stefania; Jost, Manuela; Schneider, Nicole; Bry, Maija; Detmar, Michael

2013-07-15

VEGF-C and VEGF-D were identified as lymphangiogenic growth factors and later shown to promote tumor metastasis, but their effects on carcinogenesis are poorly understood. Here, we have studied the effects of VEGF-C and VEGF-D on tumor development in the murine multistep chemical carcinogenesis model of squamous cell carcinoma by using a soluble VEGF-C/VEGF-D inhibitor. After topical treatment with a tumor initiator and repeated tumor promoter applications, transgenic mice expressing a soluble VEGF-C/VEGF-D receptor (sVEGFR-3) in the skin developed significantly fewer squamous cell tumors with a delayed onset when compared with wild-type mice or mice expressing sVEGFR-3 lacking the ligand-binding site. Epidermal proliferation was reduced in the carcinogen-treated transgenic skin, whereas epidermal keratinocyte proliferation in vitro was not affected by VEGF-C or VEGF-D, indicating indirect effects of sVEGFR-3 expression. Importantly, transgenic mouse skin was less sensitive to tumor promoter-induced inflammation, with reduced angiogenesis and blood vessel leakage. Cutaneous leukocytes, especially macrophages, were reduced in transgenic skin without major changes in macrophage polarization or blood monocyte numbers. Several macrophage-associated cytokines were also reduced in transgenic papillomas, although the dermal macrophages themselves did not express VEGFR-3. These findings indicate that VEGF-C/VEGF-D are involved in shaping the inflammatory tumor microenvironment that regulates early tumor progression. Our results support the use of VEGF-C/VEGF-D-blocking agents not only to inhibit metastatic progression, but also during the early stages of tumor growth. ©2013 AACR.

Deep inferior epigastric artery perforator flap donor-site closure with cannula-assisted, limited undermining, and progressive high-tension sutures versus standard abdominoplasty: complications, sensitivity, and cosmetic outcomes.

PubMed

Visconti, Giuseppe; Tomaselli, Federica; Monda, Anna; Barone-Adesi, Liliana; Salgarello, Marzia

2015-01-01

In deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, abdominal donor-site cosmetic and sensibility outcomes and the closure technique have drawn little attention in the literature, with many surgeons still following the principles of standard abdominoplasty. In this article, the authors report their experience with the cannula-assisted, limited undermining, and progressive high-tension suture ("CALP") technique of DIEP donor-site closure compared with standard abdominoplasty. Between December of 2008 and January of 2013, 137 consecutive women underwent DIEP flap breast reconstruction. Of these, 82 patients (between December of 2008 and November of 2011) underwent DIEP flap donor-site closure by means of standard abdominoplasty (control group) and 55 patients (from December of 2011 to January of 2013) by means of cannula-assisted, limited undermining, and progressive high-tension suture (study group). The abdominal drainage daily output, donor-site complications, abdominal skin sensitivity at 1-year follow-up, cosmetic outcomes, and patient satisfaction were recorded and analyzed statistically. Daily drainage output was significantly lower in the study group. Donor-site complications were significantly higher in the control group (37.8 percent versus 9 percent). Seroma and wound healing problems were experienced in the control group. Abdominal skin sensibility was better preserved in the study group. Overall, abdominal wall aesthetic outcomes were similar in both groups, except for scar quality (better in the study group). According to the authors' experience, cannula-assisted, limited undermining, and progressive high-tension suture should be always preferred to standard abdominoplasty for DIEP donor-site closure to reduce the complication rate to improve abdominal skin sensitivity and scar quality. Therapeutic, II.

Measles virus infection of human keratinocytes: Possible link between measles and atopic dermatitis.

PubMed

Gourru-Lesimple, Geraldine; Mathieu, Cyrille; Thevenet, Thomas; Guillaume-Vasselin, Vanessa; Jégou, Jean-François; Boer, Cindy G; Tomczak, Katarzyna; Bloyet, Louis-Marie; Giraud, Celine; Grande, Sophie; Goujon, Catherine; Cornu, Catherine; Horvat, Branka

2017-05-01

Measles virus (MV) infection is marked with a skin rash in the acute phase of the disease, which pathogenesis remains poorly understood. Moreover, the association between measles and progression of skin diseases, such as atopic dermatitis (AD), is still elusive. We have thus analysed the susceptibility of human keratinocytes to MV infection and explore the potential relationship between MV vaccination and the pathogenesis the AD. We performed immunovirological characterisation of MV infection in human keratinocytes and then tested the effect of live attenuated measles vaccine on the progression of AD in adult patients, in a prospective, double-blind study. We showed that both human primary keratinocytes and the keratinocyte cell line HaCaT express MV receptors and could be infected by MV. The infection significantly modulated the expression of several keratinocyte-produced cytokines, known to be implicated in the pathogenesis of inflammatory allergic diseases, including AD. We then analysed the relationship between exposure to MV by vaccination and the progression of AD in 20 adults during six weeks. We found a significant decrease in CCL26 and thymic stromal lymphopoietin (TSLP) mRNA in biopsies from acute lesions of vaccinated patients, suggesting MV-induced modulation of skin cytokine expression. Clinical analysis revealed a transient improvement of SCORAD index in vaccinated compared to placebo-treated patients, two weeks after vaccination. Altogether, these results clearly demonstrate that keratinocytes are susceptible to MV infection, which could consequently modulate their cytokine production, resulting with a beneficial effect in the progression of AD. This study provides thus a proof of concept for the vaccination therapy in AD and may open new avenues for the development of novel strategies in the treatment of this allergic disease. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Dermal damage promoted by repeated low-level UV-A1 exposure despite tanning response in human skin.

PubMed

Wang, Frank; Smith, Noah R; Tran, Bao Anh Patrick; Kang, Sewon; Voorhees, John J; Fisher, Gary J

2014-04-01

Solar UV irradiation causes photoaging, characterized by fragmentation and reduced production of type I collagen fibrils that provide strength to skin. Exposure to UV-B irradiation (280-320 nm) causes these changes by inducing matrix metalloproteinase 1 and suppressing type I collagen synthesis. The role of UV-A irradiation (320-400 nm) in promoting similar molecular alterations is less clear yet important to consider because it is 10 to 100 times more abundant in natural sunlight than UV-B irradiation and penetrates deeper into the dermis than UV-B irradiation. Most (approximately 75%) of solar UV-A irradiation is composed of UV-A1 irradiation (340-400 nm), which is also the primary component of tanning beds. To evaluate the effects of low levels of UV-A1 irradiation, as might be encountered in daily life, on expression of matrix metalloproteinase 1 and type I procollagen (the precursor of type I collagen). In vivo biochemical analyses were conducted after UV-A1 irradiation of normal human skin at an academic referral center. Participants included 22 healthy individuals without skin disease. Skin pigmentation was measured by a color meter (chromometer) under the L* variable (luminescence), which ranges from 0 (black) to 100 (white). Gene expression in skin samples was assessed by real-time polymerase chain reaction. Lightly pigmented human skin (L* >65) was exposed up to 4 times (1 exposure/d) to UV-A1 irradiation at a low dose (20 J/cm2), mimicking UV-A levels from strong sun exposure lasting approximately 2 hours. A single exposure to low-dose UV-A1 irradiation darkened skin slightly and did not alter matrix metalloproteinase 1 or type I procollagen gene expression. With repeated low-dose UV-A1 irradiation, skin darkened incrementally with each exposure. Despite this darkening, 2 or more exposures to low-dose UV-A1 irradiation significantly induced matrix metalloproteinase 1 gene expression, which increased progressively with successive exposures. Repeated UV-A1 exposures did not suppress type I procollagen expression. A limited number of low-dose UV-A1 exposures, as commonly experienced in daily life, potentially promotes photoaging by affecting breakdown, rather than synthesis, of collagen. Progressive skin darkening in response to repeated low-dose UV-A1 exposures in lightly pigmented individuals does not prevent UV-A1-induced collagenolytic changes. Therefore, for optimal protection against skin damage, sunscreen formulations should filter all UV wavelengths, including UV-A1 irradiation.

The Human Skin Microbiome Associates with the Outcome of and Is Influenced by Bacterial Infection.

PubMed

van Rensburg, Julia J; Lin, Huaiying; Gao, Xiang; Toh, Evelyn; Fortney, Kate R; Ellinger, Sheila; Zwickl, Beth; Janowicz, Diane M; Katz, Barry P; Nelson, David E; Dong, Qunfeng; Spinola, Stanley M

2015-09-15

The influence of the skin microbiota on host susceptibility to infectious agents is largely unexplored. The skin harbors diverse bacterial species that may promote or antagonize the growth of an invading pathogen. We developed a human infection model for Haemophilus ducreyi in which human volunteers are inoculated on the upper arm. After inoculation, papules form and either spontaneously resolve or progress to pustules. To examine the role of the skin microbiota in the outcome of H. ducreyi infection, we analyzed the microbiomes of four dose-matched pairs of "resolvers" and "pustule formers" whose inoculation sites were swabbed at multiple time points. Bacteria present on the skin were identified by amplification and pyrosequencing of 16S rRNA genes. Nonmetric multidimensional scaling (NMDS) using Bray-Curtis dissimilarity between the preinfection microbiomes of infected sites showed that sites from the same volunteer clustered together and that pustule formers segregated from resolvers (P = 0.001, permutational multivariate analysis of variance [PERMANOVA]), suggesting that the preinfection microbiomes were associated with outcome. NMDS using Bray-Curtis dissimilarity of the endpoint samples showed that the pustule sites clustered together and were significantly different than the resolved sites (P = 0.001, PERMANOVA), suggesting that the microbiomes at the endpoint differed between the two groups. In addition to H. ducreyi, pustule-forming sites had a greater abundance of Proteobacteria, Bacteroidetes, Micrococcus, Corynebacterium, Paracoccus, and Staphylococcus species, whereas resolved sites had higher levels of Actinobacteria and Propionibacterium species. These results suggest that at baseline, resolvers and pustule formers have distinct skin bacterial communities which change in response to infection and the resultant immune response. Human skin is home to a diverse community of microorganisms, collectively known as the skin microbiome. Some resident bacteria are thought to protect the skin from infection by outcompeting pathogens for resources or by priming the immune system's response to invaders. However, the influence of the skin microbiome on the susceptibility to or protection from infection has not been prospectively evaluated in humans. We characterized the skin microbiome before, during, and after experimental inoculation of the arm with Haemophilus ducreyi in matched volunteers who subsequently resolved the infection or formed abscesses. Our results suggest that the preinfection microbiomes of pustule formers and resolvers have distinct community structures which change in response to the progression of H. ducreyi infection to abscess formation. Copyright © 2015 van Rensburg et al.

IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.

PubMed

Gosmann, Christina; Mattarollo, Stephen R; Bridge, Jennifer A; Frazer, Ian H; Blumenthal, Antje

2014-09-01

Persistent infection with high-risk human papillomaviruses (HPV) causes epithelial hyperplasia that can progress to cancer and is thought to depend on immunosuppressive mechanisms that prevent viral clearance by the host. IL-17 is a cytokine with diverse functions in host defense and in the pathology of autoimmune disorders, chronic inflammatory diseases, and cancer. We analyzed biopsies from patients with HPV-associated cervical intraepithelial neoplasia grade 2/3 and murine skin displaying HPV16 E7 protein-induced epithelial hyperplasia, which closely models hyperplasia in chronic HPV lesions. Expression of IL-17 and IL-23, a major inducer of IL-17, was elevated in both human HPV-infected and murine E7-expressing lesions. Using a skin-grafting model, we demonstrated that IL-17 in HPV16 E7 transgenic skin grafts inhibited effective host immune responses against the graft. IL-17 was produced by CD3(+) T cells, predominantly CD4(+) T cells in human, and CD4(+) and γδ T cells in mouse hyperplastic lesions. IL-23 and IL-1β, but not IL-18, induced IL-17 production in E7 transgenic skin. Together, these findings demonstrate an immunosuppressive role for IL-17 in HPV-associated epithelial hyperplasia and suggest that blocking IL-17 in persistent viral infection may promote antiviral immunity and prevent progression to cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

Atopic March from Atopic Dermatitis to Asthma-Like Lesions in NC/Nga Mice Is Accelerated or Aggravated by Neutralization of Stratum Corneum but Partially Inhibited by Acidification.

PubMed

Lee, Hae-Jin; Lee, Noo Ri; Jung, Minyoung; Kim, Dong Hye; Choi, Eung Ho

2015-12-01

Prolonged and/or repeated damage to the skin barrier followed by atopic dermatitis (AD) is an initial step in atopic march that ultimately progresses to respiratory allergy. Maintaining normal stratum corneum (SC) acidity has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. We determined whether a representative AD murine model, NC/Nga mice, develops airway inflammation after repeated epicutaneous application followed by inhalation of house dust mite (HDM), implying atopic march, and whether prolongation of non-proper SC acidity accelerates respiratory allergy. HDM was applied to the skin of NC/Nga mice, accompanied by the application of neutral cream (pH 7.4) or acidic cream (pH 2.8) for 6 weeks. Intranasal inhalation of HDM was administered daily during the last 3 days. Repeated epicutaneous applications followed by inhalation of HDM in NC/Nga mice induced an atopic march-like progression from AD lesions to respiratory allergy. Concurrent neutral cream treatment accelerated or aggravated the allergic inflammation in the skin and respiratory system, whereas an acidic cream partially alleviated these symptoms. Collectively, we developed an atopic march in NC/Nga mice by HDM application, and found that prevention of a neutral environment in the SC may be an interventional method to inhibit the march.

Characterization of hair-follicle side population cells in mouse epidermis and skin tumors

PubMed Central

Kim, Sun Hye; Sistrunk, Christopher; Miliani de Marval, Paula L.; Rodriguez-Puebla, Marcelo L.

2017-01-01

A subset of cells, termed side-population (SP), which have the ability to efflux Hoeschst 33342, have previously been demonstrated to act as a potential method to isolate stem cells. Numerous stem/progenitor cells have been localized in different regions of the mouse hair follicle (HF). The present study identified a SP in the mouse HF expressing the ABCG2 transporter and MTS24 surface marker. These cells are restricted to the upper isthmus of the HF and have previously been described as progenitor cells. Consistent with their SP characteristic, they demonstrated elevated expression of ABCG2 transporter, which participates in the dye efflux. Analysis of tumor epidermal cell lines revealed a correlation between the number of SP keratinocytes and the grade of malignancy, suggesting that the SP may play a role in malignant progression. Consistent with this idea, the present study observed an increased number of cells expressing ABCG2 and MTS24 in chemically induced skin tumors and skin tumor cell lines. This SP does not express the CD34 surface marker detected in the multipotent stem cells of the bulge region of the HF, which have been defined as tumor initiation cells. The present study concluded that a SP with properties of progenitor cells is localized in the upper isthmus of the HF and is important in mouse skin tumor progression. PMID:29181098

Femoral artery blood flow and microcirculatory perfusion during acute, low-level functional electrical stimulation in spinal cord injury.

PubMed

Barton, Thomas J; Low, David A; Janssen, Thomas W J; Sloots, Maurits; Smit, Christof A J; Thijssen, Dick H J

2018-04-19

Functional electrical stimulation (FES) may help to reduce the risk of developing macro- and microvascular complications in people with SCI. Low-intensity FES has significant clinical potential since this can be applied continuously throughout the day. This study examines the acute effects of low intensity FES using wearable clothing garment on vascular blood flow and oxygen consumption in people with SCI. Cross-sectional observation study METHODS: Eight participants with a motor complete SCI received 4x3 minutes of unilateral FES to the gluteal and hamstring muscles. Skin and deep femoral artery blood flow and oxygen consumption were measured at baseline and during each bout of stimulation. Femoral artery blood flow increased by 18.1% with the application of FES (P=0.02). Moreover, femoral artery blood flow increased further during each subsequent block of FES (P=0.004). Skin perfusion did not change during an individual block of stimulation (P=0.66). Skin perfusion progressively increased with each subsequent bout (P<0.001). There was no change in femoral or skin perfusion across time in the non-stimulated leg (all P>0.05). Low-intensity FES acutely increased blood flow during stimulation, with a progressive increase across subsequent FES bouts. These observations suggest continuous, low-intensity FES may represent a practical and effective strategy to improve perfusion and reduce the risk of vascular complications.

Ethnic variation in melanin content and composition in photoexposed and photoprotected human skin.

PubMed

Alaluf, Simon; Atkins, Derek; Barrett, Karen; Blount, Margaret; Carter, Nik; Heath, Alan

2002-04-01

We have examined the quantity and composition of melanin in both photoprotected (volar upper arm) and chronically photoexposed (dorsal forearm) skin from a range of different ethnic skin types including African, Indian, Mexican, Chinese and European. The most lightly pigmented (European, Chinese and Mexican) skin types have approximately half as much epidermal melanin as the most darkly pigmented (African and Indian) skin types. However, the composition of melanin in these lighter skin types is comparatively more enriched with lightly coloured, alkali-soluble melanin components (up to three-fold). Regardless of ethnicity, epidermal melanin content is significantly greater in chronically photoexposed skin than it is in corresponding photoprotected skin (up to two-fold). However, by comparison there is only a modest enrichment of lightly coloured, alkali soluble melanin components in photoprotected skin (up to 1.3-fold). Analysis of melanosomes extracted from the epidermis in these subjects indicates that the proportion of spheroidal melanosomes is low in all skin types examined (<10%). This suggests that in human skin, pheomelanin is a very minor component of epidermal melanin, even in the lightest (European) skin types. Analysis of melanosome size revealed a significant and progressive variation in size with ethnicity: African skin having the largest melanosomes followed in turn by Indian, Mexican, Chinese and European. On the basis of these findings, we propose that variation in skin pigmentation is strongly influenced by both the amount and the composition (or colour) of the melanin in the epidermis. Variation in melanosome size may also play a significant role. However, the data also suggest that in human skin there are subtle differences in the mechanisms associated with the maintenance of constitutive pigmentation and facultative hyperpigmentation, respectively.

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

PubMed

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

2017-05-01

The effect of the production factors yielding a functional dermal substitute was investigated by means of monotonic and cyclic uniaxial tensile tests, as well as electron microscopy visualizations. The role of (i) plastic compression, (ii) product incubation, and (iii) cell permanence in the collagenous matrix in order to achieve a skin-like behavior were characterized in terms of material and structural stiffness, in-plane kinematics, and cyclic response, as well as pore size and network density. The plastic compression resulted in a denser and stiffer material, while no corresponding change was observed in the behavior of the entire structure. This was related to the progressive reduction in product thickness and amount of excess water, rather than to formation of new crosslinks between fibers. Contrary, irrespective of the presence of human fibroblasts, the product incubation induced both material and structural stiffening, indicating the formation of a denser network. These results were confirmed by similar evolutions in the construct in-plane kinematics and cyclic stress reduction. Finally, comparison of constructs incubated in different culture media indicated a determinant contribution of the biochemical environment, rather than of the seeded cells, to the achieved mechanical properties. The observed features are relevant in terms of mechanical biocompatibility of the implant and might direct future optimizations of the production process in order to rapidly attain the desired mechanical properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

3D bioprinting of skin: a state-of-the-art review on modelling, materials, and processes.

PubMed

Vijayavenkataraman, S; Lu, W F; Fuh, J Y H

2016-09-08

The skin is the largest organ of the body, having a complex multi-layered structure and guards the underlying muscles, bones, ligaments, and internal organs. It serves as the first line of defence to any external stimuli, hence it is the most vulnerable to injury and warrants the need for rapid and reliable regeneration methods. Tissue engineered skin substitutes help overcome the limitations of traditional skin treatment methods, in terms of technology, time, and cost. While there is commendable progress in the treating of superficial wounds and injuries with skin substitutes, treatment of full-thickness injuries, especially with third or fourth degree burns, still looks murkier. Engineering multi-layer skin architecture, conforming to the native skin structure is a tougher goal to achieve with the current tissue engineering methods, if not impossible, restoring all the functions of the native skin. The testing of drugs and cosmetics is another area, where engineered skins are very much needed, with bans being imposed on product testing on animals. Given this greater need, 3D bioprinting is a promising technology that can achieve rapid and reliable production of biomimetic cellular skin substitutes, satisfying both clinical and industrial needs. This paper reviews all aspects related to the 3D bioprinting of skin, right from imaging the injury site, 3D model creation, biomaterials that are used and their suitability, types of cells and their functions, actual bioprinting technologies, along with the challenges and future prospects.

Principles of skin care in the elderly.

PubMed

Surber, C; Brandt, S; Cozzio, A; Kottner, J

2015-12-01

With aging, skin undergoes progressive structural and functional degeneration that leaves it prone to a wide variety of bothersome and even serious conditions and diseases. As skin conditions and diseases may affect all ages from cradle to grave, a disproportionate burden will clearly fall on the elderly and may significantly impact on quality of life (QoL). With a reduced ability of the skin to regenerate, the elderly are at an increased risk of skin breakdowns from even the simplest insults. It is therefore vital that skin care in the late adulthood is seen as a priority among both clinicians and caregivers. The scientific literature on diagnosing and assessing age-related skin conditions and diseases is vast; however, when it comes to preventive care and treatment, the scientific data available is less profound, and the recommendations are often based on personal experience, opinions or at best on consensus documents rather than on scientific data retrieved from controlled clinical trials. In addition to the absence of the scientific data, the imprecise terminology to describe the topical products, as well as the lack of understanding the essence of the vehicle, contributes to vague and often unhelpfully product recommendations. This paper aims to elucidate some basic principles of skincare, the choice of skincare products and their regulatory status. The paper discusses adherence to topical therapies, percutaneous absorption in the elderly, and skin surface pH and skin care. Lastly, it also discusses skin care principles in selected age related skin conditions and diseases.

[The menopause and the skin (author's transl)].

PubMed

Aron-Brunetière, R

It is currently admitted that the skin and its appendages plays an important part in steroid metabolism, especially in genital androgens, estrogens and progestogens. This activity produces the cutaneous changes sometimes associated with the premenopause period : facial hyper-seborrhea, seborrhea of the scalp, loss of scalp hairs, increaed pilosity on the cheeks and upper lip, whether they occur spontaneously or after hormonal treatment. Following the menopause-onset a progressive decreases in hair growth, can be observed, especially in the axillary and pubic regions, with occasional diffuse alopecia, increase in degeneration of elastic tissue, and atrophy of the vaginal mucosa, in fact as some changes appearing in the skin show correlations with the hormonal changes, others appear to be more closely related to aging of the skin. Thus, hormonal therapy will not be able to treat efficiently all these disorders.

Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment*

PubMed Central

Clarindo, Marcos Vinícius; Possebon, Adriana Tomazzoni; Soligo, Emylle Marlene; Uyeda, Hirofumi; Ruaro, Roseli Terezinha; Empinotti, Julio Cesar

2014-01-01

Researches on DH have shown that it is not just a bullous skin disease, but a cutaneous-intestinal disorder caused by hypersensitivity to gluten. Exposure to gluten is the starting point of an inflammatory cascade capable of forming autoantibodies that are brought to the skin, where they are deposited, culminating in the formation of skin lesions. These lesions are vesico-bullous, pruritic, and localized especially on elbows, knees and buttocks, although atypical presentations can occur. Immunofluorescence of perilesional area is considered the gold standard for diagnosis, but serological tests help in cases where it is negative. Patients who follow glutenfree diets have better control of symptoms on the skin and intestine, as well as lower risks of progression to lymphoma. Dapsone remains the main drug for treatment, but it requires monitoring of possible side effects, some potentially lethal. PMID:25387490

Degradation of tropoelastin and skin elastin by neprilysin.

PubMed

Mora Huertas, Angela C; Schmelzer, Christian E H; Luise, Chiara; Sippl, Wolfgang; Pietzsch, Markus; Hoehenwarter, Wolfgang; Heinz, Andrea

2018-03-01

Neprilysin is also known as skin fibroblast-derived elastase, and its up-regulation during aging is associated with impairments of the elastic fiber network, loss of skin elasticity and wrinkle formation. However, information on its elastase activity is still limited. The aim of this study was to investigate the degradation of fibrillar skin elastin by neprilysin and the influence of the donor's age on the degradation process using mass spectrometry and bioinformatics approaches. The results showed that cleavage by neprilysin is dependent on previous damage of elastin. While neprilysin does not cleave young and intact skin elastin well, it degrades elastin fibers from older donors, which may further promote aging processes. With regards to the cleavage behavior of neprilysin, a strong preference for Gly at P1 was found, while Gly, Ala and Val were well accepted at P1' upon cleavage of tropoelastin and skin elastin. The results of the study indicate that the progressive release of bioactive elastin peptides by neprilysin upon skin aging may enhance local tissue damage and accelerate extracellular matrix aging processes. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Disturbed skin barrier in children with chronic kidney disease.

PubMed

Wojtowicz-Prus, Elzbieta; Kilis-Pstrusinska, Katarzyna; Reich, Adam; Zachwieja, Katarzyna; Miklaszewska, Monika; Szczepanska, Maria; Szepietowski, Jacek C

2015-02-01

There are limited data on skin lesions in children with end-stage renal failure. The aim of the study was an evaluation of the skin barrier in children with different stages of chronic kidney disease (CKD). The prevalence of xerosis, its severity, as well as its link selected demographic factors, were examined. The study included 103 children: 72 with CKD stages 3-5 (38 on conservative treatment and 34 on dialysis) and 31 patients with primary monosymptomatic nocturnal enuresis as a control group. Initially, the study subjects described the localisation and severity of dry skin by themselves. Next, clinical evaluation of xerosis, non-invasive corneometric assessment of epidermis moisturising and the measurement of transepidermal water loss were performed. Most CKD children reported dry skin. The problem of xerosis was identified more frequently in patients on dialysis (67.6 %) than on conservative treatment (42.1 %) (p = 0.01). CKD patients divided according to skin dryness did not differ with regards to age, sex, initial kidney disease and CKD duration. Disturbed skin barrier is an important concern of children with CKD, intensifying as the disease progresses. This symptom occurs on early stages of CKD and it should be taken into consideration in the CKD management.

Histological case-control study of peeling-induced skin changes by different peeling agents in surgically subcutaneous undermined skin flaps in facelift patients.

PubMed

Gonser, P; Kaestner, S; Jaminet, P; Kaye, K

2017-11-01

A histological evaluation of peeling-induced skin changes in subcutaneous undermined preauricular facial skin flaps of nine patients was performed. There were three treatment groups: Trichloroacetic acid (TCA) 25%, TCA 40% and phenol/croton oil; one group served as control. Two independent evaluators determined the epidermal and dermal thickness and the depth of necrosis (micrometre). The percentual tissue damage due to the peeling was calculated, and a one-sample t-test for statistical significance was performed. On the basis of the histomorphological changes, peeling depth was classified as superficial, superficial-partial, deep-partial and full thickness chemical burn. The histological results revealed a progression of wound depth for different peeling agents without full thickness necrosis. TCA peels of up to 40% can be safely applied on subcutaneous undermined facial skin flaps without impairing the vascular patency, producing a predictable chemical burn, whereas deep peels such as phenol/croton oil peels should not be applied on subcutaneous undermined skin so as to not produce skin slough or necrosis by impairing vascular patency. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Mild clinical phenotype of Kindler syndrome associated with late diagnosis and skin cancer.

PubMed

Has, C; Burger, B; Volz, A; Kohlhase, J; Bruckner-Tuderman, L; Itin, P

2010-01-01

Kindler syndrome (KS) is a heritable skin disorder with a complex phenotype consisting of congenital skin blistering, photosensitivity, progressive generalized poikiloderma and extensive skin atrophy. Here we describe 2 siblings with KS, who are, to the best of our knowledge, the oldest patients reported so far in the literature. The diagnosis was established in their seventh and eighth decades of life, and confirmed by mutation analysis. Both patients were homozygous for the recurrent FERMT1 mutation, c.328C→T, p.R110X. Because of a relatively mild course of the disease, mucosal membranes in the eyes and oesophagus being predominantly affected in recent years, they had been treated under other diagnoses, such as scleroderma. Cutaneous precancerous lesions and epithelial skin cancer arose in both siblings after the age of 50 years and were treated in an early stage. Taken together, we describe the natural course of KS, the morphological abnormalities occurring in the skin of older KS patients, we discuss the differential diagnosis and the association between KS and squamous cell carcinoma. Copyright © 2010 S. Karger AG, Basel.

From morphology to biochemical state – intravital multiphoton fluorescence lifetime imaging of inflamed human skin

PubMed Central

Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Getova, Valentina; Niemeyer, Verena; Zens, Katharina; Unnerstall, Tim R.; Feger, Julia S.; Fallah, Mohammad A.; Metze, Dieter; Ständer, Sonja; Luger, Thomas A.; Koenig, Karsten; Mess, Christian; Schneider, Stefan W.

2016-01-01

The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients’ bedsides. These ‘optical biopsies’ generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT-FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy. PMID:27004454

Azuki bean (Vigna angularis) extract inhibits the development of experimentally induced atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Collantes, Therese Marie; Rho, Mun-Chual; Kwon, Hyoung-Jun; Jung, Bock-Gie; Alfajaro, Mia Madel; Kim, Deok-Song; Kim, Hyun-Jeong; Hosmillo, Myra; Park, Jun-Gyu; Son, Kyu-Yeol; Park, Sang-Ik; Kang, Mun-Il; Park, Su-Jin; Lee, Seung Woong; Lee, Woo-Song; Cho, Kyoung-Oh

2012-06-01

The present study investigated the effects of azuki bean (Vigna angularis) extract (VAE) on the progress of atopic dermatitis (AD)-like skin lesions in NC/Nga mice induced by 1-chloro-2,4-dinitrobenzene. The efficacy of VAE in NC/Nga mice was determined by measuring gross and histological skin lesions, serum IgE levels, eosinophil ratio in peripheral leucocytes, and mRNA expression levels of interleukin (IL)-4, tumour necrosis factor (TNF)-α and interferon (IFN)-γ in splenocytes. Continuous ingestion of VAE inhibited the development of the AD-like skin lesions in a dose-dependent manner. In the VAE-treated mice, the numbers of mast cells in the skin, eosinophil ratio in peripheral leucocytes, relative mRNA expression of inflammatory cytokines in the spleen, and serum IgE levels were significantly reduced. Results suggest that VAE can inhibit the development of AD-like skin lesions in NC/Nga mice by regulating immune mediators and cells, and may be an effective alternative therapy for AD. Copyright © 2011 Elsevier Ltd. All rights reserved.

From morphology to biochemical state - intravital multiphoton fluorescence lifetime imaging of inflamed human skin

NASA Astrophysics Data System (ADS)

Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Getova, Valentina; Niemeyer, Verena; Zens, Katharina; Unnerstall, Tim R.; Feger, Julia S.; Fallah, Mohammad A.; Metze, Dieter; Ständer, Sonja; Luger, Thomas A.; Koenig, Karsten; Mess, Christian; Schneider, Stefan W.

2016-03-01

The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients’ bedsides. These ‘optical biopsies’ generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT-FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy.

MicroRNA (miR)-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma.

PubMed

Cañueto, J; Cardeñoso-Álvarez, E; García-Hernández, J L; Galindo-Villardón, P; Vicente-Galindo, P; Vicente-Villardón, J L; Alonso-López, D; De Las Rivas, J; Valero, J; Moyano-Sanz, E; Fernández-López, E; Mao, J H; Castellanos-Martín, A; Román-Curto, C; Pérez-Losada, J

2017-07-01

Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and therefore it is important to identify new markers to better predict its clinical evolution. We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR-203 and miR-205 as biomarkers of prognosis in human tumours. Seventy-nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well-established panel of murine skin cancer cell lines, and then selected miR-205 and miR-203 to evaluate their association with the clinical prognosis and evolution of human CSCC. miR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features. miR-205 and miR-203 tended to exhibit mutually exclusive expression patterns in human CSCC. This work highlights the utility of miR-205 and miR-203 as prognostic markers in CSCC. © 2016 British Association of Dermatologists.

HATT: a phase IV, single-arm, open-label study of sorafenib in Taiwanese patients with advanced hepatocellular carcinoma.

PubMed

Lin, Shi-Ming; Lu, Sheng-Nan; Chen, Ping-Tsung; Jeng, Long-Bin; Chen, Shinn-Cherng; Hu, Chi-Tan; Yang, Sien-Sing; Le Berre, Marie-Aude; Liu, Xuan; Mitchell, David Y; Prins, Klaas; Grevel, Joachim; Peña, Carol A E; Meinhardt, Gerold

2017-03-01

Sorafenib significantly improves survival in patients with advanced hepatocellular carcinoma (HCC). This phase IV study assessed sorafenib efficacy/safety in Taiwanese patients with advanced HCC and Child-Pugh A status. All patients received 400 mg sorafenib BID. Safety, efficacy, sorafenib pharmacokinetics, and Child-Pugh progression were evaluated. A hand-foot skin reaction (HFSR) prevention substudy assessed HFSR incidence and grade/severity and time to HFSR in 29 and 34 patients randomized to corticosteroid and noncorticosteroid ointments, respectively, and in 88 nonrandomized patients. The 151 patients included 120 (80%) male patients and 81 (54%) with stage IV disease. Mean sorafenib dose was 626 mg/day, and median treatment duration was 4.2 months. Median overall survival (OS), progression-free survival, and time to progression (TTP) were 8.6, 2.7, and 3.8 months, respectively. Disease control and response rates (partial responses only) were 48 and 6.6%, respectively. Median TTP from Child-Pugh A to B/C was 88 days. Drug-related adverse events (AEs) occurred in 89.4% of patients; none were new or unexpected. The most frequent grade ≥3 drug-related, treatment-emergent AEs were HFSR (13.2%), diarrhea (11.9%), and hypertension (6.6%). Corticosteroid ointment tended to reduce the severity and incidence of all HFSR-associated parameters. Pharmacokinetic exposure was unaltered by Child-Pugh progression. The final pharmacokinetic model predicted 13.1 and 33.8% reductions in sorafenib exposure over 6 and 12 months, respectively. There was a trend of longer OS and TTP in Taiwanese patients with advanced HCC compared with patients with advanced HCC in the Asia-Pacific trial. Sorafenib exposure did not correlate with liver function. Reduced pharmacokinetic exposure over time was unrelated to reduced or interrupted dosing.

EASApprox® skin-stretching system: A secure and effective method to achieve wound closure.

PubMed

Song, Mingzhi; Zhang, Zhen; Liu, Tao; Liu, Song; Li, Gang; Liu, Zhaochang; Huang, Jingyang; Chen, Song; Li, Linan; Guo, Li; Qiu, Yang; Wan, Jiajia; Liu, Yuejian; Wu, Tao; Wang, Xiaoyong; Lu, Ming; Wang, Shouyu

2017-07-01

Large skin defects are commonly observed in the clinic and have attracted much attention recently. Therefore, finding an effective solution for large skin defects is a global problem. The objective of the present study was to assess the effectiveness of the EASApprox ® skin-stretching system for closing large skin defects. Skin defects (5×5 cm) were created on the forearms of 9 Bama miniature pigs, which were randomly divided into the following three groups: Direct suture, the new EASApprox ® skin-stretching device and Kirschner wires. Microcirculation was assessed before surgery and after wound closure. Following the different treatments, the defects were sutured, and wound healing was assessed based on a clinical score. Furthermore, microscopic and ultramicroscopic structures were evaluated, including collagen, elastic fibers and the microvessel density. Significant differences in the clinical score and microvessel density were observed among the groups. Additionally, the mean length obtained for elastic fibers was larger than that obtained for the other two groups. Finally, the new EASApprox ® skin-stretching device resulted in successful wound management and with only minor side effects on skin histology and microcirculation. Therefore, this method has the potential to be used for healing large skin defects.

Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoo, Hyun; Kang, Jeong Wook; Lee, Dong Won

Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a highmore » cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. - Highlights: • The effects of radiation on skin thickness in mice. • Next generation sequencing revealed that radiation inhibited pyruvate dehydrogenase kinase 2 expression. • PDK2 inhibited irradiation-induced cytokine gene expression. • Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness.« less

Amphotericin B releasing topical nanoemulsion for the treatment of candidiasis and aspergillosis.

PubMed

Sosa, Lilian; Clares, Beatriz; Alvarado, Helen L; Bozal, Nuria; Domenech, Oscar; Calpena, Ana C

2017-10-01

The present study was designed to develop a nanoemulsion formulation of Amphotericin B (AmB) for the treatment of skin candidiasis and aspergillosis. Several ingredients were selected on the basis of AmB solubility and compatibility with skin. The formulation that exhibited the best properties was selected from the pseudo-ternary phase diagram. After physicochemical characterization its stability was assessed. Drug release and skin permeation studies were also accomplished. The antifungal efficacy and skin tolerability of developed AmB nanoemulsion was demonstrated. Finally, our results showed that the developed AmB formulation could provide an effective local antifungal effect without theoretical systemic absorption, based on its skin retention capacity, which might avoid related side effect. These results suggested that the nanoemulsion may be an optimal therapeutic alternative for the treatment of skin fungal infections with AmB. Copyright © 2017 Elsevier Inc. All rights reserved.

Cutaneous wound healing: recruiting developmental pathways for regeneration.

PubMed

Bielefeld, Kirsten A; Amini-Nik, Saeid; Alman, Benjamin A

2013-06-01

Following a skin injury, the damaged tissue is repaired through the coordinated biological actions that constitute the cutaneous healing response. In mammals, repaired skin is not identical to intact uninjured skin, however, and this disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development. Improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for wound healing complications. Here we focus on the roles of several key developmental signaling pathways (Wnt/β-catenin, TGF-β, Hedgehog, Notch) in mammalian cutaneous wound repair, and compare this to their function in skin development. We discuss the varying responses to cutaneous injury across the taxa, ranging from complete regeneration to scar tissue formation. Finally, we outline how research into the role of developmental pathways during skin repair has contributed to current wound therapies, and holds potential for the development of more effective treatments.

Nonextensive statistics and skin depth of transverse wave in collisional plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hashemzadeh, M., E-mail: hashemzade@gmail.com

Skin depth of transverse wave in a collisional plasma is studied taking into account the nonextensive electron distribution function. Considering the kinetic theory for charge particles and using the Bhatnagar-Gross-Krook collision model, a generalized transverse dielectric permittivity is obtained. The transverse dispersion relation in different frequency ranges is investigated. Obtaining the imaginary part of the wave vector from the dispersion relation, the skin depth for these frequency ranges is also achieved. Profiles of the skin depth show that by increasing the q parameter, the penetration depth decreases. In addition, the skin depth increases by increasing the electron temperature. Finally, itmore » is found that in the high frequency range and high electron temperature, the penetration depth decreases by increasing the collision frequency. In contrast, by increasing the collision frequency in a highly collisional frequency range, the skin depth of transverse wave increases.« less

Dimethyl fumarate modulation of immune and antioxidant responses: application to HIV therapy

PubMed Central

Gill, Alexander J.; Kolson, Dennis L.

2013-01-01

The persistence of chronic immune activation and oxidative stress in human immunodeficiency virus (HIV)-infected, antiretroviral drug-treated individuals are major obstacles to fully preventing HIV disease progression. The immune modulator and antioxidant dimethyl fumarate (DMF) is effective in treating immune-mediated diseases and it also has potential applications to limiting HIV disease progression. Among the relevant effects of DMF and its active metabolite monomethyl fumarate (MMF) are induction of a Th1 → Th2 lymphocyte shift, inhibition of pro-inflammatory cytokine signaling, inhibition of NF-κB nuclear translocation, inhibition of dendritic cell maturation, suppression of lymphocyte and endothelial cell adhesion molecule expression, and induction of the Nrf2-dependent antioxidant response element (ARE) and effector genes. Associated with these effects are reduced lymphocyte and monocyte infiltration into psoriatic skin lesions in humans and immune-mediated demyelinating brain lesions in rodents, which confirms potent systemic and central nervous system (CNS) effects. In addition, DMF and MMF limit HIV infection in macrophages in vitro, albeit by unknown mechanisms. Finally, DMF and MMF also suppress neurotoxin production from HIV-infected macrophages, which drives CNS neurodegeneration. Thus, DMF might protect against systemic and CNS complications in HIV infection through its effective suppression of immune activation, oxidative stress, HIV replication, and macrophage-associated neuronal injury. PMID:23971529

Tracing cell lineages in videos of lens-free microscopy.

PubMed

Rempfler, Markus; Stierle, Valentin; Ditzel, Konstantin; Kumar, Sanjeev; Paulitschke, Philipp; Andres, Bjoern; Menze, Bjoern H

2018-06-05

In vitro experiments with cultured cells are essential for studying their growth and migration pattern and thus, for gaining a better understanding of cancer progression and its treatment. Recent progress in lens-free microscopy (LFM) has rendered it an inexpensive tool for label-free, continuous live cell imaging, yet there is only little work on analysing such time-lapse image sequences. We propose (1) a cell detector for LFM images based on fully convolutional networks and residual learning, and (2) a probabilistic model based on moral lineage tracing that explicitly handles multiple detections and temporal successor hypotheses by clustering and tracking simultaneously. (3) We benchmark our method in terms of detection and tracking scores on a dataset of three annotated sequences of several hours of LFM, where we demonstrate our method to produce high quality lineages. (4) We evaluate its performance on a somewhat more challenging problem: estimating cell lineages from the LFM sequence as would be possible from a corresponding fluorescence microscopy sequence. We present experiments on 16 LFM sequences for which we acquired fluorescence microscopy in parallel and generated annotations from them. Finally, (5) we showcase our methods effectiveness for quantifying cell dynamics in an experiment with skin cancer cells. Copyright © 2018 Elsevier B.V. All rights reserved.

NIAMS Kids Pages on Muscles, Joints, Skin and Bones

MedlinePlus

... this research; and the dissemination of information on research progress in these diseases. Contact Us NIAMS Archive Viewers and Players Social Media Moderation Policy FOIA Privacy Statement Accessibility Disclaimer Digital Strategy ...

[Mucolipidoses type IV in a patient with mapuche ancestry].

PubMed

Hernández Ch, Marta; Méndez C, José Ignacio; Concha G, María José; Huete L, Isidro; González B, Sergio; Durán S, Gloria P

2008-07-01

We report a 7 year-old girl with mapuche ancestors, diagnosed as a cerebral palsy since infancy and on active rehabilitation. She acquired motor and cognitive skills at 3 years of age. At 5 years of age, a slow neurological deterioration started, associated to visual impairment. Optic atrophy was added to the typical neurological exam of ataxic cerebral palsy and the diagnosis was re-considered. Neuroimaging showed a slow and progressive atrophy of intracerebral structures and ultramicroscopy revealed intracytoplasmatic inclusions in conjunctiva and skin, compatible with mucolipidoses type IV (ML-IV). ML-IV must be included in the differential diagnosis of cerebral palsy associated with loss of acquired skills and progressive visual impairment. Electron microscopy of skin or conjunctiva is a useful diagnostic test. Suspicion of ML-IV must not be restricted to Ashkenazi Jewish population.

Progress and prospects for L2-based human papillomavirus vaccines

PubMed Central

Jiang, Rosie T; Schellenbacher, Christina; Chackerian, Bryce; Roden, Richard B.S.

2016-01-01

Summary Human papillomavirus (HPV) is a worldwide public health problem, particularly in resource-limited countries. Fifteen high-risk genital HPV types are sexually transmitted and cause 5% of all cancers worldwide, primarily cervical, anogenital and oropharyngeal carcinomas. Skin HPV types are generally associated with benign disease, but a subset is linked to non-melanoma skin cancer. Licensed HPV vaccines based on virus-like particles (VLPs) derived from L1 major capsid antigen of key high risk HPVs are effective at preventing these infections but do not cover cutaneous types and are not therapeutic. Vaccines targeting L2 minor capsid antigen, some using capsid display, adjuvant and fusions with early HPV antigens or Toll-like receptor agonists, are in development to fill these gaps. Progress and challenges with L2-based vaccines are summarized. PMID:26901354

[Progress in epidermal stem cells].

PubMed

Wang, Li-Juan; Wang, You-Liang; Yang, Xiao

2010-03-01

Mammalian skin epidermis contains different epidermal stem cell pools which contribute to the homeostasis and repair of skin epithelium. Epidermal stem cells possess two essential features common to all stem cells: self-renewal and differentiation. Disturbing the balance between self-renewal and differentiation of epidermal stem cell often causes tumors or other skin diseases. Epidermal stem cell niches provide a special microenvironment that maintains a balance of stem cell quiescence and activity. This review primarily concentrates on the following points of the epidermal stem cells: the existing evidences, the self-renewal and differentiation, the division pattern, the signal pathways regulating self-renewal and differentiation, and the microenvironment (niche) and macroenvironment maintaining the homeostasis of stem cells.

Recent progresses in application of fullerenes in cosmetics.

PubMed

Lens, Marko

2011-08-01

Cosmetic industry is a fast growing industry with the continuous development of new active ingredients for skin care products. Fullerene C(60) and its derivates have been subject of intensive research in the last few years. Fullerenes display a wide range of different biological activities. Strong antioxidant capacities and effective quenching radical oxygen species (ROS) made fullerenes suitable active compounds in the formulation of skin care products. Published evidence on biological activities of fullerenes relevant for their application in cosmetics use and examples of published patents are presented. Recent trends in the use of fullerenes in topical formulations and patents are reviewed. Future investigations covering application of fullerenes in skin care are discussed.

Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer.

PubMed

Quigley, David A; Kandyba, Eve; Huang, Phillips; Halliwill, Kyle D; Sjölund, Jonas; Pelorosso, Facundo; Wong, Christine E; Hirst, Gillian L; Wu, Di; Delrosario, Reyno; Kumar, Atul; Balmain, Allan

2016-07-26

Inherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways. Gene networks related to specific cell types and signaling pathways, including sonic hedgehog (Shh), Wnt, Lgr family stem cell markers, and keratins, differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for expression quantitative trait loci (eQTL) network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Absence of skin rash in Goodpasture's syndrome: the hyaluronan effect.

PubMed

Stern, A; Stern, R

2014-12-01

Goodpasture's syndrome is a rare disease that involves rapidly progressive kidney failure as well as hemorrhagic lung disease. It is a form of autoimmune disorder with unusual features; marked male preponderance, in contrast with other autoimmune disease in which females are at far greater risk. The autoantibodies are directed again the carboxy-extension non-collagenous (NC1) portion of one of the basement membrane-specific collagen IV alpha 3 chains. Basal laminas throughout the body share this structure, including those in kidney, lung and skin. But curiously, skin is rarely involved in Goodpasture's syndrome. Hyaluronan is a large extracellular matrix carbohydrate polymer. Half of total body hyaluronan occurs in skin. High molecular weight hyaluronan, a potent immunosuppressive polymer, might be functioning as an immune shield for skin in Goodpasture's syndrome, and be the basis for the anomaly. A summary of this putative effect is described, including possible molecular mechanisms involved, and suggestions for testing this hypothesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Three-Dimensional Printing and Cell Therapy for Wound Repair.

PubMed

van Kogelenberg, Sylvia; Yue, Zhilian; Dinoro, Jeremy N; Baker, Christopher S; Wallace, Gordon G

2018-05-01

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs.

Relationships between skin temperature and temporal summation of heat and cold pain.

PubMed

Mauderli, Andre P; Vierck, Charles J; Cannon, Richard L; Rodrigues, Anthony; Shen, Chiayi

2003-07-01

Temporal summation of heat pain during repetitive stimulation is dependent on C nociceptor activation of central N-methyl-d-aspartate (NMDA) receptor mechanisms. Moderate temporal summation is produced by sequential triangular ramps of stimulation that control skin temperature between heat pulses but do not elicit distinct first and second pain sensations. Dramatic summation of second pain is produced by repeated contact of the skin with a preheated thermode, but skin temperature between taps is not controlled by this procedure. Therefore relationships between recordings of skin temperature and psychophysical ratings of heat pain were evaluated during series of repeated skin contacts. Surface and subcutaneous recordings of skin temperatures revealed efficient thermoregulatory compensation for heat stimulation at interstimulus intervals (ISIs) ranging from 2 to 8 s. Temporal summation of heat pain was strongly influenced by the ISIs and cannot be explained by small increases in skin temperature between taps or by heat storage throughout a stimulus series. Repetitive brief contact with a precooled thermode was utilized to evaluate whether temporal summation of cold pain occurs, and if so, whether it is influenced by skin temperature. Surface and subcutaneous recordings of skin temperature revealed a sluggish thermoregulatory compensation for repetitive cold stimulation. In contrast to heat stimulation, skin temperature did not recover between cold stimuli throughout ISIs of 3-8 s. Psychophysically, repetitive cold stimulation produced an aching pain sensation that progressed gradually and radiated beyond the site of stimulation. The magnitude of aching pain was well related to skin temperature and thus appeared to be established primarily by peripheral factors.

Assessment of organ culture for the conservation of human skin allografts.

PubMed

Hautier, A; Sabatier, F; Stellmann, P; Andrac, L; Nouaille De Gorce, Y; Dignat-George, F; Magalon, G

2008-03-01

Human skin allografts are used in the treatment of severe burns and their preservation is therefore critical for optimal clinical benefit. Current preservation methods, such as 4 degrees C storage or cryopreservation, cannot prevent the decrease of tissue viability. The aim of this study was to assess viability and function of skin allografts in a new skin organ culture model, allowing conservation parameters as close as possible to physiological conditions: 32 degrees C, air-liquid interface and physiological skin tension. Twelve skin samples, harvested from 6 living surgical donors, were conserved 35 days in two conditions: conservation at 4 degrees C and organ culture. Viability and function of skin samples were investigated at Day 0, 7, 14, 21, 28 and 35 using cell culture methods (trypan blue exclusion, Colony Forming Efficiency and Growth Rate), histopathological and histoenzymological studies (Ki67 immunostaining). In the two conditions, fibroblast and keratinocyte viability was progressively affected by storage, with a significant decrease observed after 35 days. No statistical difference could be observed between the two conditions. The two methods were also comparable regarding alterations of fibroblast and keratinocyte culture parameters, which were respectively significantly reduced at Day 7 and 21, compared to fresh skin. By contrast, histopathological and histoenzymological studies revealed a better preservation of skin architecture and proliferative potential at 4 degrees C, as compared to organ culture. These results indicate that skin organ culture does not provide significant advantages for skin allograft preservation. However, its potential use as an experimental model to study skin physiology and wound healing should be further evaluated.

Electrospun Poly(lactic acid-co-glycolic acid) Scaffolds for Skin Tissue Engineering

PubMed Central

Kumbar, Sangamesh G.; Nukavarapu, Syam Prasad; James, Roshan; Nair, Lakshmi S.; Laurencin, Cato T.

2008-01-01

Electrospun fiber matrices composed of scaffolds of varying fiber diameters were investigated for potential application of severe skin loss. Few systematic studies have been performed to examine the effect of varying fiber diameter electrospun fiber matrices for skin regeneration. The present study reports the fabrication of poly[lactic acid-co-glycolic acid] (PLAGA) matrices with fiber diameters of 150–225, 200–300, 250–467, 500–900, 600–1200, 2500–3000 and 3250–6000 nm via electrospinning. All fiber matrices found to have a tensile modulus from 39.23 ± 8.15 to 79.21 ± 13.71 MPa which falls in the range for normal human skin. Further, the porous fiber matrices have porosity between 38–60 % and average pore diameters between 10–14µm. We evaluated the efficacy of these biodegradable fiber matrices as skin substitutes by seeding them with human skin fibroblasts (hSF). Human skin fibroblasts acquired a well spread morphology and showed significant progressive growth on fiber matrices in the 350–1100 nm diameter range. Collagen type III gene expression was significantly up-regulated in hSF seeded on matrices with fiber diameters in the range of 350–1100 nm. Based on the need, the proposed fiber skin substitutes can be successfully fabricated and optimized for skin fibroblast attachment and growth. PMID:18639927

Progress on Reconstructed Human Skin Models for Allergy Research and Identifying Contact Sensitizers.

PubMed

Rodrigues Neves, Charlotte; Gibbs, Susan

2018-06-23

Contact with the skin is inevitable or desirable for daily life products such as cosmetics, hair dyes, perfumes, drugs, household products, and industrial and agricultural products. Whereas the majority of these products are harmless, a number can become metabolized and/or activate the immunological defense via innate and adaptive mechanisms resulting in sensitization and allergic contact dermatitis upon following exposures to the same substance. Therefore, strict safety (hazard) assessment of actives and ingredients in products and drugs applied to the skin is essential to determine I) whether the chemical is a potential sensitizer and if so II) what is the safe concentration for human exposure to prevent sensitization from occurring. Ex vivo skin is a valuable model for skin penetration studies but due to logistical and viability limitations the development of in vitro alternatives is required. The aim of this review is to give a clear overview of the organotypic in vitro skin models (reconstructed human epidermis, reconstructed human skin, immune competent skin models incorporating Langerhans Cells and T-cells, skin-on-chip) that are currently commercially available or which are being used in a laboratory research setting for hazard assessment of potential sensitizers and for investigating the mechanisms (sensitization key events 1-4) related to allergic contact dermatitis. The limitations of the models, their current applications, and their future potential in replacing animals in allergy-related science are discussed.

[Helminth migration in the host].

PubMed

Horák, Petr

2006-08-01

Helminths belong to important human pathogens in tropical and subtropical countries. They have simple one-host life cycles or they use several hosts for their development. There are two main entry points for human helminths: the skin and the oral cavity. Skin penetration is followed by tissue migration of helminth stages towards target organs. Also some perorally acquired helminths migrate throughout the human body and then (a) they return to and mature in the intestine or (b) they search for specific final location in other (extraintestinal) tissues/organs. Particular developmental stages having different migration routes, and different roles of human beings as final, intermediate and paratenic hosts are briefly mentioned.

Fournier gangrene associated with hyper IgE syndrome (Job syndrome).

PubMed

Hori, Junichi; Yamaguchi, Satoshi; Watanabe, Masaki; Osanai, Hiroaki; Hori, Masako

2008-04-01

We report a case of a 32-year-old man with hyper IgE syndrome (Job syndrome) who developed Fournier gangrene due to infectious multiple atheromas of the scrotal skin that progressed to the right groin and thigh. The patient required surgical debridement and subsequent skin grafting. This is a rare case of Fournier gangrene associated with hyper IgE syndrome (Job syndrome). When a patient without diabetes mellitus has repeated infections and atopic-like dermatitis, Job syndrome should be considered.

A method for the generation of ectromelia virus (ECTV) recombinants: in vivo analysis of ECTV vCD30 deletion mutants.

PubMed

Alejo, Ali; Saraiva, Margarida; Ruiz-Argüello, Maria Begoña; Viejo-Borbolla, Abel; de Marco, Mar Fernández; Salguero, Francisco Javier; Alcami, Antonio

2009-01-01

Ectromelia virus (ECTV) is the causative agent of mousepox, a lethal disease of mice with similarities to human smallpox. Mousepox progression involves replication at the initial site of infection, usually the skin, followed by a rapid spread to the secondary replicative organs, spleen and liver, and finally a dissemination to the skin, where the typical rash associated with this and other orthopoxviral induced diseases appears. Case fatality rate is genetically determined and reaches up to 100% in susceptible mice strains. Like other poxviruses, ECTV encodes a number of proteins with immunomodulatory potential, whose role in mousepox progression remains largely undescribed. Amongst these is a secreted homologue of the cellular tumour necrosis factor receptor superfamily member CD30 which has been proposed to modulate a Th1 immune response in vivo. To evaluate the contribution of viral CD30 (vCD30) to virus pathogenesis in the infected host, we have adapted a novel transient dominant method for the selection of recombinant ECTVs. Using this method, we have generated an ECTV vCD30 deletion mutant, its corresponding revertant control virus as well as a virus encoding the extracellular domain of murine CD30. These viruses contain no exogenous marker DNA sequences in their genomes, as opposed to other ECTVs reported up to date. We show that the vCD30 is expressed as a secreted disulfide linked trimer and that the absence of vCD30 does not impair mousepox induced fatality in vivo. Replacement of vCD30 by a secreted version of mouse CD30 caused limited attenuation of ECTV. The recombinant viruses generated may be of use in the study of the role of the cellular CD30-CD30L interaction in the development of the immune response. The method developed might be useful for the construction of ECTV mutants for the study of additional genes.

Formulation design for topical drug and nanoparticle treatment of skin disease.

PubMed

Raphael, Anthony P; Garrastazu, Gabriela; Sonvico, Fabio; Prow, Tarl W

2015-02-01

The skin has evolved to resist the penetration of foreign substances and particles. Topical therapeutic and cosmeceutical delivery is a growing field founded on selectively overcoming this barrier. Both the biology of the skin and the nature of the formulation/active ingredient must be aligned for efficient transcutaneous delivery. This review discusses the biological changes in the skin barrier that occur with common dermatological conditions. This context is the foundation for the discussion of formulation strategies to improve penetration profiles of common active ingredients in dermatology. Finally, we compare and contrast those approaches to recent advances described in the research literature with an eye toward the future of topical formulation design.

Global Burden of Skin Disease: Inequities and Innovations.

PubMed

Seth, Divya; Cheldize, Khatiya; Brown, Danielle; Freeman, Esther F

2017-09-01

We review the current understanding of the burden of dermatological disease through the lens of the Global Burden of Disease project, evaluate the impact of skin disease on quality of life in a global context, explore socioeconomic implications, and finally summarize interventions towards improving quality of dermatologic care in resource-poor settings. The Global Burden of Disease project has shown that skin diseases continue to be the 4 th leading cause of nonfatal disease burden world-wide. However, research efforts and funding do not match with the relative disability of skin diseases. International and national efforts, such as the WHO List of Essential Medicines, are critical towards reducing the socioeconomic burden of skin diseases and increasing access to care. Recent innovations such as teledermatology, point-of-care diagnostic tools, and task-shifting help to provide dermatological care to underserved regions in a cost-effective manner. Skin diseases cause significant non-fatal disability worldwide, especially in resource-poor regions. Greater impetus to study the burden of skin disease in low resource settings and policy efforts towards delivering high quality care are essential in improving the burden of skin diseases.

Visual attention to variation in female facial skin color distribution.

PubMed

Fink, Bernhard; Matts, Paul J; Klingenberg, Heiner; Kuntze, Sebastian; Weege, Bettina; Grammer, Karl

2008-06-01

Visible skin condition of women is argued to influence human physical attraction. Recent research has shown that people are sensitive to variation in skin color distribution, and such variation affects visual perception of female facial attractiveness, healthiness, and age. The eye gaze of 39 males and females, aged 13 to 45 years, was tracked while they viewed images of shape- and topography-standardized stimulus faces that varied only in terms of skin color distribution. The number of fixations and dwell time were significantly higher when viewing stimulus faces with the homogeneous skin color distribution of young people, compared with those of more elderly people. In accordance with recent research, facial stimuli with even skin tones were also judged to be younger and received higher attractiveness ratings. Finally, visual attention measures were negatively correlated with perceived age, but positively associated with attractiveness judgments. Variation in visible skin color distribution (independent of facial form and skin surface topography) is able to selectively attract people's attention toward female faces, and this higher attention results in more positive statements about a woman's face.

Role for the epidermal growth factor receptor in chemotherapy-induced alopecia.

PubMed

Bichsel, Kyle J; Gogia, Navdeep; Malouff, Timothy; Pena, Zachary; Forney, Eric; Hammiller, Brianna; Watson, Patrice; Hansen, Laura A

2013-01-01

Treatment of cancer patients with chemotherapeutics like cyclophosphamide often causes alopecia as a result of premature and aberrant catagen. Because the epidermal growth factor receptor (EGFR) signals anagen hair follicles to enter catagen, we hypothesized that EGFR signaling may be involved in cyclophosphamide-induced alopecia. To test this hypothesis, skin-targeted Egfr mutant mice were generated by crossing floxed Egfr and Keratin 14 promoter-driven Cre recombinase mice. Cyclophosphamide treatment of control mice resulted in alopecia while Egfr mutant skin was resistant to cyclophosphamide-induced alopecia. Egfr mutant skin entered catagen normally, as indicated by dermal papilla condensation and decreased follicular proliferation, but did not progress to telogen as did Egfr wild type follicles. Egfr mutant follicles responded with less proliferation, apoptosis, and fewer p53-positive cells after cyclophosphamide. Treatment of control mice with the EGFR inhibitors erlotinib or gefitinib similarly suppressed alopecia and catagen progression by cyclophosphamide. Secondary analysis of clinical trials utilizing EGFR-targeted therapies and alopecia-inducing chemotherapy also revealed evidence for involvement of EGFR in chemotherapy-induced alopecia. Taken together, our results demonstrated the involvement of EGFR signaling in chemotherapy-induced alopecia, which will help in the design of novel therapeutic regimens to minimize chemotherapy-induced alopecia.

The effect of repeated laser stimuli to ink-marked skin on skin temperature-recommendations for a safe experimental protocol in humans.

PubMed

Madden, Victoria J; Catley, Mark J; Grabherr, Luzia; Mazzola, Francesca; Shohag, Mohammad; Moseley, G Lorimer

2016-01-01

Background. Nd:YAP laser is widely used to investigate the nociceptive and pain systems, generating perpetual and laser-evoked neurophysiological responses. A major procedural concern for the use of Nd:YAP laser stimuli in experimental research is the risk of skin damage. The absorption of Nd:YAP laser stimuli is greater in darker skin, or in pale skin that has been darkened with ink, prompting some ethics boards to refuse approval to experimenters wishing to track stimulus location by marking the skin with ink. Some research questions, however, require laser stimuli to be delivered at particular locations or within particular zones, a requirement that is very difficult to achieve if marking the skin is not possible. We thoroughly searched the literature for experimental evidence and protocol recommendations for safe delivery of Nd:YAP laser stimuli over marked skin, but found nothing. Methods. We designed an experimental protocol to define safe parameters for the use of Nd:YAP laser stimuli over skin that has been marked with black dots, and used thermal imaging to assess the safety of the procedure at the forearm and the back. Results. Using thermal imaging and repeated laser stimulation to ink-marked skin, we demonstrated that skin temperature did not increase progressively across the course of the experiment, and that the small change in temperature seen at the forearm was reversed during the rest periods between blocks. Furthermore, no participant experienced skin damage due to the procedure. Conclusion. This protocol offers parameters for safe, confident and effective experimentation using repeated Nd:YAP laser on skin marked with ink, thus paving the way for investigations that depend on it.

Targeted deletion and lipidomic analysis identify epithelial cell COX-2 as a major driver of chemically induced skin cancer.

PubMed

Jiao, Jing; Ishikawa, Tomo-O; Dumlao, Darren S; Norris, Paul C; Magyar, Clara E; Mikulec, Carol; Catapang, Art; Dennis, Edward A; Fischer, Susan M; Herschman, Harvey R

2014-11-01

Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX-2) plays a critical role in DMBA/TPA-induced skin tumor induction. Although many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell type-specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared with littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2-expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell type-specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biologic responses. Cox-2 gene deletion demonstrates that intrinsic COX-2 expression in initiated keratinocytes is a principal driver of skin carcinogenesis; lipidomic analysis identifies likely prostanoid effectors. ©2014 American Association for Cancer Research.

Ex vivo investigations of laser auricular cartilage reshaping with carbon dioxide spray cooling in a rabbit model

PubMed Central

Wu, Edward C.; Sun, Victor; Manuel, Cyrus T.; Protsenko, Dmitriy E.; Jia, Wangcun; Nelson, J. Stuart; Wong, Brian J. F.

2014-01-01

Laser cartilage reshaping (LCR) with cryogen spray cooling is a promising modality for producing cartilage shape change while reducing cutaneous thermal injury. However, LCR in thicker tissues, such as auricular cartilage, requires higher laser power, thus increasing cooling requirements. To eliminate the risks of freeze injury characteristic of high cryogen spray pulse rates, a carbon dioxide (CO2) spray, which evaporates rapidly from the skin, has been proposed as the cooling medium. This study aims to identify parameter sets which produce clinically significant reshaping while producing minimal skin thermal injury in LCR with CO2 spray cooling in ex vivo rabbit auricular cartilage. Excised whole rabbit ears were mechanically deformed around a cylindrical jig and irradiated with a 1.45-μm wavelength diode laser (fluence 12–14 J/cm2 per pulse, four to six pulse cycles per irradiation site, five to six irradiation sites per row for four rows on each sample) with concomitant application of CO2 spray (pulse duration 33–85 ms) to the skin surface. Bend angle measurements were performed before and after irradiation, and the change quantified. Surface temperature distributions were measured during irradiation/cooling. Maximum skin surface temperature ranged between 49.0 to 97.6 °C following four heating/cooling cycles. Significant reshaping was achieved with all laser dosimetry values with a 50–70 °C difference noted between controls (no cooling) and irradiated ears. Increasing cooling pulse duration yielded progressively improved gross skin protection during irradiation. CO2 spray cooling may potentially serve as an alternative to traditional cryogen spray cooling in LCR and may be the preferred cooling medium for thicker tissues. Future studies evaluating preclinical efficacy in an in vivo rabbit model are in progress. PMID:23307439

Ex vivo investigations of laser auricular cartilage reshaping with carbon dioxide spray cooling in a rabbit model.

PubMed

Wu, Edward C; Sun, Victor; Manuel, Cyrus T; Protsenko, Dmitriy E; Jia, Wangcun; Nelson, J Stuart; Wong, Brian J F

2013-11-01

Laser cartilage reshaping (LCR) with cryogen spray cooling is a promising modality for producing cartilage shape change while reducing cutaneous thermal injury. However, LCR in thicker tissues, such as auricular cartilage, requires higher laser power, thus increasing cooling requirements. To eliminate the risks of freeze injury characteristic of high cryogen spray pulse rates, a carbon dioxide (CO2) spray, which evaporates rapidly from the skin, has been proposed as the cooling medium. This study aims to identify parameter sets which produce clinically significant reshaping while producing minimal skin thermal injury in LCR with CO2 spray cooling in ex vivo rabbit auricular cartilage. Excised whole rabbit ears were mechanically deformed around a cylindrical jig and irradiated with a 1.45-μm wavelength diode laser (fluence 12-14 J/cm(2) per pulse, four to six pulse cycles per irradiation site, five to six irradiation sites per row for four rows on each sample) with concomitant application of CO2 spray (pulse duration 33-85 ms) to the skin surface. Bend angle measurements were performed before and after irradiation, and the change quantified. Surface temperature distributions were measured during irradiation/cooling. Maximum skin surface temperature ranged between 49.0 to 97.6 °C following four heating/cooling cycles. Significant reshaping was achieved with all laser dosimetry values with a 50-70 °C difference noted between controls (no cooling) and irradiated ears. Increasing cooling pulse duration yielded progressively improved gross skin protection during irradiation. CO2 spray cooling may potentially serve as an alternative to traditional cryogen spray cooling in LCR and may be the preferred cooling medium for thicker tissues. Future studies evaluating preclinical efficacy in an in vivo rabbit model are in progress.

Assessment of Regenerative Capacity in the Dolphin

DTIC Science & Technology

2011-10-10

surface markers. Cultured cells were also cryogenically frozen for future cell therapy treatment of dolphin skin wounds. Gene array analysis on the...Mammals, Atlantic Bottlenose Dolphin, Autologous Cell Therapy 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...cellular therapy for dolphin skin wounds. Finally, the cells will be tested for immunogenicity to develop an allogeneic (same species, universal

Assessment of Regenerative Capacity in the Dolphin

DTIC Science & Technology

2012-06-30

markers and stem cell related genes. Cultured cells were also cryogenically frozen for autologous and allogeneic cell therapy treatment of dolphin skin...Regenerative Cells, Marine Mammals, Atlantic Bottlenose Dolphin, Autologous Cell Therapy , Allogeneic Cell Therapy 16. SECURITY CLASSIFICATION OF...cultured ASCs will be used as autologous cellular therapy for dolphin skin wounds. Finally, the cells will be tested for immunogenicity to develop an

Atopic Dermatitis in Children: Clinical Features, Pathophysiology and Treatment

PubMed Central

Lyons, Jonathan J.; Milner, Joshua D.; Stone, Kelly D.

2014-01-01

Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic skin condition resulting from disruption of the epithelial barrier and associated immune dysregulation in the skin of genetically predisposed hosts. AD generally develops in early childhood, has a characteristic age-dependent distribution and is commonly associated with elevated IgE, peripheral eosinophilia and other allergic diseases. Staphylococcus aureus colonization is common and may contribute to disease progression and severity. Targeted therapies to restore both impaired skin barrier and control inflammation are required for optimal outcomes for patients with moderate to severe disease. Pruritus is universal among patients with AD and has a dominant impact on diminishing quality of life. Medications such as anti-histamines have demonstrated poor efficacy in controlling AD-associated itch. Education of patients regarding the primary underlying defects and provision of a comprehensive skin care plan is essential for disease maintenance and management of flares. PMID:25459583

Towards the use of OCT angiography in clinical dermatology

NASA Astrophysics Data System (ADS)

Baran, Utku; Choi, Woo June; Wang, Ruikang K.

2016-02-01

Optical coherence tomography (OCT) is a popular imaging technique used in ophthalmology, and on the way to become clinically viable alternative in dermatology due to its capability of acquiring histopathology level images of in vivo tissue, noninvasively. In this study, we demonstrate the capabilities of OCT-based angiography (OMAG) in detecting high-resolution, volumetric structural and microvascular features of in vivo human skin with various conditions using a swept source OCT system that operates on a central wavelength of 1310 nm with an A-line rate of 100 kHz. OMAG images provide detailed in vivo visualization of microvasculature of abnormal human skin conditions from face, chest and belly. Moreover, the progress of wound healing on human skin from arm is monitored during longitudinal wound healing process. The presented results promise the clinical use of OCT angiography in treatment of prevalent cutaneous diseases within human skin, in vivo.

Aggravation of atopic dermatitis in breast-fed infants by tree nut-related foods and fermented foods in breast milk.

PubMed

Uenishi, Toshiaki; Sugiura, Hisashi; Tanaka, Toshihiro; Uehara, Masami

2011-02-01

Ninety-two exclusively breast-fed Japanese infants with atopic dermatitis were studied to see whether tree nut-related foods (chocolate and coffee) and fermented foods (cheese, yogurt, bread, soy sauce, miso soup and fermented soy beans) eaten by their mothers affected their skin condition. Of the 92 infants, 67 (73%) showed improvement of skin lesions when their mothers avoided these foods and showed aggravation of skin lesions when these foods were reintroduced. The predominant offending foods were chocolate, yogurt, soy sauce and miso soup. A long-term maternal exclusion of the trigger foods brought about progressive improvement of skin lesions in the majority of the infants. These findings suggest that tree nut-related foods and fermented foods are important offending foods of atopic dermatitis in breast-fed infants. © 2010 Japanese Dermatological Association.

Detection of dermal systemic sclerosis using noncontact optical coherence elastography

NASA Astrophysics Data System (ADS)

Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Li, Jiasong; Wu, Chen; Han, Zhaolong; Raghunathan, Raksha; Hsu, Thomas; Noorani, Shezaan; Hicks, M. John; Mohan, Chandra; Larin, Kirill V.

2016-03-01

Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc is a rare disorder, but has a high mortality, particularly in last decade of life. To improve the survival rate, an accurate and early diagnosis is crucial. Currently, the modified Rodnan skin score (mRSS) is the gold standard for evaluating SSc progression based on clinical palpation at 17 sites on the body. However, this procedure can be time consuming, and the assessed score may be biased by the experience of the clinician, causing inter- and intraobserver variabilities. Moreover, the instrinsic elasticity of skin may further bias the mRSS assessment in the early stages of SSc, such as oedematous. To overcome these limitations, there is a need for a rapid, accurate, and objective assessment technique. Optical coherence elastography (OCE) is a novel, rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, we demonstrate the first use of OCE to assess the mechanical properties of control and SSc-like diseased skin non-invasively. A focused air-pulse induced an elastic wave in the skin, which was detected by a home-built OCE system. The elastic wave propagated significantly faster in SSc skin compared to healthy skin. The Young's modulus of the SSc skin was significantly higher than that of normal skin (P<0.05). Thus, OCE was able to objectively differentiate healthy and fibrotic skin completely noninvasively and is a promising and potentially useful new technology for quantifying skin involvement in SSc.

Nonmelanoma Skin Cancers After Kidney Transplant: Our 15 Years of Experience With Mammalian Target of Rapamycin Inhibitors.

PubMed

Okut, Gokalp; Alp, Alper; Tatar, Erhan; Simsek, Cenk; Tugmen, Cem; Uslu, Adam

2017-02-01

We evaluated patients with nonmelanoma skin cancer after kidney transplant and the effects of immunosuppression reduction and switching to a mammalian target of rapamycin inhibitor drugs. Kidney transplant recipients were evaluated retrospectively from patient medical records (between January 2000 and December 2014). A 30% increase in serum creatinine was accepted as indicating renal failure progression. Of 18 patients included (mean follow-up 98 ± 66 mo), 7 (38.8%) had squamous cell carcinoma, 7 (38.8%) had Kaposi sarcoma, and 4 (22.2%) had basal cell carcinoma. At cancer diagnosis, average serum creatinine was 1.6 ± 0.7 mg/dL and proteinuria was 410 ± 766 mg/d. Immunosuppression regimen was changed in 15 patients (83.3%), with new regimen being a single-drug (only prednisolone) in 4 patients, double-drug in 6 patients, and triple-drug protocol in 8 patients. Eight patients were switched to a mammalian target of rapamycin inhibitor-based double (4 patients) or triple (4 patients) regimen. During follow-up after starting new treatment (average 46 ± 50 mo), 6 patients (33.3%) had progressive kidney failure (0 were receiving triple regimen). Those that progressed were using mammalian target of rapamycin inhibitor-based drugs relatively less (33% vs 50%), although often receiving a single-drug immunosuppression treatment (50% vs 8.3%). Three patients (33.3%) had acute rejection (2 receiving double and 1 receiving single immunosuppression treatment). Five patients (27.7%) had local recurrence of the primary tumor. Mammalian target of rapamycin inhibitor use was relatively less common in patients with tumor relapse (20% vs 46%). One patient died (heart failure), and 1 with chronic rejection returned to dialysis. Mammalian target of rapamycin inhibitorbased drugs could reduce local recurrence rate in kidney transplant recipients with nonmelanoma skin cancers. Aggressive reduction and/or cessation of immunosuppressive drugs after skin cancer can lead to graft rejection.

Liposomes, lipid nanocapsules and smartCrystals®: A comparative study for an effective quercetin delivery to the skin.

PubMed

Hatahet, T; Morille, M; Hommoss, A; Devoisselle, J M; Müller, R H; Bégu, S

2018-05-05

Quercetin is a flavonoid with strong antioxidant and antiinflammatory activities considered as a potential drug candidate for skin exogenous supplementation. Nevertheless, crude quercetin suffers from poor water solubility and consequently topical inactivity. Therefore, quercetin formulation within a suitable system that overcomes its solubility limitation is a matter of investigation. Three approaches were tested to improve quercetin delivery to skin: liposomes, lipid nanocapsules (LNC) and smartCrystals®. These nanoformulations were compared in terms of average particle size, homogeneity (PDI), quercetin loading and cellular interactions with HaCaT (keratinocytes) and TPH-1 (monocytes) cell lines. Finally, two formulations were selected for testing quercetin delivery to human skin in vivo using stripping test. Different size distribution was obtained with each strategy starting from 26 nm with quercetin LNC, 179 nm with liposomes to 295 nm with quercetin smartCrystals®. The drug loading varied with each formulation from 0.56 mg/ml with liposomes, 10.8 mg/ml with LNC to 14.4 mg/ml with smartCrystals®. No toxicity was observed in HaCaT cells with quercetin and free radical scavenging ability was established at 5 µg/ml. The safety of quercetin at 5 µg/ml was further confirmed on THP-1 cells with efficient free radical scavenging ability. Finally, skin penetration evidenced different behavior between the two selected forms (LNC and SmartCrystals®), which could lead to different promising strategies for skin protection. On one side, quercetin smartCrystals® seems to enable the superficial deposition of quercetin on top of the skin, which presents a good strategy for a quercetin-based sunscreen product. On the other side, LNC seems to allow quercetin delivery to viable epidermis that holds the promise for skin inflammatory disorders such as psoriasis. Copyright © 2018. Published by Elsevier B.V.

Targeted Deletion and Lipidomic Analysis Identify Epithelial Cell COX-2 as a Major Driver of Chemically-induced Skin Cancer

PubMed Central

Jiao, Jing; Ishikawa, Tomo-o; Dumlao, Darren S.; Norris, Paul C.; Magyar, Clara E.; Mikulec, Carol; Catapang, Art; Dennis, Edward A.; Fischer, Susan M.; Herschman, Harvey R.

2014-01-01

Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX2) plays a critical role in DMBA/TPA-induced skin tumor induction. While many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell-type specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared to littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2 expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell-type specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biological responses. PMID:25063587

Skin manifestations of growth hormone-induced diseases.

PubMed

Kanaka-Gantenbein, Christina; Kogia, Christina; Abdel-Naser, Mohamed Badawy; Chrousos, George P

2016-09-01

The human skin is a well-organized organ bearing different types of cells in a well-structured interference to each other including epidermal and follicular keratinocytes, sebocytes, melanocytes, dermal papilla cells and fibroblasts, endothelial cells, sweat gland cells as well as nerves. Several hormones act on different cell types of the skin, while it is also considered an endocrine organ secreting hormones that act at several sites of the organism. GH receptors are found in almost all cell types forming the skin, while IGF-1 receptors' expression is restricted to the epidermal keratinocytes. Both Growth Hormone (GH) excess, as in the case of Acromegaly in adults, or Gigantism in growing children, and GH deficiency states lead to skin manifestations. In case of GH excess the main dermatological findings are skin thickening, coarsening of facial features, acrochordons, puffy hands and feet, oily skin and hyperhidrosis, while GH deficiency, on the contrary, is characterized by thin, dry skin and disorder of normal sweating. Moreover, special disorders associated with GH excess may have specific characteristics, as is the case of café-au-lait spots in Neurofibromatosis, or big café-au-lait skin hyperpigmented regions with irregular margins, as is the case in McCune-Albright syndrome. Meticulous examination of the skin may therefore contribute to the final diagnosis in cases of GH-induced disorders.

Beneficial effects of softened fabrics on atopic skin.

PubMed

Hermanns, J F; Goffin, V; Arrese, J E; Rodriguez, C; Piérard, G E

2001-01-01

There is general concern about the possible cutaneous adverse effects of wearing garments treated with household laundry products, particularly on atopic skin. Our objective was to compare softened and non- softened fabrics in a forearm wet and dry test, under conditions simulating real-life conditions. Twenty atopic volunteers entered a single-blind 12-day (3 sessions per day) forearm wetting and drying test. Cotton fabrics were machine washed and liquid fabric conditioner was added or not to the final rinse. To simulate conditions of skin damage, a dilute solution of sodium lauryl sulphate was applied under occlusion to the forearm of each volunteer before the start of the study. Skin effects were evaluated by visual grading (redness, dryness and smoothness), squamometry and in vivo instrumental measurements (capacitance, transepidermal water loss and colorimetry). Rubbing of atopic skin with fabrics generally resulted in discrete to moderate alterations of the structure of the stratum corneum. Both for control and pre-irritated skin, all measured parameters indicated that softened fabric was less aggressive to the skin than unsoftened fabric. In the case of pre-irritated skin, the recovery of the skin was significantly faster when rubbed with softened than with unsoftened fabrics. In conclusion, softened fabrics help mitigate the skin condition in atopic patients. Copyright 2001 S. Karger AG, Basel.

In vivo evaluation of some biophysical parameters of the facial skin of Indian women. Part I: variability with age and geographical locations.

PubMed

Colomb, L; Flament, F; Wagle, A; Agrawal, D

2018-02-01

India is a large country (a subcontinent) of about 3.3 million km 2 that covers large ranges in latitude and longitude. The last Indian census counted about 1.21 billion of inhabitants of many origins, creating a vast human diversity and skin types, the variability of which having been previously established. The present study aimed at deepening this knowledge through a set of biophysical measurements to describe, along the skin ageing process, the specificities of various Indian subjects living in different geographical locations. A total of 1204 women, aged 18-84 years, of all socio-economic status, were recruited in four Indian cities (Mumbai, Kolkata, Chennai and Delhi). Measurements of face skin colour properties, elastic properties, sebum production, skin pores and microrelief roughness were performed. With regard skin colour, this study indicates, with age, a darkening of very low amplitude that leads to an increased skin colour heterogeneity. In all subjects, at all ages, the ocular region (dark circles) presents a much darker pigmentation than the cheeks, creating a contrast that appears constant at all ages. In addition to an increased skin colour heterogeneity, a progressive alteration of the skin surface relief, increased sizes of skin pores, a loss of skin elasticity and a drop in sebum production, post-menopause, are observed. This study confirms, in Indian women, some skin ageing measurements found on women from other ethnic groups (i.e. sebum, firmness, wrinkles and pores size) and also identifies some Indian specificities: a high and constant contrast between the ocular region and the cheek colour, associated to a very slow darkening effect along the lifespan. © 2017 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

CAPN3, DCT, MLANA and TYRP1 are overexpressed in skin of vitiligo vulgaris Mexican patients.

PubMed

Salinas-Santander, Mauricio; Trevino, Víctor; De la Rosa-Moreno, Eduardo; Verduzco-Garza, Bárbara; Sánchez-Domínguez, Celia N; Cantú-Salinas, Cristina; Ocampo-Garza, Jorge; Lagos-Rodríguez, Armando; Ocampo-Candiani, Jorge; Ortiz-López, Rocio

2018-03-01

Vitiligo is a disorder causing skin depigmentation, in which several factors have been proposed for its pathogenesis: Environmental, genetic and biological aspects of melanocytes, even those of the surrounding keratinocytes. However, the lack of understanding of the mechanisms has complicated the task of predicting the development and progression. The present study used microarray analysis to characterize the transcriptional profile of skin from Vitiligo Vulgaris (VV) patients and the identified transcripts were validated using targeted high-throughput RNA sequencing in a broader set of patients. For microarrays, mRNA was taken from 20 skin biopsies of 10 patients with VV (pigmented and depigmented skin biopsy of each), and 5 biopsies of healthy subjects matched for age and sex were used as a control. A signature was identified that contains the expression pattern of 722 genes between depigmented vitiligo skin vs. healthy control, 1,108 between the pigmented skin of vitiligo vs. healthy controls and 1,927 between pigmented skin, depigmented vitiligo and healthy controls (P<0.05; false discovery rate, <0.1). When comparing the pigmented and depigmented skin of patients with vitiligo, which reflects the real difference between both skin types, 5 differentially expressed genes were identified and further validated in 45 additional VV patients by RNA sequencing. This analysis showed significantly higher RNA levels of calpain-3, dopachrome tautomerase, melan-A and tyrosinase-related protein-1 genes. The data revealed that the pigmented skin of vitiligo is already affected at the level of gene expression and that the main differences between pigmented and non-pigmented skin are explained by the expression of genes associated with pigment metabolism.

Skin autofluorescence is associated with renal function and cardiovascular diseases in pre-dialysis chronic kidney disease patients.

PubMed

Tanaka, Kenichi; Tani, Yoshihiro; Asai, Jun; Nemoto, Fumihiko; Kusano, Yuki; Suzuki, Hodaka; Hayashi, Yoshimitsu; Asahi, Koichi; Katoh, Tetsuo; Miyata, Toshio; Watanabe, Tsuyoshi

2011-01-01

Tissue accumulation of advanced glycation end-products (AGE) is thought to be a contributing factor to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non-invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has shown associations with CVD in haemodialysis patients. The present study aimed to evaluate relationships of skin autofluorescence to renal function as well as CVD in pre-dialysis patients with chronic kidney disease (CKD). Subjects in this cross-sectional analysis comprised 304 pre-dialysis CKD patients [median age, 62.0 years; median estimated glomerular filtration rate (eGFR), 54.3 mL/min/1.73 m(2); diabetes, n = 81 (26.6%)]. AGE accumulation in skin was assessed by skin autofluorescence using an autofluorescence reader. Relationships between skin autofluorescence, eGFR, CVD history and other parameters were evaluated. Skin autofluorescence correlated negatively with eGFR (r = -0.42, P < 0.01) and increased as CKD stage advanced. Multiple regression analysis revealed significant correlations of skin autofluorescence with age, presence of diabetes, eGFR and CVD history in CKD patients (R(2) = 30%). Age, male gender, smoking history, skin autofluorescence and eGFR were significantly correlated with CVD history, and multiple logistic regression analysis identified age [odds ratio (OR), 1.09; 95% confidence interval (CI), 1.03-1.15; P < 0.01], history of smoking (OR, 6.50; 95%CI, 1.94-21.83; P < 0.01) and skin autofluorescence (OR, 3.74; 95%CI, 1.54-9.24; P < 0.01) as independent factors. Tissue AGE accumulation measured as skin autofluorescence increased as GFR decreased and was related to CVD history in CKD patients. Non-invasive autofluorescence readers may provide potential markers for clinical risk assessment in pre-dialysis CKD patients.

Induction of Scleroderma Fibrosis in Skin-Humanized Mice by Administration of Anti-Platelet-Derived Growth Factor Receptor Agonistic Autoantibodies.

PubMed

Luchetti, Michele M; Moroncini, Gianluca; Jose Escamez, Maria; Svegliati Baroni, Silvia; Spadoni, Tatiana; Grieco, Antonella; Paolini, Chiara; Funaro, Ada; Avvedimento, Enrico V; Larcher, Fernando; Del Rio, Marcela; Gabrielli, Armando

2016-09-01

To describe a skin-SCID mouse chimeric model of systemic sclerosis (SSc; scleroderma) fibrosis based on engraftment of ex vivo-bioengineered skin using skin cells derived either from scleroderma patients or from healthy donors. Three-dimensional bioengineered skin containing human keratinocytes and fibroblasts isolated from skin biopsy specimens from healthy donors or SSc patients was generated ex vivo and then grafted onto the backs of SCID mice. The features of the skin grafts were analyzed by immunohistochemistry, and the functional profile of the graft fibroblasts was defined before and after treatment with IgG from healthy controls or SSc patients. Two procedures were used to investigate the involvement of platelet-derived growth factor receptor (PDGFR): 1) nilotinib, a tyrosine kinase inhibitor, was administered to mice before injection of IgG from SSc patient sera (SSc IgG) into the grafts, and 2) human anti-PDGFR monoclonal antibodies were injected into the grafts. Depending on the type of bioengineered skin grafted, the regenerated human skin exhibited either the typical scleroderma phenotype or the healthy human skin architecture. Treatment of animals carrying healthy donor skin grafts with SSc IgG resulted in the appearance of a bona fide scleroderma phenotype, as confirmed by increased collagen deposition and fibroblast activation markers. Results of the experiments involving administration of nilotinib or monoclonal antibodies confirmed the involvement of PDGFR. Our results provide the first in vivo demonstration of the fibrotic properties of anti-PDGFR agonistic antibodies. This bioengineered skin-humanized mouse model can be used to test in vivo the progression of the disease and to monitor response to antifibrotic drugs. © 2016, American College of Rheumatology.

NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal Neurometabolic Disorder of Early Childhood.

PubMed

Kremer, Laura S; Danhauser, Katharina; Herebian, Diran; Petkovic Ramadža, Danijela; Piekutowska-Abramczuk, Dorota; Seibt, Annette; Müller-Felber, Wolfgang; Haack, Tobias B; Płoski, Rafał; Lohmeier, Klaus; Schneider, Dominik; Klee, Dirk; Rokicki, Dariusz; Mayatepek, Ertan; Strom, Tim M; Meitinger, Thomas; Klopstock, Thomas; Pronicka, Ewa; Mayr, Johannes A; Baric, Ivo; Distelmaier, Felix; Prokisch, Holger

2016-10-06

To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX repair system has been unknown. Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions. Lactate was elevated in cerebrospinal fluid of all affected individuals. Disease onset was during the second year of life and clinical signs as well as episodes of deterioration were triggered by febrile infections. Disease course was rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals. NAXE levels were undetectable in fibroblasts from affected individuals of two families. In these fibroblasts we measured highly elevated concentrations of the toxic metabolite cyclic-NADHX, confirming a deficiency of the mitochondrial NAD(P)HX repair system. Finally, NAD or nicotinic acid (vitamin B3) supplementation might have therapeutic implications for this fatal disorder. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Synthetic and Bio-Artificial Tactile Sensing: A Review

PubMed Central

Lucarotti, Chiara; Oddo, Calogero Maria; Vitiello, Nicola; Carrozza, Maria Chiara

2013-01-01

This paper reviews the state of the art of artificial tactile sensing, with a particular focus on bio-hybrid and fully-biological approaches. To this aim, the study of physiology of the human sense of touch and of the coding mechanisms of tactile information is a significant starting point, which is briefly explored in this review. Then, the progress towards the development of an artificial sense of touch are investigated. Artificial tactile sensing is analysed with respect to the possible approaches to fabricate the outer interface layer: synthetic skin versus bio-artificial skin. With particular respect to the synthetic skin approach, a brief overview is provided on various technologies and transduction principles that can be integrated beneath the skin layer. Then, the main focus moves to approaches characterized by the use of bio-artificial skin as an outer layer of the artificial sensory system. Within this design solution for the skin, bio-hybrid and fully-biological tactile sensing systems are thoroughly presented: while significant results have been reported for the development of tissue engineered skins, the development of mechanotransduction units and their integration is a recent trend that is still lagging behind, therefore requiring research efforts and investments. In the last part of the paper, application domains and perspectives of the reviewed tactile sensing technologies are discussed. PMID:23348032

Skin irritation, false positives and the local lymph node assay: a guideline issue?

PubMed

Basketter, David A; Kimber, Ian

2011-10-01

Since the formal validation and regulatory acceptance of the local lymph node assay (LLNA) there have been commentaries suggesting that the irritant properties of substances can give rise to false positives. As toxicology aspires to progress rapidly towards the age of in vitro alternatives, it is of increasing importance that issues relating to assay selectivity and performance are understood fully, and that true false positive responses are distinguished clearly from those that are simply unpalatable. In the present review, we have focused on whether skin irritation per se is actually a direct cause of true false positive results in the LLNA. The body of published work has been examined critically and considered in relation to our current understanding of the mechanisms of skin irritation and skin sensitisation. From these analyses it is very clear that, of itself, skin irritation is not a cause of false positive results. The corollary is, therefore, that limiting test concentrations in the LLNA for the purpose of avoiding skin irritation may lead, unintentionally, to false negatives. Where a substance is a true false positive in the LLNA, the classic example being sodium lauryl sulphate, explanations for that positivity will have to reach beyond the seductive, but incorrect, recourse to its skin irritation potential. Copyright © 2011 Elsevier Inc. All rights reserved.

Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the stratum corneum

PubMed Central

Zaid Alkilani, Ahlam; McCrudden, Maelíosa T.C.; Donnelly, Ryan F.

2015-01-01

The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies. PMID:26506371

Wellskins and slug tests: where's the bias?

NASA Astrophysics Data System (ADS)

Rovey, C. W.; Niemann, W. L.

2001-03-01

Pumping tests in an outwash sand at the Camp Dodge Site give hydraulic conductivities ( K) approximately seven times greater than conventional slug tests in the same wells. To determine if this difference is caused by skin bias, we slug tested three sets of wells, each in a progressively greater stage of development. Results were analyzed with both the conventional Bouwer-Rice method and the deconvolution method, which quantifies the skin and eliminates its effects. In 12 undeveloped wells the average skin is +4.0, causing underestimation of conventional slug-test K (Bouwer-Rice method) by approximately a factor of 2 relative to the deconvolution method. In seven nominally developed wells the skin averages just +0.34, and the Bouwer-Rice method gives K within 10% of that calculated with the deconvolution method. The Bouwer-Rice K in this group is also within 5% of that measured by natural-gradient tracer tests at the same site. In 12 intensely developed wells the average skin is <-0.82, consistent with an average skin of -1.7 measured during single-well pumping tests. At this site the maximum possible skin bias is much smaller than the difference between slug and pumping-test Ks. Moreover, the difference in K persists even in intensely developed wells with negative skins. Therefore, positive wellskins do not cause the difference in K between pumping and slug tests at this site.

Clinical Investigation Program Annual Progress Report.

DTIC Science & Technology

1983-09-30

Antiemetics (A Phase II Study).(O) ............... 049 79/110 Evaluation of Local Anesthetic Skin Testing and Progressive Challenge in Patients with a History ...Associated with Oat Cell Carcinoma. J Assoc Mil Derm 8, 1982. Grimwood, R.E.: The History and Principles of Immunofluorescence. J Assn Mil Derm 9(1...December, 1981. ""’ PRESENTATIONS: 1.) Kindig, N.B.: D CO correction using PaCO back pressure predicted from venous bloo . Sfresented: Carl E

Cyclic neutropenia with a novel gene mutation presenting with a necrotizing soft tissue infection and severe sepsis: case report.

PubMed

Boo, Yoon Jung; Nam, Myung Hyun; Lee, Eun Hee; Lee, Kuang Chul

2015-04-02

Cyclic neutropenia is a rare disease. We report a 31-month-old girl with congenital cyclic neutropenia with a novel mutation in the ELANE gene who developed an acute necrotizing soft-tissue infection on her left axillary legion. A 31-month-old girl was admitted to our pediatric emergency room because of a necrotizing soft tissue infection of the left axillary area. The infection progressed rapidly and resulted in septic shock. Despite a medical treatment and surgical debridement, the sepsis was not controlled, and severe inflammation developed. After applying of negative-pressure wound therapy, her clinical symptoms improved. Finally, she was diagnosed with cyclic neutropenia with a novel genetic mutation. One month after admission, she was discharged with a completely recovered wound and no need for skin grafting. Both adequate medical treatment and effective control of the source of infection are critically important to reduce morbidity in such complex cases of necrotizing fasciitis as appeared in an immunocompromised pediatric patient.

3D bioprinting of functional human skin: production and in vivo analysis.

PubMed

Cubo, Nieves; Garcia, Marta; Del Cañizo, Juan F; Velasco, Diego; Jorcano, Jose L

2016-12-05

Significant progress has been made over the past 25 years in the development of in vitro-engineered substitutes that mimic human skin, either to be used as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. In this sense, laboratory-grown skin substitutes containing dermal and epidermal components offer a promising approach to skin engineering. In particular, a human plasma-based bilayered skin generated by our group, has been applied successfully to treat burns as well as traumatic and surgical wounds in a large number of patients in Spain. There are some aspects requiring improvements in the production process of this skin; for example, the relatively long time (three weeks) needed to produce the surface required to cover an extensive burn or a large wound, and the necessity to automatize and standardize a process currently performed manually. 3D bioprinting has emerged as a flexible tool in regenerative medicine and it provides a platform to address these challenges. In the present study, we have used this technique to print a human bilayered skin using bioinks containing human plasma as well as primary human fibroblasts and keratinocytes that were obtained from skin biopsies. We were able to generate 100 cm 2 , a standard P100 tissue culture plate, of printed skin in less than 35 min (including the 30 min required for fibrin gelation). We have analysed the structure and function of the printed skin using histological and immunohistochemical methods, both in 3D in vitro cultures and after long-term transplantation to immunodeficient mice. In both cases, the generated skin was very similar to human skin and, furthermore, it was indistinguishable from bilayered dermo-epidermal equivalents, handmade in our laboratories. These results demonstrate that 3D bioprinting is a suitable technology to generate bioengineered skin for therapeutical and industrial applications in an automatized manner.

[To evaluate the quality of life and peristomal skin ostomy patient with the new device Sensura].

PubMed

Crespo Fontán, Beatriz; Caparrós Sanz, María Rosario; Lainez Pardos, Pilar Lourdes; Davín Durban, Inmaculada

2010-10-01

In 2006, Coloplast launched in several European countries a new device for ostomy care called Sensura. This clinical research report includes only the results of the subpopulation included in Spain as a part of an international study involving many countries such as Denmark, United States, Canada, Australia, Poland, Netherlands, France, Slovakia, Germany, UK, Italy, Iceland, Japan, Czech Republic, Portugal, South Korea and Argentina. OBJECTIVES AND STUDY VARIABLES: The main purpose of the study is to evaluate the experience with Sensura, under normal conditions of use, with special attention to skin condition and quality of life. The main objective of the study is to evaluate the quality of life, through Quality of Life Questionnaire called "Stoma QoL". A secondary objective, is to study the correlation between quality of life and the peristomal skin condition. Other Secondary objectives include the evaluation of the patient's current device at the time of entering the study and by the other hand, the device Sensura and safety evaluation throughout the study. The study was designed as an open label non-comparative, multi-national Post Market study. The study period for each patient is 6 to 8 weeks +/- 4 days, which includes an initial visit and a final visit. The study population included people who carry a colostomy or ileostomy. Regarding Spain, a total of 10 sites participated and included a total of 131 patients. This report only presents results for nine sites and a total of 123 patients. The reason is that the last participating site began the study with a considerable delay The remaining subjects included in this site together with the other centers in Spain and the other participating countries will be included in the final international report, that will present the overall results. MEASUREMENT TOOLS. Stoma-QoL (Quality of Life Questionnaire for people with an ostomy). OST (Ostomy Skin Tool) instrument for the assessment of peristomal skin. As for the quality of life, at baseline we found a mean of 59 out of 100 (SD = 8.8), while the final study visit, mean score was 59.6 out of 100 (SD = 9.3), although the final results on this variable will be presented in the global report, since it has not reached sufficient population in Spain for the analysis of this variable. The study revealed a significant improvement in the peristomal skin condition at the end of the study, measured by the tool OST (Ostomy Skin Tool). Regarding the evaluation of the SenSura device, there was a significant improvement related to the appearance of leakage of effluent, as well as other items evaluated in relation with the device.

TCF7L1 promotes skin tumorigenesis independently of β-catenin through induction of LCN2

PubMed Central

Ku, Amy T; Shaver, Timothy M; Rao, Ajay S; Howard, Jeffrey M; Rodriguez, Christine N; Miao, Qi; Garcia, Gloria; Le, Diep; Yang, Diane; Borowiak, Malgorzata; Cohen, Daniel N; Chitsazzadeh, Vida; Diwan, Abdul H; Tsai, Kenneth Y; Nguyen, Hoang

2017-01-01

The transcription factor TCF7L1 is an embryonic stem cell signature gene that is upregulated in multiple aggressive cancer types, but its role in skin tumorigenesis has not yet been defined. Here we document TCF7L1 upregulation in skin squamous cell carcinoma (SCC) and demonstrate that TCF7L1 overexpression increases tumor incidence, tumor multiplicity, and malignant progression in the chemically induced mouse model of skin SCC. Additionally, we show that downregulation of TCF7L1 and its paralogue TCF7L2 reduces tumor growth in a xenograft model of human skin SCC. Using separation-of-function mutants, we show that TCF7L1 promotes tumor growth, enhances cell migration, and overrides oncogenic RAS-induced senescence independently of its interaction with β-catenin. Through transcriptome profiling and combined gain- and loss-of-function studies, we identified LCN2 as a major downstream effector of TCF7L1 that drives tumor growth. Our findings establish a tumor-promoting role for TCF7L1 in skin and elucidate the mechanisms underlying its tumorigenic capacity. DOI: http://dx.doi.org/10.7554/eLife.23242.001 PMID:28467300

More than skin deep? Potential nicotinamide treatment applications in chronic kidney transplant recipients

PubMed Central

Bostom, Andrew G; Merhi, Basma; Walker, Joanna; Robinson-Bostom, Leslie

2016-01-01

Non-melanoma cutaneous carcinomas, or skin cancers, predominantly squamous cell carcinomas (SCCs), are the most common malignancies occurring in kidney transplant recipients (KTRs). Squamous cell carcinoma risk is dramatically elevated in KTRs, occurring at rates of up 45-250 times those reported in general populations. New non-melanoma skin cancers in KTRs with a prior non-melanoma skin cancer also develop at 3-times the rate reported in non-KTRs with the same clinical history. The unique aggressiveness of SCCs in KTRs increases patient morbidity, due to the high rate of new lesions requiring treatment, frequently surgical excision. Oral nicotinamide shows promise in the chemoprevention of the especially aggressive non-melanoma skin cancers which occur in KTRs. This benefit might be conferred via its inhibition of sirtuin enzymatic pathways. Nicotinamide’s concurrent hypophosphatemic effect may also partially ameliorate the disturbed calcium-phosphorus homeostasis in these patients-a putative risk factor for mortality, and graft failure. Conceivably, a phase 3 trial of nicotinamide for the prevention of non-melanoma skin cancers in KTRs, lasting at least 12-mo, could also incorporate imaging and laboratory measures which assess nicotinamide’s impact on subclinical cardiovascular and chronic kidney disease risk, and progression. PMID:28058215

Fibrin gel as a scaffold for skin substitute – production and clinical experience.

PubMed

Kljenak, Antun; Tominac Trcin, Mirna; Bujić, Marina; Dolenec, Tamara; Jevak, Martina; Mršić, Gordan; Zmiš, Gordana; Barčot, Zoran; Muljačić, Ante; Popović, Maja

2016-06-01

The purpose of this study was to create a fibrin-based human skin substitute in vitro with epidermal and dermal component and to assess its healing potential in deep partial and full thickness burns. Fibrin scaffolds were prepared from commercial fibrin glue kits. Human fibroblasts were cultured in fibrin gel. Human keratinocytes were seeded on the top of the gel. Viability of cells was determined fluorimetrically. Scanning electron microscope and immunocytochemistry analysis of cultured cells were performed. After hydrosurgical preparation of deep burn necrotic tissue, wound bed was prepared for skin substitutes. Progress of healing was documented using visual estimation and photos. Scanning electron microscope images showed good cell attachment and colony spreading of keratinocytes and fibroblasts on fibrin scaff old. Immunofluorescent staining of cell cultures on fibrin scaffold showed expression of vimentin, a marker of fibroblast cells, cytokeratin 19, a marker of epithelial stem cells, as well as involucrin, a marker of differentiated keratinocytes. Clinical results clearly showed that appearance of the skin did not differ significantly from the areas of transplanted skin using split-thickness skin graft techniques. In conclusion, using these fibrin-cultured autografts on massive full-thickness burn resulted in good healing.

In vivo Molecular Evaluation of Guinea Pig Skin Incisions Healing after Surgical Suture and Laser Tissue Welding Using Raman Spectroscopy

PubMed Central

Alimova, A.; Chakraverty, R.; Muthukattil, R.; Elder, S.; Katz, A.; Sriramoju, V.; Lipper, Stanley; Alfano, R. R.

2009-01-01

The healing process in guinea pig skin following surgical incisions was evaluated at the molecular level, in vivo, by the use of Raman spectroscopy. After the incisions were closed either by suturing or by laser tissue welding (LTW), differences in the respective Raman spectra were identified. The study determined that the ratio of the Raman peaks of the amide III (1247 cm−1) band to a peak at 1326 cm−1 (the superposition of elastin and keratin bands) can be used to evaluate the progression of wound healing. Conformational changes in the amide I band (1633 cm−1 to 1682 cm−1) and spectrum changes in the range of 1450 cm−1 to 1520 cm−1 were observed in LTW and sutured skin. The stages of the healing process of the guinea pig skin following LTW and suturing were evaluated by Raman spectroscopy, using histopathology 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. A wavelet decomposition-reconstruction baseline correction algorithm was employed to remove the fluorescence wing from the Raman spectra. PMID:19581109

Thick- and thin-skinned organisations and enactment in borderline and narcissistic disorders.

PubMed

Bateman, A W

1998-02-01

In this paper the author argues that enactment is any mutual action within the patient/analyst relationship that arises in the context of difficulties in countertransference work. Such enactment is common during the treatment of borderline and narcissistic disorders. In order to delineate different forms of enactment, which in his view may be either to the detriment or to the benefit of the analytic process, the author describes a patient who was identified primarily with a sadistic mother and who threatened the analyst with a knife during treatment. Three levels of enactment involving countertransference responses are described of which two, namely a collusive countertransference and a defensive countertransference, were detrimental to the analytic process. The third level of enactment was beneficial but only because the intervention by the analyst was independent of the analytic process and yet in response to it. The author uses Rosenfeld's distinction between thin-skinned and thick-skinned narcissists to illustrate how enactment is most likely when a patient moves between thick-skinned and thin-skinned narcissistic positions. Nevertheless the move between thin and thick-skinned positions presents an opportunity for effective interpretation, allowing progress in treatment.

Hyperspectral signature analysis of skin parameters

NASA Astrophysics Data System (ADS)

Vyas, Saurabh; Banerjee, Amit; Garza, Luis; Kang, Sewon; Burlina, Philippe

2013-02-01

The temporal analysis of changes in biological skin parameters, including melanosome concentration, collagen concentration and blood oxygenation, may serve as a valuable tool in diagnosing the progression of malignant skin cancers and in understanding the pathophysiology of cancerous tumors. Quantitative knowledge of these parameters can also be useful in applications such as wound assessment, and point-of-care diagnostics, amongst others. We propose an approach to estimate in vivo skin parameters using a forward computational model based on Kubelka-Munk theory and the Fresnel Equations. We use this model to map the skin parameters to their corresponding hyperspectral signature. We then use machine learning based regression to develop an inverse map from hyperspectral signatures to skin parameters. In particular, we employ support vector machine based regression to estimate the in vivo skin parameters given their corresponding hyperspectral signature. We build on our work from SPIE 2012, and validate our methodology on an in vivo dataset. This dataset consists of 241 signatures collected from in vivo hyperspectral imaging of patients of both genders and Caucasian, Asian and African American ethnicities. In addition, we also extend our methodology past the visible region and through the short-wave infrared region of the electromagnetic spectrum. We find promising results when comparing the estimated skin parameters to the ground truth, demonstrating good agreement with well-established physiological precepts. This methodology can have potential use in non-invasive skin anomaly detection and for developing minimally invasive pre-screening tools.

Extracellular Matrix Modulation: Optimizing Skin Care and Rejuvenation Procedures.

PubMed

Widgerow, Alan D; Fabi, Sabrina G; Palestine, Roberta F; Rivkin, Alexander; Ortiz, Arisa; Bucay, Vivian W; Chiu, Annie; Naga, Lina; Emer, Jason; Chasan, Paul E

2016-04-01

Normal aging and photoaging of the skin are chronic processes that progress gradually. The extracellular matrix (ECM), constituting over 70% of the skin, is the central hub for repair and regeneration of the skin. As such, the ECM is the area where changes related to photodamage are most evident. Degradation of the ECM with fragmentation of proteins significantly affects cross talk and signaling between cells, the matrix, and its constituents. The accumulation of collagen fragments, amorphous elastin agglutinations, and abnormal cross-linkages between the collagen fragments impedes the ECM from its normal repair and regenerative capacity, which manifests as wrinkled, non-elastic skin. Similar to how the chronic wound healing process requires wound bed preparation before therapeutic intervention, treatment of chronic aging of the skin would likely benefit from a "skin bed preparation" to optimize the outcome of rejuvenation procedures and skin maintenance programs. This involves introducing agents that can combat stress-induced oxidation, proteasome dysfunction, and non-enzymatic cross linkages involved in glycation end products, to collectively modulate this damaged ECM, and upregulate neocollagenesis and elastin production. Agents of particular interest are matrikines, peptides originating from the fragmentation of matrix proteins that exhibit a wide range of biological activities. Peptides of this type (tripeptide and hexapeptide) are incorporated in ALASTIN™ Skin Nectar with TriHex™ technology (ALASTIN Skincare, Inc., Carlsbad, CA), which is designed to target ECM modulation with a goal of optimizing results following invasive and non-invasive dermal rejuvenating procedures.

Chronic progressive lymphoedema in draught horses.

PubMed

de Keyser, K; Janssens, S; Buys, N

2015-05-01

The objective of this review was to summarise and evaluate the current state of knowledge about chronic progressive lymphoedema in draught horses. Clinical signs of this multifactorial disorder are mainly restricted to the lower limbs, comprising progressively deteriorating skin, swelling and deformation. Although typical lesions were first reported at the beginning of the 20th century, chronic progressive lymphoedema was recognised as a specific syndrome only in 2003, and since then research has driven forward. Despite the high prevalence in some breeds and the serious economic impact, the pathogenesis is not fully understood, and the available treatment options remain symptomatic and noncurative. There is a need to improve diagnostic techniques and to develop selection tools. © 2014 EVJ Ltd.

Computational Aerodynamics of Shuttle Orbiter Damage Scenarios in Support of the Columbia Accident Investigation

NASA Technical Reports Server (NTRS)

Bibb, Karen L.; Prabhu, Ramadas K.

2004-01-01

In support of the Columbia Accident Investigation, inviscid computations of the aerodynamic characteristics for various Shuttle Orbiter damage scenarios were performed using the FELISA unstructured CFD solver. Computed delta aerodynamics were compared with the reconstructed delta aerodynamics in order to postulate a progression of damage through the flight trajectory. By performing computations at hypervelocity flight and CF4 tunnel conditions, a bridge was provided between wind tunnel testing in Langley's 20-Inch CF4 facility and the flight environment experienced by Columbia during re-entry. The rapid modeling capability of the unstructured methodology allowed the computational effort to keep pace with the wind tunnel and, at times, guide the wind tunnel efforts. These computations provided a detailed view of the flowfield characteristics and the contribution of orbiter components (such as the vertical tail and wing) to aerodynamic forces and moments that were unavailable from wind tunnel testing. The damage scenarios are grouped into three categories. Initially, single and multiple missing full RCC panels were analyzed to determine the effect of damage location and magnitude on the aerodynamics. Next is a series of cases with progressive damage, increasing in severity, in the region of RCC panel 9. The final group is a set of wing leading edge and windward surface deformations that model possible structural deformation of the wing skin due to internal heating of the wing structure. By matching the aerodynamics from selected damage scenarios to the reconstructed flight aerodynamics, a progression of damage that is consistent with the flight data, debris forensics, and wind tunnel data is postulated.

Automated analysis and classification of melanocytic tumor on skin whole slide images.

PubMed

Xu, Hongming; Lu, Cheng; Berendt, Richard; Jha, Naresh; Mandal, Mrinal

2018-06-01

This paper presents a computer-aided technique for automated analysis and classification of melanocytic tumor on skin whole slide biopsy images. The proposed technique consists of four main modules. First, skin epidermis and dermis regions are segmented by a multi-resolution framework. Next, epidermis analysis is performed, where a set of epidermis features reflecting nuclear morphologies and spatial distributions is computed. In parallel with epidermis analysis, dermis analysis is also performed, where dermal cell nuclei are segmented and a set of textural and cytological features are computed. Finally, the skin melanocytic image is classified into different categories such as melanoma, nevus or normal tissue by using a multi-class support vector machine (mSVM) with extracted epidermis and dermis features. Experimental results on 66 skin whole slide images indicate that the proposed technique achieves more than 95% classification accuracy, which suggests that the technique has the potential to be used for assisting pathologists on skin biopsy image analysis and classification. Copyright © 2018 Elsevier Ltd. All rights reserved.

Island composite nasal flap for nasal dorsum skin defects.

PubMed

Skitarelić, Neven; Mladina, Ranko; Mraovic, Boris; Simurina, Tatjana; Skitarelić, Nataa; Vuković, Katarina

2009-08-01

Skin defects on the nasal dorsum remain a challenge for the plastic surgeon. There are few local nasal flap options for the repair of proximally positioned nasal skin defects. During a 3-year period, 22 patients were treated after excision of skin cancer in the proximal two-thirds of the nose. Nine patients (41%) were female and 13 (59%) were male, with an average age of 69 years. All patients were operated on under local anesthesia. The average follow-up was 25 months. In all patients, after tumor ablation, the skin defect was closed with an island composite nasal skin flap. Pathohistologic analysis confirmed that the margins of the removed tumor were free of malignant cells. Six patients (27.3%) had squamous cell and 16 (72.7%) had basal cell carcinoma. There was no total or partial flap loss. None of the patients has suffered from recurrence of the tumor. The island composite nasal flap is a reliable technique for the closure of proximal nasal skin defects. Complications in the elevation of the island composite flap were rare, and the final result was acceptable.

Modeling slug tests in unconfined aquifers with both oscillatory and overdamped responses, and with low-K and high-K skin effects

NASA Astrophysics Data System (ADS)

Thoma, M. J.; Malama, B.; Barrash, W.; Bohling, G.; Butler, J. J.

2009-12-01

We extend the models for slug tests developed by Hyder et al. (1994) and Butler and Zhan (2004) to obtain a single general model for slug tests in unconfined aquifers in partially penetrating wells with a near-well disturbed zone (skin). The full range of responses, oscillatory to overdamped, is considered since both types of responses are common in wells in unconsolidated coarse fluvial aquifers, and others. The general semi-analytical solution allows for skin and formation storage as well as anisotropy in skin and formation hydraulic conductivity (K). The water table is treated as a fixed head boundary so the solution is applicable for wells screened below the water table. The model is validated by comparison with other models and by matching field data from unconfined fluvial aquifers at sites in Nebraska (MSEA) and Idaho (BHRS). We examine the effects of varying skin K and skin thickness to simulate the impact of a near-well disturbed zone that is lower (damage) or higher (filter pack) K than the formation. Results indicate that, for a given set of measured behavior at an example test zone, minor progressive decreases in estimated formation K occur with increases in assumed skin K, and moderate increases in estimated formation K occur with decreases in assumed skin K. Major increases (orders of magnitude) in estimated formation K occur with increased thickness of low-K skin. The importance of incorporating a finite-thickness representation of the skin, rather than the conventional infinitely thin representation, is also addressed.

A bio-inspired, active morphing skin for camber morphing structures

NASA Astrophysics Data System (ADS)

Feng, Ning; Liu, Liwu; Liu, Yanju; Leng, Jinson

2015-03-01

In this study, one kind of developed morphing skin embedded with pneumatic muscle fibers (PMFs) was manufactured and was employed for camber morphing structures. The output force and contraction of PMF as well as the morphing skin were experimentally characterized at a series of discrete actuator pressures varying from 0.15 to 0.35 MPa. The active morphing skin test results show that the output force is 73.59 N and the contraction is 0.097 (9.7%) at 0.35 MPa. Due to these properties, this active morphing skin could be easily used for the morphing structures. Then the proper airfoil profile was chosen to manufacture the adaptive airfoil in this study. The chord-wise bending airfoil structure was achieved by employing this kind of active morphing skin. Finally the deformed shapes of this chord-wise bending airfoil structure were obtained by 3-dimensions scanning measurement. Meanwhile the camber morphing structures were analyzed through the finite element method (FEM) and the deformed shapes of the upper surface skins were obtained. The experimental result and FEM analysis result of deformed shapes of the upper surface skins were compared in this paper.

Development of mHealth system for supporting self-management and remote consultation of skincare.

PubMed

Parmanto, Bambang; Pramana, Gede; Yu, Daihua X; Fairman, Andrea D; Dicianno, Brad E

2015-12-30

Individuals with spina bifida (SB) are vulnerable to chronic skin complications such as wounds on the buttocks and lower extremities. Most of these complications can be prevented with adherence to self-care routines. We have developed a mobile health (mHealth) system for supporting self-care and management of skin problems called SkinCare as part of an mHealth suite called iMHere (interactive Mobile Health and Rehabilitation). The objective of this research is to develop an innovative mHealth system to support self-skincare tasks, skin condition monitoring, adherence to self-care regimens, skincare consultation, and secure two-way communications between patients and clinicians. In order to support self-skincare tasks, the SkinCare app requires three main functions: (1) self-care task schedule and reminders, (2) skin condition monitoring and communications that include imaging, information about the skin problem, and consultation with clinician, and (3) secure two-way messaging between the patient and clinician (wellness coordinator). The SkinCare system we have developed consists of the SkinCare app, a clinician portal, and a two-way communication protocol connecting the two. The SkinCare system is one component of a more comprehensive system to support a wellness program for individuals with SB. The SkinCare app has several features that include reminders to perform daily skin checks as well as the ability to report skin breakdown and injury, which uses a combination of skin images and descriptions. The SkinCare app provides reminders to visually inspect one's skin as a preventative measure, often termed a "skin check." The data is sent to the portal where clinicians can monitor patients' conditions. Using the two-way communication, clinicians can receive pictures of the skin conditions, track progress in healing over time, and provide instructions for how to best care for the wound. The system was capable of supporting self-care and adherence to regimen, monitoring adherence, and supporting clinician engagement with patients, as well as testing its feasibility in a long-term implementation. The study shows the feasibility of a long-term implementation of skincare mHealth systems to support self-care and two-way interactions between patients and clinicians.

Skin-interfaced systems for sweat collection and analytics

PubMed Central

Choi, Jungil; Ghaffari, Roozbeh; Baker, Lindsay B.; Rogers, John A.

2018-01-01

Recent interdisciplinary advances in materials, mechanics, and microsystem designs for biocompatible electronics, soft microfluidics, and electrochemical biosensors establish the foundations for emerging classes of thin, skin-interfaced platforms capable of capturing, storing, and performing quantitative, spatiotemporal measurements of sweat chemistry, instantaneous local sweat rate, and total sweat loss. This review summarizes scientific and technical progress in this area and highlights the implications in real time and ambulatory modes of deployment during physical activities across a broad range of contexts in clinical health, physiology research, fitness/wellness, and athletic performance. PMID:29487915

Psychogenic Purpura (Gardner-Diamond Syndrome)

PubMed Central

Bhattacharya, Gaurav

2015-01-01

Psychogenic purpura, also known as Gardner-Diamond syndrome or autoerythrocyte sensitization syndrome, is a rare condition characterized by spontaneous development of painful edematous skin lesions progressing to ecchymosis over the next 24 hours. Severe stress and emotional trauma always precede the skin lesions. The condition is most commonly seen in women, but isolated cases have been reported in adolescents and in males. Psychodermatologic evaluation and dermatology and psychiatry liaison have been successful in the treatment of these patients. This report provides an overview of psychogenic purpura and presents the case of a 15-year-old girl. PMID:26137346

Update on Genetic Conditions Affecting the Skin and the Kidneys

PubMed Central

Reimer, Antonia; He, Yinghong; Has, Cristina

2018-01-01

Genetic conditions affecting the skin and kidney are clinically and genetically heterogeneous, and target molecular components present in both organs. The molecular pathology involves defects of cell–matrix adhesion, metabolic or signaling pathways, as well as tumor suppressor genes. This article gives a clinically oriented overview of this group of disorders, highlighting entities which have been recently described, as well as the progress made in understanding well-known entities. The genetic bases as well as molecular cell biological mechanisms are described, with therapeutic applications. PMID:29552546

Depigmentation Therapies for Vitiligo.

PubMed

Grimes, Pearl E; Nashawati, Rama

2017-04-01

The general goals of medical management of vitiligo are to repigment vitiliginous areas of skin and to stabilize the progression of depigmentation. However, for some patients with vitiligo affecting extensive body surface areas who are unresponsive to repigmentation therapies, depigmentation of the remaining normal skin may be a better choice. Candidates for depigmentation therapy should be carefully screened and patient education is essential. Permanent topical therapies used for depigmentation include monobenzyl ether of hydroquinone, 4-methoxyphenol, and 88% phenol. Physical modalities, such as cryotherapy and lasers, are also being used successfully. Copyright © 2016 Elsevier Inc. All rights reserved.

Purpura fulminans mimicking toxic epidermal necrolysis - additional value of 16S rRNA sequencing and skin biopsy.

PubMed

Dautzenberg, K H W; Polderman, F N; van Suylen, R J; Moviat, M A M

2017-05-01

Both purpura fulminans and toxic epidermal necrolysis (TEN) are rare and life-threatening disorders with a high mortality. We present a case of suspected rapidly progressive, severe pneumococcal sepsis-induced purpura fulminans complicated by multiple organ failure, severe epidermolysis and cutaneous necrosis. We show the diagnostic challenge to differentiate between purpura fulminans and TEN, as the extensive epidermolysis in purpura fulminans may mimic TEN and we highlight the additional value of repeated skin biopsies and 16S rRNA gene sequencing.

Aerospace Dermatology

PubMed Central

Arora, Sandeep

2017-01-01

Evolutionarily, man is a terrestrial mammal, adapted to land. Aviation and now space/microgravity environment, hence, pose new challenges to our physiology. Exposure to these changes affects the human body in acute and chronic settings. Since skin reflects our mental and physical well-being, any change/side effects of this environment shall be detected on the skin. Aerospace industry offers a unique environment with a blend of all possible occupational disorders, encompassing all systems of the body, particularly the skin. Aerospace dermatologists in the near future shall be called upon for their expertise as we continue to push human physiological boundaries with faster and more powerful military aircraft and look to colonize space stations and other planets. Microgravity living shall push dermatology into its next big leap-space, the final frontier. This article discusses the physiological effects of this environment on skin, effect of common dermatoses in aerospace environment, effect of microgravity on skin, and occupational hazards of this industry. PMID:28216729

Aerospace Dermatology.

PubMed

Arora, Sandeep

2017-01-01

Evolutionarily, man is a terrestrial mammal, adapted to land. Aviation and now space/microgravity environment, hence, pose new challenges to our physiology. Exposure to these changes affects the human body in acute and chronic settings. Since skin reflects our mental and physical well-being, any change/side effects of this environment shall be detected on the skin. Aerospace industry offers a unique environment with a blend of all possible occupational disorders, encompassing all systems of the body, particularly the skin. Aerospace dermatologists in the near future shall be called upon for their expertise as we continue to push human physiological boundaries with faster and more powerful military aircraft and look to colonize space stations and other planets. Microgravity living shall push dermatology into its next big leap-space, the final frontier. This article discusses the physiological effects of this environment on skin, effect of common dermatoses in aerospace environment, effect of microgravity on skin, and occupational hazards of this industry.

FERMT1 promoter mutations in patients with Kindler syndrome.

PubMed

Has, C; Chmel, N; Levati, L; Neri, I; Sonnenwald, T; Pigors, M; Godbole, K; Dudhbhate, A; Bruckner-Tuderman, L; Zambruno, G; Castiglia, D

2015-09-01

Mutations in the FERMT1 gene, encoding the focal adhesion protein kindlin-1 underlie the Kindler syndrome (KS), an autosomal recessive skin disorder with a phenotype comprising skin blistering, photosensitivity, progressive poikiloderma with extensive skin atrophy, and propensity to skin cancer. The FERMT1 mutational spectrum comprises gross genomic deletions, splice site, nonsense, and frameshift mutations, which are scattered over the coding region spanning exon 2-15. We now report three KS families with mutations affecting the promoter region of FERMT1. Two of these mutations are large deletions (∼38.0 and 1.9 kb in size) and one is a single nucleotide variant (c.-20A>G) within the 5' untranslated region (UTR). Each mutation resulted in loss of gene expression in patient skin or cultured keratinocytes. Reporter assays showed the functional relevance of the genomic regions deleted in our patients for FERMT1 gene transcription and proved the causal role of the c.-20A>G variant in reducing transcriptional activity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Implantable biosensors: analysis of fluorescent light propagation through skin

NASA Astrophysics Data System (ADS)

O'Neal, D. P.; McShane, Michael J.; Pishko, Michael V.; Cote, Gerard L.

2001-06-01

Progress towards a painless and hygienic glucose monitoring procedure for diabetics continues as the growth of diabetes mellitus reaches epidemic proportions in the American population. Utilizing an implantable fluorescence based glucose assay, the minimally invasive approach presented here has previously shown promise towards this goal in terms of glucose specificity and quantification for in vitro environments. However, in realistic physiological circumstances the depth of the implant can vary and optical properties of skin can change due to normal physiological conditions. Additionally, naturally occurring auto-fluorescence can obscure the sensor signal. An important concern under these conditions is that variations of fluorescent intensity due to these or other causes might be mistaken for glucose concentration fluctuations. New data shows that fluorescence-based glucose assays can be probed and interpreted in terms of glucose concentrations through pig skin at depths of up to 700 mm when immobilized in a bio-compatible polymer. When a combination of two fluorophores are employed as demonstrated here, reasonable changes in skin thickness and the confounding effects of the variations inherent in skin can be overcome for this glucose sensing application.

A wearable conformal bandage for non-invasive two-dimensional imaging of skin oxygenation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Li, Zongxi; Roussakis, Emmanuel; Keeley, Emily; Apiou-Sbirlea, Gabriela; Birngruber, Reginald; Huang, Christene; Evans, Conor L.

2016-03-01

The complex surface topology and soft mechanics of the skin poses a considerable challenge to the development of wearable, conformal sensors. As a results, current clinical assessments of healing-related skin parameters often rely on bulky and expensive optical systems that are difficult to deploy at the point of care. Here, using a rapid-drying, liquid bandage containing oxygen-sensing molecules, we created a wearable sensor bandage that conforms the surface geometry of skin and wounds, and provides two-dimensional maps of cutaneous oxygenation in a non-disruptive fashion. Custom oxygen sensing phosphors have been developed in house that are at least five times brighter than the commercial sensing molecules, enabling the visualization of oxygen concentration using a simple color camera or even by eye under ambient lighting conditions. The oxygen-sensing bandage has been applied to monitor tissue ischemia, graft integration, as well as the progression of burn in animal models. Recent studies have demonstrated its ability to track and quantify skin inflammation induced by complete Freund's adjuvant in an in vivo porcine model.

The development of the friction coefficient inspection equipment for skin using a load cell.

PubMed

Song, Han Wook; Park, Yon Kyu; Lee, Sung Jun; Woo, Sam Yong; Kim, Sun Hyung; Kim, Dal Rae

2008-01-01

The skin is an indispensible organ for human because it contributes to the metabolism using its own biochemical functions as well as it protects the human body from the exterior stimuli. Recently, the friction coefficient have been used as the decision index of the progress for the bacterial aliments in the field of the skin physiology and the importance of friction coefficient have been increased in the skin care market because of the needs of the well being times. In addition, the usage of friction coefficient is known to have the big discrimination ability in classification of human constitutions, which is utilized in the alternative medicine. In this study, we designed a system which used the multi axes load cell and hemi-circular probe and tried to measure the friction coefficient of hand skins repeatedly. Using this system, the relative repeatability error for the measurement of the friction coefficient was below 4 %. The coefficient is not concerned in curvatures of tips. Using this system, we will try to establish the standard for classification of constitutions.

A new protoparvovirus in human fecal samples and cutaneous T cell lymphomas (mycosis fungoides).

PubMed

Phan, Tung G; Dreno, Brigitte; da Costa, Antonio Charlys; Li, Linlin; Orlandi, Patricia; Deng, Xutao; Kapusinszky, Beatrix; Siqueira, Juliana; Knol, Anne-Chantal; Halary, Franck; Dantal, Jacques; Alexander, Kathleen A; Pesavento, Patricia A; Delwart, Eric

2016-09-01

We genetically characterized seven nearly complete genomes in the protoparvovirus genus from the feces of children with diarrhea. The viruses, provisionally named cutaviruses (CutaV), varied by 1-6% nucleotides and shared ~76% and ~82% amino acid identity with the NS1 and VP1 of human bufaviruses, their closest relatives. Using PCR, cutavirus DNA was found in 1.6% (4/245) and 1% (1/100) of diarrhea samples from Brazil and Botswana respectively. In silico analysis of pre-existing metagenomics datasets then revealed closely related parvovirus genomes in skin biopsies from patients with epidermotropic cutaneous T-cell lymphoma (CTCL or mycosis fungoides). PCR of skin biopsies yielded cutavirus DNA in 4/17 CTCL, 0/10 skin carcinoma, and 0/21 normal or noncancerous skin biopsies. In situ hybridization of CTCL skin biopsies detected viral genome within rare individual cells in regions of neoplastic infiltrations. The influence of cutavirus infection on human enteric functions and possible oncolytic role in CTCL progression remain to be determined. Copyright © 2016 Elsevier Inc. All rights reserved.

Terahertz spectroscopic investigations of leather in terahertz wave range

NASA Astrophysics Data System (ADS)

Song, Mei-jing; Li, Jiu-sheng

2012-03-01

Pulsed THz time-domain spectroscopy is a coherent technique, in which both the amplitude and the phase of a THz pulse are measured. Recently, material characterization using THz spectroscopy has been applied to biochemicals, pharmaceuticals, polymers and semiconductors and has given us important information. Moreover, THz imaging has progressed and is expected to be applicable for the identification of narcotics and explosives. The most important and characteristic point of THz spectroscopy is said to be its ability to observe intermolecular vibrations in contrast to infrared spectroscopy (IR), which observes intramolecular vibrations. Coherent detection enables direct calculations of both the imaginary and the real parts of the refractive index without using the Kramers-Kronig relations. Terahertz wave spectroscopy has been used to study the properties and absorption spectra characteristic of materials. In this paper, the spectral characteristics of cow skin, pig skin sheep skin, horse skin and deer skin have been measured with terahertz time-domain spectroscopy in the range of 0.1~2.0THz. The results show that THz-TDS technology provides an important tool for quality analysis and detection of leathers.

Genetic variants associated with skin aging in the Chinese Han population.

PubMed

Gao, Wenshan; Tan, Jingze; Hüls, Anke; Ding, Anan; Liu, Yu; Matsui, Mary S; Vierkötter, Andrea; Krutmann, Jean; Schikowski, Tamara; Jin, Li; Wang, Sijia

2017-04-01

The progression and manifestation of human skin aging has a strong genetic basis; however, most of the supporting evidence has been gathered in Caucasian populations. The genetic contribution to the variation in skin aging in non-Caucasian populations is poorly understood. To investigate the genetic risk factors of relevance for skin aging in East Asians, we conducted the first candidate gene study for signs of skin aging in Han Chinese. We collected skin aging and genotype data in 502 female Han Chinese from the Taizhou cohort. We evaluated skin aging by the validated skin aging score SCINEXA™. Confounding factors were assessed through a questionnaire. We obtained the genotype data for 21 candidate SNPs and for a further 509 SNPs from 16 related candidate genes. Associations were tested by linear and logistic regression analyses and adjusted for potential confounders. Our candidate study found a significant association between SNP rs2066853 in exon 10 of the aryl hydrocarbon receptor gene AHR and crow's feet. In addition, we found a significant association between SNP rs10733310 in intron 5 of BNC2 and pigment spots on the arms, and between SNP rs11979919, 3kb downstream of COL1A2, and laxity of eyelids. Our results identified genetic risk factors for signs of skin aging (pigmentation, wrinkles or laxity) in Han Chinese. We also found that the manifestation of skin aging is further modified by anatomical site. Together with previous work, our results also suggest that different genetic variants could be responsible for distinct skin aging signs characteristic of Caucasians compared to East Asians. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Pred-Skin: A Fast and Reliable Web Application to Assess Skin Sensitization Effect of Chemicals.

PubMed

Braga, Rodolpho C; Alves, Vinicius M; Muratov, Eugene N; Strickland, Judy; Kleinstreuer, Nicole; Trospsha, Alexander; Andrade, Carolina Horta

2017-05-22

Chemically induced skin sensitization is a complex immunological disease with a profound impact on quality of life and working ability. Despite some progress in developing alternative methods for assessing the skin sensitization potential of chemical substances, there is no in vitro test that correlates well with human data. Computational QSAR models provide a rapid screening approach and contribute valuable information for the assessment of chemical toxicity. We describe the development of a freely accessible web-based and mobile application for the identification of potential skin sensitizers. The application is based on previously developed binary QSAR models of skin sensitization potential from human (109 compounds) and murine local lymph node assay (LLNA, 515 compounds) data with good external correct classification rate (0.70-0.81 and 0.72-0.84, respectively). We also included a multiclass skin sensitization potency model based on LLNA data (accuracy ranging between 0.73 and 0.76). When a user evaluates a compound in the web app, the outputs are (i) binary predictions of human and murine skin sensitization potential; (ii) multiclass prediction of murine skin sensitization; and (iii) probability maps illustrating the predicted contribution of chemical fragments. The app is the first tool available that incorporates quantitative structure-activity relationship (QSAR) models based on human data as well as multiclass models for LLNA. The Pred-Skin web app version 1.0 is freely available for the web, iOS, and Android (in development) at the LabMol web portal ( http://labmol.com.br/predskin/ ), in the Apple Store, and on Google Play, respectively. We will continuously update the app as new skin sensitization data and respective models become available.

Oral intake of beet extract provides protection against skin barrier impairment in hairless mice.

PubMed

Kawano, Ken-Ichi; Umemura, Kazuo

2013-05-01

The epidermis acts as a functional barrier against the external environment. Disturbances in the function of this barrier cause water loss and increase the chances of penetration by various irritable stimuli, leading to skin diseases such as dry skin, atopic dermatitis, and psoriasis. Ceramides are a critical natural element of the protective epidermal barrier. The aim of this study was to evaluate whether the oral intake of beet (Beta vulgaris) extract, a natural product rich in glucosylceramide (GlcCer), may prevent disturbance in skin barrier function. When HR-1 hairless mice were fed a special diet (HR-AD), transepidermal water loss (TEWL) from the dorsal skin increased, with a compensatory increase in water intake after 5 weeks. Mice fed with HR-AD had dry skin with erythema and showed increased scratching behaviour. Histological examinations revealed a remarkable increase in the thickness of the skin at 8 weeks. Supplemental addition of beet extract, which contained GlcCer at a final concentration of 0.1%, significantly prevented an increase TEWL, water intake, cumulative scratching time, and epidermal thickness at 8 weeks. These results indicate that oral intake of beet extract shows potential for preventing skin diseases associated with impaired skin barrier function. Copyright © 2012 John Wiley & Sons, Ltd.

Robust skin color-based moving object detection for video surveillance

NASA Astrophysics Data System (ADS)

Kaliraj, Kalirajan; Manimaran, Sudha

2016-07-01

Robust skin color-based moving object detection for video surveillance is proposed. The objective of the proposed algorithm is to detect and track the target under complex situations. The proposed framework comprises four stages, which include preprocessing, skin color-based feature detection, feature classification, and target localization and tracking. In the preprocessing stage, the input image frame is smoothed using averaging filter and transformed into YCrCb color space. In skin color detection, skin color regions are detected using Otsu's method of global thresholding. In the feature classification, histograms of both skin and nonskin regions are constructed and the features are classified into foregrounds and backgrounds based on Bayesian skin color classifier. The foreground skin regions are localized by a connected component labeling process. Finally, the localized foreground skin regions are confirmed as a target by verifying the region properties, and nontarget regions are rejected using the Euler method. At last, the target is tracked by enclosing the bounding box around the target region in all video frames. The experiment was conducted on various publicly available data sets and the performance was evaluated with baseline methods. It evidently shows that the proposed algorithm works well against slowly varying illumination, target rotations, scaling, fast, and abrupt motion changes.

A Prospective, Observational Study to Assess the Use of Thermography to Predict Progression of Discolored Intact Skin to Necrosis Among Patients in Skilled Nursing Facilities.

PubMed

Cox, Jill; Kaes, Loretta; Martinez, Miguel; Moles, Daniel

2016-10-01

Skin temperature may help prospectively determine whether an area of skin discoloration will evolve into necrosis. A prospective, observational study was conducted in 7 skilled nursing facilities to determine if skin temperature measured using infrared thermography could predict the progression of discolored intact skin (blanchable erythema, Stage 1 pressure ulcer, or sus- pected deep tissue injury [sDTI]) to necrosis and to evaluate if nurses could effectively integrate thermography into the clinical setting. Patients residing in or presenting to the facility between October 2014 and August 2015 with a pressure-related area of discolored skin determined to be blanchable erythema, a Stage 1 pressure ulcer, or sDTI and anticipated length of stay >6 days were assessed at initial presentation of the discolored area and after 7 and 14 days by facility nurses trained on camera operation and study protocol. Variables included patient demographic and clinical data, data related to the discolored area (eg, size, date of initial discovery), and temperature and appearance differences between discolored and adjacent intact skin. Skin temperatures at the discolored and adjacent areas were measured during the initial assessment. All facility pressure ulcer prevention and treatment protocols derived from evidence-based clinical practice guidelines remained in use during the study time period. Participating nurses completed a 2-part, pencil/paper survey to examine the feasibility of incorporating thermography for skin assessment into practice. Data analyses were performed using descriptive statistics (frequency analyses) and bivariate analysis (t-tests and chi-squared tests); logistic regression was used to assess associations among patient and pressure ulcer variables. Of the 67 patients studied, the overall mean age was 85 years (SD 10); 52 were women; 63 were Caucasian; and the top 3 diagnoses, accounting for 60% of the study sample, included neurologic (ie, cardiovascular acci- dent/dementia [14, 21%]), cardiac-related (14, 21%), and orthopedic (13, 19%) conditions. Twenty-eight (28) participants were long-term care patients, and 39 were admitted as short-stay patients. The most frequently reported location of discolored intact skin on presentation was the heel (27, 40%). The mean temperature at the site of the discolored skin was 33.6 ̊ C (SD 3) and at the adjacent skin was 33.5 ̊ C (SD 2.5). The mean size of the areas of discoloration was 11 cm2 (SD 21). Capillary refill of the discolored area was absent on initial presentation in 49 patients (72%), and demarcation of the discolored borders was evident for 45 (66%). Of the 67 patients, 30 (45%) experienced complete resolution of the discolored area. At day 7, 8 (16%) of the remaining 50 patients in the sample exhibited skin necrosis and at day 14, a total of 12 patients of the remaining 37 (32%) exhibited skin necrosis. At day 7, skin necrosis was significantly associated with admission to a subacute unit (P = 0.01) and at day 14 to negative capillary refill at initial presentation (P = 0.02). Regardless of skin temperature, negative capillary refill at presentation was significantly associated with skin necrosis at day 7 (P = 0.04). A dichotomous variable was constructed to examine patients with cooler temperatures at the site as compared to their adjacent skin and persons with warmer skin temperatures at the center of the discolored skin for the presence of skin necrosis at both day 7 and day 14. In multivariate analysis, patients with cooler rather than warmer skin temperatures at the center of the discolored area as compared to the adjacent skin were more likely to develop necrosis by day 7 (OR 18.8; P = 0.05; CI: 104-342.44). Participating nurses were uncertain about the feasibility of integrating thermography into practice. Larger prospective studies with more heterogeneous samples are needed to determine the validity of skin temperature measurement as a predictor of skin necrosis and the utility of implementing thermography into clinical practice.

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells.

PubMed

Testa, Ugo; Castelli, Germana; Pelosi, Elvira

2017-11-20

Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells.

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

PubMed Central

Castelli, Germana; Pelosi, Elvira

2017-01-01

Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells. PMID:29156643

Use of wound dressings with soft silicone adhesive technology.

PubMed

Morris, Clare; Emsley, Paulene; Marland, Elizabeth; Meuleneire, Frans; White, Richard

2009-04-01

To evaluate how pain, during and in-between dressing changes, is affected by the introduction of Mepilex Border Lite, a wound dressing manufactured by Mölnlycke Health Care using Safetac soft silicone adhesive technology, to the treatment of different types of paediatric wounds/skin injuries. Wounds/skin injuries that met the criteria for inclusion in the study were dressed with Mepilex Border Lite. Patients were followed for six weeks or until their wounds/skin injuries had healed, whichever occurred earlier. At each dressing change, pain severity before and during dressing removal was rated by the patient and the investigator on a scale from zero (no pain at all) to ten (worst pain ever). Other variables measured included: signs of trauma to wound/skin injury and surrounding skin, the proportion of viable/non-viable tissue, the quantity and appearance of exudate, odour, and clinical signs of infection. At the final dressing change, patients and investigators completed questionnaires to rate the dressing performance. Mean pain severity scores were significantly lower (p < or = 0.003) at the first dressing change than at baseline. Over 99.5 per cent of the Mepilex Border Lite dressing changes were reported to be atraumatic and more than half of the wounds healed within the study period. Conformability, ease of use, ease of removal, patient comfort, and overall experience with the dressing were rated as 'good' to 'very good' at the vast majority of final visit evaluations. This study provides further evidence of the ability of dressings with Safetac soft silicone adhesive technology to minimise trauma and pain and demonstrates the ability of Mepilex Border Lite to overcome the clinical challenges associated with the use of dressings on the wounds/skin injuries of paediatric patients.

Wetting and adhesion evaluation of cosmetic ingredients and products: correlation of in vitro-in vivo contact angle measurements.

PubMed

Capra, P; Musitelli, G; Perugini, P

2017-08-01

The aim of this work was to use the contact angle measurement in order to predict the behaviour of ingredients and finished cosmetic products on skin to improve skin feel and product texture. Different classes of cosmetic ingredients and formulations were evaluated. The contact angle measurements were carried out by the sessile drop method using an apparatus, designed and set up in laboratory. Glass, Teflon and human skin were the reference substrates. In a preliminary phase, TEWL parameter, sebum content and hydration of human skin were measured to set up method. Data demonstrated that glass substrate may be used as replacement of the skin:critical surface tension of skin and glass were about of 27 and 31 dyne cm -1 , respectively. Non-ionic surfactant with increasing HLB was evaluated: a correlation between contact angle measured and HLB was not observed because of different and complex molecular structure. In detail, ethylhexyl hydroxystearate (θ glass = 17.1°) showed lower contact angle value with respect to Polysorbate 20 (θ glass = 28.1°). Sodium laureth sulphate and stearalkonium chloride were also evaluated: anionic molecule showed more affinity for glass with respect to Teflon (θ glass = 21.7° and θ Teflon = 52.3°). Lipids and silicones showed different affinity for substrate according to hydrophilic groups and hydrocarbon chain: contact angles of silicones remained unchanged independently from substrate. Finished cosmetic products (O/W, W/O emulsions, cleansing oil, dry skin oil) showed different profiles according to surfactant and its affinity for continuous phase of the formulation. Comparing the values of the contact angle on skin of non-ionic surfactants, as ethylhexyl hydroxystearate and Polysorbate 20, they showed values lower (near to zero) than ones of sodium laureth sulphate and Stearalkonium Chloride (21.7° and 66.8°, respectively). Finally, finished cosmetic products tested on human skin showed different profile: corresponded contact angle values were less than 20°. The product tended to be quickly adsorbed on human skin. Systematic study carried out by evaluating the wettability of single cosmetic ingredients on different substrates allowed to find correlations between the use of certain ingredients and the final performance of a cosmetic product. © 2017 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Principles and methodology for translation and cross-cultural adaptation of the Nordic Occupational Skin Questionnaire (NOSQ-2002) to Spanish and Catalan.

PubMed

Sala-Sastre, Nohemi; Herdman, Mike; Navarro, Lidia; de la Prada, Miriam; Pujol, Ramón M; Serra, Consol; Alonso, Jordi; Flyvholm, Mari-Ann; Giménez-Arnau, Ana M

2009-08-01

Occupational skin diseases are among the most frequent work-related diseases in industrialized countries. The Nordic Occupational Skin Questionnaire (NOSQ-2002), developed in English, is a useful tool for screening of occupational skin diseases. To culturally adapt the NOSQ-2002 to Spanish and Catalan and to assess the clarity, comprehension, cultural relevance and appropriateness of the translated versions. The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) principles of good practice for the translation and cultural adaptation of patient-reported outcomes were followed. After translation into the target language, a first consensus version of the questionnaire was evaluated in multiple cognitive debriefing interviews. The expert panel introduced some modifications in 39 (68%) and 27 (47%) items in the Spanish and Catalan version, respectively (e.g. addition of examples and definitions, reformulation of instructions and use of direct question format). This version was back translated and submitted to the original authors, who suggested a further seven and two modifications in the Spanish and Catalan versions, respectively. A second set of cognitive interviews were performed. A consensus version of both questionnaires was obtained after final modifications based on comments by the patients. The final versions of the Spanish and Catalan NOSQ-2002 questionnaires are now available at www.NRCWE.dk/NOSQ.

75 FR 77884 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... stearoyl-Co desaturase (SCD), which has been implicated in several disease states, including cardiovascular disease, obesity, non-insulin-dependent diabetes mellitus, skin disease, hypertension, neurological... Spinal Muscular Atrophy (SMA), which constitutes a group of inherited diseases that cause progressive...

Experimental metagenomics and ribosomal profiling of the human skin microbiome.

PubMed

Ferretti, Pamela; Farina, Stefania; Cristofolini, Mario; Girolomoni, Giampiero; Tett, Adrian; Segata, Nicola

2017-03-01

The skin is the largest organ in the human body, and it is populated by a large diversity of microbes, most of which are co-evolved with the host and live in symbiotic harmony. There is increasing evidence that the skin microbiome plays a crucial role in the defense against pathogens, immune system training and homoeostasis, and microbiome perturbations have been associated with pathological skin conditions. Studying the skin resident microbial community is thus essential to better understand the microbiome-host crosstalk and to associate its specific configurations with cutaneous diseases. Several community profiling approaches have proved successful in unravelling the composition of the skin microbiome and overcome the limitations of cultivation-based assays, but these tools remain largely inaccessible to the clinical and medical dermatology communities. The study of the skin microbiome is also characterized by specific technical challenges, such as the low amount of microbial biomass and the extensive human DNA contamination. Here, we review the available community profiling approaches to study the skin microbiome, specifically focusing on the practical experimental and analytical tools necessary to generate and analyse skin microbiome data. We describe all the steps from the initial samples collection to the final data interpretation, with the goal of enabling clinicians and researchers who are not familiar with the microbiome field to perform skin profiling experiments. © 2016 The Authors. Experimental Dermatology Published by John Wiley & Sons Ltd.

Immune response in pemphigus and beyond: progresses and emerging concepts.

PubMed

Di Zenzo, Giovanni; Amber, Kyle T; Sayar, Beyza S; Müller, Eliane J; Borradori, Luca

2016-01-01

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients' results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies.

Skin sensitisation--moving forward with non-animal testing strategies for regulatory purposes in the EU.

PubMed

Basketter, David; Alépée, Nathalie; Casati, Silvia; Crozier, Jonathan; Eigler, Dorothea; Griem, Peter; Hubesch, Bruno; de Knecht, Joop; Landsiedel, Robert; Louekari, Kimmo; Manou, Irene; Maxwell, Gavin; Mehling, Annette; Netzeva, Tatiana; Petry, Thomas; Rossi, Laura H

2013-12-01

In a previous EPAA-Cefic LRI workshop in 2011, issues surrounding the use and interpretation of results from the local lymph node assay were addressed. At the beginning of 2013 a second joint workshop focused greater attention on the opportunities to make use of non-animal test data, not least since a number of in vitro assays have progressed to an advanced position in terms of their formal validation. It is already recognised that information produced from non-animal assays can be used in regulatory decision-making, notably in terms of classifying a substance as a skin sensitiser. The evolution into a full replacement for hazard identification, where the decision is not to classify, requires the generation of confidence in the in vitro alternative, e.g. via formal validation, the existence of peer reviewed publications and the knowledge that the assay(s) are founded on key elements of the Adverse Outcome Pathway for skin sensitisation. It is foreseen that the validated in vitro assays and relevant QSAR models can be organised into formal testing strategies to be applied for regulatory purposes by the industry. To facilitate progress, the European Partnership for Alternative Approaches to animal testing (EPAA) provided the platform for cross-industry and regulatory dialogue, enabling an essential and open debate on the acceptability of an in vitro based integrated strategy. Based on these considerations, a follow up activity was agreed upon to explore an example of an Integrated Testing Strategy for skin sensitisation hazard identification purposes in the context of REACH submissions. Copyright © 2013 Elsevier Inc. All rights reserved.

Changes in Tannin Composition of Syrah Grape Skins and Seeds during Fruit Ripening under Contrasting Water Conditions.

PubMed

Kyraleou, Maria; Kallithraka, Stamatina; Theodorou, Nikolaos; Teissedre, Pierre-Louis; Kotseridis, Yorgos; Koundouras, Stefanos

2017-09-01

Tannin accumulation and composition were determined in skins and seeds isolated from Vitis vinifera cv. Syrah grapes submitted to contrasting water regimes under semiarid climatic conditions. Three irrigation treatments were conducted, starting at berry set through harvest of two growing seasons, 2011 and 2012: irrigation at 100% of crop evapotranspiration ETc (FI), irrigation at 50% of ETc (DI) and non-irrigated (NI). Seed total tannins did not vary with maturity but those of skins underwent a progressive decline (especially in 2011), expressed both on a fresh weight and on a per berry basis. Skin total tannin concentration and content per berry were increased under NI and DI conditions, mainly in 2012. In contrast, seed total tannins (in 2012) and flavan-3-ol monomers and tannin oligomers (both years) were higher in the fully irrigated vines (FI). Skin polymer size increased during ripening, NI and DI skins showing higher mean degree of polymerization (mDP) compared to FI at harvest. NI was also associated with a lower percentage of galloylation (%G) in skin oligomeric fraction (in 2012) and a lower percentage of prodelphinidins in the skin polymeric fraction (both years) at harvest. The mDP and %G of seed extracts did not vary during ripening and were higher in NI but only in 2012. According to the results, management of vine water status was shown to influence tannin amount and composition of Syrah grapes grown under semiarid conditions.

Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation.

PubMed

Carvalho, Ricardo Filipe da Silva; Nilsson, Gunnar; Harvima, Ilkka Tapani

2010-02-01

Mast cells are increasingly present in the lesional skin of chronic skin inflammatory diseases including psoriasis and basal cell carcinoma (BCC). It has previously been shown that proteinase-activated receptor (PAR)-2 is expressed by mast cells, and tryptase is a potent activator of this receptor. In this study, skin biopsies from both healthy-looking and lesional skin of patients with psoriasis and superficial spreading BCC were collected and the expression of PAR-2 immunoreactivity in tryptase-positive mast cells was analysed. PAR-2 expression was confirmed in vitro in different mast cell populations. Cord-blood derived mast cells (CBMC) were stimulated with a PAR-2 activating peptide, 2-furoyl-LIGRLO-NH(2). Consequently, IL-8 and histamine production was analysed in the supernatants. We observed a significant increase in the percentage of mast cells expressing PAR-2 in the lesional skin of psoriasis and BCC patients compared with the healthy-looking skin. HMC-1.2, LAD-2 and CBMC mast cells all expressed PAR-2 both intracellularly and on the cell surface. CBMC activation with the PAR-2 activating peptide resulted in an increased secretion of IL-8, but no histamine release was observed. Furthermore, both PAR-2 and IL-8 were co-localized to the same tryptase-positive mast cells in the lesional BCC skin. These results show that mast cells express increased levels of PAR-2 in chronic skin inflammation. Also, mast cells can be activated by a PAR-2 agonist to secrete IL-8, a chemokine which can contribute to the progress of inflammation.

Mechanism for prevention of infection in preterm neonates by topical emollients: a randomized, controlled clinical trial.

PubMed

Darmstadt, Gary L; Ahmed, Saifuddin; Ahmed, A S M Nawshad Uddin; Saha, Samir K

2014-11-01

Topical applications of emollients such as sunflower seed oil and Aquaphor have been shown to reduce the incidence of bloodstream infections and mortality of preterm infants in resource-poor settings. The causal mechanism for prevention of infection through cutaneous portals of entry is not well understood. We examined the relationship between skin condition score as a measure of skin barrier integrity and risk for bloodstream infection, and the effect of emollients on that relationship. Data for this study come from a randomized controlled trial of the impact of topical emollient therapy on nosocomial infections in 491 preterm infants <33 weeks gestational age at Dhaka Shishu Hospital, Bangladesh. Latent growth trajectory model with random-coefficient and multivariable logistic regression were utilized. Rate of deterioration of skin condition was significantly lower (P < 0.05) in both emollient arms compared with the untreated control group. Adjusted odds ratio of skin score for infection was 1.32 (95% confidence interval: 1.06-1.65). Emollients reduced the incidence of infection only when the skin had no signs of deterioration [Aquaphor incidence rate ratio: 0.43 (95% confidence interval: 0.19-0.97) and sunflower seed oil incidence rate ratio: 0.46 (95% confidence interval: 0.21-0.99)]. Skin condition deteriorated progressively after birth and compromised skin condition increased the risk of infection. Emollients preserved skin integrity and thus prevented infection in preterm neonates. To optimize benefits of emollients for the prevention of bloodstream infection, use of emollients should begin immediately after birth when the skin is still intact.

Skin autofluorescence predicts cardiovascular mortality in patients on chronic hemodialysis.

PubMed

Kimura, Hiroshi; Tanaka, Kenichi; Kanno, Makoto; Watanabe, Kimio; Hayashi, Yoshimitsu; Asahi, Koichi; Suzuki, Hodaka; Sato, Keiji; Sakaue, Michiaki; Terawaki, Hiroyuki; Nakayama, Masaaki; Miyata, Toshio; Watanabe, Tsuyoshi

2014-10-01

Tissue accumulation of advanced glycation end products (AGE) is thought to contribute to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non-invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has been reported to be an independent predictor of mortality associated with CVD in Caucasian patients on chronic hemodialysis. The aim of this study was to assess the predictive value of skin autofluorescence on all-cause and cardiovascular mortality in non-Caucasian (Japanese) patients on chronic hemodialysis. Baseline skin autofluorescence was measured with an autofluorescence reader in 128 non-Caucasian (Japanese) patients on chronic hemodialysis. All-cause and cardiovascular mortality was monitored prospectively during a period of 6 years. During the follow-up period, 42 of the 128 patients died; 19 of those patients died of CVD. Skin autofluorescence did not have a significant effect on all-cause mortality. However, age, carotid artery intima-media thickness (IMT), serum albumin, high-sensitivity C-reactive protein (hsCRP), skin autofluorescence and pre-existing CVD were significantly correlated with cardiovascular mortality. Multivariate Cox regression analysis showed skin autofluorescence (adjusted hazard ratio [HR] 3.97; 95% confidence interval [CI]1.67-9.43), serum albumin (adjusted HR 0.05; 95% CI 0.01-0.32), and hsCRP (adjusted HR 1.55; 95% CI 1.18-2.05) to be independent predictors of cardiovascular mortality. The present study suggests that skin autofluorescence is an independent predictor of cardiovascular mortality in non-Caucasian (Japanese) patients on chronic hemodialysis. © 2014 The Authors. Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis.

Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: Implications of probiotics in acne vulgaris

PubMed Central

Wang, Yanhan; Kuo, Sherwin; Shu, Muya; Yu, Jinghua; Huang, Stephen; Dai, Ashley; Two, Aimee; Gallo, Richard L.; Huang, Chun-Ming

2014-01-01

Increasing evidence demonstrates that commensal microorganisms in the human skin microbiome help fight pathogens and maintain homeostasis of the microbiome. However, it is unclear how these microorganisms maintain biological balance when one of them overgrows. The overgrowth of Propionibacterium acnes (P. acnes), a commensal skin bacterium, has been associated with the progression of acne vulgaris. Our results demonstrate that skin microorganisms can mediate fermentation of glycerol, which is naturally produced in skin, to enhance their inhibitory effects on P. acnes growth. The skin microorganisms, most of which have been identified as Staphylococcus epidermidis (S. epidermidis), in the microbiome of human fingerprints can ferment glycerol and create inhibition zones to repel a colony of overgrown P. acnes. Succinic acid, one of four short-chain fatty acids (SCFAs) detected in fermented media by nuclear magnetic resonance (NMR) analysis, effectively inhibits the growth of P. acnes in vitro and in vivo. Both intralesional injection and topical application of succinic acid to P. acnes-induced lesions markedly suppress the P. acnes-induced inflammation in mice. We demonstrate for the first time that bacterial members in the skin microbiome can undergo fermentation to rein in the overgrowth of P. acnes. The concept of bacterial interference between P. acnes and S. epidermidis via fermentation can be applied to develop probiotics against acne vulgaris and other skin diseases. In addition, it will open up an entirely new area of study for the biological function of the skin microbiome in promoting human health. PMID:24265031

New insights into HIV-1-primary skin disorders

PubMed Central

2011-01-01

Since the first reports of AIDS, skin involvement has become a burdensome stigma for seropositive patients and a challenging task for dermatologist and infectious disease specialists due to the severe and recalcitrant nature of the conditions. Dermatologic manifestations in AIDS patients act as markers of disease progression, a fact that enhances the importance of understanding their pathogenesis. Broadly, cutaneous disorders associated with HIV type-1 infection can be classified as primary and secondary. While the pathogenesis of secondary complications, such as opportunistic infections and skin tumours, is directly correlated with a decline in the CD4+ T cell count, the origin of the certain manifestations primarily associated with the retroviral infection itself still remains under investigation. The focus of this review is to highlight the immunological phenomena that occur in the skin of HIV-1-seropositive patients, which ultimately lead to skin disorders, such as seborrhoeic dermatitis, atopic dermatitis, psoriasis and eosinophilic folliculitis. Furthermore, we compile the latest data on how shifts in the cytokines milieu, impairments of the innate immune compartment, reactions to xenobiotics and autoimmunity are causative agents in HIV-1-driven skin diseases. Additionally, we provide a thorough analysis of the small animal models currently used to study HIV-1-associated skin complications, centering on transgenic rodent models, which unfortunately, have not been able to fully unveil the role of HIV-1 genes in the pathogenesis of their primarily associated dermatological manifestations. PMID:21261982

Infant skin maturation: Preliminary outcomes for color and biomechanical properties.

PubMed

Visscher, M O; Burkes, S A; Adams, D M; Hammill, A M; Wickett, R R

2017-11-01

Newborn infant skin changes after birth but studies have focused on the epidermal barrier. Dermal properties are relevant for care, but literature on postnatal changes is sparse. We further characterized skin maturational changes in lightness, color and response to biomechanical stress. Normal skin sites from subsets of participants in a trial on the progression and stage of infantile hemangiomas were retrospectively examined. Standardized photographs were analyzed as L*, a*, and b* images. Biomechanics were measured with the Cutometer ® . Color changed significantly with increasing age. Skin was darker and redder at 2.0 vs. 5.4, 8.5 and 12.8 months. Yellow color increased, with higher values at 12.8 vs. 2.0, 3.5 and 5.4 months. Chest tissue was consistently more elastic than arm and face sites, with significantly higher elasticity for the youngest and oldest age groups. Biological elasticity, elastic recovery, and total recovery were significantly greater for the oldest subjects. Viscoelasticity and elastic deformation were lower at 5.5 vs. 8.8 and 17.6 months. Arm viscoelastic creep was highest at 2.8 months. Skin maturation continues into year two. Increasing elasticity and decreasing viscoelasticity may reflect increased collagen structure/function. The findings have implications for prevention of skin injury associated with mechanical forces. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Optical coherence tomography angiography of normal skin and inflammatory dermatologic conditions.

PubMed

Deegan, Anthony J; Talebi-Liasi, Faezeh; Song, Shaozhen; Li, Yuandong; Xu, Jingjiang; Men, Shaojie; Shinohara, Michi M; Flowers, Mary E; Lee, Stephanie J; Wang, Ruikang K

2018-03-01

In clinical dermatology, the identification of subsurface vascular and structural features known to be associated with numerous cutaneous pathologies remains challenging without the use of invasive diagnostic tools. To present an advanced optical coherence tomography angiography (OCTA) method to directly visualize capillary-level vascular and structural features within skin in vivo. An advanced OCTA system with a 1310 nm wavelength was used to image the microvascular and structural features of various skin conditions. Subjects were enrolled and OCTA imaging was performed with a field of view of approximately 10 × 10 mm. Skin blood flow was identified using an optical microangiography (OMAG) algorithm. Depth-resolved microvascular networks and structural features were derived from segmented volume scans, representing tissue slabs of 0-132, 132-330, and 330-924 μm, measured from the surface of the skin. Subjects with both healthy and pathological conditions, such as benign skin lesions, psoriasis, chronic graft-versus-host-disease (cGvHD), and scleroderma, were OCTA scanned. Our OCTA results detailed variations in vascularization and local anatomical characteristics, for example, depth-dependent vascular, and structural alterations in psoriatic skin, alongside their resolve over time; vascular density changes and distribution irregularities, together with corresponding structural depositions in the skin of cGvHD patients; and vascular abnormalities in the nail folds of a patient with scleroderma. OCTA can image capillary blood flow and structural features within skin in vivo, which has the potential to provide new insights into the pathophysiology, as well as dynamic changes of skin diseases, valuable for diagnoses, and non-invasive monitoring of disease progression and treatment. Lasers Surg. Med. 50:183-193, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

A comparative review of cutaneous pH.

PubMed

Matousek, Jennifer L; Campbell, Karen L

2002-12-01

This review describes the role of pH in cutaneous structure and function. We first describe the molecules that contribute to the acidity or alkalinity of the skin. Next, differences in cutaneous pH among species, among individuals of the same species and within individuals are described. The potential functions of cutaneous pH in normal and diseased skin are analysed. For example, cutaneous pH has a role in the selection and maintenance of the normal cutaneous microbiota. In addition, cutaneous acidity may protect the skin against infection by microbes. Finally, there is evidence that a cutaneous pH gradient activates pH-dependent enzymes involved in the process of keratinization.

Controversial role of mast cells in skin cancers.

PubMed

Varricchi, Gilda; Galdiero, Maria R; Marone, Giancarlo; Granata, Francescopaolo; Borriello, Francesco; Marone, Gianni

2017-01-01

Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumor initiation and progression. The stromal microenvironment can promote tumor development. Mast cells, widely distributed throughout all tissues, are a stromal component of many solid and haematologic tumors. Mast cells can be found in human and mouse models of skin cancers such as melanoma, basal and squamous cell carcinomas, primary cutaneous lymphomas, haemangiomas and Merkel cell carcinoma. However, human and animal studies addressing potential functions of mast cells and their mediators in skin cancers have provided conflicting results. In several studies, mast cells play a pro-tumorigenic role, whereas in others, they play an anti-tumorigenic role. Other studies have failed to demonstrate a clear role for tumor-associated mast cells. Many unanswered questions need to be addressed before we understand whether tumor-associated mast cells are adversaries, allies or simply innocent bystanders in different types and subtypes of skin cancers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Penicillin skin testing: potential implications for antimicrobial stewardship.

PubMed

Unger, Nathan R; Gauthier, Timothy P; Cheung, Linda W

2013-08-01

As the progression of multidrug-resistant organisms and lack of novel antibiotics move us closer toward a potential postantibiotic era, it is paramount to preserve the longevity of current therapeutic agents. Moreover, novel interventions for antimicrobial stewardship programs are integral to combating antimicrobial resistance worldwide. One unique method that may decrease the use of second-line antibiotics (e.g., fluoroquinolones, vancomycin) while facilitating access to a preferred β-lactam regimen in numerous health care settings is a penicillin skin test. Provided that up to 10% of patients have a reported penicillin allergy, of whom ~10% have true IgE-mediated hypersensitivity, significant potential exists to utilize a penicillin skin test to safely identify those who may receive penicillin or a β-lactam antibiotic. In this article, we provide information on the background, associated costs, currently available literature, pharmacists' role, antimicrobial stewardship implications, potential barriers, and misconceptions, as well as future directions associated with the penicillin skin test. © 2013 Pharmacotherapy Publications, Inc.

Age, class and race discrimination: their interactions and associations with mental health among Brazilian university students.

PubMed

Bastos, João Luiz; Barros, Aluisio J D; Celeste, Roger Keller; Paradies, Yin; Faerstein, Eduardo

2014-01-01

Although research on discrimination and health has progressed significantly, it has tended to focus on racial discrimination and US populations. This study explored different types of discrimination, their interactions and associations with common mental disorders among Brazilian university students, in Rio de Janeiro in 2010. Associations between discrimination and common mental disorders were examined using multiple logistic regression models, adjusted for confounders. Interactions between discrimination and socio-demographics were tested. Discrimination attributed to age, class and skin color/race were the most frequently reported. In a fully adjusted model, discrimination attributed to skin color/race and class were both independently associated with increased odds of common mental disorders. The simultaneous reporting of skin color/race, class and age discrimination was associated with the highest odds ratio. No significant interactions were found. Skin color/race and class discrimination were important, but their simultaneous reporting, in conjunction with age discrimination, were associated with the highest occurrence of common mental disorders.

Energy Metabolism Rewiring Precedes UVB-Induced Primary Skin Tumor Formation.

PubMed

Hosseini, Mohsen; Dousset, Léa; Mahfouf, Walid; Serrano-Sanchez, Martin; Redonnet-Vernhet, Isabelle; Mesli, Samir; Kasraian, Zeinab; Obre, Emilie; Bonneu, Marc; Claverol, Stephane; Vlaski, Marija; Ivanovic, Zoran; Rachidi, Walid; Douki, Thierry; Taieb, Alain; Bouzier-Sore, Anne-Karine; Rossignol, Rodrigue; Rezvani, Hamid Reza

2018-06-19

Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation. By applying a quantitative proteomic approach and targeted metabolomics, we find that specific metabolic modifications precede primary skin tumor formation. Using a multistage model of ultraviolet B (UVB) radiation-induced skin cancer, we show that glycolysis, tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation are decreased at a very early stage of photocarcinogenesis, while the distal part of the electron transport chain (ETC) is upregulated. Reductive glutamine metabolism and the activity of dihydroorotate dehydrogenase (DHODH) are both necessary for maintaining high ETC. Mice with decreased DHODH activity or impaired ETC failed to develop pre-malignant and malignant lesions. DHODH activity represents a major link between DNA repair efficiency and bioenergetic patterning during skin carcinogenesis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms.

PubMed

Syrjänen, Leo; Luukkaala, Tiina; Leppilampi, Mari; Kallioinen, Matti; Pastorekova, Silvia; Pastorek, Jaromir; Waheed, Abdul; Sly, William S; Parkkila, Seppo; Karttunen, Tuomo

2014-09-01

Purpose of the study was to evaluate the presence of hypoxia-inducible, tumour-associated carbonic anhydrases IX and XII in normal skin and a series of cutaneous tumours. Human tumour samples were taken during surgical operations performed on 245 patients and were immunohistochemically stained. A histological score value was calculated for statistical analyses which were performed using SPSS for Windows, versions 17.0 and 20.0. In normal skin, the highest expression of CA IX was detected in hair follicles, sebaceous glands, and basal parts of epidermis. CA XII was detected in all epithelial components of skin. Both CA IX and CA XII expression levels were significantly different in epidermal, appendigeal, and melanocytic tumour categories. Both CA IX and XII showed the most intense immunostaining in epidermal tumours, whereas virtually all melanocytic tumours were devoid of CA IX and XII immunostaining. In premalignant lesions, CA IX expression significantly increased when the tumours progressed to more severe dysplasia forms. Both CA IX and XII are highly expressed in different epithelial components of skin. They are also highly expressed in epidermal tumours, in which CA IX expression levels also correlate with the dysplasia grade. Interestingly, both isozymes are absent in melanocytic tumours. © 2014 APMIS. Published by John Wiley & Sons Ltd.

An updated review of mechanotransduction in skin disorders: transcriptional regulators, ion channels, and microRNAs.

PubMed

Wang, Jing; Zhang, Yifan; Zhang, Ning; Wang, Chuandong; Herrler, Tanja; Li, Qingfeng

2015-06-01

The skin is constantly exposed and responds to a wide range of biomechanical cues. The mechanobiology of skin has already been known and applied by clinicians long before the fundamental molecular mechanisms of mechanotransduction are elucidated. Despite increasing knowledge on the mediators of biomechanical signaling such as mitogen-associated protein kinases, Rho GTPases or FAK-ERK pathways, the key elements of mechano-responses transcription factors, and mechano-sensors remain unclear. Recently, canonical biochemical components of Hippo and Wnt signaling pathway YAP and β-catenin were found to exhibit undefined mechanical sensitivity. Mechanical forces were identified to be the dominant regulators of YAP/TAZ activity in a multicellular context. Furthermore, different voltage or ligand sensitive ion channels in the cell membrane exhibited their mechanical sensitivity as mechano-sensors. Additionally, a large number of microRNAs have been confirmed to regulate cellular behavior and contribute to various skin disorders under mechanical stimuli. Mechanosensitive (MS) microRNAs could not only be activated by distinct mechanical force pattern, but also responsively target MS sensors such as e-cadherin and cytoskeleton constituent RhoA. Thus, a comprehensive understanding of this regulatory network of cutaneous mechanotransduction will facilitate the development of novel approaches to wound healing, hypertrophic scar formation, skin regeneration, and the progression or initiation of skin diseases.

Investigation into Z-Pin Reinforced Composite Skin/Stiffener Debond under Monotonic and Cyclic Bending

NASA Astrophysics Data System (ADS)

Zhang, Xiangyang; Li, Yong; Van Hoa, Suong; Xiao, Jun; Chu, Qiyi

2018-02-01

Skin/stiffener debonding has been a longstanding concern for the users of stiffened composite panels in long-term service. Z-pinning technology is an emerging solution to reinforce the composite assembly joints. This work experimentally characterizes the progressive debonding of Z-pinned skin/stiffener interface with the skin under static bend loading. The three-stage failure process is identified as: flange edge debonding, pin/laminate debonding, and ultimate structural failure. Three different distribution patterns were compared in terms of the static debonding properties revealed the affirmative fact that locating pins in high normal stress regions, that is close to the flange edges in skin/stiffener structures, is more beneficial to utilize the full potential of Z-pinning reinforcement. The unit strip FE model was developed and demonstrated effective to analysis the effect of Z-pin distribution on the ultimate debond load. On the other hand, the evolution of fatigue cracks at Z-pinned skin/flange interface was investigated with a series of displacement-controlled fatigue bending tests and microscopic observations. Results show that Z-pinning postpones crack initiations at low displacement levels, and the remarkable crack-arresting function of pins enables the structure a prolonged fatigue life. However, pins become less effective when the maximum displacement exceeds the crack initiation level due to gradually pullout of pins.

TIMES-SS--recent refinements resulting from an industrial skin sensitisation consortium.

PubMed

Patlewicz, G; Kuseva, C; Mehmed, A; Popova, Y; Dimitrova, G; Ellis, G; Hunziker, R; Kern, P; Low, L; Ringeissen, S; Roberts, D W; Mekenyan, O

2014-01-01

The TImes MEtabolism Simulator platform for predicting Skin Sensitisation (TIMES-SS) is a hybrid expert system, first developed at Bourgas University using funding and data from a consortium of industry and regulators. TIMES-SS encodes structure-toxicity and structure-skin metabolism relationships through a number of transformations, some of which are underpinned by mechanistic 3D QSARs. The model estimates semi-quantitative skin sensitisation potency classes and has been developed with the aim of minimising animal testing, and also to be scientifically valid in accordance with the OECD principles for (Q)SAR validation. In 2007 an external validation exercise was undertaken to fully address these principles. In 2010, a new industry consortium was established to coordinate research efforts in three specific areas: refinement of abiotic reactions in the skin (namely autoxidation) in the skin, refinement of the manner in which chemical reactivity was captured in terms of structure-toxicity rules (inclusion of alert reliability parameters) and defining the domain based on the underlying experimental data (study of discrepancies between local lymph node assay Local Lymph Node Assay (LLNA) and Guinea Pig Maximisation Test (GPMT)). The present paper summarises the progress of these activities and explains how the insights derived have been translated into refinements, resulting in increased confidence and transparency in the robustness of the TIMES-SS predictions.

[Risk factors for skin cancer development in patients after organ transplantation].

PubMed

Imko-Walczuk, Beata; Piesiaków, Maria Luiza; Okuniewska, Aleksandra; Jaśkiewicz, Janusz; Lizakowski, Sławomir; Dębska-Ślizień, Alicja; Rutkowski, Bolesław

2012-11-13

Cancer has become the second most common cause of death in patients after organ transplantation. Among all cancers arising de novo after transplantation skin cancers are the most common, accounting for 95% of all skin neoplasms. Due to the significantly higher morbidity, aggressive, rapid progression of cancer and unfavorable prognosis, the population requires a specific oncological approach. Therefore, special attention should be paid to factors predisposing to the development of cancer, including skin cancer, in patients after organ transplantation. Some of these factors are well understood, while the role of others is still ambiguous. Among the etiological factors mentioned are those that are associated with the recipient. These include genetic factors such as male sex, fair skin and inability to be tanned, and compatibility of the HLA system, and non genetic factors such as patient age, chronic skin ulcers and scars, the type of transplanted organ, immunosuppression, and particularly the type and cumulative doses of drugs. In addition, the pathogenesis of cancer is influenced by environmental factors such as exposure to sunlight and therefore latitude, ionizing radiation, chemical carcinogens and viral infections. Knowledge of etiological factors and mechanisms of etiopathogenesis allow for indication and observation of patients with increased risk of cancer as well as faster healing in these patients.  

Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome.

PubMed

Sandler, B; Aronson, P

1993-04-01

Yohimbine is an indole alkaloid obtained from the yohimbe tree, a common tree in West Africa. We describe a forty-two-year black man in whom a generalized erythrodermic skin eruption, progressive renal failure, and lupus-like syndrome developed following treatment with the drug, yohimbine. A literature review failed to reveal any reported association of these side effects. We review current information on yohimbine's use in male impotence, reported side effects, and its role as a drug allergen.

Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation.

PubMed

Matsumura, Y; Marchevsky, A; Zuo, X J; Kass, R M; Matloff, J M; Jordan, S C

1995-06-15

Lung transplantation is now routinely performed for a wide range of end-stage cardiopulmonary disorders. Despite overcoming the problems associated with early acute rejection, chronic rejection (CR) in the form of obliterative bronchiolitis has emerged as the primary cause of late graft loss. The mechanisms involved in the development of CR of lung allografts are poorly understood, and no effective therapy is currently available. To better understand the pathological events associated with CR and tolerance, we examined two models of lung allograft rejection established in our laboratory. First, we exchanged left lung allografts between moderately histoincompatible inbred rat strains (WKY-->F344: n = 42 and F344-->WKY: n = 40). The WKY-->F344 model was previously shown to develop spontaneous tolerance, while the converse model (F344-->WKY) showed persistent acute rejection. The purpose of this investigation was to assess histopathological changes associated with long-term grafts left in place up to 140 days after transplant. To confirm that tolerance had developed, skin-grafting experiments were performed. Five skin grafts from each strain were placed on lung allograft recipients on day 35 after transplant and skin allograft survival was assessed and compared with controls. Acute rejection (AR) was graded histologically (stage O-IV) and the pathologic intensity of inflammation and CR were graded (0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = 76-100%) on percentage of involvement with the following categories being examined: (a) lymphocytic infiltration (perivascular, peribronchial, and peribronchiolar) and (b) vasculitis, edema, hemorrhage, and necrosis. Finally, chronic rejection was diagnosed by the presence of intimal hyperplasia, interstitial fibrosis, peribronchiolar fibrosis, bronchiolitis obliterans, and bronchiectasis. The WKY-->F344 animals showed progressive AR (stage III, day 21). Thereafter, the AR subsided spontaneously and was stage 0 on day 140. There were no signs of CR in these animals. In the F344-->WKY model, the AR progressed up to stage III-IV (day 21) and maintained for several weeks at stage III. Thereafter, pictures of the lungs showed CR on days 49, 70, and 98. There were significant differences between the two models during the chronic phase, such as interstitial fibrosis (0 +/- 0 vs. 1.8 +/- 1.3, P < 0.005), peribronchiolar fibrosis (0 +/- 0 vs. 3.6 +/- 0.55, P < 0.01), vasculitis (0.2 +/- 0.45 vs. 2.0 +/- 0, P < 0.008), and intimal hyperplasia (0.2 +/- 0.45 vs. 2.6 +/- 0.9, P < 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery.

PubMed

Amjadi, Morteza; Mostaghaci, Babak; Sitti, Metin

2017-01-01

There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ex vivo permeation of carprofen from nanoparticles: A comprehensive study through human, porcine and bovine skin as anti-inflammatory agent.

PubMed

Parra, Alexander; Clares, Beatriz; Rosselló, Ana; Garduño-Ramírez, María L; Abrego, Guadalupe; García, María L; Calpena, Ana C

2016-03-30

The purpose of this study was the development of poly(d,l-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) for the dermal delivery of carprofen (CP). The developed nanovehicle was then lyophilized using hydroxypropyl-β-cyclodextrin (HPβCD) as cryoprotectant. The ex vivo permeation profiles were evaluated using Franz diffusion cells using three different types of skin membranes: human, porcine and bovine. Furthermore, biomechanical properties of skin (trans-epidermal water loss and skin hydration) were tested. Finally, the in vivo skin irritation and the anti-inflammatory efficacy were also assayed. Results demonstrated the achievement of NPs 187.32 nm sized with homogeneous distribution, negatively charged surface (-23.39 mV) and high CP entrapment efficiency (75.38%). Permeation studies showed similar diffusion values between human and porcine skins and higher for bovine. No signs of skin irritation were observed in rabbits. Topically applied NPs significantly decreased in vivo inflammation compared to the reference drug in a TPA-induced mouse ear edema model. Thus, it was concluded that NPs containing CP may be a useful tool for the dermal treatment of local inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment considerations in actinic keratosis.

PubMed

Goldenberg, G

2017-03-01

The chronic skin condition actinic keratosis (AK) is characterized by the formation of keratotic lesions of variable thickness that are poorly delimited. AK occurs on areas of the skin that have had long-term exposure to the sun or UV radiation. Although AKs may regress, they usually persist and can progress to squamous cell carcinoma (SCC). Clinicians are unable to predict which AKs will progress; therefore, both clinically visible lesions and subclinical, non-visible (i.e. the entire area affected by AK/field cancerization) should be treated. AK treatment options include lesion-directed therapies that target specific AK lesions and field-directed therapies that target multiple clinical lesions and the underlying field damage. This article reviews currently available treatment options in AK, with a focus on patient-applied field therapies, and their suitability according to specific disease characteristics and patient needs. Choice of treatment in AK depends on lesion-, patient- and treatment-related factors and should be individualized. Considerations when choosing a therapy include site of application, treatment duration, surface area of application, tolerability profiles and implications on adherence. Field-directed therapies treat clinical and subclinical damage (i.e. the entire area affected by AK), achieve high rates of sustained clearance of AKs and may reduce the risk of progression to SCC. There is a clear need for field therapies with short duration of treatment and predictable, short-lived, mild local skin reactions that can be used over a large surface area. Therapies with shorter and simpler treatment courses are often associated with better adherence than treatments with longer courses. These may, therefore, represent more appropriate choices in patients for whom convenience and/or adherence are an issue. © 2017 European Academy of Dermatology and Venereology.

An Ex Vivo Comparison of 2 Cyanoacrylate Skin Protectants.

PubMed

Gibson, Daniel J

The purpose of these experiments was to compare 2 commercially available skin protectants with different chemical compositions. Two materially different skin protectants were applied to ex vivo pig skin, subjected to stresses, and the resulting skin was observed and analyzed. Using ex vivo pig skin, we sought to better understand the physical differences between a cyanoacrylate-based and a mixed cyanoacrylate/acrylic polymer-based skin protectant. A combination of imaging techniques and microscopic analyses was used to observe and quantify differences in layer thickness and the degree of steadfastness of the layers to liquid stresses. The experiments revealed that the solely cyanoacrylate-based protectant created a layer that was, on average, 5.1 times thicker than the mixed polymer product (p= 1.8 × 10). Observation via electron microscopy also revealed that the extent of coverage varied between the 2 products. In a final experiment, we observed that the mixed polymer product maintained a high degree of adhesiveness, which led to the removal of sheets of epithelium upon gentle blotting. The experiments revealed that while the 2 skin protectants share a common ingredient, both the quantity of that ingredient and the inclusion of other materials in one of them lead to substantially different properties when tested in the research setting.

Visibility of Surgical Site Marking After Preoperative Skin Preparation

PubMed Central

Mears, Simon C.; Dinah, A. Feroz; Knight, Trevor A.; Frassica, Frank J.; Belkoff, Stephen M.

2008-01-01

Objective: It is important that during preoperative skin preparation surgical site markings are not erased. The effects of 2 common types of skin preparation solutions on surgical site markings were compared. Methods: Fasciocutaneous skin flaps were harvested and 20 random combinations of 3 letters were written on the skin flaps with a black permanent marker. Ten of the 3-letter combinations received Chloraprep (chlorhexidine gluconate, 2% w/v, plus isopropyl alcohol, 70% v/v) and the other 10 received Duraprep (iodine povacrylex [0.7% available iodine] and isopropyl alcohol [74% w/w]), both according to the manufacturer's guidelines. The skin flaps were photographed digitally before and after application of the solutions. The final pictures were assessed subjectively by 10 surgeons and then objectively to determine the change in visibility of the marking on each specimen. Results: Of the 300 letters in each group, the number of correctly identified letters was 254 (84.7%) in the Chloraprep group and 284 (94.7%) in the Duraprep group. On the basis of the visibility of skin markings, Chloraprep was 21.8 times more likely (95% credible interval, 7.3–86.7) to erase the site markings than was Duraprep. Conclusions: Skin preparation with Chloraprep erased more surgical site markings than did Duraprep. PMID:18709136

Prx-1 expression in Xenopus laevis scarless skin-wound healing and its resemblance to epimorphic regeneration.

PubMed

Yokoyama, Hitoshi; Maruoka, Tamae; Aruga, Akio; Amano, Takanori; Ohgo, Shiro; Shiroishi, Toshihiko; Tamura, Koji

2011-12-01

Despite a strong clinical need for inducing scarless wound healing, the molecular factors required to accomplish it are unknown. Although skin-wound healing in adult mammals often results in scarring, some amphibians can regenerate injured body parts, even an amputated limb, without it. To understand the mechanisms of perfect skin-wound healing in regenerative tetrapods, we studied the healing process in young adult Xenopus "froglets" after experimental skin excision. We found that the excision wound healed completely in Xenopus froglets, without scarring. Mononuclear cells expressing a homeobox gene, prx1, accumulated under the new epidermis of skin wounds on the limb and trunk and at the regenerating limb. In transgenic Xenopus froglets expressing a reporter for the mouse prx1 limb-specific enhancer, activity was seen in the healing skin and in the regenerating limb. Comparable activity did not accompany skin-wound healing in adult mice. Our results suggest that scarless skin-wound healing may require activation of the prx1 limb enhancer, and competence to activate the enhancer is probably a prerequisite for epimorphic regeneration, such as limb regeneration. Finally, the induction of this prx1 enhancer activity may be useful as a reliable marker for therapeutically induced scarless wound healing in mammals.

[Hypertrophic adipose tissue transplantation secondary to a lipopenisculpture].

PubMed

Moullot, P; Nguyen, P-S; Philandrianos, C; Casanova, D

2014-10-01

Reconstruction of the penile skin requires a functional and esthetically perfect result, combining a high degree of skin elasticity to allow regular erections and a satisfactory cosmetic appearance. Demand for cosmetic surgery penile augmentation continues to increase for several years. The surgical technique most commonly used is now widening and lengthening lipopenisculpture (LPS), combining an adipocyte graft to a section of the suspensory ligament of the penis. A patient who underwent LPS presented several years after a major hypertrophy of the adipocyte graft, making it impossible to have sexual activities, imposing to perform liposuction. This liposuction was being complicated by necrosis of the penile skin. Reconstruction was required and consisted of an unexpanded thin skin graft associated with artificial dermis. Through technical adaptation of the skin graft on the erect penis, the use of artificial dermis and external stabilization by negative pressure therapy, reconstruction of the penile skin provides excellent aesthetic and functional results. Finally, it is rarely reported in the literature complications of lipofilling like alteration of the aesthetic result after weight gain. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Dermatological Feasibility of Multimodal Facial Color Imaging Modality for Cross-Evaluation of Facial Actinic Keratosis

PubMed Central

Bae, Youngwoo; Son, Taeyoon; Nelson, J. Stuart; Kim, Jae-Hong; Choi, Eung Ho; Jung, Byungjo

2010-01-01

Background/Purpose Digital color image analysis is currently considered as a routine procedure in dermatology. In our previous study, a multimodal facial color imaging modality (MFCIM), which provides a conventional, parallel- and cross-polarization, and fluorescent color image, was introduced for objective evaluation of various facial skin lesions. This study introduces a commercial version of MFCIM, DermaVision-PRO, for routine clinical use in dermatology and demonstrates its dermatological feasibility for cross-evaluation of skin lesions. Methods/Results Sample images of subjects with actinic keratosis or non-melanoma skin cancers were obtained at four different imaging modes. Various image analysis methods were applied to cross-evaluate the skin lesion and, finally, extract valuable diagnostic information. DermaVision-PRO is potentially a useful tool as an objective macroscopic imaging modality for quick prescreening and cross-evaluation of facial skin lesions. Conclusion DermaVision-PRO may be utilized as a useful tool for cross-evaluation of widely distributed facial skin lesions and an efficient database management of patient information. PMID:20923462

Occupational skin diseases from 1997 to 2004 at the Department of Dermatology, University Hospital of Northern Norway (UNN): an investigation into the course and treatment of occupational skin disease 10-15 years after first consultations with a dermatologist.

PubMed

Braun, Rosemarie; Dotterud, Lars Kåre

2016-01-01

We investigate the impact of occupational skin disease consultations among outpatients at the Dermatological Department, University Hospital, Northern Norway. From 1997 until 2004, 386 patients with occupational skin disease were examined and given advice on skin care, skin disease treatment, skin protection in further work, and on the legal rights of patients with this disease. Ten to fifteen years later, we wanted to look at these patients in terms of their work situation, the current status of their disease, the help they received from the labour offices, and their subjective quality of life. In the autumn of 2011 until the spring of 2012, a number of the patients examined in the period from 1997 to 2004 were selected and sent a questionnaire, which they were asked to answer and return, regarding their work situation and the progress and current status of their occupational disease. A total of 153 (77%) patients answered the questionnaire; 71% of these patients were still in work, and further 15% had old-age retired, 13% were working until then; 16% had retired early because of disability; 54% had changed jobs because of their occupational skin disease; 86% of the patients indicated that the skin disease had improved since our previous investigation. Our investigation into patients with occupational skin disease documented that the majority of patients who had received professional dermatological consultation and intervention offers were still in the labour market and had good control of their skin disease 10-15 years later. We discovered that 71% of the patients were still employed. 13% had remained in work until they became old age pensioners. Only 16% dropped out of work because of disability. These high percentages may indicate that our intervention has contributed positively to patients' work conditions and the course of their skin disease.

Modeling Burns for Pre-Cooled Skin Flame Exposure

PubMed Central

2017-01-01

On a television show, a pre-cooled bare-skinned person (TV host) passed through engulfing kerosene flames. The assumption was that a water film should protect him during 0.74 s flame exposure in an environment of 86 kW/m2 heat flux. The TV host got light burn inflammation on the back, arms and legs. The present work studies skin temperatures and burn damage integral of such dangerous flame exposure. The skin temperature distribution during water spray pre-cooling, transport to the flames, flame exposure, transport to the water pool, and final water pool cooling is modelled numerically. Details of the temperature development of the skin layers are presented, as well as the associated damage integral. It is shown that 5 °C water spray applied for a 30 s period pre-cooled the skin sufficiently to prevent severe skin injury. Soot marks indicate that the water layer evaporated completely in some areas resulting in skin flame contact. This exposed dry skin directly to the flames contributing significantly to the damage integral. It is further analyzed how higher water temperature, shorter pre-cooling period or longer flame exposure influence the damage integral. It is evident that minor changes in conditions could lead to severe burns and that high heat flux levels at the end of the exposure period are especially dangerous. This flame stunt should never be repeated. PMID:28880253

Accumulation of p53 is associated with tumour progression in cutaneous lesions of renal allograft recipients.

PubMed Central

Stark, L. A.; Arends, M. J.; McLaren, K. M.; Benton, E. C.; Shahidullah, H.; Hunter, J. A.; Bird, C. C.

1994-01-01

Renal allograft recipients suffer from a markedly increased susceptibility to premalignant and malignant cutaneous lesions. Although various aetiological factors have been implicated, little is known of the associated genetic events. In this study we initially employed immunocytochemical techniques to investigate the prevalence and localisation of accumulated p53 in over 200 cutaneous biopsies (including 56 squamous cell carcinomas) from renal allograft recipients and immunocompetent controls. In renal allograft recipients accumulated p53 was present in 24% of uninvolved skin samples, 14% of viral warts, 41% of premalignant keratoses, 65% of intraepidermal carcinomas and 56% of squamous cell carcinomas [squamous cell carcinoma and intraepidermal carcinoma differed significantly from uninvolved skin (P < 0.005) and viral warts (P < 0.01)]. A similar trend was revealed in immunocompetent patients (an older, chronically sun-exposed population) but with lower prevalence of p53 immunoreactivity: 25% of uninvolved skin samples, 0% of viral warts, 25% of keratoses, 53% of intraepidermal carcinomas and 53% of squamous cell carcinomas. These differences were not statistically significant. Morphologically, p53 immunoreactivity strongly associated with areas of epidermal dysplasia and the abundance of staining correlated positively with the severity of dysplasia. These data suggest that p53 plays a role in skin carcinogenesis and is associated with progression towards the invasive state. No correlation was observed between accumulated p53 and the presence of human papillomavirus (HPV) DNA in any of the lesions. Single-strand conformational polymorphism analysis (exons 5-8) was used to determine the frequency of mutated p53 in 28 malignancies with varying degrees of immunopositivity. p53 mutations were found in 5/9 (56%) malignancies with p53 staining in > 50% of cells, reducing to 1/6 (17%) where 10-50% of cells were positively stained and none where < 10% of cells were stained. These data imply that factors other than p53 gene mutation play a part in accumulation of p53 in skin cancers. Images Figure 2 Figure 3 PMID:7917913

A decrease in D-dimer concentration and an occurrence of skin rash as iatrogenic events and complementary predictors of survival in lung cancer patients treated with EGFR tyrosine kinase inhibitors.

PubMed

Zaborowska-Szmit, Magdalena; Kowalski, Dariusz M; Piórek, Aleksandra; Krzakowski, Maciej; Szmit, Sebastian

2016-12-01

Progression of lung cancer is associated with some abnormalities in coagulation. The aim of the study was to determine the predictive and prognostic value of changes in D-dimer concentration in non-small cell lung cancer (NSCLC) patients on anti-EGFR targeted therapy. The analysis included fifty two NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKIs): erlotinib or gefitinib. All clinical data were collected before treatment and after 2 cycles (60days) of therapy and correlated with progression free and overall survival (PFS, OS). Two iatrogenic events were noted within the first 60days of anti-EGFR treatment: typical skin rash in 38 (73.1%) and a decrease in D-dimer concentration in 26 (50%) patients. Multivariate analysis revealed a decrease of D-dimer concentration as the strongest factor associated with longer PFS (HR=0.39; 95%CI: 0.16-0.91; p=0.029) and OS (HR=0.33; 95%CI: 0.13-0.82, p=0.017) independently of skin rash, baseline level of D-dimer and other clinical characteristics. Coexisting a decrease in D-dimer concentration with an occurrence of skin rash correlated significantly with the positive objective response after 60days of anti-EGFR therapy (p=0.0175) and indicated the longest PFS (HR=0.31; 95%CI: 0.16-0.60, p=0.0005) as well as OS (HR=0.30; 95%CI: 0.15-0.59, p=0.0005). Adverse events may predict the outcomes of cancer patients. Apart from skin rash, change in D-dimer concentration may be valuable parameter in creation of predictive and prognostic models in NSCLC patients receiving anti-EGFR targeted therapy. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Concurrent Hand and Penile Gangrene following Prolonged Warfarin Use; a Case Report.

PubMed

Mahdizadeh, Fatemeh; Safari, Saeed

2017-01-01

Warfarin induced skin necrosis (WISN) is a rare but important side effect of warfarin. Early diagnosis may lessen the amount of permanent tissue damage and can prevent progression to full thickness skin necrosis. So, physicians should be aware of such a complication. Screening for protein C or S or anti-thrombin deficiencies, or presence of anti-phospholipid antibodies before beginning warfarin therapy, could be helpful to avoid high levels of international normalized ratio (INR). Here, we report a 54-year-old man who presented to the emergency department with acral and penile gangrene following prolonged use of warfarin.

Kindler syndrome.

PubMed

Kaviarasan, P K; Prasad, P V S; Shradda; Viswanathan, P

2005-01-01

Kindler syndrome is a rare autosomal recessive disorder associated with skin fragility. It is characterized by blistering in infancy, photosensitivity and progressive poikiloderma. The syndrome involves the skin and mucous membrane with radiological changes. The genetic defect has been identified on the short arm of chromosome 20. This report describes an 18-year-old patient with classical features like blistering and photosensitivity in childhood and the subsequent development of poikiloderma. The differential diagnosis of Kindler syndrome includes diseases like Bloom syndrome, Cockayne syndrome, dyskeratosis congenita, epidermolysis bullosa, Rothmund-Thomson syndrome and xeroderma pigmentosum. Our patient had classical cutaneous features of Kindler syndrome with phimosis as a complication.

(Oncogenic action of ionizing radiation)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-01-01

An extensive experiment involving approximately 400 rats exposed to the neon ion beam at the Bevalac in Berkeley, CA and to electrons is nearing completion. The carcinogenicity of energetic electrons was determined for comparison with the neon ion results. As in past reports we will describe progress in three areas corresponding to the specific aims of the proposal: (1) carcinogenesis and DNA strand breaks in rat skin following exposure by the neon ions or electrons; (2) DNA strand breaks in the epidermis as a function of radiation penetration; (3) oncogene activation in radiation-induced rat skin cancers. 72 refs., 6 tabs.

A novel missense mutation of COL5A2 in a patient with Ehlers-Danlos syndrome.

PubMed

Watanabe, Miki; Nakagawa, Ryuji; Naruto, Takuya; Kohmoto, Tomohiro; Suga, Ken-Ichi; Goji, Aya; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

2016-01-01

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. For molecular diagnosis, targeted exome sequencing was performed on a 9-year-old male patient who was clinically suspected to have EDS. The patient presented with progressive kyphoscoliosis, joint hypermobility and hyperextensible skin without scars. Ultimately, classical EDS was diagnosed by identifying a novel, mono-allelic mutation in COL5A2 [NM_000393.3(COL5A2_v001):c.682G>A, p.Gly228Arg].

A novel missense mutation of COL5A2 in a patient with Ehlers–Danlos syndrome

PubMed Central

Watanabe, Miki; Nakagawa, Ryuji; Naruto, Takuya; Kohmoto, Tomohiro; Suga, Ken-ichi; Goji, Aya; Kagami, Shoji; Masuda, Kiyoshi; Imoto, Issei

2016-01-01

Ehlers–Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. For molecular diagnosis, targeted exome sequencing was performed on a 9-year-old male patient who was clinically suspected to have EDS. The patient presented with progressive kyphoscoliosis, joint hypermobility and hyperextensible skin without scars. Ultimately, classical EDS was diagnosed by identifying a novel, mono-allelic mutation in COL5A2 [NM_000393.3(COL5A2_v001):c.682G>A, p.Gly228Arg]. PMID:27656288

Skin hydration, microrelief and greasiness of normal skin in Antarctica.

PubMed

Tsankov, N; Mateev, D; Darlenski, R

2018-03-01

The skin is the primary defence of the human body against external factors from physical, chemical, mechanical and biologic origin. Climatic factors together with low temperature and sun radiation affect the skin. The effect of climatic conditions in Antarctica on healthy skin has not been previously addressed. The aim of this study was to evaluate the changes in the skin hydration, greasiness and microrelief due to the extreme climatic environmental factors during the stay of the members of the Bulgarian Antarctic expedition. Fifty-nine Caucasian healthy subjects, 42 men and 17 women with mean age 50.9 years (27-68), were enrolled. The study was performed in five consecutive years from 2011 to 2016 at the Bulgarian Antarctic base camp at Livingston Island. The study protocol consisted of two parts: study A: duration of 15 days with measurement of skin physiology parameters on a daily basis, and study B: five measurements at baseline and at days 14, 30, 45 and 50 upon arrival in Antarctica. We measured three biophysical parameters related to skin physiology at cheek skin by an impedance measuring device. No statistically significant difference between parameters at the different measurement points. There is a variation in skin hydration reaching its lower point at day 11 and then returning to values similar to baseline. Initially, an increase in skin greasiness was witnessed with a sharp depression at day 11 and final values at day 15 resembling the ones at baseline. An increase, although not statistically significant, in skin roughness was observed in the first 15 days of the study. Study B showed no statistically significant variances between values of the three parameters. Our studies show the pioneer results of the effect of Antarctic climate on human skin physiology. © 2017 European Academy of Dermatology and Venereology.

Adult-Onset Acral Peeling Skin Syndrome in a Non-Identical Twin: A Case Report in South Africa

PubMed Central

Mathew, Reshmi; Omole, Olufemi B.; Rigby, Jonathan; Grayson, Wayne

2014-01-01

Patient: Female, 44 Final Diagnosis: Acral peeeling skin syndrome Symptoms: Recurrent skin exfoliation Medication: — Clinical Procedure: Skin biopsy Specialty: Dermatology Objective: Rare disease Background: Acral peeling skin syndrome is a rare autosomal recessive disorder in which skin exfoliation is limited to the hands and feet. While it typically manifests from early childhood, in this first reported case from South Africa, the patient did not manifest clinically until the fourth decade of life. Case Report: A 44-year-old woman of African descent, 1 of a set of non-identical twins, presented with recurrent episodes of skin peeling of the upper and lower limbs. The first episode occurred 4 years prior, followed by perennial skin peeling during the spring seasons. She was not on treatment for any chronic disease and reported no exposure to chemicals or other irritants. The family, including the non-identical twin sister, has no history of skin disorders and the patient’s HIV antibody test was negative. At presentation, physical examination revealed ongoing exfoliation with new skin formation on the palms and soles. The mucous membranes and nails were spared. Other systems were normal. Skin biopsy taken from the palms confirmed peeling skin syndrome. The patient was managed with topical aqueous cream and analgesics. She was briefly counseled on the nature and prognosis of the disease, and referred for genetic testing and counseling. On follow-up, she continues to have skin peeling once or twice a year. Conclusions: This first reported case of this rare disease in South Africa contributes to the growing body of literature on the disease and highlights the need for clinicians to be aware of its variable clinical onset. PMID:25549719

Bacterial diseases of the skin.

PubMed

Edlich, Richard F; Winters, Kathryne L; Britt, L D; Long, William B

2005-01-01

When considering common bacterial diseases of the skin, rather distinct clinical responses to a variety of bacterial infections have been identified. In these cases, it is the specific site of infection and the attendant inflammatory responses that provide the characteristic clinical picture. When the pyoderma extends just below the stratum corneum, it is called impetigo. Nonbullous impetigo is the most common pediatric skin infection. It usually starts in a traumatized area. The typical lesion begins as an erythematous papule, after which it becomes a unilocular vesicle. When the subcorneal vesicle becomes pustular, it ruptures and eventually becomes a yellow, golden crust that is a hallmark of the disease process. Bullous impetigo is a less common form of impetigo, accounting for fewer than 30% of all impetigo cases. It occurs in infants and is characterized by rapid progression of vesicles to the formation of bullae measuring larger than 5 mm in diameter in previously untraumatized skin. Treatment of nonbullous impetigo must include intervention against the pathogen as well as improvements in the hygiene and living conditions of the patient. A fundamental tenet is to debride the crust (scab) from the wound surface using poloxamer 188. If the lesions are not widespread, topical mupirocin is the treatment of choice. Treatment of bullous impetigo is similar, except that the local cleansing and topical antibiotic must be complemented by systemic antibiotics if there is evidence of disseminating infections. Ecthyma is usually a consequence of failure to treat effectively impetigo. The untreated infection extends deep into the tissue in shallow ulcerations that often heal without scar. Treatment for ecthyma usually requires systemic antibiotics against either staphylococcus or streptococcus. Folliculitis is a pyoderma located within a hair follicle, secondary to follicular occlusion by keratin, overhydration, or either bacterial or fungal infection. Folliculitis may be divided into either a deep or a superficial type. In the superficial type, the pustule is located at the opening of the hair follicle. In the deep form, the infection may extend beyond the confines of the hair follicle, becoming a furuncle or boil. Carbuncles are aggregates of interconnected furuncles that drain through multiple openings of the skin. Treatment of folliculitis must include searching for and avoiding any factors predisposing to infection. If topical antibiotic therapy is ineffective in controlling the infection, surgical drainage of the infected skin abscess will be necessary. Paronychia is the most common bacterial infection of the hand, which often requires surgical incisional drainage. Similarly, a felon that is an infection of the distal pulp of a finger usually requires surgical drainage. Finally, cellulitis is an acute inflammatory reaction involving the skin and underlying subcutaneous tissue. It usually starts as erysipelas and may advance to lymphangitis, lymphadenitis, or gangrene,which will respond to life-saving interventions in the hospital that usually include systemic antibiotic treatment as well as surgical intervention.

Characterization and Modulation of Proteins Involved in SM Vesication

DTIC Science & Technology

2005-05-01

shown to be the major etiological factor leading to the precancerous stage of actinic keratosis (AK) and to induction and progression of skin cancers...representing a transient regression-prone precancerous stage equivalent to actinic keratosis . To further examine which caspases are apical and

7 CFR 989.5 - Raisins.

Code of Federal Regulations, 2011 CFR

2011-01-01

... significant part of the natural moisture means removal which has progressed to the point where the grape skin... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN CALIFORNIA Order Regulating Handling Definitions § 989.5 Raisins. Raisins means grapes of any variety grown...

7 CFR 989.5 - Raisins.

Code of Federal Regulations, 2012 CFR

2012-01-01

... significant part of the natural moisture means removal which has progressed to the point where the grape skin... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN CALIFORNIA Order Regulating Handling Definitions § 989.5 Raisins. Raisins means grapes of any variety grown...

7 CFR 989.5 - Raisins.

Code of Federal Regulations, 2013 CFR

2013-01-01

... significant part of the natural moisture means removal which has progressed to the point where the grape skin... ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN CALIFORNIA Order Regulating Handling Definitions § 989.5 Raisins. Raisins means grapes of any variety grown...

7 CFR 989.5 - Raisins.

Code of Federal Regulations, 2014 CFR

2014-01-01

... significant part of the natural moisture means removal which has progressed to the point where the grape skin... ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN CALIFORNIA Order Regulating Handling Definitions § 989.5 Raisins. Raisins means grapes of any variety grown...

Relationships between harvest time and wine composition in Vitis vinifera L. cv. Cabernet Sauvignon 1. Grape and wine chemistry.

PubMed

Bindon, Keren; Varela, Cristian; Kennedy, James; Holt, Helen; Herderich, Markus

2013-06-01

The study aimed to quantify the effects of grape maturity on wine alcohol, phenolics, flavour compounds and polysaccharides in Vitis vinifera L. cv Cabernet Sauvignon. Grapes were harvested at juice soluble solids from 20 to 26 °Brix which corresponded to a range of wine ethanol concentrations between 12% and 15.5%. Grape anthocyanin and skin tannin concentration increased as ripening progressed, while seed tannin declined. In the corresponding wines, monomeric anthocyanin and wine tannin concentration increased with harvest date, consistent with an enhanced extraction of skin-derived phenolics. In wines, there was an observed increase in yeast-derived metabolites, including volatile esters, dimethyl sulfide, glycerol and mannoproteins with harvest date. Wine volatiles which were significantly influenced by harvest date were isobutyl methoxypyrazine, C(6) alcohols and hexyl acetate, all of which decreased as ripening progressed. The implications of harvest date for wine composition is discussed in terms of both grape composition and yeast metabolism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Phenotypic variations of cartilage hair hypoplasia: granulomatous skin inflammation and severe T cell immunodeficiency as initial clinical presentation in otherwise well child with short stature.

PubMed

McCann, Liza J; McPartland, Jo; Barge, Dawn; Strain, Lisa; Bourn, David; Calonje, Eduardo; Verbov, Julian; Riordan, Andrew; Kokai, George; Bacon, Chris M; Wright, Michael; Abinun, Mario

2014-01-01

We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation. Whilst search for HLA matched unrelated donor for haematopoietic stem cell transplantation (HSCT) was underway, she developed rapidly progressive EBV-related lymphoproliferative disorder requiring laparotomy and small bowel resection, and was treated with anti-B cell monoclonal antibody and eventually curative allogeneic HSCT. Screening for RMRP gene mutations should be part of immunological evaluation of patients with 'severe and/or combined' T cell immunodeficiency of unknown origin, especially when associated with short stature and regardless of presence or absence of radiological skeletal features.

Electrochemical monitoring of native catalase activity in skin using skin covered oxygen electrode.

PubMed

Nocchi, Sarah; Björklund, Sebastian; Svensson, Birgitta; Engblom, Johan; Ruzgas, Tautgirdas

2017-07-15

A skin covered oxygen electrode, SCOE, was constructed with the aim to study the enzyme catalase, which is part of the biological antioxidative system present in skin. The electrode was exposed to different concentrations of H 2 O 2 and the amperometric current response was recorded. The observed current is due to H 2 O 2 penetration through the outermost skin barrier (referred to as the stratum corneum, SC) and subsequent catalytic generation of O 2 by catalase present in the underlying viable epidermis and dermis. By tape-stripping the outermost skin layers we demonstrate that SC is a considerable diffusion barrier for H 2 O 2 penetration. Our experiments also indicate that skin contains a substantial amount of catalase, which is sufficient to detoxify H 2 O 2 that reaches the viable epidermis after exposure of skin to high concentrations of peroxide (0.5-1mM H 2 O 2 ). Further, we demonstrate that the catalase activity is reduced at acidic pH, as compared with the activity at pH 7.4. Finally, experiments with often used penetration enhancer thymol shows that this compound interferes with the catalase reaction. Health aspect of this is briefly discussed. Summarizing, the results of this work show that the SCOE can be utilized to study a broad spectrum of issues involving the function of skin catalase in particular, and the native biological antioxidative system in skin in general. Copyright © 2017 Elsevier B.V. All rights reserved.

Skin aging: molecular pathology, dermal remodelling and the imaging revolution.

PubMed

Newton, V L; Mcconnell, J C; Hibbert, S A; Graham, H K; Watson, R E

2015-12-01

Skin is a multifunctional organ but, alongside every other organ system, is subject to both intrinsic (chronological) and extrinsic (environmental) aging, resulting in a loss of functional capacity. Cutaneous aging manifests as an observable change in the external appearance of the skin, the major accelerator of the aging process being our interactions with our environment, such as chronic exposure to solar irradiation (UV, IR or visible wavelengths of light). The aim of this contribution, therefore, was to provide a review of the pathological mechanisms which may play roles in the development of extrinsic, mainly photo-, aging and to review how these molecular changes impact on the structure of the organ as a whole, resulting in loss of function. Finally, we will describe the advances which are occurring in imaging techniques which may allow further characterisation of aged skin.

Chronic inflammation is etiology of extrinsic aging.

PubMed

Thornfeldt, Carl R

2008-03-01

Skin care regimens using active ingredients that are recommended by physicians who treat mucocutaneous conditions including aging should become more focused on reversing and preventing chronic inflammation. This adjustment of therapeutic and preventive strategies is necessary because chronic inflammation appears strongly linked to many preventable and treatable skin diseases and conditions such as visible skin aging. Mucocutaneous inflammation as the final common pathway of many systemic and mucocutaneous diseases including extrinsic aging has been established at the molecular and cellular levels. The corollary to this strategy includes inhibition of primary activators of mucocutaneous inflammation such as stratum corneum permeability barrier disruption, blocking any pro-inflammatory environmental insult such as ultraviolet radiation, and quenching tissue responses to these insults. This review will present the scientific rationale substantiating the conclusion that chronic inflammation is the common denominator in many mucocutaneous pathophysiologic processes including extrinsic skin aging.

Final Progress Report for Ionospheric Dusty Plasma In the Laboratory [Smokey Plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, Scott

2010-07-31

“Ionospheric Dusty Plasma in the Laboratory” is a research project with the purpose of finding and reproducing the characteristics of plasma in the polar mesosphere that is unusually cold (down to 140 K) and contains nanometer-sized dust particles. This final progress report summarizes results from four years of effort that include a final year with a no-cost extension.

Obsessive-compulsive skin disorders: a novel classification based on degree of insight.

PubMed

Zhu, Tian Hao; Nakamura, Mio; Farahnik, Benjamin; Abrouk, Michael; Reichenberg, Jason; Bhutani, Tina; Koo, John

2017-06-01

Individuals with obsessive-compulsive features frequently visit dermatologists for complaints of the skin, hair or nails, and often progress towards a chronic relapsing course due to the challenge associated with accurate diagnosis and management of their psychiatric symptoms. The current DSM-5 formally recognizes body dysmorphic disorder, trichotillomania, neurotic excoriation and body focused repetitive behavior disorder as psychodermatological disorders belonging to the category of Obsessive-Compulsive and Related Disorders. However there is evidence that other relevant skin diseases such as delusions of parasitosis, dermatitis artefacta, contamination dermatitis, AIDS phobia, trichotemnomania and even lichen simplex chronicus possess prominent obsessive-compulsive characteristics that do not necessarily fit the full diagnostic criteria of the DSM-5. Therefore, to increase dermatologists' awareness of this unique group of skin disorders with OCD features, we propose a novel classification system called Obsessive-Compulsive Insight Continuum. Under this new classification system, obsessive-compulsive skin manifestations are categorized along a continuum based on degree of insight, from minimal insight with delusional obsessions to good insight with minimal obsessions. Understanding the level of insight is thus an important first step for clinicians who routinely interact with these patients.

Gerodermia osteodysplastica and wrinkly skin syndrome: are they the same?

PubMed

Al-Gazali, L I; Sztriha, L; Skaff, F; Haas, D

2001-07-01

Gerodermia osteodysplastica (GO) is a connective tissue disorder characterized by premature aging, wrinkled, and lax skin with reduced elasticity which is more marked on the dorsum of the hands and feet associated with hyperextensible joints and osteoporosis. The wrinkly skin syndrome (WSS) is characterized by wrinkled skin over the dorsum of the hands, feet, and abdomen; hyperextensible joints, particularly of the hands; intrauterine growth retardation; postnatal failure to thrive; and mental and developmental delay. We report on five children from two consanguineous Arab families with features overlapping both GO and WSS. All five children had similar dysmorphic facial features consisting of broad and prominent forehead, hypotelorism with epicanthal folds, prominent bulbous nose, flat malar region, and large protruding ears. All had wrinkling of the skin more marked on the dorsum of the hands, feet, and abdomen; hyperextensibility of the joints, particularly of the hands; and aged appearance. Intrauterine growth retardation, subsequent failure to thrive, developmental delay, and variable degree of osteoporosis was also present in all of them. The older three children developed progressive prognathism. We suggest that GO and WSS could represent variable manifestation of the same disorder. Copyright 2001 Wiley-Liss, Inc.

Texture-based characterization of subskin features by specified laser speckle effects at λ = 650 nm region for more accurate parametric 'skin age' modelling.

PubMed

Orun, A B; Seker, H; Uslan, V; Goodyer, E; Smith, G

2017-06-01

The textural structure of 'skin age'-related subskin components enables us to identify and analyse their unique characteristics, thus making substantial progress towards establishing an accurate skin age model. This is achieved by a two-stage process. First by the application of textural analysis using laser speckle imaging, which is sensitive to textural effects within the λ = 650 nm spectral band region. In the second stage, a Bayesian inference method is used to select attributes from which a predictive model is built. This technique enables us to contrast different skin age models, such as the laser speckle effect against the more widely used normal light (LED) imaging method, whereby it is shown that our laser speckle-based technique yields better results. The method introduced here is non-invasive, low cost and capable of operating in real time; having the potential to compete against high-cost instrumentation such as confocal microscopy or similar imaging devices used for skin age identification purposes. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Microvesicating effects of sulfur mustard on an in vitro human skin model.

PubMed

Hayden, Patrick J; Petrali, John P; Stolper, Gina; Hamilton, Tracey A; Jackson, George R; Wertz, Philip W; Ito, Susumu; Smith, William J; Klausner, Mitchell

2009-10-01

Bis-(beta-chloroethyl) sulfide (SM) is a potent skin vesicant previously used for chemical warfare. Progress in determination of the mechanistic basis of SM pathology, and development of prophylactic and/or therapeutic countermeasures to SM exposure has been hampered by lack of physiologically relevant models of human skin. The current work evaluated a newly developed tissue engineered full-thickness human skin model in a completely in vitro approach to investigation of SM-induced dermal pathology. The model was first characterized with regard to overall morphology, lipid composition, basement membrane (BM) composition and ultrastructural features that are important targets of SM pathologic activity. Well-developed BM ultrastructural features were observed at the dermal-epidermal junction (DEJ), thus demonstrating successful resolution of a primary deficiency of models previously evaluated for SM studies. Studies were then conducted to evaluate histopathological effects of SM on the model. Good replication of in vivo effects was observed, including apoptosis of basal keratinocytes (KC) and microblister formation at the DEJ. Tissue engineered skin models with well-developed basement membrane structures thus appear to be useful tools for in vitro mechanistic studies of SM vesicant activity and development of preventive/therapeutic approaches for SM pathology.

Investigation on large-area fabrication of vivid shark skin with superior surface functions

NASA Astrophysics Data System (ADS)

Chen, Huawei; Zhang, Xin; Ma, Lingxi; Che, Da; Zhang, Deyuan; Sudarshan, T. S.

2014-10-01

Shark skin has attracted worldwide attention because of its superior drag reduction, antifouling performance induced from its unique surface morphology. Although the vivid shark skin has been fabricated by a bio-replicated micro-imprinting approach in previous studies and superior drag reduction effect has been validated in water tunnel, continuous large-area fabrication is still an obstacle to wide apply. In this paper, one novel bio-replication coating technology is proposed for large-area transfer of shark skin based on rapid UV curable paint. Apart from design of coating system, bio-replication accuracy of surface morphology was validated about 97% by comparison between shark skin template and coating surface morphology. Finally, the drag reduction and anti-fouling function of coating surface were tested in water tunnel and open algae pond respectively. Drag reduction rate of coating surface was validated about 12% higher and anti-fouling was proved to about hundred times ameliorate, all of which are more excellent than simple 2D riblet surface.

The touch dome defines an epidermal niche specialized for mechanosensory signaling

PubMed Central

Doucet, Yanne S.; Woo, Seung-Hyun; Ruiz, Marlon E.; Owens, David M.

2013-01-01

Summary In mammalian skin, Merkel cells are mechanoreceptor cells that are required for the perception of gentle touch. Recent evidence indicates that mature Merkel cells descend from the proliferative layer of skin epidermis; however, the stem cell niche for Merkel cell homeostasis has not been reported. Here, we provide the first genetic evidence for maintenance of mature Merkel cells during homeostasis by Krt17+ stem cells located in epidermal touch domes of hairy skin and in the tips of the rete ridges of glabrous skin. Lineage tracing analysis indicated that the entire pool of mature Merkel cells is turned over every 7–8 weeks in adult epidermis and that Krt17+ stem cells also maintain squamous differentiation in the touch dome and in glabrous skin. Finally, selective genetic ablation of Krt17+ touch dome keratinocytes indicates that these cells, and not mature Merkel cells, are primarily responsible for maintaining innervation of the Merkel cell-neurite complex. PMID:23727240

Genetic polymorphisms and skin aging: the identification of population genotypic groups holds potential for personalized treatments.

PubMed

Naval, Jordi; Alonso, Vicente; Herranz, Miquel Angel

2014-01-01

Skin changes are among the most visible signs of aging. Skin properties such as hydration, elasticity, and antioxidant capacity play a key role in the skin aging process. Skin aging is a complex process influenced by heritable and environmental factors. Recent studies on twins have revealed that up to 60% of the skin aging variation between individuals can be attributed to genetic factors, while the remaining 40% is due to non-genetic factors. Recent advances in genomics and bioinformatics approaches have led to the association of certain single nucleotide polymorphisms (SNPs) to skin properties. Our aim was to classify individuals based on an ensemble of multiple polymorphisms associated with certain properties of the skin for providing personalized skin care and anti-aging therapies. We identified the key proteins and SNPs associated with certain properties of the skin that contribute to skin aging. We selected a set of 13 SNPs in gene coding for these proteins which are potentially associated with skin aging. Finally, we classified a sample of 120 female volunteers into ten clusters exhibiting different skin properties according to their genotypic signature. This is the first study that describes the actual frequency of genetic polymorphisms and their distribution in clusters involved in skin aging in a Caucasian population. Individuals can be divided into genetic clusters defined by genotypic variables. These genotypic variables are linked with polymorphisms in one or more genes associated with certain properties of the skin that contribute to a person's perceived age. Therefore, by using this classification, it is possible to characterize human skin care and anti-aging needs on the basis of an individual's genetic signature, thus opening the door to personalized treatments addressed at specific populations. This is part of an ongoing effort towards personalized anti-aging therapies combining genetic signatures with environmental and life style evaluations.

Genetic polymorphisms and skin aging: the identification of population genotypic groups holds potential for personalized treatments

PubMed Central

Naval, Jordi; Alonso, Vicente; Herranz, Miquel Angel

2014-01-01

Introduction Skin changes are among the most visible signs of aging. Skin properties such as hydration, elasticity, and antioxidant capacity play a key role in the skin aging process. Skin aging is a complex process influenced by heritable and environmental factors. Recent studies on twins have revealed that up to 60% of the skin aging variation between individuals can be attributed to genetic factors, while the remaining 40% is due to non-genetic factors. Recent advances in genomics and bioinformatics approaches have led to the association of certain single nucleotide polymorphisms (SNPs) to skin properties. Our aim was to classify individuals based on an ensemble of multiple polymorphisms associated with certain properties of the skin for providing personalized skin care and anti-aging therapies. Methods and results We identified the key proteins and SNPs associated with certain properties of the skin that contribute to skin aging. We selected a set of 13 SNPs in gene coding for these proteins which are potentially associated with skin aging. Finally, we classified a sample of 120 female volunteers into ten clusters exhibiting different skin properties according to their genotypic signature. Conclusion This is the first study that describes the actual frequency of genetic polymorphisms and their distribution in clusters involved in skin aging in a Caucasian population. Individuals can be divided into genetic clusters defined by genotypic variables. These genotypic variables are linked with polymorphisms in one or more genes associated with certain properties of the skin that contribute to a person’s perceived age. Therefore, by using this classification, it is possible to characterize human skin care and anti-aging needs on the basis of an individual’s genetic signature, thus opening the door to personalized treatments addressed at specific populations. This is part of an ongoing effort towards personalized anti-aging therapies combining genetic signatures with environmental and life style evaluations. PMID:25061327

Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

PubMed Central

Huang, Yuanshen; Wang, Yang; Yu, Jie; Gao, Min; Levings, Megan; Wei, Shencai; Zhang, Shengquan; Xu, Aie; Su, Mingwan; Dutz, Jan; Zhang, Xuejun; Zhou, Youwen

2012-01-01

Background Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients. Methods and Materials Paired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy. Results Compared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients. Conclusions and Clinical Implications As the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting the entire skin surface may improve treatment outcomes. Finally, this study revealed novel mediators that may facilitate future development of vitiligo therapies. PMID:23251420

CCD-Based Skinning Injury Recognition on Potato Tubers (Solanum tuberosum L.): A Comparison between Visible and Biospeckle Imaging

PubMed Central

Gao, Yingwang; Geng, Jinfeng; Rao, Xiuqin; Ying, Yibin

2016-01-01

Skinning injury on potato tubers is a kind of superficial wound that is generally inflicted by mechanical forces during harvest and postharvest handling operations. Though skinning injury is pervasive and obstructive, its detection is very limited. This study attempted to identify injured skin using two CCD (Charge Coupled Device) sensor-based machine vision technologies, i.e., visible imaging and biospeckle imaging. The identification of skinning injury was realized via exploiting features extracted from varied ROIs (Region of Interests). The features extracted from visible images were pixel-wise color and texture features, while region-wise BA (Biospeckle Activity) was calculated from biospeckle imaging. In addition, the calculation of BA using varied numbers of speckle patterns were compared. Finally, extracted features were implemented into classifiers of LS-SVM (Least Square Support Vector Machine) and BLR (Binary Logistic Regression), respectively. Results showed that color features performed better than texture features in classifying sound skin and injured skin, especially for injured skin stored no less than 1 day, with the average classification accuracy of 90%. Image capturing and processing efficiency can be speeded up in biospeckle imaging, with captured 512 frames reduced to 125 frames. Classification results obtained based on the feature of BA were acceptable for early skinning injury stored within 1 day, with the accuracy of 88.10%. It is concluded that skinning injury can be recognized by visible and biospeckle imaging during different stages. Visible imaging has the aptitude in recognizing stale skinning injury, while fresh injury can be discriminated by biospeckle imaging. PMID:27763555

CCD-Based Skinning Injury Recognition on Potato Tubers (Solanum tuberosum L.): A Comparison between Visible and Biospeckle Imaging.

PubMed

Gao, Yingwang; Geng, Jinfeng; Rao, Xiuqin; Ying, Yibin

2016-10-18

Skinning injury on potato tubers is a kind of superficial wound that is generally inflicted by mechanical forces during harvest and postharvest handling operations. Though skinning injury is pervasive and obstructive, its detection is very limited. This study attempted to identify injured skin using two CCD (Charge Coupled Device) sensor-based machine vision technologies, i.e., visible imaging and biospeckle imaging. The identification of skinning injury was realized via exploiting features extracted from varied ROIs (Region of Interests). The features extracted from visible images were pixel-wise color and texture features, while region-wise BA (Biospeckle Activity) was calculated from biospeckle imaging. In addition, the calculation of BA using varied numbers of speckle patterns were compared. Finally, extracted features were implemented into classifiers of LS-SVM (Least Square Support Vector Machine) and BLR (Binary Logistic Regression), respectively. Results showed that color features performed better than texture features in classifying sound skin and injured skin, especially for injured skin stored no less than 1 day, with the average classification accuracy of 90%. Image capturing and processing efficiency can be speeded up in biospeckle imaging, with captured 512 frames reduced to 125 frames. Classification results obtained based on the feature of BA were acceptable for early skinning injury stored within 1 day, with the accuracy of 88.10%. It is concluded that skinning injury can be recognized by visible and biospeckle imaging during different stages. Visible imaging has the aptitude in recognizing stale skinning injury, while fresh injury can be discriminated by biospeckle imaging.

Evaluation of Antimicrobial and Healing Activities of Frog Skin on Guinea Pigs Wounds

PubMed Central

Rezazade Bazaz, Mahere; Mashreghi, Mohammad; Mahdavi Shahri, Nasser; Mashreghi, Mansour; Asoodeh, Ahmad; Behnam Rassouli, Morteza

2015-01-01

Background: Frog skin secretions have potentials against a wide spectrum of bacteria. Also, frog skin compositions have healing properties. Objectives: The aim of this study was to investigate the antibacterial potentials along with healing properties of frog skin Rana ridibunda, a species which thoroughly lives in Iran marshes, as a biological dressing on wounds. Materials and Methods: In this study, excisional wounds, dressed with frog skin, were compared between experimental and control groups of guinea pigs. In the experimental groups, wounds were dressed with the dermal (FS) and epidermal (RFS) sides of fresh frog R. ridibunda skin, while only usual cotton gauze covered the wounds of the control group. Furthermore, microbial samples were taken on different days (0, 3, 5, and 7 days post injury) to count the number of the colony-forming units. Additionally, the microbial penetration test was performed on frog skin and then the progression of wound closure was evaluated. Results: In the microbial studies, the bacterial load considerably declined in the wounds treated with FS and RFS compared with the control wounds. On day 7 post injury, the numbers of the colony-forming units for the FS, RFS, and control groups were 6.75, 105, and 375, respectively. In the penetration test, fresh frog skin showed to be a bacterial resistant dressing. The results revealed that the rate of wound closure in the experimental groups significantly was accelerated in comparison with that in the control group. Conclusions: Our results demonstrated the antimicrobial properties of frog skin as a wound dressing, which has antimicrobial effects per se. This biological dressing shows promise as an effective biological wound dressing insofar as not only is it capable of resisting microbes and accelerating wound healing but also it is cost-effective and easy to use. PMID:26468364

Physicians involved in the care of patients with high risk of skin cancer should be trained regarding sun protection measures: evidence from a cross sectional study.

PubMed

Thomas, M; Rioual, E; Adamski, H; Roguedas, A-M; Misery, L; Michel, M; Chastel, F; Schmutz, J-L; Aubin, F; Marguery, M-C; Meyer, N

2011-01-01

Knowledge, regarding sun protection, is essential to change behaviour and to reduce sun exposure of patients at risk for skin cancer. Patient education regarding appropriate or sun protection measures, is a priority to reduce skin cancer incidence. The aim of this study was to evaluate the knowledge about sun protection and the recommendations given in a population of non-dermatologists physicians involved in the care of patients at high risk of skin cancer. This study is a cross-sectional study. Physicians were e-mailed an anonymous questionnaire evaluating the knowledge about risk factors for skin cancer, sun protection and about the role of the physician in providing sun protection recommendations. Of the responders, 71.4% considered that the risk of skin cancer of their patients was increased when compared with the general population. All the responders knew that UV-radiations can contribute to induce skin cancers and 71.4% of them declared having adequate knowledge about sun protection measures. A proportion of 64.2% of them declared that they were able to give sun protection advices: using sunscreens (97.8%), wearing covering clothes (95.5%), performing regular medical skin examination (91.1%), to avoid direct sunlight exposure (77.8%), avoiding outdoor activities in the hottest midday hours (73.3%) and practising progressive exposure (44.4%). Non-dermatologist physicians reported a correct knowledge of UV-induced skin cancer risk factors. The majority of responders displayed adequate knowledge of sun protection measures and declared providing patients with sun protection recommendation on a regular basis. Several errors persisted. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

β-adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and non-burned skin under neutral and hot environments in children

PubMed Central

Rivas, Eric; McEntire, Serina J.; Herndon, David N.; Mlcak, Ronald P.; Suman, Oscar E.

2017-01-01

Objective Tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. Methods In a randomized double-blind study, a placebo was given to 8 burned children while propranolol was given to 13 burned children with similar characteristics (mean ± SD: 11.9±3y, 147±20cm, 45±23kg, 56±12% TBSA). Non-burned children (n=13, 11.4±3y, 152±15cm, 52±13kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and non-burned control skin under the two environmental conditions (23°C and 34°C) via laser-Doppler flowmetry. Results Resting SkBF was greater in burned and unburned skin compared to the non-burned control (main effect: skin, P<0.0001; 57±32 burned; 38±36 unburned vs 9±8 control %SkBFmax). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and non-burned control skin (EC50, P>0.05) under either condition. Conclusion Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children. PMID:28071840

Assessment of tissue fibrosis in skin biopsies from patients with systemic sclerosis employing confocal laser scanning microscopy: an objective outcome measure for clinical trials?

PubMed Central

Busquets, Joanna; Del Galdo, Francesco; Kissin, Eugene Y.

2010-01-01

Objectives. To obtain an objective, unbiased assessment of skin fibrosis in patients with SSc for use in clinical trials of SSc disease-modifying therapeutics. Methods. Skin biopsies from the dorsal forearm of six patients with diffuse SSc and six healthy controls, and skin biopsies from the forearm of one patient with diffuse SSc before and following 1 year treatment with mycophenolate mofetil were analysed by confocal laser scanning microscopy (CLSM) with specific antibodies against collagen types I and III or fibronectin. The integrated density of fluorescence (IDF) was calculated employing National Institutes of Health-ImageJ software in at least four different fields per biopsy spanning the full dermal thickness. Results. The intensities of collagen types I and III and fibronectin IDF were 174, 147 and 139% higher in SSc skin than in normal skin, respectively. All differences were statistically significant. The sum of the IDF values obtained for the three proteins yielded a comprehensive fibrosis score. The average fibrosis score for the six SSc samples was 28.3 × 106 compared with 18.6 × 106 for the six normal skin samples (P < 0.0001). Comparison of skin biopsies obtained from the same SSc patient before treatment and after 12 months of treatment with mycophenolate mofetil showed a reduction of 39% in total fibrosis score after treatment. Conclusions. CLSM followed by quantitative image analysis provides an objective and unbiased assessment of skin fibrosis in SSc and could be a useful end-point for clinical trials with disease-modifying agents to monitor the response or progression of the disease. PMID:20202926

Bacterial recolonization of the skin and wound contamination during cardiac surgery: a randomized controlled trial of the use of plastic adhesive drape compared with bare skin.

PubMed

Falk-Brynhildsen, K; Söderquist, B; Friberg, O; Nilsson, U G

2013-06-01

Sternal wound infection after cardiac surgery is a serious complication. Various perioperative strategies, including plastic adhesive drapes, are used to reduce bacterial contamination of surgical wounds. To compare plastic adhesive drape to bare skin regarding bacterial growth in wound and time to recolonization of the adjacent skin intraoperatively, in cardiac surgery patients. This single-blinded randomized controlled trial (May 2010 to May 2011) included 140 patients scheduled for cardiac surgery via median sternotomy. The patients were randomly allocated to the adhesive drape (chest covered with plastic adhesive drape) or bare skin group. Bacterial samples were taken preoperatively and intraoperatively every hour during surgery until skin closure. Disinfection with 0.5% chlorhexidine solution in 70% alcohol decreased coagulase-negative staphylococci (CoNS), while the proportion colonized with Propionibacterium acnes was not significantly reduced and was still present in more than 50% of skin samples. P. acnes was significantly more common in men than in women. Progressive bacterial recolonization of the skin occurred within 2-3 h. At 120 min there were significantly more positive cultures in the adhesive drape group versus bare skin group for P. acnes (63% vs 44%; P = 0.034) and for CoNS (45% vs 24%; P = 0.013). The only statistically significant difference in bacterial growth in the surgical wound was higher proportion of CoNS at the end of surgery in the adhesive drape group (14.7% vs 4.4%; P = 0.044). Plastic adhesive drape does not reduce bacterial recolonization. P. acnes colonized men more frequently, and was not decreased by disinfection with chlorhexidine solution in alcohol. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

β-Adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and nonburned skin under neutral and hot environments in children.

PubMed

Rivas, Eric; McEntire, Serina J; Herndon, David N; Mlcak, Ronald P; Suman, Oscar E

2017-05-01

We tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. In a randomized double-blind study, a placebo was given to eight burned children, while propranolol was given to 13 burned children with similar characteristics (mean±SD: 11.9±3 years, 147±20 cm, 45±23 kg, 56±12% Total body surface area burned). Nonburned children (n=13, 11.4±3 years, 152±15 cm, 52±13 kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and nonburned control skin under the two environmental conditions (23 and 34°C) via laser Doppler flowmetry. Resting SkBF was greater in burned and unburned skin compared to the nonburned control (main effect: skin, P<.0001; 57±32 burned; 38±36 unburned vs 9±8 control %SkBF max ). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose-response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and nonburned control skin (EC 50 , P>.05) under either condition. Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children. © 2017 John Wiley & Sons Ltd.

Novel Fish Oil-based Bigel System for Controlled Drug Delivery and its Influence on Immunomodulatory Activity of Imiquimod Against Skin Cancer.

PubMed

Rehman, Khurram; Zulfakar, Mohd Hanif

2017-01-01

To characterize bigel system as a topical drug delivery vehicle and to establish the immunomodulatory role of imiquimod-fish oil combination against skin cancer and inflammation resulting from chemical carcinogenesis. Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model. Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer. Imiquimod administration through a bigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.

From morphology to clinical pathophysiology: multiphoton fluorescence lifetime imaging at patients' bedside

NASA Astrophysics Data System (ADS)

Mess, Christian; Zens, Katharina; Gorzelanny, Christian; Metze, Dieter; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.; Huck, Volker

2017-02-01

Application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of skin diseases. By means of multiphoton excitation, endogenous biomolecules like NADH, collagen or elastin show autofluorescence or second harmonic generation. Thus, these molecules provide information about the subcellular morphology, epidermal architecture and physiological condition of the skin. To gain a deeper understanding of the linkage between cellular structure and physiological processes, non-invasive multiphotonbased intravital tomography (MPT) and fluorescence lifetime imaging (FLIM) were combined within the scopes of inflammatory skin, chronic wounds and drug delivery in clinical application. The optical biopsies generated via MPT were morphologically analyzed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Independent morphometric algorithms reliably showed a perinuclear accumulation in lesional skin in contrast to an even distribution in healthy skin. Confirmatively, MPT-FLIM showed an obvious metabolic shift in lesions. Moreover, detection of the onset and progression of inflammatory processes could be achieved. The feasibility of primary in vivo tracking of applied therapeutic agents further broadened our scope: We examined the permeation and subsequent distribution of agents directly visualized in patientś skin in short-term repetitive measurements. Furthermore, we performed MPT-FLIM follow-up investigations in the long-term course of therapy. Therefore, clinical MPT-FLIM application offers new insights into the pathophysiology and the individual therapeutic course of skin diseases, facilitating a better understanding of the processes of inflammation and wound healing.

Heat Shock Protein-70 Expression in Vitiligo and its Relation to the Disease Activity.

PubMed

Doss, Reham William; El-Rifaie, Abdel-Aziz A; Abdel-Wahab, Amr M; Gohary, Yasser M; Rashed, Laila A

2016-01-01

Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis. The aim of this study was to map the level of HSP-70 in vitiligo lesions to declare its role in the pathogenesis and activity of vitiligo. The study included thirty patients with vitiligo and 30 age- and sex-matched healthy controls. Vitiligo patients were divided as regards to the disease activity into highly active, moderately active, and inactive vitiligo groups. Skin biopsies were taken from the lesional and nonlesional skin of patients and from the normal skin of the controls. HSP-70 messenger RNA (mRNA) expression was estimated using quantitative real-time polymerase chain reaction. Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease. HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease.

7 CFR 989.5 - Raisins.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN... artificial dehydration, either prior to or after such grapes have been removed from the vines. Removal of a significant part of the natural moisture means removal which has progressed to the point where the grape skin...

Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review.

PubMed

Barbero, Ana M; Frasch, H Frederick

2009-02-01

Both human and animal skin in vitro models are used to predict percutaneous penetration in humans. The objective of this review is a quantitative comparison of permeability and lag time measurements between human and animal skin, including an evaluation of the intra and inter species variability. We limit our focus to domestic pig and rodent guinea pig skin as surrogates for human skin, and consider only studies in which both animal and human penetration of a given chemical were measured jointly in the same lab. When the in vitro permeability of pig and human skin were compared, the Pearson product moment correlation coefficient (r) was 0.88 (P<0.0001), with an intra species average coefficient of variation of skin permeability of 21% for pig and 35% for human, and an inter species average coefficient of variation of 37% for the set of studied compounds (n=41). The lag times of pig skin and human skin did not correlate (r=0.35, P=0.26). When the in vitro permeability of guinea pig and human skin were compared, r=0.96 (P<0.0001), with an average intra species coefficient of variation of 19% for guinea pig and 24% for human, and an inter species coefficient of variation of permeability of 41% for the set of studied compounds (n=15). Lag times of guinea pig and human skin correlated (r=0.90, P<0.0001, n=12). When permeability data was not reported a factor of difference (FOD) of animal to human skin was calculated for pig skin (n=50) and guinea pig skin (n=25). For pig skin, 80% of measurements fell within the range 0.3

The progression in the mouse skin carcinogenesis model correlates with ERK1/2 signaling.

PubMed Central

Katsanakis, Kostas D.; Gorgoulis, Vassilis; Papavassiliou, Athanasios G.; Zoumpourlis, Vassilis K.

2002-01-01

BACKGROUND: The ras family of proto-oncogenes encodes for small GTPases that play critical roles in cell-cycle progression and cellular transformation. ERK1/2 MAP kinases are major ras effectors. Tumors in chemically treated mouse skin contain mutations in the Ha-ras proto- oncogene. Amplification and mutation of Ha-ras has been shown to correlate with malignant progression of these tumors. Cell lines isolated from mouse skin tumors represent the stages of tumor development, such as the PDV:PDVC57 cell line pair and B9 squamous carcinoma and A5 spindle cells. PDVC57 cells were selected from PDV cells, which were transformed with dimethyl-benzanthracene (DMBA) in vitro and then transplanted in adult syngeneic mice. The PDV:PDVC57 pair contains ratio of normal:mutant Ha-ras 2:1 and 1:2, respectively. This genetic alteration correlates with more advanced tumorigenic characteristics of PDVC57 compared to PDV. The squamous carcinoma B9 cell clone was isolated from the same primary tumor as A5 spindle cell line. The mutant Ha-ras allele, also present in B9, is amplified and overexpressed in A5 cells. Therefore these cell line pairs represent an in vivo model for studies of Ha-ras and ERK1/2 signaling in mouse tumorigenesis. MATERIALS AND METHODS: The ERK1/2 status in the above mouse cell lines was examined by using various molecular techniques. For the study of the tumorigenic properties and the role of the ras/MEK/ERK1/2 pathway in the cell lines mentioned, phenotypic characteristics, colony formation assay, anchorage-independent growth, and gelatin zymography were assessed, after or without treatment with the MEK inhibitor, PD98059. RESULTS: ERK1/2 phosphorylation was found to be increased in PDVC57 when compared to PDV. This also applies to A5 spindle carcinoma cells when compared to squamous carcinoma and papilloma cells. The above finding was reproduced when transfecting human activated Ha-ras allele into PDV, thus demonstrating that Ha-ras enhances ERK1/2 signaling. To further test whether ERK1/2 activation was required for growth we used the MEK-1 inhibitor, PD98059. The latter inhibited cell proliferation and anchorage-independent growth of squamous and spindle cells. In addition, PD98059 treatment partially reverted the spindle morphology of A5 cells. CONCLUSIONS: These data suggest, for the first time, that oncogenicity and the degree of progression in the mouse skin carcinogenesis model correlates with ERK1/2 signaling. PMID:12477973

[Study of skin retraction applied to the treatment of skin tumors. Mapping of the human body].

PubMed

Dumas, P; Benatar, M; Cardot-Leccia, N; Lebreton, E; Chignon-Sicard, B

2012-04-01

Skin, the main organ of the human body, is equipped with own biomechanical characteristics, highly variable depending on intra-individual factors (location, weight status, dermatological diseases…) and interindividual (age, sex…). Despite some recent cutometric studies, our review of the literature shows that there is no currently reliable analytical model representing the biomechanical behavior of the skin. Yet, this is a central issue in dermatology surgery, especially in the treatment of skin tumors, for the proper observance of surgical margins. We studied prospectively on 75 resection specimens (about 71 patient(s)), for the treatment of skin lesions tumor suspicious or known malignant or benign. Room dimensions were measured before and 5 minutes after excision, leading us to calculate a ratio of retraction of the skin surface. This retraction was correlated with age, gender, tumor type, and anatomic location of the site of excision. The power of retraction of the skin varies significantly by region of the body. It is maximum in the upper limb (hand excluded) and in the cervical region. At the cephalic region, skin of the ear and periorbital skin have capacities of important early retraction. Unlike the lower limb (foot excluded), the back skin of the nose and face appear to be a minimum of shrinkage. Age also seems to change on that capacity shrinkage, sex would have no influence. Our study confirms the variations in the ability of skin retraction based on a number of factors. In dermato-oncology, that power retraction could cause significant differences between clinical surgical margins and final pathologist margins. We believe it must be taken into account by the couple surgeon-pathologist, especially in the context of invasive and/or recurrent tumors. Copyright © 2012. Published by Elsevier SAS.

Resurfacing the Penis of Complex Hypospadias Repair ("Hypospadias Cripples").

PubMed

Fam, Mina M; Hanna, Moneer K

2017-03-01

After the creation of a neourethra in a "hypospadias cripple," resurfacing the penis with healthy skin is a significant challenge because local tissue is often scarred and unusable. We reviewed our experience with various strategies to resurface the penis of hypospadias cripples. We retrospectively reviewed the records of 215 patients referred after multiple unsuccessful hypospadias repairs from 1981 to 2014. In 130 of 215 patients we performed resurfacing using local penile flaps using various techniques, including Byars flaps, Z-plasty or double Z-plasty, or a dorsal relaxing incision. Of the 215 patients 85 did not have adequate healthy local penile skin to resurface the penis after urethroplasty. Scrotal skin was used to resurface the penis in 54 patients, 6 underwent tissue expansion of the dorsal penile skin during a 12 to 16-week period prior to penile resurfacing, 23 underwent full-thickness skin grafting and another 4 received a split-thickness skin graft. Of the 56 patients who underwent fasciomyocutaneous rotational flaps, tissue expansion or a combination of both approaches 54 (96.4%) finally had a successful outcome. All 6 patients who underwent tissue expansion had a successful outcome without complications and were reported on previously. All 23 full-thickness skin grafts took with excellent results. All 4 patients who underwent fenestrated split-thickness skin grafting had 100% graft take but secondary contraction and ulceration were associated with sexual activity. In our experience scrotal skin flaps, tissue expansion of the dorsal penile skin and full-thickness skin grafts serve as reliable approaches in resurfacing the penis in almost any hypospadias cripple lacking healthy local skin. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Skin Color in the Development of Identity: A Biopsychosocial Model

PubMed Central

Fullilove, Mindy Thompson; Reynolds, Tyrone

1984-01-01

The role of skin color in the development of identity has been studied by a variety of paradigms. This paper applies the biopsychosocial model to this problem, with the hope that systems hierarchies offer a way to understand how many variables have an impact on a single point. This model postulates that complex social interactions are the life setting for the individual whose development also reflects biological endowment, including the contributions of heredity and nurturance. The final personal integration of an adult understanding of skin color requires an active assertion by the individual. This model is explored through the writings of Jessie Fauset, a leading participant in the literary movement known as the Harlem Renaissance. PMID:6748102

Proposal for an in vivo histopathologic scoring system for skin aging by means of confocal microscopy.

PubMed

Longo, Caterina; Casari, Alice; De Pace, Barbara; Simonazzi, Silvia; Mazzaglia, Giovanna; Pellacani, Giovanni

2013-02-01

Many instrumental devices have been testing in analysing and quantifying the skin aging signs. However, histopathology still remains the only methods that allow a microscopic assessment of the skin. However, a skin biopsy is not feasible in aesthetically critical areas such as the face. Recently, confocal microscopy has been discovered as a noninvasive tool with a nearly histologic resolution. Distinct morphologic confocal aspects on facial skin have been described and correlated with the histopathologic counterparts. In our study we aim to develop an easy to use confocal aging score to quantify the skin aging related signs. A sample of facial skin of fifty volunteers has been subjected to confocal imaging. Combining the previously identified confocal features, three different semi-quantitative scores were calculated: - epidermal disarray score (irregular honeycombed pattern + epidermal thickness + furrow pattern); - epidermal hyperplasia score (mottled pigmentation + extent of polycyclic papillary + epidermal thickness; - collagen score (curled fibers, 2 for huddles of collagen, 1 for coarse collagen structures, and 0 for thin reticulated collagen) The epidermal disarray score showed a stable trend up to 65 years and a dramatic increase in the elderly subjects epidermal. Hyperplasia score was characterized by an ascending trend from younger subjects to middle age. The total collagen score showed a progressive trend with age with a different proportion of distinct collagen type. RCM is a powerful, noninvasive technique that could permit to microscopically quantify the aging signs and to test cosmetic efficacy. © 2012 John Wiley & Sons A/S.

[Changes in the incidence of skin cancer between 1978 and 2002].

PubMed

Aceituno-Madera, P; Buendía-Eisman, A; Arias-Santiago, S; Serrano-Ortega, S

2010-01-01

Ultraviolet radiation is the main risk factor for skin cancer. Changes in lifestyle over recent decades have led to greater exposure to ultraviolet radiation; this phenomenon, coupled with aging of the population, increases the risk of developing skin cancer. Our objective was to analyze the trends in the incidence of skin cancer worldwide, in Europe,and in Spain during the period 1978 to 2002. Both skin cancer incidence and trends were investigated during the period 1978 to 2002 using the publication Cancer Incidence in Five Continents. The incidence of cutaneous melanoma increased progressively throughout the period, with higher rates among women. The highest incidence was found in Australia. In Spain, the standardized rates of melanoma had tripled in both sexes by the end of the study period. The incidence of non melanoma skin cancer (NMSC) increased throughout the study period, with higher rates among men.The highest incidences were found in Australia, Brazil, and among the European inhabitants of Zimbabwe. Within Spain, the standardized rates of NMSC doubled or tripled in both sexes by the end of the study period. The rise in the incidence of skin cancer leads us to conclude that measures of primary prevention are failing or insufficient, or that it is still too soon to evaluate their efficacy. There are certain limitations to this study, such as the fact that it was impossible to analyze the most recent period, from 2003 to 2007, and that cancer registries are not available for all populations.

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

PubMed Central

Fuentes-Duculan, Judilyn; Moussai, Dariush; Gulati, Nicholas; Sullivan-Whalen, Mary; Gilleaudeau, Patricia; Cohen, Jules A.; Krueger, James G.

2011-01-01

Background Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis. Methodology/Principal Findings In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo. Conclusions/Significance These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses. PMID:21541348

Early excision and grafting, an alternative approach to the surgical management of large body surface area levamisole-adulterated cocaine induced skin necrosis.

PubMed

Miner, Jason; Gruber, Paul; Perry, Travis L

2015-05-01

Levamisole-adulterated cocaine as a cause of retiform purpura progressing to full-thickness skin necrosis was first documented in 2003 and currently comprises over 200 reported cases. Whereas, its presentation, pathophysiology, and diagnostic workup have been reasonably well-defined, only one publication has significantly detailed its surgical management. For this reason there exists a relative absence of data in comparison to its reported incidence to suggest a preferred treatment strategy. In the case mentioned, treatment emphasized delayed surgical intervention while awaiting lesion demarcation and the monitoring of autoantibodies. At our institution we offer an alternative approach and present the case of a 34 year old female who presented with 49% TBSA, levamisole-induced skin necrosis managed with early surgical excision and skin grafting. The patient presented three days following cocaine exposure with painful, purpura involving the ears, nose, buttocks, and bilateral lower extremities which quickly progressed to areas of full-thickness necrosis. Lab analysis demonstrated elevated p-ANCA and c-ANCA, as well as leukopenia, decreased C4 complement, and urinalysis positive for levamisole, corroborating the diagnosis. Contrasting the most thoroughly documented case in which the patient underwent first surgical excision on hospital day 36 and underwent 18 total excisions, our patient underwent first excision on hospital day 10 and received only one primary excision prior to definitive autografting. To our knowledge, this is the largest surface area surgically treated that did not result in surgical amputation or autoamputation of limbs or appendages, respectively. We contend that early excision and grafting provides optimal surgical management of this syndrome while avoiding the morbidity seen with delayed intervention. Published by Elsevier Ltd.

Pirfenidone-induced severe phototoxic reaction in a patient with idiopathic lung fibrosis.

PubMed

Papakonstantinou, E; Prasse, A; Schacht, V; Kapp, A; Raap, U

2016-08-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disease with an estimated 5-year survival of approximately 20%. Pirfenidone is a novel orally available antifibrotic agent that reduces disease progression and improves survival of patients with IPF. The most common adverse effects of pirfenidone include gastrointestinal symptoms, hepatic dysfunction or skin photosensitivity and rash. A 64-year-old male patient presented in our clinic with a strong generalized exfoliative erythema and intense itching accompanied by fatigue and mild fever after a mild sun exposure for 5 days during holidays in Turkey. The patient had been diagnosed with IPF 2 months ago and 1 month later he started a therapy with pirfenidone with good tolerability. In this report, we noted a severe phototoxic reaction under treatment with pirfenidone which underlies the potential phototoxic effect of this drug besides the already reported photosensitivity. Routine laboratory tests and a skin biopsy were performed. Laboratory tests indicated increased markers of inflammation. The skin biopsy showed a perivascular lymphocytic inflammatory infiltrate, ballooning of keratinocytes with increased apoptosis. These findings were most consistent with a severe phototoxic reaction to pirfenidone which had been directly discontinued. The patient was started on oral methylprednisolone 100 mg/day which was gradually tapered off along with topical corticosteroids (mometasone furoate 0.1% cream) and oral antihistamines. This treatment led to a slow but complete resolution of the skin lesions within 20 days. To our knowledge, this is the first reported case of a severe phototoxic reaction during treatment with pirfenidone. Our aim by presenting this case is to increase the awareness of clinicians for severe phototoxic effects of oral pirfenidone. © 2016 European Academy of Dermatology and Venereology.

Continuous subcutaneous insulin infusion allows tolerance induction and diabetes treatment in a type 1 diabetic child with insulin allergy.

PubMed

Hasselmann, C; Pecquet, C; Bismuth, E; Raverdy, C; Sola-Gazagnes, A; Lobut, J-B; Carel, J-C; Tubiana-Rufi, N

2013-04-01

Insulin allergy is a rare but serious and challenging condition in patients with type 1 diabetes (T1D). This is a case report of an 8-year-old boy with T1D and an allergy to insulin. Three months after being diagnosed with T1D, the patient developed progressive skin reactions to insulin, characterized by small 1.5-cm pruritic wheals at injection sites that persisted for several days. Seven months after diagnosis, he experienced two episodes of generalized urticaria with systemic symptoms that were seen within a few seconds of insulin injection. Examination revealed lipoatrophy of the thighs. Intradermal skin tests were positive for protamine, glargine and lispro. The patient was started on a continuous subcutaneous insulin infusion (CSII) tolerance induction protocol, consisting of a very low basal rate that was progressively increased, with the first bolus given under medical supervision, and was well tolerated for 4 months. After this period of time, the skin wheals reappeared, localized to the infusion sites, but without urticaria or any other generalized reactions. Intradermal skin tests were repeated and were again positive. Serum insulin-specific IgE measured 30 months after the first allergic reactions were positive. After 3 years, pump therapy is ongoing and blood glucose control has remained relatively good (HbA1c 7.6%). In T1D children with insulin allergy, CSII can successfully be used to both induce insulin tolerance and allow diabetes insulin therapy, although insulin desensitization cannot always be fully achieved. The induction protocol was easily manageable partly due to the "honeymoon" period that the patient was still in, but it should nonetheless be used even when the patient has higher insulin requirements. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Kindler syndrome with severe mucosal involvement in a large Palestinian pedigree.

PubMed

El Hachem, May; Diociaiuti, Andrea; Proto, Vittoria; Fortugno, Paola; Zambruno, Giovanna; Castiglia, Daniele; Naim, Majdy

2015-01-01

Kindler syndrome (KS) is a rare autosomal recessive disease of skin fragility, photosensitivity and progressive poikiloderma. Mucous membranes may also be involved. KS is caused by mutations in the FERMT1 gene encoding kindlin-1. We report the clinical and molecular features of the largest kindred with KS to date, comprising 18 affected family members (age range: 12-63 years) from the Gaza Strip. All the affected family members were clinically examined. In addition a skin biopsy for immunofluorescence testing was obtained from the index case. Molecular analysis of the FERMT1 gene was performed on genomic DNA extracted from peripheral blood of 5 patients. All patients presented skin and eye photosensitivity, cutaneous atrophy, dyschromia and poikiloderma, oral cavity involvement, dysphagia and constipation with anal fissures. In addition, nail dystrophy and digit webbing were observed in most of them. Ocular manifestations detected in all patients comprised ectropion and keratoconjunctivitis, with early development of symblepharon in 17 out of 18 cases and blindness in one. Of note, 17 out of 18 affected family members also suffered from urethral strictures since childhood. Diagnosis was supported by immunofluorescence findings and definitely confirmed by FERMT1 sequencing which identified the homozygous frame-shift mutation c.137_140delTAGT. The high rate of mucosal involvement, its early onset and progressive course are noticeable features of our kindred. Also noteworthy is the lack of muco-cutaneous malignancies, despite the sunny habitat.

Primary cutaneous anaplastic large-cell lymphoma: A case report

PubMed Central

Abed, Kamil; Stopa, Zygmunt; Siewert-Gutowska, Marta

2018-01-01

Abstract Rationale: Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a rare cancer belonging to the group of primary T-cell lymphoproliferative diseases. C-ALCL is characterized by the presence of single or multiple ulcerated lesions on the skin's surface. Patient concerns: This is the case of a 73-year-old man who reported to the Clinic of Cranio-Maxillofacial and Oral Surgery and Implantology, Medical University of Warsaw, owing to a skin tumor in the right parotideomasseteric region, initially diagnosed as discoid lupus erythematosus. During treatment for discoid lupus erythematosus, biopsy was repeated because of significant disease progression and dynamic tumor growth. Histopathological examination revealed the presence of pilomatrix carcinoma (trichilemmal carcinoma). Because of the discrepancy between clinical and histopathological findings, the tumor specimen was submitted to another facility, wherein lymphoma infiltration by anaplastic large cells was found in the dermis and subcutaneous tissue. Diagnosis: C-ALCL. Interventions: The patient was transferred to the Lymphoid Tumours Clinic of the Maria Skłodowska Curie Memorial Cancer Centre and Institute of Oncology in Warsaw, where chemotherapy was initiated. Outcomes: After 4 cycles of chemotherapy, a complete remission of skin lesions was achieved. During the 5-year follow-up, no recurrence occurred. Lessons: C-ALCL is a rare type of cancer. Misdiagnosis can lead to inappropriate therapy and result in disease progression or unnecessary harm to the patient. PMID:29369180

PSI-Center Final Progress Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarboe, Thomas R.; Shumlak, Uri; Sovinec, Carl

This is the Final Progress Report of the Plasma Science and Innovation Center (PSI-Center) covering March 2014 through February 2017. The Center has accomplished a great deal during this period. The PSI-Center is organized into four groups: Edge and Dynamic Neutrals; Transport and Kinetic Effects; Equilibrium, Stability, and Kinetic Effects in 3D Topologies; and Interface for Validation. Each group has made good progress and the results from each group are given in detail.

Dissociation between mental fatigue and motivational state during prolonged mental activity.

PubMed

Gergelyfi, Mónika; Jacob, Benvenuto; Olivier, Etienne; Zénon, Alexandre

2015-01-01

Mental fatigue (MF) is commonly observed following prolonged cognitive activity and can have major repercussions on the daily life of patients as well as healthy individuals. Despite its important impact, the cognitive processes involved in MF remain largely unknown. An influential hypothesis states that MF does not arise from a disruption of overused neural processes but, rather, is caused by a progressive decrease in motivation-related task engagement. Here, to test this hypothesis, we measured various neural, autonomic, psychometric and behavioral signatures of MF and motivation (EEG, ECG, pupil size, eye blinks, Skin conductance responses (SCRs), questionnaires and performance in a working memory (WM) task) in healthy volunteers, while MF was induced by Sudoku tasks performed for 120 min. Moreover extrinsic motivation was manipulated by using different levels of monetary reward. We found that, during the course of the experiment, the participants' subjective feeling of fatigue increased and their performance worsened while their blink rate and heart rate variability (HRV) increased. Conversely, reward-induced EEG, pupillometric and skin conductance signal changes, regarded as indicators of task engagement, remained constant during the experiment, and failed to correlate with the indices of MF. In addition, MF did not affect a simple reaction time task, despite the strong influence of extrinsic motivation on this task. Finally, alterations of the motivational state through monetary incentives failed to compensate the effects of MF. These findings indicate that MF in healthy subjects is not caused by an alteration of task engagement but is likely to be the consequence of a decrease in the efficiency, or availability, of cognitive resources.

A Systematic Review of Wearable Systems for Cancer Detection: Current State and Challenges.

PubMed

Ray, Partha Pratim; Dash, Dinesh; De, Debashis

2017-10-02

Rapid growth of sensor and computing platforms have introduced the wearable systems. In recent years, wearable systems have led to new applications across all medical fields. The aim of this review is to present current state-of-the-art approach in the field of wearable system based cancer detection and identify key challenges that resist it from clinical adoption. A total of 472 records were screened and 11 were finally included in this study. Two types of records were studied in this context that includes 45% research articles and 55% manufactured products. The review was performed per PRISMA guidelines where considerations was given to records that were published or reported between 2009 and 2017. The identified records included 4 cancer detecting wearable systems such as breast cancer (36.3%), skin cancer (36.3%), prostate cancer (18.1%), and multi-type cancer (9%). Most works involved sensor based smart systems comprising of microcontroller, Bluetooth module, and smart phone. Few demonstrated Ultra-Wide Band (i.e. UWB) antenna based wearable systems. Skin cancer detecting wearable systems were most comprehensible ones. The current works are gradually progressing with seamless integration of sensory units along with smart networking. However, they lack in cloud computing and long-range communication paradigms. Artificial intelligence and machine learning are key ports that need to be attached with current wearable systems. Further, clinical inertia, lack of awareness, and high cost are altogether pulling back the actual growth of such system. It is well comprehended that upon sincere orientation of all identified challenges, wearable systems would emerge as vital alternative to futuristic cancer detection.

Skin health and safety at work in Croatian hairdressing apprentices.

PubMed

Samardžić, Tea; Varnai, Veda Marija; Bakotić, Marija; Babić, Željka; Brans, Richard; Cvijetić Avdagić, Selma; Štampar Šmaguc, Darinka; Kovačević, Iva; Macan, Jelena

2016-07-01

The risk of developing occupational skin disease (OSD) is high in hairdressers, but may differ between countries. To evaluate safety at work measures, and the prevalence and severity of skin symptoms and their impact on quality of life (QoL), among Croatian hairdressing apprentices. Data on self-reported skin symptoms, safety measures and QoL were collected for 101 final-year apprentices. The presence and severity of skin lesions were assessed with the Osnabrueck Hand Eczema Severity Index (OHSI). Transepidermal water loss (TEWL) was measured on the forearm and hand. Ninety-one percent of apprentices reported wearing gloves while dyeing hair, 45% while rinsing hair dyes, and 4% while washing hair. A history of skin symptoms was found in 35% of apprentices, and a history of dry hands in 37%. Skin changes were clinically observed in 40% of apprentices, most frequently erythema, infiltration, and desquamation. The OHSI score ranged from 0 to 6. Only washing hands >20 times per day was positively associated with TEWL. A history of skin symptoms negatively correlated with self-esteem, and social and mental functioning, and positively with anxiety and depression. The results indicate the need for the continuation of efforts to establish effective primary preventive programmes for OSDs at national and EU levels. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing.

PubMed

Belvedere, Raffaella; Bizzarro, Valentina; Parente, Luca; Petrella, Francesco; Petrella, Antonello

2017-07-25

Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma ® Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with mesoglycan and Prisma ® Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that mesoglycan and Prisma ® Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma ® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses.

Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study 

PubMed Central

Rezaei, Ezzatollah; Beiraghi-Toosi, Arash; Ahmadabadi, Ali; Tavousi, Seyed Hassan; Alipour Tabrizi, Arash; Fotuhi, Kazem; Jabbari Nooghabi, Mehdi; Manafi, Amir; Ahmadi Moghadam, Shokoofeh

2017-01-01

BACKGROUND Skin allograft is the gold standard of wound coverage in patients with extensive burns; however, it is considered as a temporary wound coverage and rejection of the skin allograft is considered inevitable. In our study, skin allograft as a permanent coverage in deep burns is evaluated. METHODS Skin allograft survival was assessed in 38 patients from March 2009 to March 2014, retrospectively. Because of the lack of tissue specimen from the skin donors, patients with long skin allograft survival in whom the gender of donor and recipient of allograft was the same were excluded. Seven cases with skin allograft longevity and opposite gender in donor and recipient were finally enrolled. A polymerase chain reaction (PCR) test on the biopsy specimen from recipients and donors were undertaken. RESULTS PCR on the biopsy specimen from recipients confirmed those specimens belong to the donors. All patients received allograft from the opposite sex. Two (28.57%) patients received allograft from their first-degree blood relatives, and in one (14.29%) case, the allograft was harvested from an alive individual with no blood relation. The rest were harvested from multiorgan donors. In eight months of follow up, no clinical evidence of graft rejection was noted. CONCLUSION Long term persistence of skin allograft in patients is worthy of more attention. Further studies An increase in knowledge of factors influencing this longevity could realize the dream of burn surgeons to achieve a permanent coverage other than autograft for major burn patients. PMID:28289620

Performance of mid infrared spectroscopy in skin cancer cell type identification

NASA Astrophysics Data System (ADS)

Kastl, Lena; Kemper, Björn; Lloyd, Gavin R.; Nallala, Jayakrupakar; Stone, Nick; Naranjo, Valery; Penaranda, Francisco; Schnekenburger, Jürgen

2017-02-01

Marker free optical spectroscopy is a powerful tool for the rapid inspection of pathologically suspicious skin lesions and the non-invasive detection of early skin tumors. This goal can be reached by the combination of signal localization and the spectroscopical detection of chemical cell signatures. We here present the development and application of mid infrared spectroscopy (midIR) for the analysis of skin tumor cell types and three dimensional tissue phantoms towards the application of midIR spectroscopy for fast and reliable skin diagnostics. We developed standardized in vitro skin systems with increasing complexity, from single skin cell types as fibroblasts, keratinocytes and melanoma cells, to mixtures of these and finally three dimensional skin cancer phantoms. The cell systems were characterized with different systems in the midIR range up to 12 μm. The analysis of the spectra by novel data processing algorithms demonstrated the clear separation of all cell types, especially melanoma cells. Special attention and algorithm training was required for closely related mesenchymal cell types as dedifferentiated melanoma cells and fibroblasts. Proof of concept experiments with mixtures of in vivo fluorescence labelled skin cell types allowed the test of the new algorithms performance for the identification of specific cell types. The intense training of the software systems with various samples resulted in a increased sensitivity and specificity of the combined midIR and software system. These data highlight the potential of midIR spectroscopy as sensitive and specific future optical biopsy technology.

Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study.

PubMed

Rezaei, Ezzatollah; Beiraghi-Toosi, Arash; Ahmadabadi, Ali; Tavousi, Seyed Hassan; Alipour Tabrizi, Arash; Fotuhi, Kazem; Jabbari Nooghabi, Mehdi; Manafi, Amir; Ahmadi Moghadam, Shokoofeh

2017-01-01

Skin allograft is the gold standard of wound coverage in patients with extensive burns; however, it is considered as a temporary wound coverage and rejection of the skin allograft is considered inevitable. In our study, skin allograft as a permanent coverage in deep burns is evaluated. Skin allograft survival was assessed in 38 patients from March 2009 to March 2014, retrospectively. Because of the lack of tissue specimen from the skin donors, patients with long skin allograft survival in whom the gender of donor and recipient of allograft was the same were excluded. Seven cases with skin allograft longevity and opposite gender in donor and recipient were finally enrolled. A polymerase chain reaction (PCR) test on the biopsy specimen from recipients and donors were undertaken. PCR on the biopsy specimen from recipients confirmed those specimens belong to the donors. All patients received allograft from the opposite sex. Two (28.57%) patients received allograft from their first-degree blood relatives, and in one (14.29%) case, the allograft was harvested from an alive individual with no blood relation. The rest were harvested from multiorgan donors. In eight months of follow up, no clinical evidence of graft rejection was noted. Long term persistence of skin allograft in patients is worthy of more attention. Further studies An increase in knowledge of factors influencing this longevity could realize the dream of burn surgeons to achieve a permanent coverage other than autograft for major burn patients.

Withaferin A suppresses the up-regulation of acetyl-coA carboxylase 1 and skin tumor formation in a skin carcinogenesis mouse model.

PubMed

Li, Wenjuan; Zhang, Chunjing; Du, Hongyan; Huang, Vincent; Sun, Brandi; Harris, John P; Richardson, Quitin; Shen, Xinggui; Jin, Rong; Li, Guohong; Kevil, Christopher G; Gu, Xin; Shi, Runhua; Zhao, Yunfeng

2016-11-01

Withaferin A (WA), a natural product derived from Withania somnifera, has been used in traditional oriental medicines to treat neurological disorders. Recent studies have demonstrated that this compound may have a potential for cancer treatment and a clinical trial has been launched to test WA in treating melanoma. Herein, WA's chemopreventive potential was tested in a chemically-induced skin carcinogenesis mouse model. Pathological examinations revealed that WA significantly suppressed skin tumor formation. Morphological observations of the skin tissues suggest that WA suppressed cell proliferation rather than inducing apoptosis during skin carcinogenesis. Antibody Micro array analysis demonstrated that WA blocked carcinogen-induced up-regulation of acetyl-CoA carboxylase 1 (ACC1), which was further confirmed in a skin cell transformation model. Overexpression of ACC1 promoted whereas knockdown of ACC1 suppressed anchorage-independent growth and oncogene activation of transformable skin cells. Further studies demonstrated that WA inhibited tumor promotor-induced ACC1 gene transcription by suppressing the activation of activator protein 1. In melanoma cells, WA was also able to suppress the expression levels of ACC1. Finally, results using human skin cancer tissues confirmed the up-regulation of ACC1 in tumors than adjacent normal tissues. In summary, our results suggest that withaferin A may have a potential in chemoprevention and ACC1 may serve as a critical target of WA. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

What determines skin sensitization potency: Myths, maybes ...

EPA Pesticide Factsheets

It is widely considered to be a self-evident truth that substances must have a molecular weight (MW) less than 500 to effectively penetrate through the skin in order to induce sensitisation. However, Roberts et al. 2010, evaluated a data set of 699 substances taken from the TIMES-SS expert system and identified that of the 13 substances with a MW above 500, 5 were reported as skin sensitisers. This provided good evidence to refute such a MW threshold. The present study set about compiling a larger and more diverse set of substances such as those evaluated for their skin sensitisation potential under the EU REACH regulation. A dataset of 2575 substances that had been tested for skin sensitisation, using guinea pigs and/or mice was collected. The dataset contained 197 substances with a MW>500: 33 of these were categorised as skin sensitisers. Each of the 33 substances were then evaluated in turn – metal containing complexes, reaction products and mixtures were excluded from further consideration. The final set of 14 sensitisers with a MW>500 were considered on the basis of their reaction chemistry to propose likely mechanistic explanations for their sensitisation behaviour. Penetration ability is correlated with MW (and LogKow): if the MW threshold is shown to be inapplicable for skin sensitisation potency, in turn it also indicates that penetration is not a relevant parameter for skin sensitisation. Exercise to search and extract REACH data for the skin se

Prevalent Signs and Symptoms in Patients with Skin Cancer and Nursing Diagnoses.

PubMed

Lisboa, Isabel Neves Duarte; Azevedo Macena, Monica Suela de; Conceicao Dias, Maria Isabel Fernandes da; Almeida Medeiros, Ana Beatriz de; Lima, Cyndi Fernandes de; Carvalho Lira, Ana Luisa Brandao de

2016-01-01

Skin cancer has a remarkable importance given the high incidence in the population. In Brazil, it is estimated that there were 98,420 new cases of nonmelanoma skin cancer among men and 83,710 new cases among women in 2014. To verify signs and symptoms present in patients with skin neoplasms according to the literature and relate them to the nursing diagnoses of NANDA International. Integrative literature review carried out from March to May 2015 in the databases: Cumulative Index to Nursing and Allied Health Literature, SCOPUS, National Library of Medicine and Nattional Institutes of Health, Latin American and Caribbean Sciences of Health and Web of Science. The descriptors used were: 'Signs and Symptoms' and 'Skin Neoplasms'. Sixteen articles were identified as the final sample. After review, the signs and symptoms of skin cancer identified in the literature were related to the defining characteristics present in NANDA International, with the aim to trace possible nursing diagnoses. The most prevalent signs and symptoms were: asymmetric and well circumscribed nodules with irregular borders; speckles with modified color aspect; ulcerations; blisters; pain; itching; and bleeding. The principal nursing diagnoses outlined were: risk for impaired skin integrity; impaired skin integrity; acute pain; risk of shock; and impaired comfort. The identification of signs and symptoms present in patients with skin cancer and the relationships of these with the nursing diagnoses of NANDA International provide a basis for qualified and systematized nursing care to this clientele.

Skin mucus of Cyprinus carpio inhibits cyprinid herpesvirus 3 binding to epidermal cells

PubMed Central

2011-01-01

Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of a mortal and highly contagious disease in common and koi carp. The skin is the major portal of entry of CyHV-3 in carp after immersion in water containing the virus. In the present study, we used in vivo bioluminescence imaging to investigate the effect of skin mucus removal and skin epidermis lesion on CyHV-3 entry. Physical treatments inducing removal of the mucus up to complete erosion of the epidermis were applied on a defined area of carp skin just before inoculation by immersion in infectious water. CyHV-3 entry in carp was drastically enhanced on the area of the skin where the mucus was removed with or without associated epidermal lesion. To investigate whether skin mucus inhibits CyHV-3 binding to epidermal cells, tail fins with an intact mucus layer or without mucus were inoculated ex vivo. While electron microscopy examination revealed numerous viral particles bound on the fins inoculated after mucus removal, no particle could be detected after infection of mucus-covered fins. Finally, anti-CyHV-3 neutralising activity of mucus extract was tested in vitro. Incubation of CyHV-3 with mucus extract reduced its infectivity in a dose dependent manner. The present study demonstrates that skin mucus removal and epidermal lesions enhance CyHV-3 entry in carp. It highlights the role of fish skin mucus as an innate immune protection against viral epidermal entry. PMID:21816061

The Skin-Mucus Microbial Community of Farmed Atlantic Salmon (Salmo salar)

PubMed Central

Minniti, Giusi; Hagen, Live Heldal; Porcellato, Davide; Jørgensen, Sven Martin; Pope, Phillip B.; Vaaje-Kolstad, Gustav

2017-01-01

The skin of the teleost is a flexible and scaled structure that protects the fish toward the external environment. The outermost surface of the skin is coated with mucus, which is believed to be colonized by a diverse bacterial community (commensal and/or opportunistic). Little is known about such communities and their role in fish welfare. In aquaculture, fish seem to be more susceptible to pathogens compared to wild fish. Indeed common fish farming practices may play important roles in promoting their vulnerability, possibly by causing changes to their microbiomes. In the present study, 16S rRNA gene amplicon sequencing was employed to analyze the composition of the farmed Salmo salar skin-mucus microbiome before and after netting and transfer. The composition of the bacterial community present in the rearing water was also investigated in order to evaluate its correlation with the community present on the fish skin. Our results reveal variability of the skin-mucus microbiome among the biological replicates before fish handling. On the contrary, after fish handling, the skin-mucus community exhibited structural similarity among the biological replicates and significant changes were observed in the bacterial composition compared to the fish analyzed prior to netting and transfer. Limited correlation was revealed between the skin-mucus microbiome and the bacterial community present in the rearing water. Finally, analysis of skin-mucus bacterial biomasses indicated low abundance for some samples, highlighting the need of caution when interpreting community data due to the possible contamination of water-residing bacteria. PMID:29104567

Successive Release of Tissue Inhibitors of Metalloproteinase-1 Through Graphene Oxide-Based Delivery System Can Promote Skin Regeneration

NASA Astrophysics Data System (ADS)

Zhong, Cheng; Shi, Dike; Zheng, Yixiong; Nelson, Peter J.; Bao, Qi

2017-09-01

The purpose of this study was to testify the hypothesis that graphene oxide (GO) could act as an appropriate vehicle for the release of tissue inhibitors of metalloproteinase-1 (TIMP-1) protein in the context of skin repair. GO characteristics were observed by scanning electron microscopy, atomic force microscopy, and thermal gravimetric analysis. After TIMP-1 absorbing GO, the release profiles of various concentrations of TIMP-1 from GO were compared. GO biocompatibility with fibroblast viability was assessed by measuring cell cycle and apoptosis. In vivo wound healing assays were used to determine the effect of TIMP-1-GO on skin regeneration. The greatest intensity of GO was 1140 nm, and the most intensity volume was 10,674.1 nm (nanometer). TIMP-1 was shown to be continuously released for at least 40 days from GO. The proliferation and viability of rat fibroblasts cultured with TIMP-1-GO were not significantly different as compared with the cells grown in GO or TIMP-1 alone ( p > 0.05). Skin defect of rats treated with TIMP-1 and TIMP-1-GO showed significant differences in histological and immunohistochemical scores ( p < 0.05). GO can be controlled to release carrier materials. The combination of TIMP-1 and GO promoted the progression of skin tissue regeneration in skin defect.

Functions of Vγ4 T Cells and Dendritic Epidermal T Cells on Skin Wound Healing

PubMed Central

Li, Yashu; Wu, Jun; Luo, Gaoxing; He, Weifeng

2018-01-01

Wound healing is a complex and dynamic process that progresses through the distinct phases of hemostasis, inflammation, proliferation, and remodeling. Both inflammation and re-epithelialization, in which skin γδ T cells are heavily involved, are required for efficient skin wound healing. Dendritic epidermal T cells (DETCs), which reside in murine epidermis, are activated to secrete epidermal cell growth factors, such as IGF-1 and KGF-1/2, to promote re-epithelialization after skin injury. Epidermal IL-15 is not only required for DETC homeostasis in the intact epidermis but it also facilitates the activation and IGF-1 production of DETC after skin injury. Further, the epidermal expression of IL-15 and IGF-1 constitutes a feedback regulatory loop to promote wound repair. Dermis-resident Vγ4 T cells infiltrate into the epidermis at the wound edges through the CCR6-CCL20 pathway after skin injury and provide a major source of IL-17A, which enhances the production of IL-1β and IL-23 in the epidermis to form a positive feedback loop for the initiation and amplification of local inflammation at the early stages of wound healing. IL-1β and IL-23 suppress the production of IGF-1 by DETCs and, therefore, impede wound healing. A functional loop may exist among Vγ4 T cells, epidermal cells, and DETCs to regulate wound repair.

The Role of AKT/mTOR Pathway in Stress Response to UV-Irradiation: Implication in Skin Carcinogenesis by Regulation of Apoptosis, Autophagy and Senescence

PubMed Central

Strozyk, Elwira; Kulms, Dagmar

2013-01-01

Induction of DNA damage by UVB and UVA radiation may generate mutations and genomic instability leading to carcinogenesis. Therefore, skin cells being repeatedly exposed to ultraviolet (UV) light have acquired multilayered protective mechanisms to avoid malignant transformation. Besides extensive DNA repair mechanisms, the damaged skin cells can be eliminated by induction of apoptosis, which is mediated through the action of tumor suppressor p53. In order to prevent the excessive loss of skin cells and to maintain the skin barrier function, apoptotic pathways are counteracted by anti-apoptotic signaling including the AKT/mTOR pathway. However, AKT/mTOR not only prevents cell death, but is also active in cell cycle transition and hyper-proliferation, thereby also counteracting p53. In turn, AKT/mTOR is tuned down by the negative regulators being controlled by the p53. This inhibition of AKT/mTOR, in combination with transactivation of damage-regulated autophagy modulators, guides the p53-mediated elimination of damaged cellular components by autophagic clearance. Alternatively, p53 irreversibly blocks cell cycle progression to prevent AKT/mTOR-driven proliferation, thereby inducing premature senescence. Conclusively, AKT/mTOR via an extensive cross talk with p53 influences the UV response in the skin with no black and white scenario deciding over death or survival. PMID:23887651

Laser lipolysis: skin tightening in lipoplasty using a diode laser.

PubMed

Wolfenson, Moisés; Hochman, Bernardo; Ferreira, Lydia Massako

2015-05-01

New devices have been developed for surgical repair of deformities caused by localized fat deposits associated with skin laxity. The use of these devices requires the adoption of safety parameters. The aim of this study was to investigate skin tightening by laser lipolysis, using a dual-wavelength diode laser. This prospective, cross-sectional study was conducted between June of 2008 and July of 2010 with 41 consecutive patients who underwent laser lipolysis to correct contour deformities. Laser lipolysis was performed with a diode laser operating at two wavelengths (924 and 975 nm) controlled independently, and using three different tip lengths, allowing treatment of small, medium, and large areas of adipose tissue. The procedure was performed under local anesthesia in a surgical setting. To calculate the optimal cumulative energy, a total energy dose of 5 kJ/10 × 10-cm skin area was used as a safety parameter to prevent treatment complications. The circumferences of body regions were measured preoperatively, immediately after surgery, and 90 days later. Measurements were compared using the Wilcoxon test at a significance level of 0.05 (p < 0.05). A significant skin tightening was observed in all patients, regardless of the body site involved (i.e., face, breast, arms, or waist regions), and no complications occurred. Laser lipolysis results in progressive skin tightening over time. Therapeutic, IV.

PTEN positively regulates UVB-induced DNA damage repair

PubMed Central

Ming, Mei; Feng, Li; Shea, Christopher R.; Soltani, Keyoumars; Zhao, Baozhong; Han, Weinong; Smart, Robert C.; Trempus, Carol S.; He, Yu-Ying

2011-01-01

Non-melanoma skin cancer is the most common cancer in the U.S., where DNA-damaging UVB radiation from the sun remains the major environmental risk factor. However, the critical genetic targets of UVB radiation are undefined. Here we show that attenuating PTEN in epidermal keratinocytes is a predisposing factor for UVB-induced skin carcinogenesis in mice. In skin papilloma and squamous cell carcinoma (SCC), levels of PTEN were reduced compared to skin lacking these lesions. Likewise, there was a reduction in PTEN levels in human premalignant actinic keratosis and malignant SCC, supporting a key role for PTEN in human skin cancer formation and progression. PTEN downregulation impaired the capacity of global genomic nucleotide excision repair (GG-NER), a critical mechanism for removing UVB-induced mutagenic DNA lesions. In contrast to the response to ionizing radiation, PTEN downregulation prolonged UVB-induced growth arrest and increased the activation of the Chk1 DNA damage pathway in an AKT-independent manner, likely due to reduced DNA repair. PTEN loss also suppressed expression of the key GG-NER protein xeroderma pigmentosum C (XPC) through the AKT/p38 signaling axis. Reconstitution of XPC levels in PTEN-inhibited cells restored GG-NER capacity. Taken together, our findings define PTEN as an essential genomic gatekeeper in the skin, through its ability to positively regulate XPC-dependent GG-NER following DNA damage. PMID:21771908

Bryostatin and its synthetic analog, picolog rescue dermal fibroblasts from prolonged stress and contribute to survival and rejuvenation of human skin equivalents.

PubMed

Khan, Tapan K; Wender, Paul A; Alkon, Daniel L

2018-02-01

Skin health is associated with the day-to-day activity of fibroblasts. The primary function of fibroblasts is to synthesize structural proteins, such as collagen, extracellular matrix proteins, and other proteins that support the structural integrity of the skin and are associated with younger, firmer, and more elastic skin that is better able to resist and recover from injury. At sub-nanomolar concentrations (0.03-0.3 nM), bryostatin-1 and its synthetic analog, picolog (0.1-10 nM) sustained the survival and activation of human dermal fibroblasts cultured under the stressful condition of prolonged serum deprivation. Bryostatin-1 treatment stabilized human skin equivalents (HSEs), a bioengineered combination of primary human skin cells (keratinocytes and dermal fibroblasts) on an extracellular matrix composed of mainly collagen. Fibroblasts activated by bryostatin-1 protected the structural integrity of HSEs. Bryostatin-1 and picolog prolonged activation of Erk in fibroblasts to promote cell survival. Chronic stress promotes the progression of apoptosis. Dermal fibroblasts constitutively express all components of Fas associated apoptosis, including caspase-8, an initiator enzyme of apoptosis. Prolong bryostatin-1 treatment reduced apoptosis by decreasing caspase-8 and protected dermal fibroblasts. Our data suggest that bryostatin-1 and picolog could be useful in anti-aging skincare, and could have applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

Complement System in Dermatological Diseases – Fire Under the Skin

PubMed Central

Panelius, Jaana; Meri, Seppo

2015-01-01

The complement system plays a key role in several dermatological diseases. Overactivation, deficiency, or abnormality of the control proteins are often related to a skin disease. Autoimmune mechanisms with autoantibodies and a cytotoxic effect of the complement membrane attack complex on epidermal or vascular cells can cause direct tissue damage and inflammation, e.g., in systemic lupus erythematosus (SLE), phospholipid antibody syndrome, and bullous skin diseases like pemphigoid. By evading complement attack, some microbes like Borrelia spirochetes and staphylococci can persist in the skin and cause prolonged symptoms. In this review, we present the most important skin diseases connected to abnormalities in the function of the complement system. Drugs having an effect on the complement system are also briefly described. On one hand, drugs with free hydroxyl on amino groups (e.g., hydralazine, procainamide) could interact with C4A, C4B, or C3 and cause an SLE-like disease. On the other hand, progress in studies on complement has led to novel anti-complement drugs (recombinant C1-inhibitor and anti-C5 antibody, eculizumab) that could alleviate symptoms in diseases associated with excessive complement activation. The main theme of the manuscript is to show how relevant the complement system is as an immune effector system in contributing to tissue injury and inflammation in a broad range of skin disorders. PMID:25688346

Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skin.

PubMed

Qiao, W; Li, A G; Owens, P; Xu, X; Wang, X-J; Deng, C-X

2006-01-12

Smad4 is the common mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFbeta and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGFbeta/BMP pathway, which interacts with the Pten signaling pathway.

Primary vascularization of allografts governs their immunogenicity and susceptibility to tolerogenesis

PubMed Central

Kant, Cavit D.; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Connolly, Sarah E; Germana, Sharon; Winn, Henry J.; LeGuern, Christian; Tocco, Georges; Benichou, Gilles

2013-01-01

We investigated the influence of allograft primary vascularization on alloimmunity, rejection and tolerance in mice. First, we showed that fully allogeneic primarily vascularized and conventional skin transplants were rejected at the same pace. Remarkably, however, short-term treatment of mice with anti-CD40L antibodies achieved long-term survival of vascularized skin and cardiac transplants but not conventional skin grafts. Non-vascularized skin transplants triggered vigorous direct and indirect pro-inflammatory type 1 T cell responses (IL-2 and γIFN) while primarily-vascularized skin allografts failed to trigger a significant indirect alloresponse. Similar lack of indirect alloreactivity was also observed after placement of different vascularized organ transplants including hearts and kidneys while hearts placed under the skin (non-vascularized) triggers potent indirect alloresponses. Altogether, these results suggest that primary vascularization of allografts is associated with lack of indirect T cell alloreactivity. Finally, we show that long-term survival of vascularized skin allografts induced by anti-CD40L antibodies was associated with a combined lack of indirect alloresponse and a shift of the direct alloresponse towards a type 2 cytokine (IL-4, IL-10) secretion pattern but no activation/expansion of regulatory T cells. Therefore, primary vascularization of allografts governs their immunogenicity and tolerogenicity. PMID:23833234

Some Physical and Computational Issues in Land Surface Data Assimilation of Satellite Skin Temperatures

NASA Astrophysics Data System (ADS)

Mackaro, Scott M.; McNider, Richard T.; Biazar, Arastoo Pour

2012-03-01

Skin temperatures that reflect the radiating temperature of a surface observed by infrared radiometers are one of the most widely available products from polar orbiting and geostationary satellites and the most commonly used satellite data in land surface assimilation. Past work has indicated that a simple land surface scheme with a few key parameters constrained by observations such as skin temperatures may be preferable to complex land use schemes with many unknown parameters. However, a true radiating skin temperature is sometimes not a prognostic variable in weather forecast models. Additionally, recent research has shown that skin temperatures cannot be directly used in surface similarity forms for inferring fluxes. This paper examines issues encountered in using satellite derived skin temperatures to improve surface flux specifications in weather forecast and air quality models. Attention is given to iterations necessary when attempting to nudge the surface energy budget equation to a desired state. Finally, the issue of mathematical operator splitting is examined in which the surface energy budget calculations are split with the atmospheric vertical diffusion calculations. However, the high level of connectivity between the surface and first atmospheric level means that the operator splitting leads to high frequency oscillations. These oscillations may hinder the assimilation of skin temperature derived moisture fluxes.

Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids.

PubMed

Kopečná, Monika; Macháček, Miloslav; Prchalová, Eva; Štěpánek, Petr; Drašar, Pavel; Kotora, Martin; Vávrová, Kateřina

2017-03-01

Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin. To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of D-glucose derivatives, both hydrophilic and amphiphilic. Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-D-glucopyranoside 5 as a promising enhancer. Furthermore, this amino sugar 5 increased epidermal concentration of a highly hydrophilic antiviral cidofovir by a factor of 7. The effect of compound 5 on skin electrical impedance suggested its direct interaction with the skin barrier. Infrared spectroscopy of isolated stratum corneum revealed no effect of enhancer 5 on the stratum corneum proteins but an overall decrease in the lipid chain order. The enhancer showed acceptable toxicity on HaCaT keratinocyte and 3T3 fibroblast cell lines. Finally, transepidermal water loss returned to baseline values after enhancer 5 had been removed from the skin. Compound 5, a dodecyl amino glucoside, is a promising enhancer that acts through a reversible interaction with the stratum corneum lipids.

Phenolic composition of the edible parts (flesh and skin) of Bordô grape (Vitis labrusca) using HPLC-DAD-ESI-MS/MS.

PubMed

Lago-Vanzela, Ellen Silva; Da-Silva, Roberto; Gomes, Eleni; García-Romero, Esteban; Hermosín-Gutiérrez, Isidro

2011-12-28

The aim of this study was the detailed characterization of the phenolic composition and the determination of the antioxidant activity of the Bordô grape (Vitis labrusca) cultivated in South Brazil. The edible parts of Bordô grapes (flesh and skin) contained 1130 mg/kg of total phenolic compounds (as gallic acid), mainly located in the skins. Anthocyanin content in the skins was high, largely as 3,5-diglucosides (1359 mg/kg, as malvidin 3,5-diglucoside). Total flavonols accounted for 154 μmol/kg, mainly located in the skins and with myricetin 3-glucoside as the principal flavonol in both grape parts. Very low amounts of flavan-3-ol monomers and dimers and low amounts of polymeric proanthocyanidins, with a composition similar to that reported for V. vinifera grape varieties, were found in Bordô grape skins. Hydroxycinnamic acid derivatives mainly derived from caffeic acid and were found in the skins in high amounts, ten times higher than in the flesh (total amount: 483 μmol/kg). Finally, the Bordô grape cultivar can be considered a high resveratrol producer (10.91 mg/kg) and also exhibited a high value of total antioxidant capacity (37.6 ± 1.0 mmol/kg, as Trolox).

Significant skin burns may occur with the use of a water balloon in HIFU treatment

NASA Astrophysics Data System (ADS)

Ritchie, Robert; Collin, Jamie; Wu, Feng; Coussios, Constantin; Leslie, Tom; Cranston, David

2012-10-01

HIFU is a minimally-invasive therapy suitable for treating selected intra-abdominal tumors. Treatment is safe although skin burns may occur due to pre-focal heating. HIFU treatment of a renal transplant tumor located in the left lower abdomen was undertaken in our centre. Treatment was performed prone, requiring displacement of the abdominal wall away from the treatment field using a water balloon, constructed of natural rubber latex and filled with degassed water. Intra-operatively, ultrasound imaging and physical examination of the skin directly over the focal region was normal. Immediately post-operative, a full-thickness skin burn was evident at the periphery of the balloon location, outside the expected HIFU path. Three possibilities may account for this complication. Firstly, the water balloon may have acted as a lens, focusing the HIFU to a neo-focus off axis. Secondly, air bubbles may have been entrapped between the balloon and the skin, causing heating at the interface. Finally, heating of the isolated water within the balloon may have been sufficient to cause burning. In this case, the placement of a water balloon caused a significant skin burn. Care should be taken in their use as burns, situated off axis, may occur even if the overlying skin appears normal.

Comparisons between conventional optical imaging and parametric indirect microscopic imaging on human skin detection

NASA Astrophysics Data System (ADS)

Liu, Guoyan; Gao, Kun; Liu, Xuefeng; Ni, Guoqiang

2016-10-01

We report a new method, polarization parameters indirect microscopic imaging with a high transmission infrared light source, to detect the morphology and component of human skin. A conventional reflection microscopic system is used as the basic optical system, into which a polarization-modulation mechanics is inserted and a high transmission infrared light source is utilized. The near-field structural characteristics of human skin can be delivered by infrared waves and material coupling. According to coupling and conduction physics, changes of the optical wave parameters can be calculated and curves of the intensity of the image can be obtained. By analyzing the near-field polarization parameters in nanoscale, we can finally get the inversion images of human skin. Compared with the conventional direct optical microscope, this method can break diffraction limit and achieve a super resolution of sub-100nm. Besides, the method is more sensitive to the edges, wrinkles, boundaries and impurity particles.

The role of skin substitutes in the treatment of burn injuries.

PubMed

Shakespeare, Peter G

2005-01-01

Extensive burn wounds are difficult to manage and repair. Several engineered skin substitutes have been developed to aid in this process. These substitutes are designed with particular objectives in mind which dictate the circumstances under which they can, and should, be employed to promote healing or prepare the burn wound for final closure with autograft. This article discusses some of the rationale behind the use of skin substitutes and reviews some of the substitutes in use at the present time. Current perspectives suggest that skin substitute use is still in its infancy and that there is some way to go before their role in clinical practice becomes clear. Nevertheless the prospect of being able to supply new wound repair components and to influence the healing process to modify outcome and improve the quality of the healed burn wound will ensure a continuing high degree of interest in these potentially useful and beneficial medical devices.

78 FR 16690 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-18

... of rapamycin (mTOR) mediates stem cells exhaustion in the skin and leads to progressive hair loss... be used to prevent mucositis and hair loss in patients undergoing chemotherapy and stem cell... chemotherapeutic regimen in animal models effectively suppressed the growth of chordoma cells and resulted in...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

Relationship between arsenic skin lesions and the age of natural menopause.

PubMed

Yunus, Fakir Md; Rahman, Musarrat Jabeen; Alam, Md Zahidul; Hore, Samar Kumar; Rahman, Mahfuzar

2014-05-02

Chronic exposure to arsenic is associated with neoplastic, cardiovascular, endocrine, neuro-developmental disorders and can have an adverse effect on women's reproductive health outcomes. This study examined the relationship between arsenic skin lesions (a hallmark sign of chronic arsenic poisoning) and age of natural menopause (final menopausal period) in populations with high levels of arsenic exposure in Bangladesh. We compared menopausal age in two groups of women--with and without arsenic skin lesions; and presence of arsenic skin lesions was used as an indicator for chronic arsenic exposure. In a cross-sectional study, a total of 210 participants were randomly identified from two ongoing studies--participants with arsenic skin lesions were identified from an ongoing clinical trial and participants with no arsenic skin lesions were identified from an ongoing cohort study. Mean age of menopause between these two groups were calculated and compared. Multivariable linear regression was used to estimate the relationship between the status of the arsenic skin lesions and age of natural menopause in women. Women with arsenic skin lesions were 1.5 years younger (p <0.001) at the time of menopause compared to those without arsenic skin lesions. After adjusting with contraceptive use, body mass index, urinary arsenic level and family history of premature menopause, the difference between the groups' age at menopause was 2.1 years earlier (p <0.001) for respondents with arsenic skin lesions. The study showed a statistically significant association between chronic exposure to arsenic and age at menopause. Heavily exposed women experienced menopause two years earlier than those with lower or no exposure.

A Projectile for a Rectangular Barreled Rail Gun

DTIC Science & Technology

1999-12-01

fins Cfb ’ skin friction drag coefficient for nose/body combination modified for equations of motion Cff’ skin friction drag coefficient for fins...occasionally referred to as the last point method, uses a loop , shown in simplified form in Figure (2) as a flow chart. The program loop takes the final... Cfb ’ = CfofCf(Sno/s+Sbs)/ScsS (4.11) Cff = CfffcfSw/Scss (4.12) 2. Form Drag The form drag coefficients are determined by the methods from

In vitro LED and laser light photoinactivation of Propionibacterium acnes

NASA Astrophysics Data System (ADS)

Tuchina, Elena S.; Tuchin, Valery V.

2008-06-01

Acne is a genetic, hormonal disease characterized by overproduction of oil by the sebaceous glands, plugging of the sebaceous glands to form micro- and macro- comedons and, finally, action of skin bacteria on oil trapped underneath the skin to red inflammatory cystic lesions. It was shown, that Propionibacterium acnes, the bacteria responsible for acne, was rather subjected to action of red and infrared radiation. The effect of the given radiation amplified at this bacteria by various solutions of photosensitizes.

Medical applications of atomic force microscopy and Raman spectroscopy.

PubMed

Choi, Samjin; Jung, Gyeong Bok; Kim, Kyung Sook; Lee, Gi-Ja; Park, Hun-Kuk

2014-01-01

This paper reviews the recent research and application of atomic force microscopy (AFM) and Raman spectroscopy techniques, which are considered the multi-functional and powerful toolkits for probing the nanostructural, biomechanical and physicochemical properties of biomedical samples in medical science. We introduce briefly the basic principles of AFM and Raman spectroscopy, followed by diagnostic assessments of some selected diseases in biomedical applications using them, including mitochondria isolated from normal and ischemic hearts, hair fibers, individual cells, and human cortical bone. Finally, AFM and Raman spectroscopy applications to investigate the effects of pharmacotherapy, surgery, and medical device therapy in various medicines from cells to soft and hard tissues are discussed, including pharmacotherapy--paclitaxel on Ishikawa and HeLa cells, telmisartan on angiotensin II, mitomycin C on strabismus surgery and eye whitening surgery, and fluoride on primary teeth--and medical device therapy--collagen cross-linking treatment for the management of progressive keratoconus, radiofrequency treatment for skin rejuvenation, physical extracorporeal shockwave therapy for healing of Achilles tendinitis, orthodontic treatment, and toothbrushing time to minimize the loss of teeth after exposure to acidic drinks.

Dracunculiasis (Guinea Worm Disease) and the Eradication Initiative

PubMed Central

Cairncross, Sandy; Muller, Ralph; Zagaria, Nevio

2002-01-01

Dracunculiasis, also known as guinea worm disease, is caused by the large female of the nematode Dracunculus medinensis, which emerges painfully and slowly from the skin, usually on the lower limbs. The disease can infect animals, and sustainable animal cycles occur in North America and Central Asia but do not act as reservoirs of human infection. The disease is endemic across the Sahel belt of Africa from Mauritania to Ethiopia, having been eliminated from Asia and some African countries. It has a significant socioeconomic impact because of the temporary disability that it causes. Dracunculiasis is exclusively caught from drinking water, usually from ponds. A campaign to eradicate the disease was launched in the 1980s and has made significant progress. The strategy of the campaign is discussed, including water supply, health education, case management, and vector control. Current issues including the integration of the campaign into primary health care and the mapping of cases by using geographic information systems are also considered. Finally, some lessons for other disease control and eradication programs are outlined. PMID:11932231

New Language and Old Problems in Breast Cancer Radiotherapy.

PubMed

Chiricuţă, Ion Christian

2017-01-01

New developments in breast cancer radiotherapy make possible new standards in treatment recommandations based on international guidelines. Developments in radiotherapy irradiation techniques from 2D to 3D-Conformal RT and to IMRT (Intensity Modulated Arc Therapy) make possible to reduce the usual side effects on the organs at risk as: skin, lung, miocard, bone, esophagus and brahial plexus. Dispite of all these progresses acute and late side effects are present. Side effects are as old as the radiotherapy was used. New solutions are available now by improving irradiation techniques. New techniques as sentinel node procedure (SNP) or partial breast irradiation (PBRT) and immediate breast reconstruction with silicon implants (IBRIS) make necessary new considerations regarding the target volume delineations. A new language for definition of gross tumor volume (GTV), clinical target volume (CTV) based on the new diagnostic methods as PET/CT,nonaparticle MRI will have real impact on target delineation and irradiation techniques. "The new common language in breast cancer therapy" would be the first step to improve the endresults and finally the quality of life of the patients. Celsius.

Dopamine: Just the Right Medicine for Membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Hao-Cheng; Waldman, Ruben Z.; Wu, Ming-Bang

Mussel-inspired chemistry has attracted widespread interest in membrane science and technology. Demonstrating the rapid growth of this field over the past several years, substantial progress has been achieved in both mussel-inspired chemistry and membrane surface engineering based on mussel-inspired coatings. At this stage, it is valuable to summarize the most recent and distinctive developments, as well as to frame the challenges and opportunities remaining in this field. In this review, recent advances in rapid and controllable deposition of mussel-inspired coatings, dopamine-assisted codeposition technology, and photoinitiated grafting directly on mussel-inspired coatings are presented. Some of these technologies have not yet beenmore » employed directly in membrane science. Beyond discussing advances in conventional membrane processes, emerging applications of mussel-inspired coatings in membranes are discussed, including as a skin layer in nanofiltration, interlayer in metal-organic framework based membranes, hydrophilic layer in Janus membranes, and protective layer in catalytic membranes. Finally, some critical unsolved challenges are raised in this field and some potential pathways are proposed to address them.« less

Dopamine: Just the Right Medicine for Membranes

DOE PAGES

Yang, Hao-Cheng; Waldman, Ruben Z.; Wu, Ming-Bang; ...

2018-01-09

Mussel-inspired chemistry has attracted widespread interest in membrane science and technology. Demonstrating the rapid growth of this field over the past several years, substantial progress has been achieved in both mussel-inspired chemistry and membrane surface engineering based on mussel-inspired coatings. At this stage, it is valuable to summarize the most recent and distinctive developments, as well as to frame the challenges and opportunities remaining in this field. In this review, recent advances in rapid and controllable deposition of mussel-inspired coatings, dopamine-assisted codeposition technology, and photoinitiated grafting directly on mussel-inspired coatings are presented. Some of these technologies have not yet beenmore » employed directly in membrane science. Beyond discussing advances in conventional membrane processes, emerging applications of mussel-inspired coatings in membranes are discussed, including as a skin layer in nanofiltration, interlayer in metal-organic framework based membranes, hydrophilic layer in Janus membranes, and protective layer in catalytic membranes. Finally, some critical unsolved challenges are raised in this field and some potential pathways are proposed to address them.« less

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

PubMed

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

2016-01-01

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

Combination fracturing/gravel-packing completion technique on the Amberjack, Mississippi Canyon 109 field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hannah, R.R.; Park, E.I.; Porter, D.A.

1994-11-01

This paper describes a one-step fracturing/gravel-pack (frac-and-pack) completion procedure conducted on the BP Exploration Amberjack platform beginning in early 1992. This platform is 35 miles southwest of Venice, LA. The first four completions on this platform had an average positive skin values of 21. The goal of the frac-and-pack procedure was to reduce these skins to nearly zero. In total, 24 frac-and-pack operations were performed. Details of the fracture design, prefracture testing, fracture design and execution, and production response and a continuing optimization program are discussed. The fractures were performed with the screens in place with the gravel pack aftermore » the fracturing operation. The treatments were designed for the tip screenout technique to create wide fractures and to provide proppant loadings exceeding 8 lbm/ft. This paper presents the trend of the declining skin values, along with a discussion of time-dependent skins. The changes in fluids, breakers, and proppants are also presented. The average skin on 14 frac-and-pack completions was 5.3. The average skin on the final eight completions was 0.2.« less

Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation.

PubMed

Chu, Chung-Ching; Ali, Niwa; Karagiannis, Panagiotis; Di Meglio, Paola; Skowera, Ania; Napolitano, Luca; Barinaga, Guillermo; Grys, Katarzyna; Sharif-Paghaleh, Ehsan; Karagiannis, Sophia N; Peakman, Mark; Lombardi, Giovanna; Nestle, Frank O

2012-05-07

Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141(+) DDCs). CD141(+) DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D(3) (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141(+) DDCs from human blood DCs. These CD141(+) DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141(+) DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141(+) DDC-like cells have potential clinical use for their capacity to induce immune tolerance.

Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation

PubMed Central

Chu, Chung-Ching; Ali, Niwa; Karagiannis, Panagiotis; Di Meglio, Paola; Skowera, Ania; Napolitano, Luca; Barinaga, Guillermo; Grys, Katarzyna; Sharif-Paghaleh, Ehsan; Karagiannis, Sophia N.; Peakman, Mark; Lombardi, Giovanna

2012-01-01

Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141+ DDCs). CD141+ DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D3 (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141+ DDCs from human blood DCs. These CD141+ DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141+ DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141+ DDC-like cells have potential clinical use for their capacity to induce immune tolerance. PMID:22547651

Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models

PubMed Central

Brendtke, Rico; Wiehl, Michael; Groeber, Florian; Schwarz, Thomas; Walles, Heike; Hansmann, Jan

2016-01-01

Tissue dehydration results in three major types of exsiccosis—hyper-, hypo-, or isonatraemia. All three types entail alterations of salt concentrations leading to impaired biochemical processes, and can finally cause severe morbidity. The aim of our study was to demonstrate the feasibility of a microwave-based sensor technology for the non-invasive measurement of the hydration status. Electromagnetic waves at high frequencies interact with molecules, especially water. Hence, if a sample contains free water molecules, this can be detected in a reflected microwave signal. To develop the sensor system, human three-dimensional skin equivalents were instituted as a standardized test platform mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a specific hydration and density of matrix components were generated and microwave measurements were performed. Hydration-specific spectra allowed deriving the hydration state of the skin models. A further advantage of the skin equivalents was the characterization of the impact of distinct skin components on the measured signals to investigate mechanisms of signal generation. The results demonstrate the feasibility of a non-invasive microwave-based hydration sensor technology. The sensor bears potential to be integrated in a wearable medical device for personal health monitoring. PMID:27046226

Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models.

PubMed

Brendtke, Rico; Wiehl, Michael; Groeber, Florian; Schwarz, Thomas; Walles, Heike; Hansmann, Jan

2016-01-01

Tissue dehydration results in three major types of exsiccosis--hyper-, hypo-, or isonatraemia. All three types entail alterations of salt concentrations leading to impaired biochemical processes, and can finally cause severe morbidity. The aim of our study was to demonstrate the feasibility of a microwave-based sensor technology for the non-invasive measurement of the hydration status. Electromagnetic waves at high frequencies interact with molecules, especially water. Hence, if a sample contains free water molecules, this can be detected in a reflected microwave signal. To develop the sensor system, human three-dimensional skin equivalents were instituted as a standardized test platform mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a specific hydration and density of matrix components were generated and microwave measurements were performed. Hydration-specific spectra allowed deriving the hydration state of the skin models. A further advantage of the skin equivalents was the characterization of the impact of distinct skin components on the measured signals to investigate mechanisms of signal generation. The results demonstrate the feasibility of a non-invasive microwave-based hydration sensor technology. The sensor bears potential to be integrated in a wearable medical device for personal health monitoring.

Identification of a novel PPARβ/δ/miR-21-3p axis in UV-induced skin inflammation.

PubMed

Degueurce, Gwendoline; D'Errico, Ilenia; Pich, Christine; Ibberson, Mark; Schütz, Frédéric; Montagner, Alexandra; Sgandurra, Marie; Mury, Lionel; Jafari, Paris; Boda, Akash; Meunier, Julien; Rezzonico, Roger; Brembilla, Nicolò Costantino; Hohl, Daniel; Kolios, Antonios; Hofbauer, Günther; Xenarios, Ioannis; Michalik, Liliane

2016-08-01

Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPARβ/δ is known to control mouse cutaneous repair and UV-induced skin cancer development. Here, we describe a novel PPARβ/δ-dependent molecular cascade involving TGFβ1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR-21-3p reduces UV-induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA-based topical therapies for cutaneous disorders. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Fusion of cone-beam CT and 3D photographic images for soft tissue simulation in maxillofacial surgery

NASA Astrophysics Data System (ADS)

Chung, Soyoung; Kim, Joojin; Hong, Helen

2016-03-01

During maxillofacial surgery, prediction of the facial outcome after surgery is main concern for both surgeons and patients. However, registration of the facial CBCT images and 3D photographic images has some difficulties that regions around the eyes and mouth are affected by facial expressions or the registration speed is low due to their dense clouds of points on surfaces. Therefore, we propose a framework for the fusion of facial CBCT images and 3D photos with skin segmentation and two-stage surface registration. Our method is composed of three major steps. First, to obtain a CBCT skin surface for the registration with 3D photographic surface, skin is automatically segmented from CBCT images and the skin surface is generated by surface modeling. Second, to roughly align the scale and the orientation of the CBCT skin surface and 3D photographic surface, point-based registration with four corresponding landmarks which are located around the mouth is performed. Finally, to merge the CBCT skin surface and 3D photographic surface, Gaussian-weight-based surface registration is performed within narrow-band of 3D photographic surface.