New-onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases.

PubMed

Méry-Bossard, L; Bagny, K; Chaby, G; Khemis, A; Maccari, F; Marotte, H; Perrot, J L; Reguiai, Z; Sigal, M L; Avenel-Audran, M; Boyé, T; Grasland, A; Gillard, J; Jullien, D; Toussirot, E

2017-01-01

The development of vitiligo during treatment with biological agents is an unusual event and only a few isolated cases have been reported. To describe the clinical characteristics and evolution of patients developing new-onset vitiligo following initiation of a biological agent for chronic inflammatory disease; and also to report the clinical course of pre-existing vitiligo under biological therapy. This nationwide multicentre, retrospective study, carried out between July 2013 and January 2015, describes the characteristics of a large series of 18 patients (psoriasis N = 8, inflammatory rheumatic diseases N = 8, ulcerative colitis N = 1, uveitis N = 1) who developed new-onset vitiligo while receiving a biological agent. TNFα inhibitors were the most common biological agent involved (13/18) while anti-IL-12/23 and anti-IL-17 agents or abatacept were less common (4/18 and 1/18 respectively). Mean duration of biological agent exposure before vitiligo onset was 13.9 ± 16.5 months. Outcome was favourable for most patients (15/17) while maintaining the biological agent. Data were also collected for 18 patients (psoriasis N = 5, inflammatory rheumatic diseases N = 10, inflammatory bowel diseases N = 2, SAPHO N = 1) who had pre-existing vitiligo when treatment with a biological agent started (TNFα inhibitors N = 15, ustekinumab N = 1, rituximab N = 1, tocilizumab N = 1). Vitiligo progressed in seven patients and was stable or improved in eight cases. Vitiligo may thus emerge and/or progress during treatment with various biological agents, mainly TNFα inhibitors and could be a new paradoxical skin reaction. De novo vitiligo displays a favourable outcome when maintaining the biological agent, whereas the prognosis seems worse in cases of pre-existing vitiligo. © 2016 European Academy of Dermatology and Venereology.

Concise review of recent studies in vitiligo

PubMed Central

Allam, Mohamed; Riad, Hassan

2013-01-01

Vitiligo is an acquired pigmentry disorder of the skin and mucous membranes which manifests as white macules and patches due to selective loss of melanocytes. Etiological hypotheses of vitiligo include genetic, immunological, neurohormonal, cytotoxic, biochemical, oxidative stress and newer theories of melanocytorrhagy and decreased melanocytes survival. There are several types of vitiligo which are usually diagnosed clinically and by using a Wood's lamp; also vitiligo may be associated with autoimmune diseases, audiological and ophthalmological findings or it can be a part of polyendocrinopathy syndromes. Several interventions are available for the treatment for vitiligo to stop disease progression and/or to attain repigmentation or even depigmentation. In this article, we will present an overall view of current standing of vitiligo research work especially in the etiological factors most notably the genetic components, also, types and associations and various and newer treatment modalities. PMID:25003059

Vitiligo: Focus on Clinical Aspects, Immunopathogenesis, and Therapy.

PubMed

Boniface, Katia; Seneschal, Julien; Picardo, Mauro; Taïeb, Alain

2018-02-01

Vitiligo is an acquired chronic depigmenting disorder of the skin, with an estimated prevalence of 0.5% of the general population, characterized by the development of white macules resulting from a loss of epidermal melanocytes. The nomenclature has been revised after an extensive international work within the vitiligo global issues consensus conference, and vitiligo (formerly non-segmental vitiligo) is now a consensus umbrella term for all forms of generalized vitiligo. Two other subsets of vitiligo are segmental vitiligo and unclassified/undetermined vitiligo, which corresponds to focal disease and rare variants. A series of hypopigmented disorders may masquerade as vitiligo, and some of them need to be ruled out by specific procedures including a skin biopsy. Multiple mechanisms are involved in melanocyte disappearance, namely genetic predisposition, environmental triggers, metabolic abnormalities, impaired renewal, and altered inflammatory and immune responses. The auto-immune/inflammatory theory is the leading hypothesis because (1) vitiligo is often associated with autoimmune diseases; (2) most vitiligo susceptibility loci identified through genome-wide association studies encode immunomodulatory proteins; and (3) prominent immune cell infiltrates are found in the perilesional margin of actively depigmenting skin. However, other studies support melanocyte intrinsic abnormalities with poor adaptation of melanocytes to stressors leading to melanocyte instability in the basal layer, and release of danger signals important for the activation of the immune system. Recent progress in the understanding of immune pathomechanisms opens interesting perspectives for innovative treatment strategies. The proof of concept in humans of targeting of the IFNγ /Th1 pathway is much awaited. The interplay between oxidative stress and altered immune responses suggests that additional strategies aiming at limiting type I interferon activation pathway as background stabilizing

Psoriasis superimposed on vitiligo: the tricolored vulva.

PubMed

Tin, Kyi Saw; Scurry, James; Dyall-Smith, Delwyn

2014-01-01

This study aimed to describe 2 cases of vulvar psoriasis and vitiligo resulting in a striking clinical appearance. Case 1 was of a 41-year-old woman concerned about a dark pigmentation around the introitus. Case 2 was of an 80-year-old woman with vulvar itch and red, white, and brown areas. The vulva in each case showed a tricolored appearance of well-demarcated red, white, and brown colors. Biopsies showed psoriasis superimposed on vitiligo in the red, vitiligo in the white, and normal skin in the brown areas. When psoriasis and vitiligo are colocalized, the redness of the psoriasis may mask the vitiligo resulting in a striking red, white, and brown tricolored appearance.

The Vitiligo Working Group recommendations for narrowband ultraviolet B light phototherapy treatment of vitiligo.

PubMed

Mohammad, Tasneem F; Al-Jamal, Mohammed; Hamzavi, Iltefat H; Harris, John E; Leone, Giovanni; Cabrera, Raúl; Lim, Henry W; Pandya, Amit G; Esmat, Samia M

2017-05-01

Treatment of vitiligo with narrowband ultraviolet B light (NBUVB) is an important component of the current standard of care. However, there are no consistent guidelines regarding the dosing and administration of NBUVB in vitiligo, reflected by varied treatment practices around the world. To create phototherapy recommendations to facilitate clinical management and identify areas requiring future research. The Vitiligo Working Group (VWG) Phototherapy Committee addressed 19 questions regarding the administration of phototherapy over 3 conference calls. Members of the Photomedicine Society and a group of phototherapy experts were surveyed regarding their phototherapy practices. Based on comparison and analysis of survey results, expert opinion, and discussion held during conference calls, expert recommendations for the administration of NBUVB phototherapy in vitiligo were created. There were several areas that required further research before final recommendations could be made. In addition, no standardized methodology was used during literature review and to assess the strength of evidence during the development of these recommendations. This set of expert recommendations by the VWG is based on the prescribing practices of phototherapy experts from around the world to create a unified, broadly applicable set of recommendations on the use of NBUVB in vitiligo. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Vitiligo

MedlinePlus

... Care Medical Treatment Living With Vitiligo Print Fair, dark, or any shade in between — most of us ... but rather by how active the cells are. Dark-skinned people have cells that naturally produce a ...

Prevalence of Vitiligo and Associated Comorbidities in Korea

PubMed Central

Lee, Hemin; Lee, Mu-Hyoung; Lee, Dong Youn; Kang, Hee Young; Kim, Ki Ho; Choi, Gwang Seong; Shin, Jeonghyun; Lee, Hee Jung; Kim, Dong Hyun; Kim, Tae Heung; Lee, Ai-Young; Lee, Seung Chul; Lee, Sanghoon; Kim, Kyoung Wan; Hann, Seung-Kyung

2015-01-01

Purpose Vitiligo prevalence and its associated comorbidities rate have been reported variably among different populations. We aimed to determine the prevalence of vitiligo in Korea along with the baseline rate of comorbidities and compared the risks to the general population using hospital visit information of the total population in Korea. Materials and Methods We assessed demographic characteristics of vitiligo patients in Korean population from 2009 to 2011 in a nationwide data from Health Insurance Review Assessment Service. Patients who had at least one visit to Korea's primary, secondary, or tertiary referral hospitals with International Classification of Diseases, 10th Revision, Clinical Modification diagnosis code for vitiligo were identified. As a supplementary study, comorbidities associated with vitiligo were selected for further review to calculate relative risks compared to the general population. Results The annual prevalence of vitiligo determined by hospital-visiting rate in Korea was 0.12% to 0.13% over a three year period. In sync with other previous epidemiological studies, there was bimodal distribution among the age groups and no difference between genders. Also, vitiligo in Korean population was associated with various autoimmune/non-autoimmune diseases such as thyroiditis, atopic dermatitis, and psoriasis. Conclusion This study was by far the most comprehensive review on prevalence of vitiligo using a data of total population in Korea. The prevalence is within a range of those reported in previous literatures, and increased risk of comorbidities such as thyroid diseases and psoriasis in vitiligo might aid clinicians in the initial work up of vitiligo patients and concurrent follow ups. PMID:25837178

[Vitiligo and emotions].

PubMed

Nogueira, Lucas S C; Zancanaro, Pedro C Q; Azambuja, Roberto D

2009-01-01

On average, vitiligo affects one percent of the world population. More than 75% of the patients have negative self-image on account of the disease. The emotional impact of the dermatosis is frequently neglected by the caretaker, which has negative influence on therapy and prognosis. OBJECTIVE; To check the effect of vitiligo on patients emotions and discuss the mind-body interaction and its impact on the disease. METHODS; In their first medical visit, one hundred patients with various forms of vitiligo answered a question about which emotions were elicited by the presence of the spots. RESULTS; Eighty-eight percent of the patients with spots in exposed areas complained of unpleasant emotions versus twenty-seven percent of those with spots in unexposed areas. The most frequently referred emotions were fear, specifically of expansion of the spots (71%), shame (57%), insecurity (55%), sadness (55%) and inhibition (53%). CONCLUSION; Chronic illnesses generate in human beings a negative experience propitiated by the expectation of suffering. Besides appropriate scientific guidance, vitiligo patients need emotional comfort. Treatment outcomes and patients compliance to it, and even their resilience to face occasional therapeutic failures, rely on good physician-patient relationship. At a time when doctors make use of reputable therapeutic resources, it is indispensable that dermatologists become able to evaluate the patient in an integrative fashion.

Current Management of Pediatric Vitiligo.

PubMed

Van Driessche, Freya; Silverberg, Nanette

2015-08-01

Vitiligo is a common inflammatory disorder with worldwide prevalence of 0.4-2 % of the population, with half of cases beginning in childhood. The management of childhood vitiligo should be tailored to avoid negative effects on the overall growth and psychological development of the patient. Therapy of vitiligo in childhood is chosen based on the location of the lesions, lesion age, and extent of lesions in the context of the child's age and the developmental status of the child. There are four age categories in childhood vitiligo: [1] infantile and toddler (rare) (ages 0-3 years), [2] ages 4-8 years, [3] ages 9-12 years, and [4] 13+ years of age, based on developmental stage, psychological maturation, and ability to comply or participate in therapy. These categories are also differentiated psychologically by susceptibility to bullying, self-image development, and personal concern with lesion appearance, which increases with time. Intervention is advisable in cases with facial and leg involvement due to prominence of lesions and cosmetic defect. Medical interventions are largely the usage of topical therapies including corticosteroids and calcineurin inhibitors, some vitamin therapy (oral and topical vitamin D), and judicious introduction of phototherapy sources based on age and severity. Screening and appropriate subspecialist referral for co-morbidities (e.g., thyroid disease, celiac disease, psychological distress, and vitamin D deficiency) may enhance overall health. Cosmesis and camouflage are generally safe in childhood and have been noted to improve overall quality of life in this grouping. Genetic transmission of vitiligo is minimal at 5-6 % in first-degree relatives. This article reviews the therapeutics of pediatric vitiligo from the perspective of developmental stages and response to therapy.

Impact of Ultraviolet Light on Vitiligo.

PubMed

Singh, Rasnik K

2017-01-01

Vitiligo is a disorder of the melanocytes that results in a dynamic spectrum of skin depigmentation. Its etiology is complex and multifactorial, with data supporting several different hypotheses. Given its prominent phenotype, vitiligo has a significant negative impact on quality of life. Coupled with the chronic and incurable nature of the disease, this presents a formidable treatment challenge. Several treatment modalities have been instituted over the years, with varying efficacy. This chapter focuses on the use of ultraviolet light in vitiligo as an established therapeutic option.

Chemical-induced Vitiligo

PubMed Central

Harris, John E.

2016-01-01

Synopsis Chemical-induced depigmentation of the skin has been recognized for over 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. The importance of recognizing this phenomenon was highlighted during an outbreak of vitiligo in Japan during the summer of 2013, when over 16,000 users of a new skin lightening cosmetic cream developed skin depigmentation at the site of contact with the cream and many in remote areas as well. Depigmenting chemicals appear to be analogs of the amino acid tyrosine that disrupt melanogenesis and result in autoimmunity and melanocyte destruction. Because chemical-induced depigmentation is clinically and histologically indistinguishable from non-chemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as “chemical-induced vitiligo”, rather than less accurate terms that have been previously used. PMID:28317525

Vi-da: vitiligo diagnostic assistance mobile application

NASA Astrophysics Data System (ADS)

Nugraha, G. A.; Nurhudatiana, A.; Bahana, R.

2018-03-01

Vitiligo is a skin disorder in which white patches of depigmentation appear on different parts of the body. Usually, patients come to hospitals or clinics to have their vitiligo conditions assessed. This can be very tiring to the patients, as vitiligo treatments usually take a relatively long period of time, which can range from months to years. To address this challenge, we present in this paper a prototype of an Android-based mobile application called Vi-DA, which stands for Vitiligo Diagnostic Assistance. Vi-DA consists of three subsystems, which are user sign-up subsystem, camera and image analysis subsystem, and progress report subsystem. The mobile application was developed in Java programming language and uses MySQL as the database system. Vi-DA adopts a vitiligo segmentation algorithm to segment input image into normal skin area, vitiligo skin area, and non-skin area. Results showed that Vi-DA gave comparable results to the previous system implemented in Matlab. User acceptance testing results also showed that all respondents agreed on the usefulness of the system and agreed to use Vi-DA again in the future. Vi-DA benefits both dermatologists and patients as not only a computer-aided diagnosis (CAD) tool but also as a smart application that can be used for self-assessment at home.

Vitiligo and disorders of the retinal pigment epithelium.

PubMed Central

Albert, D M; Wagoner, M D; Pruett, R C; Nordlund, J J; Lerner, A B

1983-01-01

The association of vitiligo with inflammation of the uveal tract is well established. The relationship between vitiligo and hypopigmentation and/or degeneration of the retinal pigment epithelium (RPE) not secondary to ocular inflammation has not been adequately investigated. Sixty (27%) of 223 consecutive patients with vitiligo were found to have some evidence of RPE hypopigmentation ranging from mild, focal areas of involvement in most cases to extensive RPE degeneration with a retinitis pigmentosa-like syndrome in one patient. Fifteen (25%) patients complained of night blindness. Only 6 (4%) of 148 patients in a control group had similar funduscopic findings (p less than 0.001). None of these patients were symptomatic. There have been isolated reports of vitiligo occurring with tapetoretinal degeneration. We report 2 patients with both vitiligo and retinitis pigmentosa. Images PMID:6824621

Prepubertal and postpubertal vitiligo: a multivariate comparative study in 375 patients.

PubMed

Khurrum, Huma; AlGhamdi, Khalid M

2017-01-01

The onset of vitiligo during childhood is common. Limited data exist that compare the clinical associations of prepubertal and postpubertal vitiligo in Arabs. To compare the clinical profile of pre and postpubertal onset vitiligo. A cross-sectional observational study was conducted. The Vitiligo European Task Force questionnaire was completed for each patient. A total of 375 patients were included; 199 had postpubertal vitiligo (>12 years), and 176 had prepubertal onset vitiligo (<12years). There were more females in the prepubertal group (49%) than in the postpubertal group (29%), p-value <0.001. The prepubertal group has had more involvement than the postpubertal group (45% vs 30%, p=0.004). Only 8 cases of segmental vitiligo were observed; five were observed in the prepubertal group of patients. Female gender (OR=2.3; 95% CI:1.5, 3.5), presence of halo nevus (OR=2.2; 95% CI:1.1, 4.4) and face involvement (OR=1.9; 95% CI:1.2, 2.9) were positively associated with prepubertal vitiligo. Stress, as an onset factor, was positively associated (OR=0.51; 95% CI:0.3, 0.8) with postpubertal onset vitiligo. A possible selection bias toward more severe vitiligo cases can be a limitation, because the study was conducted in a clinic specialized in vitiligo. Moreover, a likelihood of false recall bias cannot be excluded. Our data present clinical evidence that vitiligo behaves mostly the same way in the prepubertal group as in the postpubertal group. However, female over-representation, more face involvement and more halo nevi were observed in prepubertal vitiligo, while stress was more prevalent as an aggravating factor in postpubertal vitiligo patients.

Regulatory T-cell cytokines in patients with nonsegmental vitiligo.

PubMed

Kidir, Mehtap; Karabulut, Ayse A; Ercin, Mustafa E; Atasoy, Pınar

2017-05-01

In the etiopathogenesis of vitiligo, the role of suppressor cytokines, such as transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), associated with regulatory T-cells (Treg) is not completely known. In this study, the role of Treg-cell functions in the skin of patients with nonsegmental vitiligo was investigated. Lesional and nonlesional skin samples from 30 adult volunteers ranging in age from 18 to 36 years with nonsegmental vitiligo were compared with normal skin area excision specimens of 30 benign melanocytic nevus cases as controls. All samples were evaluated staining for forkhead box P3 (Foxp3), TGF-β, and IL-10 using the standardized streptavidin-biotin immunoperoxidase immunohistochemistry method. Foxp3 expression was lower in lesional vitiligo skin specimens compared to controls; it was also lower in lesional vitiligo specimens than nonlesional vitiligo specimens. IL-10 levels were lower in lesional vitiligo specimens compared to the controls, whereas IL-10 expression was significantly lower in lesional specimens compared with nonlesional specimens. TGF-β expression was higher in both lesional and nonlesional skin specimens of patients with vitiligo compared to controls. TGF-β expression was lower in lesional skin specimens than nonlesional skin specimens. In addition, there was no significant correlation between Foxp3 expression with TGF-β and IL-10 expressions in lesional skin specimens in the vitiligo group. In this study, results supporting the contribution of Treg cells and IL-10 deficiency to the autoimmune process were obtained. Therefore, future studies are necessary to demonstrate the definitive role of Treg-cell functions in the etiopathogenesis of vitiligo. © 2017 The International Society of Dermatology.

Water Buffalo (Bubalus bubalis) as a spontaneous animal model of Vitiligo.

PubMed

Singh, Vijay Pal; Motiani, Rajender K; Singh, Archana; Malik, Garima; Aggarwal, Rangoli; Pratap, Kunal; Wani, Mohan R; Gokhale, Suresh B; Natarajan, Vivek T; Gokhale, Rajesh S

2016-07-01

Vitiligo is a multifactorial acquired depigmenting disorder. Recent insights into the molecular mechanisms driving the gradual destruction of melanocytes in vitiligo will likely lead to the discovery of novel therapies, which need to be evaluated in animal models that closely recapitulate the pathogenesis of human vitiligo. In humans, vitiligo is characterized by a spontaneous loss of functional melanocytes from the epidermis, but most animal models of vitiligo are either inducible or genetically programmed. Here, we report that acquired depigmentation in water buffalo recapitulates molecular, histological, immunohistochemical, and ultrastructural changes observed in human vitiligo and hence could be used as a model to study vitiligo pathogenesis and facilitate the discovery and evaluation of therapeutic interventions for vitiligo. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Role of IL-17 in Vitiligo: A Review

PubMed Central

Singh, Rasnik K.; Lee, Kristina M.; Vujkovic-Cvijin, Ivan; Ucmak, Derya; Farahnik, Benjamin; Abrouk, Michael; Nakamura, Mio; Zhu, Tian Hao; Bhutani, Tina; Wei, Maria; Liao, Wilson

2016-01-01

IL-17 is involved in the pathogenesis of several autoimmune diseases, however its role in vitiligo has not been well defined. Emerging human and mouse studies have demonstrated that systemic, tissue, and cellular levels of IL-17 are elevated in vitiligo. Many studies have also shown significant positive correlations between these levels and disease activity, extent, and severity. Treatments that improve vitiligo, such as ultraviolet B phototherapy, also modulate IL-17 levels. This review synthesizes our current understanding of how IL-17 may influence the pathogenesis of autoimmune vitiligo at the molecular level. This has implications for defining new vitiligo biomarkers and treatments. PMID:26804758

Reduced immunohistochemical expression of adhesion molecules in vitiligo skin biopsies.

PubMed

Reichert Faria, Adriane; Jung, Juliana Elizabeth; Silva de Castro, Caio César; de Noronha, Lucia

2017-03-01

Because defects in adhesion impairment seem to be involved in the etiopathogenesis of vitiligo, this study aimed to compare the immunohistochemical expression of several adhesion molecules in the epidermis of vitiligo and non lesional vitiligo skin. Sixty-six specimens of lesional and non lesional skin from 33 volunteers with vitiligo were evaluated by immunohistochemistry using anti-beta-catenin, anti-E-cadherin, anti-laminin, anti-beta1 integrin, anti-collagen IV, anti-ICAM-1 and anti-VCAM-1 antibodies. Biopsies of vitiligo skin demonstrated a significant reduction in the expression of laminin and integrin. The average value of the immunohistochemically positive reaction area of the vitiligo specimens was 3053.2μm 2 , compared with the observed value of 3431.8μm 2 in non vitiligo skin (p=0.003) for laminin. The immuno-positive area was 7174.6μm 2 (vitiligo) and 8966.7μm 2 (non lesional skin) for integrin (p=0.042). A reduction in ICAM-1 and VCAM-1 expression in the basal layer of the epidermis in vitiligo samples was also observed (p=0.001 and p<0.001, respectively). However, no significant differences were observed with respect to the expression of beta-catenin, E-cadherin, and collagen IV between vitiligo and non lesional skin. Our results suggest that an impairment in adhesion exists in vitiligo skin, which is supported by the diminished immunohistochemical expression of laminin, beta1 integrin, ICAM-1 and VCAM-1. Copyright © 2017 Elsevier GmbH. All rights reserved.

Macrophage migration inhibitory factor as an incriminating agent in vitiligo.

PubMed

Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Habib, Mona SalahEldeen; Elnaidany, Nada Farag; Kamh, Mona Eaid

2018-03-01

Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Small number of investigated subjects. Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

Prepubertal and postpubertal vitiligo: a multivariate comparative study in 375 patients*

PubMed Central

Khurrum, Huma; AlGhamdi, Khalid M

2017-01-01

Background The onset of vitiligo during childhood is common. Limited data exist that compare the clinical associations of prepubertal and postpubertal vitiligo in Arabs. Objective To compare the clinical profile of pre and postpubertal onset vitiligo. Methods A cross-sectional observational study was conducted. The Vitiligo European Task Force questionnaire was completed for each patient. Results A total of 375 patients were included; 199 had postpubertal vitiligo (>12 years), and 176 had prepubertal onset vitiligo (<12years). There were more females in the prepubertal group (49%) than in the postpubertal group (29%), p-value <0.001. The prepubertal group has had more involvement than the postpubertal group (45% vs 30%, p=0.004). Only 8 cases of segmental vitiligo were observed; five were observed in the prepubertal group of patients. Female gender (OR=2.3; 95% CI:1.5, 3.5), presence of halo nevus (OR=2.2; 95% CI:1.1, 4.4) and face involvement (OR=1.9; 95% CI:1.2, 2.9) were positively associated with prepubertal vitiligo. Stress, as an onset factor, was positively associated (OR=0.51; 95% CI:0.3, 0.8) with postpubertal onset vitiligo. Study limitations A possible selection bias toward more severe vitiligo cases can be a limitation, because the study was conducted in a clinic specialized in vitiligo. Moreover, a likelihood of false recall bias cannot be excluded. Conclusions Our data present clinical evidence that vitiligo behaves mostly the same way in the prepubertal group as in the postpubertal group. However, female over-representation, more face involvement and more halo nevi were observed in prepubertal vitiligo, while stress was more prevalent as an aggravating factor in postpubertal vitiligo patients. PMID:29364437

The role of IL-17 in vitiligo: A review.

PubMed

Singh, Rasnik K; Lee, Kristina M; Vujkovic-Cvijin, Ivan; Ucmak, Derya; Farahnik, Benjamin; Abrouk, Michael; Nakamura, Mio; Zhu, Tian Hao; Bhutani, Tina; Wei, Maria; Liao, Wilson

2016-04-01

IL-17 is involved in the pathogenesis of several autoimmune diseases; however its role in vitiligo has not been well defined. Emerging human and mouse studies have demonstrated that systemic, tissue, and cellular levels of IL-17 are elevated in vitiligo. Many studies have also shown significant positive correlations between these levels and disease activity, extent, and severity. Treatments that improve vitiligo, such as ultraviolet B phototherapy, also modulate IL-17 levels. This review synthesizes our current understanding of how IL-17 may influence the pathogenesis of autoimmune vitiligo at the molecular level. This has implications for defining new vitiligo biomarkers and treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment methods for the evaluation of vitiligo.

PubMed

Alghamdi, K M; Kumar, A; Taïeb, A; Ezzedine, K

2012-12-01

There is no standardized method for assessing vitiligo. In this article, we review the literature from 1981 to 2011 on different vitiligo assessment methods. We aim to classify the techniques available for vitiligo assessment as subjective, semi-objective or objective; microscopic or macroscopic; and as based on morphometry or colorimetry. Macroscopic morphological measurements include visual assessment, photography in natural or ultraviolet light, photography with computerized image analysis and tristimulus colorimetry or spectrophotometry. Non-invasive micromorphological methods include confocal laser microscopy (CLM). Subjective methods include clinical evaluation by a dermatologist and a vitiligo disease activity score. Semi-objective methods include the Vitiligo Area Scoring Index (VASI) and point-counting methods. Objective methods include software-based image analysis, tristimulus colorimetry, spectrophotometry and CLM. Morphometry is the measurement of the vitiliginous surface area, whereas colorimetry quantitatively analyses skin colour changes caused by erythema or pigment. Most methods involve morphometry, except for the chromameter method, which assesses colorimetry. Some image analysis software programs can assess both morphometry and colorimetry. The details of these programs (Corel Draw, Image Pro Plus, AutoCad and Photoshop) are discussed in the review. Reflectance confocal microscopy provides real-time images and has great potential for the non-invasive assessment of pigmentary lesions. In conclusion, there is no single best method for assessing vitiligo. This review revealed that VASI, the rule of nine and Wood's lamp are likely to be the best techniques available for assessing the degree of pigmentary lesions and measuring the extent and progression of vitiligo in the clinic and in clinical trials. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Impact of Vitiligo on Quality of Life.

PubMed

Morales-Sánchez, M A; Vargas-Salinas, M; Peralta-Pedrero, M L; Olguín-García, M G; Jurado-Santa Cruz, F

2017-09-01

Vitiligo is a chronic autoimmune skin disease caused by the destruction of melanocytes. Although quality of life (QOL) in vitiligo has been studied in different countries, it has not yet been investigated in Mexico. The aim of this study was to assess the QOL of Mexican patients with vitiligo. We conducted a cross-sectional study at the research unit of Centro Dermatológico Dr. Ladislao de la Pascua in Mexico City. We included adults with vitiligo and excluded those with other pigmentation disorders or a neurological or psychiatric disorder. Patients on psychoactive medications were also excluded. All the patients were administered the Dermatology Life Quality Index (DLQI), a vitiligo-specific quality of life instrument (the VitiQoL), and the Beck Depression and Anxiety Inventories. We studied 150 patients with vitiligo (103 women [68.7%] and 47 men [31.3%]). The median (interquartile range) age was 38 (20) years. The mean (SD) scores on the DLQI and VitiQoL were 5.2 (5.4) and 32.1 (22.7) out of total possible scores of 30 and 90, respectively. The correlation between questionnaire scores was 0.675 (P<.001). Patients with genital involvement scored significantly worse on the VitiQoL than those without lesions in this area (43.95 [28.4]) vs. 28.98 [20.08], P<.001). The prevalence of depression and anxiety was 34% and 60%, respectively. Vitiligo has a minimal impact on the QOL of our patients. QOL was worse in patients with genital lesions. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Vitiligo on the back and arm (image)

MedlinePlus

Vitiligo is characterized by patches of depigmented skin. Here, the contrast is seen very clearly. People with ... light skin may not notice small areas of vitiligo. This person is receiving ultraviolet light treatment to ...

Development and validation of a patient-reported outcome measure in vitiligo: The Self Assessment Vitiligo Extent Score (SA-VES).

PubMed

van Geel, Nanja; Lommerts, Janny E; Bekkenk, Marcel W; Prinsen, Cecilia A C; Eleftheriadou, Viktoria; Taieb, Alain; Picardo, Mauro; Ezzedine, Khaled; Wolkerstorfer, Albert; Speeckaert, Reinhart

2017-03-01

The Vitiligo Extent Score (VES) has recently been introduced as a physicians' score for the clinical assessment of the extent of vitiligo, but a good patient self-assessment score is lacking. The objective is to develop and validate a simplified version of the VES as a patient-reported outcome measure (PROM). After extensive pilot testing, patients were asked to score their vitiligo extent twice with an interval of 2 weeks using the Self Assessment Vitiligo Extent Score (SA-VES). The scores were compared with the physicians' evaluation (VES). The SA-VES demonstrated very good test-retest reliability (intraclass correlation = 0.948, 95% confidence interval [CI]: 0.911-0.970) that was not affected by age, skin type, or vitiligo distribution pattern. According to patients, this evaluation method was easy to use (22% very easy; 49% easy; 29% normal) and required <5 minutes in the majority of patients (73%, <5 minutes; 24%, 5-10 minutes; 2%, 10-15 minutes). Comparison of the SA-VES and the VES demonstrated excellent correlation (r = 0.986, P <.001). Few patients had a dark skin type. The results demonstrate excellent reliability of the SA-VES and excellent correlation with its investigator-reported counterpart (VES). This patient-oriented evaluation method provides a useful tool for the assessment of vitiligo extent. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Quality of Life in a Vitiligo Support Group.

PubMed

Zabetian, Saba; Jacobson, Gordon; Lim, Henry W; Eide, Melody J; Huggins, Richard H

2017-04-01

BACKGROUND: No study has examined the impact of vitiligo support group membership on vitiligo patient quality of life (QoL).

OBJECTIVE: We sought to examine the QoL impact of vitiligo support groups by comparing QoL and associated patient characteristics between vitiligo patients who are and are not members of a vitiligo support group.

METHODS: Members of a Henry Ford Hospital-sponsored, Southeast Michigan Vitiligo Support Group were compared to non-member vitiligo patients recruited from a previous study cohort.17 Eligible patients were asked to complete the Dermatology Life Quality Index (DLQI) and a study-specific questionnaire designed to collect relevant patient characteristics.

RESULTS: The mean DLQI scores for the support group members and non-members were similar (7.1 ± 5.4 and 6.0 ± 6.5, respectively; P-value 0.2), despite the support group members reporting more severe overall disease and increased disease severity in exposed portions of the body. The African-American: Caucasian ratio and the prevalence of unemployment were both significantly higher among the support group participants. Small sample size may have limited the study's ability to demonstrate the differences between the support group participants and the controls.

CONCLUSIONS: The similar QoL despite an increased prevalence of poorer QoL indicators among the support group participants suggests a protective effect of support group membership.

J Drugs Dermatol. 2017;16(4):344-350.

Autoantibodies and their clinical significance in a black vitiligo population.

PubMed

Grimes, P E; Halder, R M; Jones, C; Chakrabarti, S G; Enterline, J; Minus, H R; Kenney, J A

1983-04-01

The frequency of autoantibodies was determined in 70 black vitiligo patients and controls. Both groups were screened for antithyroid, antinuclear, antigastric parietal cell, anti-smooth muscle cell, and antimitochondrial autoantibodies. The significance of autoantibodies was determined in vitiligo patients by correlating their presence or absence with various clinical features of the patients. The overall frequencies of autoimmune and endocrine diseases were also assessed in vitiligo patients, controls, and their respective families. Vitiligo patients had an increased frequency of antithyroid antibodies and an increased frequency of autoimmune and/or endocrine diseases. These diseases included, especially, hyperthyroidism, hypothyroidism, and alopecia areata. Autoantibody-positive vitiligo patients had an increased frequency of first- and second-degree relatives having autoimmune and/or endocrine diseases. These findings tend to support an autoimmune cause of vitiligo in black patients.

Hypochromic vitiligo: delineation of a new entity.

PubMed

Ezzedine, K; Mahé, A; van Geel, N; Cardot-Leccia, N; Gauthier, Y; Descamps, V; Al Issa, A; Ly, F; Chosidow, O; Taïeb, A; Passeron, T

2015-03-01

Hypochromic vitiligo is a rare entity that has been reported only twice under the term 'vitiligo minor', with an absence of clear delineation. To delineate hypochromic vitiligo through a case series of patients with typical bilateral hypopigmented lesions affecting the face and trunk. This is a retrospective multicentric evaluation study conducted in eight departments of dermatology in France, Belgium, Senegal and Saudi Arabia. Twenty-four cases of hypochromic vitiligo were identified. Fourteen were men and 10 women. The mean age at diagnosis was 35·4 years (range 8-66). Strikingly, all patients were dark skinned, with skin types V and VI. The pattern of distribution was highly similar in most of the patients (18 of 24), with involvement of the face and neck area predominating on seborrhoeic areas associated with multiple isolated hypopigmented macules involving predominantly the scalp. The retrospective nature of this study is its main limitation. Hypochromic vitiligo is not yet part of a conventional classification. The disease seems to be limited to individuals with dark skin types. Hypopigmented seborrhoeic face and neck involvement associated with hypopigmented macules of the trunk and scalp is the hallmark of the disease. © 2014 British Association of Dermatologists.

Quality of life in patients with vitiligo: a cross-sectional study based on Vitiligo Quality of Life index (VitiQoL).

PubMed

Hedayat, Kosar; Karbakhsh, Mojgan; Ghiasi, Maryam; Goodarzi, Azadeh; Fakour, Yousef; Akbari, Zahra; Ghayoumi, Afsaneh; Ghandi, Narges

2016-06-07

Vitiligo is a multi-factorial pigmentary skin disorder. Recently, the importance of emotional and psychological issues is proposed in incidence, progression, relapse and remission of vitiligo. There are limited studies conducted in developing countries, which assess life quality of patients with vitiligo. The aim of this study was the application and evaluation of a disease-specific quality of life index in Iranian patients, for the first time. This cross-sectional biphasic study was conducted on 25 patients as a pilot and another 173 patients as the main study group, in Razi Hospital, Tehran, Iran, 2013-2014. Persian version of Vitiligo Quality of Life index (VitiQoL) was developed with backward-forward method. Based on the pilot study, the validity and reliability were assessed. The Vitiligo Area and Score Index (VASI), VitiQoL, and their relationship, demographic and clinical characteristic of patients were measured. The Mean and standard deviation of the VitiQoL score was 30.5 ± 14.5 (range 0-60 in Persian version). There was a significant relationship between VASI score and VitiQoL (p = 0.015, r = 0.187). Confirmatory factor analysis revealed three important factors within VitiQoL: participation limitation, stigma, and behavior. In subscale analysis based on behavior factor, female patients had poorer quality of life (p = 0.02). Concomitant psychiatric problems, e.g. anxiety and depression, were not associated with QOL; however, they were near to being meaningful (p = 0.06, r = 0.14). VitiQoL is a valid index in estimating life quality of vitiligo patients and has proper relation to disease severity. Focusing on patient's life quality is an important entity in the management of vitiligo patients; relevant supportive group-based consultations and therapies are also important arms when approaching vitiligo.

Low glutathione peroxidase activity levels in patients with vitiligo.

PubMed

Zedan, Hatem; Abdel-Motaleb, Amira Ali; Kassem, Nahed Mahmoud Ali; Hafeez, Heba Ahmed Abdel; Hussein, Mahmoud Rezk Abdelwhahed

2015-01-01

Vitiligo is an idiopathic skin disease characterized by white areas on the skin due to loss of the functional melanocytes, with possible involvement of oxidative stress. Glutathione peroxidase (GPx) is an antioxidant enzyme that protects cells against oxidative damage. To examine serum GPx levels in patients with vitiligo and to relate the findings to the clinical features. The study group included 60 patients with vitiligo and 30 matching healthy controls. GPx activity was evaluated using enzyme-linked immunosorbent assay. We found a significant decrease in serum GPx activity level in the patients with vitiligo compared to the healthy controls (0.29 ± 0.14 versus 0.47 ± 0.13, p < .001). The levels were significantly low in skin phenotypes III and IV (p < .001). Higher levels were also observed with increasing age (≥ 14 years), prolonged disease duration (≥ 3 years), and generalized and extensive vitiligo (< 50%). However, these variations were statistically insignificant. Low levels of serum GPx activity, indicative of a disturbed oxidant-antioxidant system, may contribute to the development of vitiligo. © 2014 Canadian Dermatology Association.

Vitiligo: concise evidence based guidelines on diagnosis and management.

PubMed

Gawkrodger, David J; Ormerod, Anthony D; Shaw, Lindsay; Mauri-Sole, Inma; Whitton, Maxine E; Watts, M Jane; Anstey, Alex V; Ingham, Jane; Young, Katharine

2010-08-01

Vitiligo is a common disease that causes a great degree of psychological distress. In its classical forms it is easily recognised and diagnosed. This review provides an evidence based outline of the management of vitiligo, particularly with the non-specialist in mind. Treatments for vitiligo are generally unsatisfactory. The initial approach to a patient who is thought to have vitiligo is to make a definite diagnosis, offer psychological support, and suggest supportive treatments such as the use of camouflage cosmetics and sunscreens, or in some cases after discussion the option of no treatment. Active therapies open to the non-specialist, after an explanation of potential side effects, include the topical use of potent or highly potent steroids or calcineurin inhibitors for a defined period of time (usually 2 months), following which an assessment is made to establish whether or not there has been a response. Patients whose condition is difficult to diagnose, unresponsive to straightforward treatments, or is causing psychological distress, are usually referred to a dermatologist. Specialist dermatology units have at their disposal phototherapy, either narrow band ultraviolet B or in some cases photochemotherapy, which is the most effective treatment presently available and can be considered for symmetrical types of vitiligo. Depigmenting treatments and possibly surgical approaches may be appropriate for vitiligo in selected cases. There is no evidence that presently available systemic treatments are helpful and safe in vitiligo. There is a need for further research into the causes of vitiligo, and into discovering better treatments.

Knowledge, beliefs, and perceptions of Turkish vitiligo patients regarding their condition*

PubMed Central

Topal, Ilteris Oguz; Duman, Hatice; Goncu, Ozgur Emek Kocaturk; Durmuscan, Mustafa; Gungor, Sule; Ulkumen, Pelin Kuteyla

2016-01-01

BACKGROUND Vitiligo is an acquired pigmentary skin disorder that affects 0.5% to 2.0% of the population. OBJECTIVE Patients' knowledge, opinions, and attitudes about vitiligo were evaluated. METHODS The team conducted a cross-sectional, descriptive, prospective study between June 2014 and May 2015. The study included 100 patients aged over 12 years who were diagnosed with vitiligo. A questionnaire including items on knowledge, opinions, and beliefs about vitiligo and the Illness Perception Questionnaire (IPQ) were filled out by the patients, and the results were analyzed. RESULTS In total, 100 (58 female, 42 male) patients were included in the study. Of them, 74% knew the name of their disease, 90% thought that vitiligo was not contagious, 48% reported that they obtained information on the disease from a doctor, and 69% believed they had adequate information on vitiligo. Eighty percent reported no negative effects from vitiligo on relationships with friends or family. It was believed that stress, excessive sun exposure, and heredity were causes of vitiligo, according to 84%, 37%, and 22% of the patients, respectively. Thirty-six patients (36%) believed that their illness was a serious disease and 35% deemed that it did not have a major impact on their lives. CONCLUSIONS Our results show that vitiligo patients were generally highly aware of their condition. The disease did not negatively affect patient opinions or attitudes about vitiligo. The authors believe that improving patient-physician communication will impact positively on the course of the disease. PMID:28099599

Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib.

PubMed

Rothstein, Brooke; Joshipura, Deep; Saraiya, Ami; Abdat, Rana; Ashkar, Huda; Turkowski, Yana; Sheth, Vaneeta; Huang, Victor; Au, Shiu Chung; Kachuk, Courtney; Dumont, Nicole; Gottlieb, Alice B; Rosmarin, David

2017-06-01

Existing therapies for vitiligo are limited in efficacy and can be associated with undesirable side effects. Topical Janus kinase inhibitors may offer a new therapeutic option for vitiligo. We sought to assess the role of topical ruxolitinib 1.5% cream, a Janus kinase inhibitor, in vitiligo treatment. This 20-week, open-label, proof-of-concept trial of twice-daily topical ruxolitinib 1.5% cream was conducted in 12 patients with a minimum of 1% affected body surface area of vitiligo. The primary outcome was percent improvement in Vitiligo Area Scoring Index from baseline to week 20. Of 12 patients screened, 11 were enrolled and 9 completed the study (54.5% men; mean age, 52 years). Four patients with significant facial involvement at baseline had a 76% improvement in facial Vitiligo Area Scoring Index scores at week 20 (95% confidence interval, 53-99%; P = .001). A 23% improvement in overall Vitiligo Area Scoring Index scores was observed in all enrolled patients at week 20 (95% confidence interval, 4-43%; P = .02). Three of 8 patients responded on body surfaces and 1 of 8 patients responded on acral surfaces. Adverse events were minor, including erythema, hyperpigmentation, and transient acne. Limitations of the study include the small sample size and open-label study design. Topical ruxolitinib 1.5% cream provided significant repigmentation in facial vitiligo and may offer a valuable new treatment for vitiligo. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Isotretinoin and vitiligo: can chronic cheilitis cause koebnerization?

PubMed

Garner, Michael L; McShane, Diana B; Burkhart, Craig N; Morrell, Dean S

2015-01-01

Vitiligo after trauma through koebnerization is a widely reported phenomenon. Herein we present a case of vitiligo in an area of chronic cheilitis after isotretinoin treatment. © 2015 Wiley Periodicals, Inc.

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.

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

Prevalence and Clinical Characteristics of Itch in Vitiligo and Its Clinical Significance.

PubMed

Vachiramon, Vasanop; Onprasert, Woranit; Harnchoowong, Sarawin; Chanprapaph, Kumutnart

2017-01-01

Vitiligo usually presented as asymptomatic depigmented macules and patches. Little is known regarding itch in vitiligo. This study aimed to evaluate the prevalence and characteristics of itch in vitiligo patients. A cross-sectional study was conducted on vitiligo patients. Itch character and intensity were determined through questionnaires. Evaluation was also made by dermatologists to define vitiligo subtype, body surface area, Koebner phenomenon (KP), and so on. Data were assessed by computer software. Results were considered statistically significant if p < 0.05. Among 402 patients, itch on vitiliginous lesion presented in 20.2%. Prevalence of itch was most common in focal vitiligo (29.4%), followed by segmental vitiligo (20.3%) and nonsegmental vitiligo (19.6%), respectively. Tingling sensation was the most common itch-related symptom (82.7%). The median itch intensity is 5 by 10-point visual analog scale. Daily activity and sleep disturbance were observed in 60.5% and 39.5% of patients who experience itch. Itch occurred approximately 3 days prior to the development of lesions in 48.1% of patients. Thirty-two patients (78.1%) with both itch and KP type IIb had active disease. Itch in vitiligo is not uncommon. The presence of itch with KP type IIb may warrant the active vitiligo.

Vitiligo susceptibility and catalase gene (CAT) polymorphisms in sicilian population.

PubMed

Caputo, Valentina; Niceta, Marcello; Fiorella, Santi; La Vecchia, Marco; Bastonini, Emanuela; Bongiorno, Maria R; Pistone, Giuseppe

2017-02-15

Catalase gene (CAT) polymorphisms were analyzed as responsible for the deficiency of catalase enzyme activity and concomitant accumulation of excessive hydrogen peroxide in Vitiligo patients. Catalase is a well known oxidative stress regulator that could play an important role in the pathogenesis of Vitiligo. This study was conducted to evaluate three CAT gene polymorphisms (-89A/T, 389C/T, 419C/T) and their association with Vitiligo susceptibility in Sicilian population. 60 out of 73 Sicilian patients with Vitiligo were enrolled and submitted to CAT gene analysis. Contrary to the Northern part of Europe but likewise to the Mediterranean area, the frequency of the CAT genotypes in Sicily is equally distributed. Out of all CAT genotypes, only CAT -89 T/T frequency was found to be significantly higher amongst Vitiligo patients than controls. Despite the involvement of the CAT enzyme in the pathogenesis of Vitiligo, the biological significance of CAT gene polymorphisms is still controversial. With the only exception for CAT variant -89A/T, the other studied CAT gene polymorphisms (389C/T and 419C/T) might not to be associated with Vitiligo in Sicilian population.

Homeopathic Treatment of Vitiligo: A Report of Fourteen Cases.

PubMed

Mahesh, Seema; Mallappa, Mahesh; Tsintzas, Dionysios; Vithoulkas, George

2017-12-02

BACKGROUND Vitiligo, also known as leukoderma, is an autoimmune skin condition that results in the loss of melanin pigment. Vitiligo is not a rare condition but is difficult to treat and is associated with psychological distress. CASE REPORT A series of 14 cases of vitiligo are presented that were treated with individualized homeopathic remedies that were based on plant, animal, or mineral compounds. There were 13 women and one man in the case series, with a mean age 29.8 years, and a mean follow-up from treatment of 58 months. The mean time between the onset of the appearance of vitiligo and the first consultation at our clinic was 96 months. Homeopathic treatment for patients is holistic and was performed on an individualized basis as described in this case series. Photographic images of the skin are presented before and after treatment. CONCLUSIONS In 14 patients with vitiligo treated with individualized homeopathy, the best results were achieved in the patients who were treated in the early stages of the disease. We believe that homeopathy may be effective in the early stages of vitiligo, but large controlled clinical studies are needed in this area.

[ELEMENTAL STATUS OF PATIENTS WITH VARIOUS FORMS OF VITILIGO].

PubMed

Tsiskarishvili, N I; Katsitadze, A; Tsiskarishvili, N V; Charischarishvili, I

2017-12-01

Vitiligo is a multifactorial disease in which, in each specific case of its manifestation, different mechanisms of its pathogenesis and different levels of melanin formation in the skin can be involved. Skin is one of the most metabolically active organs. Carrying out a number of vital functions (barrier, protective, respiratory, excretory, metabolic, immune, etc.), it needs microelementss. Of the 92 naturally occurring chemical elements, 81 are found in the human body. Lack of the vital elements, leads to the emergence of diseases, which are based on deficiency, excess or imbalance of micro- and macroelements in the body. To assess the elemental status of patients with various forms of vitiligo, fluorescent x-ray spectroscopy was used. The method has good informativeness, since the hair most fully reflects the level of content of both toxic and vital elements. According to the results obtained, in patients with segmental vitiligo, a slight decrease in the content of manganese and copper was detected in the hair. In the group of patients with non-segmental form of vitiligo, along with a significant decrease in the concentration of basic elements (on average from 20 to 50%) copper, manganese, selenium, zinc, there was an increase in the indices of such toxic elements as lead and cadmium. The data of multi-element hair analysis, as are confirmed by well-known information about the role of certain chemical elements in the pathogenesis of vitiligo, also allow us to make new assumptions about the possible relationship between the violation of the microelement balance of the organism with the emergence and peculiarity of the flow of various forms of vitiligo. The correct approach to understanding the mechanisms of the emergence of vitiligo, will allow to offer new effective schemes for the treatment of vitiligo.

Understanding Autoimmunity of Vitiligo and Alopecia Areata

PubMed Central

Rork, Jillian F.; Rashighi, Mehdi; Harris, John E.

2016-01-01

Purpose of review Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include non-targeted approaches such as corticosteroids, topical calcineurin inhibitors, narrow band UVB phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. Recent findings Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFN-γ, IFN-γ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. Summary The identification of IFN-γ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials. PMID:27191524

Micropigmentation for Vitiligo

MedlinePlus

... for Varicose Veins Sclerotherapy for Varicose Veins Back Hair Transplants Laser Treatments for Pre-Cancerous Growth Back ... for Vitiligo Micropigmentation involves implanting small particles of natural pigment under the skin similar to a tattoo. ...

Vitiligo: An Update on Pathophysiology and Treatment Options.

PubMed

Speeckaert, Reinhart; van Geel, Nanja

2017-12-01

The pathophysiology of vitiligo is becoming increasingly clarified. In non-segmental vitiligo, early factors include activation of innate immunity, inflammasome activation, oxidative stress, and loss of melanocyte adhesion. Nonetheless, the main mechanism leading to non-segmental vitiligo involves an immune-mediated destruction of melanocytes. Anti-melanocyte-specific cytotoxic T cells exert a central role in the final effector stage. Genetic research revealed a multi-genetic inheritance displaying an overlap with other autoimmune disorders. However, some melanocyte-specific genes were also affected. Segmental vitiligo carries a different pathogenesis with most evidence indicating a mosaic skin disorder. Current management includes topical corticosteroids and immunomodulators. Narrow-band ultraviolet B can be used in patients not responding to topical treatment or in patients with extensive disease. Pigment cell transplantation offers an alternative for the treatment of segmental vitiligo or stable non-segmental lesions. Recent findings have revealed new targets for treatment that could lead to more efficient therapies. Targeted immunotherapy may halt the active immune pathways, although combination therapy may still be required to induce satisfying repigmentation. A recently established core set of outcome measures, new measurement instruments, and biomarker research pave the way for future standardized clinical trials.

Epidermal Permeability Barrier Recovery Is Delayed in Vitiligo-Involved Sites

PubMed Central

Liu, J.; Man, W.Y.; Lv, C.Z.; Song, S.P.; Shi, Y.J.; Elias, P.M.; Man, M.Q.

2010-01-01

Background/Objectives Prior studies have demonstrated that both the skin surface pH and epidermal permeability barrier function vary with skin pigmentation types. Although melanin deficiency is the main feature of vitiligo, alterations in cutaneous biophysical properties in vitiligo have not yet been well defined. In the present study, stratum corneum (SC) hydration, the skin surface pH and epidermal permeability barrier function in vitiligo were evaluated. Methods A total of 30 volunteers with vitiligo comprising 19 males and 11 females aged 13–51 years (mean age: 27.91 ± 2.06 years) were enrolled in this study. The skin surface pH, SC hydration, melanin/erythema index and transepidermal water loss (TEWL) were measured by respective probes connected to a Courage-Khazaka MPA5. SC integrity was determined by measuring the TEWL following each D-Squame application. The barrier recovery rate was assessed at 5 h following barrier disruption by repeated tape stripping. Results In addition to SC hydration, both melanin and erythema index were significantly lower in vitiligo lesions than in contralateral, nonlesional sites, while no difference in skin surface pH between vitiligo-involved and uninvolved areas was observed. In addition, neither the basal TEWL nor SC integrity in the involved areas differed significantly from that in the uninvolved areas. However, barrier recovery in vitiligo-involved sites was significantly delayed in comparison with uninvolved sites (40.83 ± 5.39% vs. 58.30 ± 4.71%; t = 2.441; p < 0.02). Conclusion Barrier recovery following tape stripping of the SC is delayed in vitiligo. Therefore, improvement in epidermal permeability barrier function may be an important unrecognized factor to be considered in treating patients with vitiligo. PMID:20185976

Vitiligo and overt thyroid diseases: A nationwide population-based study in Korea.

PubMed

Bae, Jung Min; Lee, June Hyunkyung; Yun, Jae Seung; Han, Byeol; Han, Tae Young

2017-05-01

Associations between vitiligo and thyroid diseases have been reported repeatedly. We investigated the associations between vitiligo and overt autoimmune thyroid diseases and thyroid cancer using the Korean National Health Insurance claims database. We defined patients with vitiligo as those whose records showed ≥4 physician contacts between 2009 and 2013 in which vitiligo was the principal diagnosis. We also established an age- and sex-matched control group without vitiligo (2 per 1 vitiligo patient). The outcomes of interest were concurrent Graves disease and Hashimoto thyroiditis (the patients were taking relevant thyroid medications) and thyroid cancer. The study enrolled 73,336 vitiligo patients and 146,672 controls. Patients with vitiligo were at increased risks of Graves disease (odds ratio [OR] 2.610 [95% confidence interval {CI} 2.319-02.938]), Hashimoto thyroiditis (OR 1.609 [95% CI 1.437-1.802]), and thyroid cancer (OR 1.127 [95% CI 1.022-1.242]), compared with the controls. The associations were consistently stronger in males and younger patients. Individual clinical information was not available, and the homogeneous population may limit the generalizability of the results. Vitiligo was significantly associated with overt autoimmune thyroid diseases and overt thyroid cancer. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Association analysis of class II cytokine and receptor genes in vitiligo patients.

PubMed

Traks, Tanel; Karelson, Maire; Reimann, Ene; Rätsep, Ranno; Silm, Helgi; Vasar, Eero; Kõks, Sulev; Kingo, Külli

2016-05-01

The loss of melanocytes in vitiligo is mainly attributed to defective autoimmune mechanisms and lately autoinflammatory mediators have become more emphasized. Among these, a number of class II cytokines and their receptors have displayed altered expression patterns in vitiligo. Thus, we selected 30 SNPs from the regions of respective genes to be genotyped in Estonian case-control sample (109 and 328 individuals, respectively). For more precise analyses, patients were divided into subgroups based on vitiligo progression activity, age of onset, sex, occurrence of vitiligo among relatives, extent of depigmented areas, appearance of Köbner's phenomenon, existence of halo nevi, occurrence of spontaneous repigmentation, and amount of thyroid peroxidase antibodies. No associations appeared in whole vitiligo group. In subgroups, several allelic and haplotype associations were found. The strongest involved SNPs rs12301088 (near IL26 gene), that was associated with familial vitiligo and existence of halo nevi, and rs2257167 (IFNAR1 gene), that was associated with female vitiligo. Additionally, haplotypes consisting of rs12301088 and rs12321603 alleles (IL26-IL22 genes), that were associated with familial vitiligo and existence of halo nevi. In conclusion, several genetic associations with vitiligo subphenotypes were revealed and functional explanations to these remain to be determined in respective studies. Copyright © 2016. Published by Elsevier Inc.

Unconventional Treatments for Vitiligo: Are They (Un) Satisfactory?

PubMed

Gianfaldoni, Serena; Tchernev, Georgi; Lotti, Jacopo; Wollina, Uwe; Satolli, Francesca; Rovesti, Miriam; França, Katlein; Lotti, Torello

2018-01-25

The authors show a brief overview of the vitiligo's unconventional therapies. A part for well-documented effectiveness of L-phenylalanine, PGE2 and antioxidant agents in the treatment of vitiligo, for the other therapeutical approaches more investigations are needed.

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

Vitiligo: Pathogenesis, clinical variants and treatment approaches.

PubMed

Iannella, Giannicola; Greco, Antonio; Didona, Dario; Didona, Biagio; Granata, Guido; Manno, Alessandra; Pasquariello, Benedetta; Magliulo, Giuseppe

2016-04-01

Vitiligo is a common chronic acquired disease of pigmentation whose etiology is unknown, which usually occurs with asymptomatic whitish patch or macule. Although several hypotheses have been proposed in the literature, the leading theory is still the auto-immune etiology linked to specific genetic mutations. Vitiligo can also be associated with several autoimmune diseases, including autoimmune thyroid diseases, alopecia areata, and halo nevi. Sensorineural hearing loss was reported in several vitiligo patients due to a reduction in the number of melanocytes contained in the membranous labyrinth of the inner ear. Because of its complexity, several therapeutic options are available to treat this systemic disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population.

PubMed

Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael

2016-08-01

Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected.

MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligo.

PubMed

Sahoo, Anupama; Lee, Bongyong; Boniface, Katia; Seneschal, Julien; Sahoo, Sanjaya K; Seki, Tatsuya; Wang, Chunyan; Das, Soumen; Han, Xianlin; Steppie, Michael; Seal, Sudipta; Taieb, Alain; Perera, Ranjan J

2017-09-01

Vitiligo is a common chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical causes, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. In this study we characterized the human vitiligo cell line PIG3V and the normal human melanocyte line HEM-l by RNA sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched microRNA-211, a known metabolic switch in nonpigmented melanoma cells, was severely down-regulated in vitiligo cell line PIG3V and skin biopsy samples from vitiligo patients, whereas its predicted targets PPARGC1A, RRM2, and TAOK1 were reciprocally up-regulated. microRNA-211 binds to PGC1-α 3' untranslated region locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated microRNA-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of microRNA-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Association between FOXP3 polymorphisms and vitiligo in a Han Chinese population.

PubMed

Song, P; Wang, X-W; Li, H-X; Li, K; Liu, L; Wei, C; Jian, Z; Yi, X-L; Li, Q; Wang, G; Li, C-Y; Gao, T-W

2013-09-01

Vitiligo is an autoimmune chronic depigmentation disorder caused by melanocyte loss. Previous studies found that CD4(+)CD25(+) regulatory T-cell (Treg) dysfunction was involved in the pathogenesis of vitiligo and that gene polymorphisms in forkhead box P3 (FOXP3) - a master regulator of Treg development and function - were associated with susceptibility to some autoimmune disorders. Therefore, we hypothesized that functional polymorphisms of the FOXP3 gene might be associated with vitiligo via dysregulation of Treg cells. To evaluate whether FOXP3 polymorphisms are associated with vitiligo risk. In this hospital-based case-control study of 682 patients with vitiligo and 682 vitiligo-free age- and sex-matched controls, we genotyped three single nucleotide polymorphisms (SNPs) of the FOXP3 gene - rs2232365, rs3761548 and rs5902434 - by performing polymerase chain reaction with sequence-specific primers (PCR-SSP). Significantly increased vitiligo risk was associated with the rs2232365 GG [odds ratio (OR) 1·68, 95% confidence interval (CI) 1·17-2·39, P = 0·004] and rs3761548 AA (OR 1·82, 95% CI 1·10-3·01, P = 0·033) genotypes compared with the rs2232365 AA and rs3761548 CC genotypes. On combined analysis of these three variant alleles, we found that individuals carrying 2-6 variant alleles had significantly increased vitiligo risk (OR 1·34, 95% CI 1·08-1·66). This risk was more pronounced in the following subgroups: age > 20 years, male sex, active vitiligo, nonsegmental vitiligo and other accompanying autoimmune diseases. FOXP3 gene polymorphisms contributed to vitiligo risk in a Han Chinese population. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Camouflage for patients with vitiligo vulgaris improved their quality of life.

PubMed

Tanioka, Miki; Yamamoto, Yosuke; Kato, Mayumi; Miyachi, Yoshiki

2010-03-01

Cosmetic camouflage is important for patients with vitiligo vulgaris. However, few studies have investigated its benefit for vitiligo patients. To analyze the psychological effects on patients with vitiligo vulgaris by camouflage lessons performed in vitiligo clinics in Kyoto University Hospital and Fukui Red Cross Hospital, Dermatological Life Quality Index (DLQI) questionnaires were collected before and 1 month after camouflage lessons. Patients with vitiligo vulgaris, who visited our clinics in 2008 and had never experienced camouflage, were enrolled in this study. They took camouflage lessons and continued subsequent self-camouflage for 1 month. Control patients took no lessons and no camouflage. Camouflage improved the scores of DLQI when compared with those without camouflage (P = 0.005). Camouflage improved DLQI scores from 5.90 to 4.48. In DLQI subcategories, camouflage lessons improved a subcategory of "symptoms and feelings" (P = 0.0037). These data supported the idea that camouflage for patients with vitiligo not only covers the white patches but also improves their quality of life.

Increased risk of comorbid rheumatic disorders in vitiligo patients: A nationwide population-based study.

PubMed

Choi, Chong Won; Eun, Sung Hye; Choi, Kwang Hyun; Bae, Jung Min

2017-08-01

Vitiligo is a common acquired depigmentation disorder. Previous studies have shown that vitiligo is associated with a variety of autoimmune disorders. However, a large-scale epidemiological study focused on comorbid rheumatic disorders has not been undertaken. To clarify the associations between vitiligo and various rheumatic disorders, we performed a cross-sectional study using data from the Korean National Health Insurance claims database. Between 2009 and 2013, totals of 86 210 patients with vitiligo and 172 420 age- and sex-matched controls without vitiligo were enrolled in this study. Vitiligo patients were found to be at increased risk of systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome and rheumatoid arthritis, but no significant association was found between vitiligo and dermatomyositis/polymyositis, Behçet's disease or ankylosing spondylitis. Subgroup analysis showed an increased risk of dermatomyositis/polymyositis in male and ankylosing spondylitis in female vitiligo patients. The risks of dermatomyositis/polymyositis or ankylosing spondylitis were higher in young vitiligo patients. Our study confirms a significant association between vitiligo and rheumatic disorders. Differences in comorbid rheumatic disorders by age group and sex suggest the need for patient-specific approaches. Careful consideration of rheumatic disorders is required for the proper management of comorbidities in vitiligo patients. © 2017 Japanese Dermatological Association.

Homeopathic Treatment of Vitiligo: A Report of Fourteen Cases

PubMed Central

Mahesh, Seema; Mallappa, Mahesh; Tsintzas, Dionysios; Vithoulkas, George

2017-01-01

Case series Patient: — Final Diagnosis: — Symptoms: Skin lesions Medication: — Clinical Procedure: — Specialty: Dermatology Objective: Unusual or unexpected effect of treatment Background: Vitiligo, also known as leukoderma, is an autoimmune skin condition that results in the loss of melanin pigment. Vitiligo is not a rare condition but is difficult to treat and is associated with psychological distress. Case Reports: A series of 14 cases of vitiligo are presented that were treated with individualized homeopathic remedies that were based on plant, animal, or mineral compounds. There were 13 women and one man in the case series, with a mean age 29.8 years, and a mean follow-up from treatment of 58 months. The mean time between the onset of the appearance of vitiligo and the first consultation at our clinic was 96 months. Homeopathic treatment for patients is holistic and was performed on an individualized basis as described in this case series. Photographic images of the skin are presented before and after treatment. Conclusions: In 14 patients with vitiligo treated with individualized homeopathy, the best results were achieved in the patients who were treated in the early stages of the disease. We believe that homeopathy may be effective in the early stages of vitiligo, but large controlled clinical studies are needed in this area. PMID:29196612

HYPOTHESIS: ZINC CAN BE EFFECTIVE IN TREATMENT OF VITILIGO

PubMed Central

Bagherani, Nooshin; Yaghoobi, Reza; Omidian, Mohammad

2011-01-01

Vitiligo is a common depigmenting skin disorder (prevalence 0.1-2%), still represents a cause of stigmatization and quality of life impairment in a large population. Several theories on vitiligo etiopathogenesis have been suggested including in trauma, stress, and autoimmune and genetic predisposition, accumulation of toxic compounds, altered cellular environment, imbalance in the oxidant-antioxidant system, impaired melanocyte migration and/or proliferation, infection, and psychological factors. Zinc, as a trace element, has many vital functions in human. It is antiapoptotic factor and needed as a cofactor for antioxidant defense system. It plays an important role in the process of melanogenesis. It may be effective in prevention and treatment of vitiligo via some mechanism. Herein, we suggested some probable protective mechanism for zinc in association with vitiligo. PMID:22121258

Vitiligo on black skin: epidemiological and clinical aspects in dermatology, Cotonou (Benin).

PubMed

Dégboé, Bérénice; Atadokpèdé, Félix; Saka, Bayaki; Adégbidi, Hugues; Koudoukpo, Christiane; Yédomon, Hubert; do Ango-Padonou, Florencia

2017-01-01

Vitiligo is unsightly on darkly pigmented skin and leads important stigmatization because of the mix-up with leprosy. We analyzed retrospectively the epidemiological and clinical patterns of vitiligo on darkly pigmented skin between 1988 and 2008 in the Department of Dermatology in Cotonou (Benin). The diagnosis was made based on the clinical characteristics of vitiligo. Two hundred and forty-six patients were seen, representing 0.9% of new consultations. The gender ratio was 1 : 1, and the mean age of patients was 25.9 years. The mean duration of the lesions was 30.9 months. Among the 246 patients, an associated pathology was found in 26% of cases. These included atopy (23.2%), diabetes (1.6%), thyroid disease (0.8%), and alopecia (0.4%). A family history of vitiligo was present in 1.2% of cases. The sites of the lesions were in descending order of frequency: head (60.6%), lower limbs (40.2%), upper limbs (33.3%), trunk (22.4%), genitals (13.0%), and neck (8.9%). On the head, the most common sites affected were the lips (65.1%), cheek (20.8%), and ears (16.8%). According to the different clinical forms, vitiligo was achromic (76%), speckled (12.6%), and trichromic (11.4%). Vitiligo vulgaris was the commonest form of the disease (52.4%), followed by localized vitiligo (36.2%), segmental vitiligo (9.8%), and vitiligo universalis (1.6%). Triggering factors were identified in 4.5% of patients. Our survey shows that the patterns of vitiligo are similar to that reported from other African countries with a few distinguishing particularities. © 2016 The International Society of Dermatology.

Oxidation products are increased in patients affected by non-segmental generalized vitiligo.

PubMed

Vaccaro, Mario; Bagnato, Gianluca; Cristani, Mariateresa; Borgia, Francesco; Spatari, Giovanna; Tigano, Valeria; Saja, Antonina; Guarneri, Fabrizio; Cannavò, Serafinella P; Gangemi, Sebastiano

2017-08-01

Several lines of evidence support the relevance of reactive oxygen species (ROS) in vitiligo, but the exact role of glycation and oxidation of macromolecules needs to be better addressed. To investigate the involvement of advanced oxidation protein products (AOPPs) and advanced glycation end-products (AGEs), we performed a case-control association study by spectrofluorimetry and spectrophotometry, in 47 patients with non-segmental generalized vitiligo and 47 age- and sex-matched controls. Significantly higher levels of both AOPPs (p < 0.0001) and AGEs (p < 0.0001) were observed in vitiligo patients compared to healthy controls. In vitiligo patients, AGEs and AOPPs serum levels were directly associated with extension, duration of vitiligo, and disease activity. ROS, and in particular AGEs and AOPPs, could represent one of the main biomarkers to assess the onset and progression of vitiligo, due to the potential role as direct inducers of cell damage and also as autoimmunity triggers. Further longitudinal studies involving larger cohorts of patients are required to elucidate the role of oxidation products in the pathogenesis of vitiligo.

Retrospective study on the characteristics and treatment of late-onset vitiligo.

PubMed

Kong, Yan Ling; Ching, Vanessa Hui Ling; Chuah, Sai Yee; Thng, Tien Guan

2017-01-01

Late-onset vitiligo, defined as being aged 50 years and above at the point of clinical onset, remains poorly characterized till now. This study aims to describe the clinical characteristics and treatment response of patients with late-onset vitiligo. We retrospectively reviewed the case records of all patients diagnosed with late-onset vitiligo, from January 1, 2010 to December 31, 2014. Information obtained included patient demographics, characteristics of vitiligo and treatment responses. Of the 3128 patients diagnosed with vitiligo over the 5-year period, 461 (14.7%) had late-onset disease. The study had more females (n = 260, 56.4%) than males, with an average onset age of 59.4 ± 7.4 years. Majority of patients were Chinese (n = 308, 66.8%) and 45 (9.8%) patients had an associated autoimmune disease. Focal vitiligo, defined as the localized presence of depigmented patches, was most common (n = 209, 45.3%). Treatment response was evaluated in 359 patients, of which 216 received monotherapy (topical creams: n = 210, 97.2%; phototherapy: n = 6, 2.8%) and 143 received both modalities. Fifty six (15.6%) patients received oral steroids. Patients who were treated with both topical creams and phototherapy yielded better clinical responses compared to those on monotherapy (P < 0.001) with 56.6% (n = 81) of them achieving good epidermal repigmentation, defined as >50% return of pigmentation compared to baseline (vs. n = 66, 30.6% in the monotherapy group). The choice of phototherapy (targeted, narrowband ultraviolet B or psoralen + ultraviolet A) did not significantly affect clinical response (P = 0.774). This study is limited by its retrospective nature, the nonstandardized documentation resulting in the inability to determine disease progression and associated metabolic comorbidities and also by the gradual loss to follow-up of patients. Late-onset vitiligo is not uncommon and tends to be of the focal vitiligo subtype. Nonsegmented vitiligo is more prevalent than

Modern vitiligo genetics sheds new light on an ancient disease

PubMed Central

SPRITZ, Richard A.

2013-01-01

Vitiligo is a complex disorder in which autoimmune destruction of melanocytes results in white patches of skin and overlying hair. Over the past several years, extensive genetic studies have outlined a biological framework of vitiligo pathobiology that underscores its relationship to other autoimmune diseases. This biological framework offers insight into both vitiligo pathogenesis and perhaps avenues towards more effective approaches to treatment and even disease prevention. PMID:23668538

Vitiligo: A Possible Model of Degenerative Diseases

PubMed Central

Bellei, Barbara; Pitisci, Angela; Ottaviani, Monica; Ludovici, Matteo; Cota, Carlo; Luzi, Fabiola; Dell'Anna, Maria Lucia; Picardo, Mauro

2013-01-01

Vitiligo is characterized by the progressive disappearance of pigment cells from skin and hair follicle. Several in vitro and in vivo studies show evidence of an altered redox status, suggesting that loss of cellular redox equilibrium might be the pathogenic mechanism in vitiligo. However, despite the numerous data supporting a pathogenic role of oxidative stress, there is still no consensus explanation underlying the oxidative stress-driven disappear of melanocytes from the epidermis. In this study, in vitro characterization of melanocytes cultures from non-lesional vitiligo skin revealed at the cellular level aberrant function of signal transduction pathways common with neurodegenerative diseases including modification of lipid metabolism, hyperactivation of mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB), constitutive p53-dependent stress signal transduction cascades, and enhanced sensibility to pro-apoptotic stimuli. Notably, these long-term effects of subcytotoxic oxidative stress are also biomarkers of pre-senescent cellular phenotype. Consistent with this, vitiligo cells showed a significant increase in p16 that did not correlate with the chronological age of the donor. Moreover, vitiligo melanocytes produced many biologically active proteins among the senescence-associated secretory phenotype (SAPS), such as interleukin-6 (IL-6), matrix metallo proteinase-3 (MMP3), cyclooxygenase-2 (Cox-2), insulin-like growth factor-binding protein-3 and 7 (IGFBP3, IGFBP7). Together, these data argue for a complicated pathophysiologic puzzle underlying melanocytes degeneration resembling, from the biological point of view, neurodegenerative diseases. Our results suggest new possible targets for intervention that in combination with current therapies could correct melanocytes intrinsic defects. PMID:23555779

Simultaneous improvement and worsening of vitiligo lesions during the course of NB-UVB phototherapy; vitiligo may not act as one unit.

PubMed

Anbar, Tag; Abdel-Rahman, Amal; Hegazy, Rehab; El-Khayyat, Mohamed; Ragaie, Maha

2017-01-01

Re-pigmentation and stabilization are the two ultimate goals of any re-pigmenting plan designed for vitiligo management. Furthermore, whether the improvement of some vitiligo lesions could be considered a guarantee for a similar response and/or stabilization of the rest of the lesions or not, remains to be clarified. To evaluate the behavior of non-segmental vitiligo (NSV), while on narrow band-ultraviolet B (NB-UVB) phototherapy. 25 patients with stable generalized NSV were included and received NB-UVB twice weekly. For the sake of ensuring accuracy of follow up, up to four lesions were randomly chosen in each patient and regularly measured using the point counting technique. The over-all point counting technique of all included patients showed a significant reduction (18.5 ± 8.4 cm 2 to 8.2± 3.1 cm 2 ) after 6 months of therapy (p < .001). Nine patients (36%), showed mixed response in the different lesions. Improvement was documented in some lesions, while other lesions showed no response or even worsening. No significant correlations were detected between the behavior of vitiligo during NB-UVB and any of the demographic or clinical data of the patients. NB-UVB is a pillar in the management of vitiligo, however close follow-up of the patient as a whole and his lesions, by both subjective and objective measures are mandatory to detect activity as early as possible, as vitiligo at many times may not act as one unit. This early detection of activity and the subsequent change in the treatment policy may ultimately change the final outcome of treatment. © 2016 Wiley Periodicals, Inc.

Epithelial expression of cytokeratins 15 and 19 in vitiligo.

PubMed

Saleh, Fatma Y; Awad, Sherif S; Nasif, Ghada A; Halim, Christein

2016-12-01

Cytokeratins (CK) belong to the family of intermediate filament proteins, and among them specific epithelial keratins are considered markers for stem cells activation. This study aims to investigate the expression of CK15 and CK19 as possible stem cell markers in vitiligo during phototherapy. The study was conducted on vitiligo patients receiving narrow-band ultraviolet therapy. Immunohistochemical staining for CK15 and CK19 was carried out, and clinical follow-up continued for 4 weeks. Of 28 patients, CK15 expression was demonstrated in 17 cases (61%) while CK19 expression was demonstrated in 11 cases (39%). Cells expressing positive staining were demonstrated in follicular and interfollicular epithelium. Expression was clearly demonstrated in patients younger than 20 years old, with shorter disease duration, with disease stability, and with normally pigmented hairs. Expression of cytokeratins was significantly correlated to improvement of vitiligo lesions. CK15 and CK19 are expressed in vitiligo during UV repigmentation in the follicular and interfollicular epithelium. This expression of cytokeratins was significantly correlated to improvement and can be considered valuable tool to monitor stem cells stimulation for the sake of the repigmentation process in vitiligo. © 2016 Wiley Periodicals, Inc.

Epidermal skin grafting in vitiligo: a pilot study.

PubMed

Janowska, Agata; Dini, Valentina; Panduri, Salvatore; Macchia, Michela; Oranges, Teresa; Romanelli, Marco

2016-09-01

Vitiligo is a multifactorial acquired dermatosis characterised by achromic or hypochromic macules and by the absence of functioning melanocytes. Treatment depends on the extent of the affected areas and on disease activity. Surgical techniques have proven to be effective in stable cases but can be time-consuming and, in some cases, aesthetically unsatisfying or painful for the patients. The aim of the study was to assess the clinical safety and effectiveness of a new automatic epidermal skin harvesting device in patients with stable localised vitiligo over a minimum 12-month period. This new system (CELLUTOME™ Epidermal Harvesting System, KCI, an ACELITY Company, San Antonio, TX) is a commercially available epidermal skin harvesting system that can be used without local anaesthesia or other pre-treatments and has been shown to have low rates of donor site morbidity. Epidermal skin grafts can used in patients with acute and hard to heal chronic wounds, burns and stable vitiligo. The use of advanced therapies may improve the quality of life, have cost benefits and accelerate re-pigmentation of patients with vitiligo. In our preliminary study, this system was seen to be a safe and efficacious means of harvesting epidermal micrografts containing melanocytes for use in patients with stable vitiligo unresponsive to standard therapies. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Pigmentation Traits, Sun Exposure, and Risk of Incident Vitiligo in Women.

PubMed

Dunlap, Rachel; Wu, Shaowei; Wilmer, Erin; Cho, Eunyoung; Li, Wen-Qing; Lajevardi, Newsha; Qureshi, Abrar

2017-06-01

Vitiligo is the most common cutaneous depigmentation disorder worldwide, yet little is known about specific risk factors for disease development. Using data from the Nurses' Health Study, a prospective cohort study of 51,337 white women, we examined the associations between (i) pigmentary traits and (ii) reactions to sun exposure and risk of incident vitiligo. Nurses' Health Study participants responded to a question about clinician-diagnosed vitiligo and year of diagnosis (2001 or before, 2002-2005, 2006-2009, 2010-2011, or 2012+). We used Cox proportional hazards regression models to estimate the multivariate-adjusted hazard ratios and 95% confidence intervals of incident vitiligo associated with exposures variables, adjusting for potential confounders. We documented 271 cases of incident vitiligo over 835,594 person-years. Vitiligo risk was higher in women who had at least one mole larger than 3 mm in diameter on their left arms (hazard ratio = 1.37, 95% confidence interval = 1.02-1.83). Additionally, vitiligo risk was higher among women with better tanning ability (hazard ratio = 2.59, 95% confidence interval = 1.21-5.54) and in women who experienced at least one blistering sunburn (hazard ratio = 2.17, 95% confidence interval = 1.15-4.10). In this study, upper extremity moles, a higher ability to achieve a tan, and history of a blistering sunburn were associated with a higher risk of developing vitiligo in a population of white women. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Concepciones Alternativas de "Fotosintesis" en estudiantes Universitarios del curso basico de Biologia y posibles correcciones con el Modelo Educativo MODEF

NASA Astrophysics Data System (ADS)

De Jesus Roman, Sandra

Concepciones Alternativas de Fotosíntesis en estudiantes Universitariosdel curso básico de Biología y posibles correcciones con el Modelo Educativo MODEF El modelo educativo para la enseñanza de Fotosíntesis (MODEF) se implantó para trabajar el problema de las concepciones alternativas (CA) en un curso de Biología General. Se evaluaron los resultados en cuanto al logro del aprendizaje significativo. La pregunta central de la investigación fue: ¿Cómo aporta el modelo educativo en la didáctica y comprensión del tema de fotosíntesis? Se efectuó una investigación acción con una fase cuantitativa y una cualitativa. Para la fase cuantitativa se elaboró una prueba para determinar las concepciones alternativas, se validó y se sometió a los estudiantes que participaron en el estudio antes y después de ofrecer la unidad de metabolismo celular. Los participantes eran estudiantes de primer año de la Universidad de Puerto Rico en Bayamón (UPRB). Se llevó a cabo un análisis de consistencia interna de la prueba mediante el método Alfa de Cronbach. Se analizaron las contestaciones a cada pregunta mediante la prueba de Ji cuadrado de contingencia, se efectuó la prueba de t y el coeficiente r de Pearson. La fase cualitativa incluyó la observación participativa de la investigadora- profesora, las reflexiones de los estudiantes y la información de las entrevistas semi-estructuradas que se realizaron a tres estudiantes del curso. El análisis se llevó a cabo mediante el Modelo de Wolcott. Se trabajaron diez CA de las cuales siete fueron corregidas mediante el Modelo MODEF. Las actividades más importantes para el proceso de aprendizaje incluyeron el trabajo de investigación o búsqueda de información para hacer una presentación digital, la elaboración de tablas, los mapas de conceptos, el uso de visuales o videos y las analogías para explicar conceptos o procesos. En conclusión: se recomienda el uso del Modelo MODEF para la discusión del tema de

Gender differences in clinicoepidemiological features of vitiligo: a cross-sectional analysis.

PubMed

Patil, Sharmila; Gautam, Manjyot; Nadkarni, Nitin; Saboo, Neha; Godse, Kiran; Setia, Maninder Singh

2014-01-01

Background. Vitiligo has important clinical and social consequences particularly in the pigmented skin. The present study was conducted to assess the differences in clinicoepidemiological presentation of vitiligo in males and females and to understand the factors associated with spread of vitiligo in them. Methods. This is a cross-sectional analysis of secondary clinical data of 168 vitiligo patients at a tertiary medical centre at Navi Mumbai. We used logistic regression models to estimate the association between gender and clinical characteristics of vitiligo and to evaluate the factors associated with spread of vitiligo. Results. There were no significant differences between the mean ages of males and females; however, males reported a longer duration of disease (6.9 (10.4) years) compared with females (4.9 (7.4) years). Males were significantly more likely to report a family history of vitiligo compared with females (adjusted OR (aOR): 16.87, 95% CI: 2.16 to 131.69). Even though females were more likely to report spread of lesions, the association was not statistically significant (OR: 1.21, 95% CI: 0.62 to 2.36). Discussion. The differences in the clinical presentations between genders highlight the need to understand the different factors (possibly genetic) that may play a part in the pathogenesis of this multifactorial disease in males and females.

Immunohistochemical expression of AQP-3 in vitiligo: a new potential guide for disease activity.

PubMed

Hodeib, Abeer; Hegab, Doaa; Rizk, Omnia; Mohammed, Shahdan

2017-08-01

Vitiligo is a depigmenting skin disorder, with disappearance of functioning epidermal melanocytes. Aquaporin-3 (AQP-3) is an aquaglyceroporin expressed in epidermal keratinocytes, where it shares in regulating their proliferation and differentiation, and so it might affect melanocytes indirectly. So far, little is known regarding its possible role in vitiligo. This work aimed to study the changes in immunohistochemical expression of AQP-3 protein in vitiligo to detect its possible role in disease pathogenesis. Skin biopsies were taken from lesional skin of 30 vitiligo patients in addition to 20 normal controls. Epidermal immunohistochemical expression of AQP-3 was assessed as: +3 = strong expression, +2 = moderate, +1= weak and 0= negative expression. AQP-3 was significantly less expressed in vitiligo epidermis than control (P<0.001) with an inverse correlation with Vitiligo Index of Disease Activity (r =-0.505, P=0.004). Reduced epidermal AQP-3 may have a role in impaired melanocyte survival in vitiligo, and might be a potential negative biological marker for vitiligo activity. Larger trials should further elucidate the effect of changes in epidermal AQP-3 expression in development of vitiligo, and that might pave the road for discovering new therapeutic modalities for the disease.

Resolution of vitiligo following excision of halo congenital melanocytic nevus: a rare case report.

PubMed

Wang, Kai; Wang, Zhi; Huang, Weiqing

2016-05-01

Halo congenital melanocytic nevus (CMN) associated with vitiligo is rare, especially with regard to CMN excision. Only two reports of excision of halo CMN following repigmentation of vitiligo are found in the literature. We present a case of a girl with halo CMN and periorbital vitiligo. The halo CMN was excised and followed by spontaneous improvement of vitiligo. The result suggests excision of the inciting lesion may be a promising way to control vitiligo. © 2015 Wiley Periodicals, Inc.

Engineering a new mouse model for vitiligo.

PubMed

Manga, Prashiela; Orlow, Seth J

2012-07-01

Although the precise mechanisms that trigger vitiligo remain elusive, autoimmune responses mediate its progression. The development of therapies has been impeded by a paucity of animal models, since mice lack interfollicular melanocytes, the primary targets in vitiligo. In this issue, Harris et al. describe a mouse model in which interfollicular melanocytes are retained by Kit ligand overexpression and an immune response is initiated by transplanting melanocyte-targeting CD8+ T cells.

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.

New Perspectives on the Role of Vitiligo in Immune Responses to Melanoma

PubMed Central

Byrne, Katelyn T.; Turk, Mary Jo

2011-01-01

Melanoma-associated vitiligo is the best-studied example of the linkage between tumor immunity and autoimmunity. Although vitiligo is an independent positive prognostic factor for melanoma patients, the autoimmune destruction of melanocytes was long thought to be merely a side effect of robust anti-tumor immunity. However, new data reveal a key role for vitiligo in supporting T cell responses to melanoma. This research perspective reviews the history of melanoma-associated vitiligo in patients, the experimental studies that form the basis for understanding this relationship, and the unique characteristics of melanoma-specific CD8 T cells found in hosts with vitiligo. We also discuss the implications of our recent findings for the interpretation of patient responses, and the design of next-generation cancer immunotherapies. PMID:21911918

American Vitiligo Research Foundation

MedlinePlus

... The AVRF is a nonprofit organization that raises money for Vitiligo research and raises awareness for the ... grateful for that. The AVRF not only raises money for itself, but has a "pay it forward" ...

Systematic understanding the mechanisms of vitiligo pathogenesis and its treatment by Qubaibabuqi formula.

PubMed

Pei, Tianli; Zheng, Chunli; Huang, Chao; Chen, Xuetong; Guo, Zihu; Fu, Yingxue; Liu, Jianling; Wang, Yonghua

2016-08-22

Vitiligo is a depigmentation disorder, which results in substantial cosmetic disfigurement and poses a detriment to patients' physical as well as mental. Now the molecular pathogenesis of vitiligo still remains unclear, which leads to a daunting challenge for vitiligo therapy in modern medicine. Herbal medicines, characterized by multi-compound and multi-target, have long been shown effective in treating vitiligo, but their molecular mechanisms of action also remain ambiguous. Here we proposed a systems pharmacology approach using a clinically effective herb formula as a tool to detect the molecular pathogenesis of vitiligo. This study provided an integrative analysis of active chemicals, drug targets and interacting pathways of the Uygur medicine Qubaibabuqi formula for curing Vitiligo. The results show that 56 active ingredients of Qubaibabuqi interacting with 83 therapeutic proteins were identified. And Qubaibabuqi probably participate in immunomodulation, neuromodulation and keratinocytes apoptosis inhibition in treatment of vitiligo by a synergistic/cooperative way. The drug-target network-based analysis and pathway-based analysis can provide a new approach for understanding the pathogenesis of vitiligo and uncovering the molecular mechanisms of Qubaibabuqi, which will also facilitate the application of traditional Chinese herbs in modern medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The changes of gene expression profiling between segmental vitiligo, generalized vitiligo and healthy individual.

PubMed

Wang, Ping; Li, Yong; Nie, Huiqiong; Zhang, Xiaoyan; Shao, Qiongyan; Hou, Xiuli; Xu, Wen; Hong, Weisong; Xu, Aie

2016-10-01

Vitiligo is a common acquired depigmentation skin disease characterized by loss or dysfunction of melanocytes within the skin lesion, but its pathologenesis is far from lucid. The gene expression profiling of segmental vitiligo (SV) and generalized vitiligo (GV) need further investigation. To better understanding the common and distinct factors, especially in the view of gene expression profile, which were involved in the diseases development and maintenance of segmental vitiligo (SV) and generalized vitiligo (GV). Peripheral bloods were collected from SV, GV and healthy individual (HI), followed by leukocytes separation and total RNA extraction. The high-throughput whole genome expression microarrays were used to assay the gene expression profiles between HI, SV and GV. Bioinformatics tools were employed to annotated the biological function of differently expressed genes. Quantitative PCR assay was used to validate the gene expression of array. Compared to HI, 239 over-expressed genes and 175 down-expressed genes detected in SV, 688 over-expressed genes and 560 down-expressed genes were found in GV, following the criteria of log2 (fold change)≥0.585 and P value<0.05. In these differently expressed genes, 60 over-expressed genes and 60 down-expressed genes had similar tendency in SV and GV. Compared to SV, 223 genes were up regulated and 129 genes were down regulated in GV. In the SV with HI as control, the differently expressed genes were mainly involved in the adaptive immune response, cytokine-cytokine receptor interaction, chemokine signaling, focal adhesion and sphingolipid metabolism. The differently expressed genes between GV and HI were mainly involved in the innate immune, autophagy, apoptosis, melanocyte biology, ubiquitin mediated proteolysis and tyrosine metabolism, which was different from SV. While the differently expressed genes between SV and GV were mainly involved in the metabolism pathway of purine, pyrimidine, glycolysis and sphingolipid

A Quantitative Increase in Regulatory T Cells Controls Development of Vitiligo

PubMed Central

Chatterjee, Shilpak; Eby, Jonathan; Al-Khami, Amir A.; Soloshchenko, Myroslawa; Kang, Hee-Kap; Kaur, Navtej; Naga, Osama; Murali, Anuradha; Nishimura, Michael I.; Le Poole, I. Caroline; Mehrotra, Shikhar

2014-01-01

T cell cytolytic activity targeting epidermal melanocyte is shown to cause progressive depigmentation and autoimmune vitiligo. Using the recently developed transgenic mice h3TA2 that carry T cell with a HLA-A2 restricted human tyrosinase reactive TCR and develop spontaneous vitiligo from an early age, we addressed the mechanism regulating autoimmune vitiligo. Depigmentation was significantly impaired only in IFN-γ knockout h3TA2 mice but not in TNF-α or perforin knockout h3TA2 mouse strains, confirming a central role for IFN-γ in vitiligo development. Additionally, the regulatory T cells (Treg) were relatively abundant in h3TA2-IFN-γ−/− mice, and depletion of Treg employing anti-CD25 antibody fully restored the depigmentation phenotype in h3TA2-IFN-γ−/− mice mediated in part through upregulation of pro-inflammatory cytokines as IL-17and IL-22. Further therapeutic potential of Treg abundance in preventing progressive depigmentation was evaluated by adoptively transferring purified Treg or using rapamycin. Both adoptive transfer of Treg and rapamycin induced lasting remission of vitiligo in mice treated at the onset of disease, or in mice with established disease. This leads us to conclude that reduced regulatory responses are pivotal to the development of vitiligo in disease-prone mice, and that a quantitative increase in the Treg population may be therapeutic for vitiligo patients with active disease. PMID:24366614

Comorbid autoimmune diseases in patients with vitiligo: A cross-sectional study.

PubMed

Gill, Liza; Zarbo, Allison; Isedeh, Prescilia; Jacobsen, Gordon; Lim, Henry W; Hamzavi, Iltefat

2016-02-01

Few large-scale studies have quantified the burden of comorbid autoimmune diseases in patients with vitiligo. We sought to determine the prevalence of comorbid autoimmune diseases in patients with vitiligo. We conducted a manual chart review on a cohort of 1873 patients with vitiligo seen between January 2002 and October 2012 at the Henry Ford Health System in Detroit, MI. Patients were excluded if they had fewer than 2 dermatology notes (N = 595) or if they were never given a diagnosis of vitiligo by a dermatologist (N = 180). Of 1098 patients with vitiligo, nearly 20% had at least 1 comorbid autoimmune disease. Compared with the general US population, we found a higher prevalence of thyroid disease (12.9%, P < .001), alopecia areata (3.8%, P < .001), inflammatory bowel disease (0.9%, P = .046), pernicious anemia (0.5%, P = .007), systemic lupus erythematosus (0.3%, P = .048), Guillain-Barre syndrome (0.3%, P < .001), discoid lupus (0.2%, P = .003), linear morphea (0.2%, P < .001), myasthenia gravis (0.2%, P = .002), and Sjögren syndrome (0.2%, P = .011). The study lacked a control group. This was a single-institution study with possible selection bias, and thus the findings may not be representative of the overall population of patients with vitiligo. We observed a high prevalence of comorbid autoimmune diseases in patients with vitiligo and report several new associations. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

The assessment of macular electrophysiology and macular morphology in patients with vitiligo.

PubMed

Aydin, Rukiye; Ozsutcu, Mustafa; Erdur, Sevil Karaman; Dikkaya, Funda; Balevi, Ali; Ozbek, Merve; Senturk, Fevzi

2018-02-01

We aimed to analyze the electrophysiologic function and morphology of macula in vitiligo patients. Seventeen patients with vitiligo and 11 healthy subjects were studied. All participants underwent multifocal electroretinography (mfERG) and spectral domain optical coherence tomography (SD-OCT) evaluations. The mfERG (P1 mfERG responses central and peripheral) and retinal layer segmentation parameters (nine ETDRS subfields) were compared in vitiligo and control groups. The mean P1 response amplitudes were significantly decreased in central and peripheral rings of the fovea in patients with vitiligo compared with controls (p = 0.002 and p = 0.006, respectively). There was a tendency toward a prolonged mean implicit time for both central and peripheral in patients with vitiligo compared to controls, however, with no statistical significance (p = 0.453 and p = 0.05, respectively). There was no statistically significant difference in all retinal layers thickness between two groups. In patients with vitiligo, while photoreceptor segment preserved in SD-OCT, mfERG reduced showing potential decline in central retinal function. This study showed a potential decline in central retinal function in patients with vitiligo even if they have normal fundus appearance and SD-OCT findings.

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.

VIEWPOINT – Vitiligo and alopecia areata: Apples and oranges?

PubMed Central

Harris, John E.

2013-01-01

Vitiligo and alopecia areata are common autoimmune diseases of the skin. Vitiligo is caused by the destruction of melanocytes and results in the appearance of white patches on any part of the body, while alopecia areata is characterized by patchy hair loss primarily on the scalp, but may also involve other areas as well. At first glance, the two diseases appear to be quite different, targeting different cell types and managed using different treatment approaches. However, the immune cell populations and cytokines that drive each disease are similar, they are closely associated within patients and their family members, and vitiligo and alopecia areata have common genetic risk factors, suggesting that they share a similar pathogenesis. Like apples and oranges, vitiligo and alopecia areata have some obvious differences, but similarities abound. Recognizing both similarities and differences will promote research into the pathogenesis of each disease, as well as the development of new treatments. PMID:24131336

Increased levels of mitochondrial DNA copy number in patients with vitiligo.

PubMed

Vaseghi, H; Houshmand, M; Jadali, Z

2017-10-01

Oxidative stress is known to be involved in the pathogenesis of autoimmune diseases such as vitiligo. Evidence suggests that the human mitochondrial DNA copy number (mtDNAcn) is vulnerable to damage mediated by oxidative stress. The purpose of this study was to examine and compare peripheral blood mtDNAcn and oxidative DNA damage byproducts (8-hydroxy-2-deoxyguanosine; 8-OHdG) in patients with vitiligo and healthy controls (HCs). The relative mtDNAcn and the oxidative damage (formation of 8-OHdG in mtDNA) of each sample were determined by real-time quantitative PCR. Blood samples were obtained from 56 patients with vitiligo and 46 HCs. The mean mtDNAcn and the degree of mtDNA damage were higher in patients with vitiligo than in HCs. These data suggest that increase in mtDNAcn and oxidative DNA damage may be involved in the pathogenesis of vitiligo. © 2017 British Association of Dermatologists.

Oxidative Stress and Immune System in Vitiligo and Thyroid Diseases

PubMed Central

Colucci, Roberta; Dragoni, Federica

2015-01-01

Vitiligo is an acquired dermatological disease frequently associated with autoimmune thyroid disorders. Several theories have been proposed so far to unravel the complex vitiligo pathogenesis. Currently, the autocytotoxic and the autoimmune theories are the most accredited hypothesis, since they are sustained by several important clinical and experimental evidences. A growing body of evidences shows that autoimmunity and oxidative stress strictly interact to finally determine melanocyte loss. In this scenario, associated thyroid autoimmunity might play an active and important role in triggering and maintaining the depigmentation process of vitiligo. PMID:25838868

Vitiligo linked to stigmatization in British South Asian women: a qualitative study of the experiences of living with vitiligo.

PubMed

Thompson, A R; Clarke, S A; Newell, R J; Gawkrodger, D J

2010-09-01

Vitiligo is a visible condition that is more noticeable in darker-skinned people. Beliefs about illness have been linked to psychosocial adjustment. There is some evidence that such beliefs may be influenced by cultural factors. Surprisingly little is known about beliefs in relation to vitiligo. The study sought to explore in depth the ways in which British Asian women manage and adjust psychosocially to vitiligo, and the potential role of ethnicity and culture in this process. In-depth semistructured interviews were conducted with seven British women of South Asian decent and analysed using the qualitative method of template analysis. Participants described feeling visibly different and all had experienced stigmatization to some extent. Avoidance and concealment were commonplace. Experiences of stigmatization were often perceived to be associated with cultural values related to appearance, status, and myths linked to the cause of the condition. The findings of this study present a unique in-depth analysis of British South Asians living with vitiligo and suggest there is a need for further research to explore cultural associations of disfigurement and of adjustment to chronic skin conditions. Furthermore, they suggest that in addition to individual therapeutic interventions there may be a need for community interventions aimed at dispelling myths and raising awareness of sources of support and treatment. © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.

A similar local immune and oxidative stress phenotype in vitiligo and halo nevus.

PubMed

Yang, Yuqi; Li, Shuli; Zhu, Guannan; Zhang, Qian; Wang, Gang; Gao, Tianwen; Li, Chunying; Wang, Lin; Jian, Zhe

2017-07-01

Vitiligo and halo nevus are two common T-cell-mediated skin disorders. Although autoimmunity has been suggested to be involved in both diseases, the relationship between vitiligo and halo nevus is not fully understood. The aim of the current study was to investigate whether vitiligo and halo nevus share the same immunological and oxidative stress response. Infiltrations of T cells, and expressions of chemokine receptors (CXCR3, CCR4, CCR5) and cytotoxic markers (Granzyme B, Perforin) in the lesions of vitiligo and halo nevus were examined by immunohistochemistry. Enzyme-linked immunosorbent assay was performed to analyze the expressions of chemokines in the serum samples and cytotoxic markers secreted by CD8 + T cells which were sorted from the peripheral blood mononuclear cells in healthy donors, vitiligo and halo nevus patients. Tissue levels of chemokine receptors and CXCR3 ligands in healthy controls, vitiligo patients and halo nevus patients were determined by qRT-PCR analysis. The percentages of CXCR3 + CD4 + T and CXCR3 + CD8 + T cells from the peripheral blood samples were examined by flow cytometry. Tissue and serum hydrogen peroxide (H 2 O 2 ) concentrations were measured using H 2 O 2 assay kit. Immunohistochemistry revealed a significant T-cell response, with pronounced dermal infiltrates of CD8 + T cells in vitiligo and halo nevus. The inflammatory cytotoxic markers such as Granzyme B and Perforin were also elevated in vitiligo and halo nevus, suggesting inflammatory responses in situ. By qRT-PCR and ELISA assay, we found significantly increased expressions of the chemokine receptor CXCR3 and its ligands, especially the accumulated CXCL10 in the skin lesions of vitiligo and halo nevus. Moreover, the level of H 2 O 2 , a key player involved in regulation of the immune response was significantly upregulated in the skin lesions of vitiligo and halo nevus. In addition, the increased H 2 O 2 concentration correlated positively with CXCL10 level in skin

[Possible role of psychological and environmental factors in the genesis of childhood vitiligo].

PubMed

Schwartz, Rodrigo; Sepúlveda, Juan Enrique; Quintana, Teresa

2009-01-01

The exposure to stressing situations may play a role in the appearance of vitiligo. Patients with the disease have a greater sensitivity to environmental stress and a lower threshold to generate catecholamine mediated responses. To evaluate the temperament and character of patients with vitiligo and explore the relationship of the disease with negative life events and life quality impairment. The study population were 21 patients with vitiligo aged 5 to 12 years, and two control groups (Gl and G2). Gl was composed by 14 healthy siblings of vitiligo patients. G2 was composed by 21 age and gender matched healthy students from two schools in Santiago, Chile. The Junior Temperament and Character Inventory (JTCI), the Qualitative Psychosocial Development Survey (QPDS), the Life Event Checklist (LEC) and the Children's Life Quality index (CDLQI) were applied (LEC only to vitiligo patients). On the temperament dimensions, vitiligo patients scored high on the "harm avoidance" scale in comparison to G2 (13.7 v/s 10.6). Compared with Gl, QPDS showed in vitiligo patients a higher frequency of fear to strangers (71% and 36%, respectively) and a predominant feeling of fear and shyness in response to changes in a close relative (80% and 8%, respectively). There was a negative correlation (protective factor) between the character dimension "self-directedness" and CDLQI score (r =-0.703). In this group of patients, we found a possible relationship between a specific temperament dimension, vitiligo and its impact on life quality.

PREFERENTIAL SECRETION OF INDUCIBLE HSP70 BY VITILIGO MELANOCYTES UNDER STRESS

PubMed Central

Mosenson, Jeffrey A.; Flood, Kelsey; Klarquist, Jared; Eby, Jonathan M.; Koshoffer, Amy; Boissy, Raymond E.; Overbeck, Andreas; C.Tung, Rebecca; Poole, I. Caroline Le

2014-01-01

SUMMARY Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them from apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether HSP70i differentially protects control and vitiligo melanocytes from stress and subsequent immune responses. We compared expression of HSP70i in skin samples, evaluated the viability of primary vitiligo and control melanocytes exposed to bleaching phenols, and measured secreted HSP70i. We determined whether HSP70i traffics to melanosomes to contact immunogenic proteins by cell fractionation, western blotting, electron microscopy and confocal microscopy. Viability of vitiligo and control melanocytes was equally affected under stress. However, vitiligo melanocytes secreted increased amounts of HSP70i in response to MBEH, corroborating with aberrant HSP70i expression in patient skin. Intracellular HSP70i colocalized with melanosomes, and more so in response to MBEH in vitiligo melanocytes. Thus whereas either agent is cytotoxic to melanocytes, MBEH preferentially induces immune responses to melanocytes. PMID:24354861

Autoimmune encephalitis associated with vitiligo?

PubMed

Haitao, Ren; Huiqin, Liu; Tao, Qu; Xunzhe, Yang; Xiaoqiu, Shao; Wei, Li; Jiewen, Zhang; Liying, Cui; Hongzhi, Guan

2017-09-15

The autoimmune encephalitis can develop with or without an underlying tumor. For tumor-negative autoimmune encephalitis, the causes are still largely unknown. Here we presented three patients with autoimmune encephalitis accompanied with vitiligo. Among them, two patients suffered from anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis and one patient suffered from anti-IgLON5 encephalopathy. All of them received intravenous immunoglobulin and steroids as immunotherapy. The two patients with anti-LGI1 encephalitis recovered and got a good prognosis. For the patient with anti-IgLON5 encephalopathy, he only got a moderate and transient improvement. Based on the above, we speculate that vitiligo may be a clue to an autoimmune cause for encephalitis. Copyright © 2017. Published by Elsevier B.V.

The autoimmune regulator gene (AIRE) is strongly associated with vitiligo.

PubMed

Tazi-Ahnini, R; McDonagh, A J G; Wengraf, D A; Lovewell, T R J; Vasilopoulos, Y; Messenger, A G; Cork, M J; Gawkrodger, D J

2008-09-01

Vitiligo is an autoimmune disorder that occurs with greatly increased frequency in the rare recessive autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) caused by mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. We have previously detected an association between alopecia areata and single nucleotide polymorphisms (SNPs) in the AIRE gene. To report the findings of an extended study including haplotype analysis on six AIRE polymorphisms (AIRE C-103T, C4144G, T5238C, G6528A, T7215C and T11787C) in vitiligo, another APECED-associated disease. A case-control analysis was performed. Results showed a strong association between AIRE 7215C and vitiligo [P = 1.36 x 10(-5), odds ratio (OR) 3.12, 95% confidence interval (CI) 1.87-5.46]. We found no significant association with the other polymorphisms individually. However, haplotype analysis revealed that the AIRE haplotype CCTGCC showed a highly significant association with vitiligo (P = 4.14 x 10(-4), OR 3.00, 95% CI 1.70-5.28). To select the most informative minimal haplotypes, we tagged the polymorphisms using SNP tag software. Using AIRE C-103T, G6528A, T7215C and T11787C as tag SNPs, the haplotype AIRE CGCC was associated with vitiligo (P = 0.003, OR 2.49, 95% CI 1.45-4.26). The link between vitiligo and AIRE raises the possibility that defective skin peripheral antigen selection in the thymus is involved in the changes that result in melanocyte destruction in this disorder.

Childhood- and later-onset vitiligo have diverse epidemiologic and clinical characteristics.

PubMed

Nicolaidou, Electra; Antoniou, Christina; Miniati, Alexandra; Lagogianni, Eirini; Matekovits, Athina; Stratigos, Alex; Katsambas, Andreas

2012-06-01

Vitiligo onset during childhood is common. There are limited data regarding childhood-onset vitiligo. We sought to provide an epidemiologic and clinical comparison between childhood- and later-onset vitiligo. Two groups of patients were included in this cross-sectional study. Consecutive patients examined at the Vitiligo Clinic of Andreas Sygros Hospital for Skin and Venereal Diseases, Athens, Greece, from January 2005 to December 2009 with a disease onset before the age of 12 years were included in the childhood-onset group. The later-onset group included randomly selected patients who were examined at the same period and had a disease onset after the age of 12 years. After clinical examination, a standardized questionnaire was completed for each patient. In all, 126 patients were included in the childhood-onset and 107 patients in the later-onset group. Childhood-onset vitiligo: (1) involved different sites at initial presentation, (2) included more cases of segmental type, and (3) was characterized by a higher prevalence of allergic diseases and a lower prevalence of thyroid diseases. Longer duration of disease and a positive family history of thyroid disease were associated with the presence of thyroid disease only in the childhood-onset group. In the later-onset group, only female sex was associated with the presence of thyroid disease. The study was conducted in a hospital specializing in skin diseases and a selection bias toward more severe vitiligo cases is possible. Childhood-onset vitiligo had distinct epidemiologic and clinical characteristics, compared with later-onset disease. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Fluorescence excitation-emission matrix spectroscopy of vitiligo skin in vivo (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhao, Jianhua; Richer, Vincent; Al Jasser, Mohammed; Zandi, Soodabeh; Kollias, Nikiforos; Kalia, Sunil; Zeng, Haishan; Lui, Harvey

2016-02-01

Fluorescence signals depend on the intensity of the exciting light, the absorption properties of the constituent molecules, and the efficiency with which the absorbed photons are converted to fluorescence emission. The optical features and appearance of vitiligo have been explained primarily on the basis of reduced epidermal pigmentation, which results in abnormal white patches on the skin. The objective of this study is to explore the fluorescence properties of vitiligo and its adjacent normal skin using fluorescence excitation-emission matrix (EEM) spectroscopy. Thirty five (35) volunteers with vitiligo were acquired using a double-grating spectrofluorometer with excitation and emission wavelengths of 260-450 nm and 300-700 nm respectively. As expected, the most pronounced difference between the spectra obtained from vitiligo lesions compared to normally pigmented skin was that the overall fluorescence was much higher in vitiligo; these differences increased at shorter wavelengths, thus matching the characteristic spectral absorption of epidermal melanin. When comparing the fluorescence spectra from vitiligo to normal skin we detected three distinct spectral bands centered at 280nm, 310nm, and 335nm. The 280nm band may possibly be related to inflammation, whereas the 335 nm band may arise from collagen or keratin cross links. The source of the 310 nm band is uncertain; it is interesting to note its proximity to the 311 nm UV lamps used for vitiligo phototherapy. These differences are accounted for not only by changes in epidermal pigment content, but also by other optically active cutaneous biomolecules.

Quality of Life, Burden of Disease, Co-morbidities, and Systemic Effects in Vitiligo Patients.

PubMed

Elbuluk, Nada; Ezzedine, Khaled

2017-04-01

Vitiligo is a complex, systemic disease associated with many autoimmune and autoinflammatory conditions. Additionally, the cutaneous changes of vitiligo have significant effects on quality of life and self-esteem. Further efforts are needed to increase our understanding of vitiligo comorbidities as well as to increase awareness of the psychological effects of vitiligo. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Vitiligo iridis and glaucoma: a rare sequelae of small pox.

PubMed

Kavitha, S; Patel, S R; Mohini, P; Venkatesh, R; Sengupta, S

2015-10-01

Vitiligo iridis refers to focal areas of iris atrophy as sequelae of small pox infection. We report a series of patients with unilateral vitiligo iridis, some of whom presented with secondary open-angle glaucoma. Three patients with vitiligo iridis underwent a comprehensive ophthalmic examination including intraocular pressure (IOP) measurement, slit lamp biomicroscopy, gonioscopy, and fundus evaluation. Patients' facial features were also documented and photographed. All patients were in their sixth decade. Two out the three had elevated IOP (52 mm Hg and 36 mm Hg) in the same eye as vitiligo iridis, at initial presentation. Gonioscopy showed patchy iris hyperpigmentation and fundus evaluation showed glaucomatous optic disc changes in the involved eye. One patient responded favourably to topical antiglaucoma medications, whereas the other was taken up for combined phacoemulsification-trabeculectomy with good results. The third patient had normal IOP in the involved eye. All three patients gave a history of small pox in childhood and had pitted facial scars typical of previous small pox infection. Vitiligo iridis may be associated with the secondary glaucoma as a long-term sequelae of small pox. It may be prudent to periodically follow-up such patients for development of raised IOP in the future.

Effect of different types of therapeutic trauma on vitiligo lesions.

PubMed

El Mofty, Medhat; Esmat, Samia; Hunter, Nahla; Mashaly, Heba M; Dorgham, Dina; Shaker, Olfat; Ibrahim, Sarah

2017-03-01

New treatment modalities for vitiligo acting by changing certain cytokines and metalloproteinases are newly emerging. The aim of this work is to To assess the efficacy of trichloroacetic acid (TCA) chemical peel, dermapen, and fractional CO 2 laser in treatment of stable non-segmental vitiligo and to detect their effects on IL-17 and MMP-9 levels. Thirty patients with stable vitiligo were recruited in a randomized controlled study. They were randomly categorized into three equal groups. Group 1: TCA peel, Group 2: dermapen machine, and Group 3: Fractional CO 2 laser. Skin biopsies were taken from treated areas and from control areas for which MMP-9 and IL-17 tissue levels were measured using ELISA. The 30 vitiligo patients had low basal tissue MMP-9 levels and high baseline IL-17 tissue levels. As regards the three different used modalities, all of them caused rise in MMP-9 as well as IL-17 levels and almost their levels were much more elevated with repetition of the previously mentioned traumatic procedures. TCA 25% peel proved to be the most effective modality both clinically and laboratory and it can be used prior or with other conventional therapies in the treatment of vitiligo. © 2016 Wiley Periodicals, Inc.

Vitiligo in a patient with lung adenocarcinoma treated with nivolumab: A case report.

PubMed

Uenami, Takeshi; Hosono, Yuki; Ishijima, Mikako; Kanazu, Masaki; Akazawa, Yuki; Yano, Yukihiro; Mori, Masahide; Yamaguchi, Toshihiko; Yokota, Soichiro

2017-07-01

Nivolumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for treating patients with late-stage non-small-cell lung cancer. Immune checkpoint inhibitors such as nivolumab induce various kinds of immune-related adverse events, including vitiligo. Vitiligo has been reported in patients with melanoma but not lung cancer. We describe a 75-year-old man with lung adenocarcinoma, stage 4 with pleural and pericardial effusion, that progressed after first-line chemotherapy. Subsequently, he was treated with nivolumab as second-line therapy. After 6days of administering nivolumab, he developed vitiligo suddenly on the trunk of his body. Except for vitiligo, his physical examination was normal, and treatment with nivolumab was well tolerated. Therefore, this treatment was continued without further development or expansion of vitiligo. A computed tomography scan showed a reduction in the size of the lung nodule and stabilization of the pleural and pericardial effusion. This is the first case of vitiligo associated with the use of nivolumab in a patient with lung adenocarcinoma. Copyright © 2017. Published by Elsevier B.V.

The Relationship Between the Serum Level of Vitamin D and Vitiligo: A Controlled Study on 300 Subjects.

PubMed

Khurrum, Huma; AlGhamdi, Khalid M

2016-01-01

Low vitamin D levels have been associated with several autoimmune diseases. Vitiligo could be associated with low vitamin D levels. To determine the level of serum vitamin D in vitiligo patients compared to controls and reveal the possible association of vitamin levels with the pathogenesis of vitiligo. A case-controlled study was conducted. After excluding factors that may affect serum vitamin D levels, blood samples were taken from vitiligo patients and controls. The association between vitamin D levels and various vitiligo subgroups (duration of vitiligo, site of onset, age, etc) was measured and correlated. A total of 150 vitiligo patients, 90 (60%) males with a mean age of 30.6 ± 11.4 years, were recruited. The study also had 150 age- and gender-matched vitiligo-free control subjects. There was no significant difference in median serum vitamin D levels between the cases and the controls (P = .25). The serum levels of vitamin D of the vitiligo patients were found to be lower in males (P = .01), the younger age group (P = .01), and patients not treated with ultraviolet (UV) treatment (P = .01). There is no difference between the vitamin D levels of the vitiligo patients and the control subjects. However, deficiency of 25(OH)D levels within the vitiligo subgroups may be linked to younger age, male gender, short duration of vitiligo, and non-use of phototherapy. © The Author(s) 2015.

A systematic review of natural health product treatment for vitiligo

PubMed Central

Szczurko, Orest; Boon, Heather S

2008-01-01

Background Vitiligo is a hypopigmentation disorder affecting 1 to 4% of the world population. Fifty percent of cases appear before the age of 20 years old, and the disfigurement results in psychiatric morbidity in 16 to 35% of those affected. Methods Our objective was to complete a comprehensive, systematic review of the published scientific literature to identify natural health products (NHP) such as vitamins, herbs and other supplements that may have efficacy in the treatment of vitiligo. We searched eight databases including MEDLINE and EMBASE for vitiligo, leucoderma, and various NHP terms. Prospective controlled clinical human trials were identified and assessed for quality. Results Fifteen clinical trials were identified, and organized into four categories based on the NHP used for treatment. 1) L-phenylalanine monotherapy was assessed in one trial, and as an adjuvant to phototherapy in three trials. All reported beneficial effects. 2) Three clinical trials utilized different traditional Chinese medicine products. Although each traditional Chinese medicine trial reported benefit in the active groups, the quality of the trials was poor. 3) Six trials investigated the use of plants in the treatment of vitiligo, four using plants as photosensitizing agents. The studies provide weak evidence that photosensitizing plants can be effective in conjunction with phototherapy, and moderate evidence that Ginkgo biloba monotherapy can be useful for vitiligo. 4) Two clinical trials investigated the use of vitamins in the therapy of vitiligo. One tested oral cobalamin with folic acid, and found no significant improvement over control. Another trial combined vitamin E with phototherapy and reported significantly better repigmentation over phototherapy only. It was not possible to pool the data from any studies for meta-analytic purposes due to the wide difference in outcome measures and poor quality ofreporting. Conclusion Reports investigating the efficacy of NHPs for

Combination treatment with excimer laser and narrowband UVB light in vitiligo patients.

PubMed

Shin, Sungsik; Hann, Seung-Kyung; Oh, Sang Ho

2016-01-01

For the treatment of vitiligo, narrowband UVB (NBUVB) light is considered the most effective for nonsegmental vitiligo, while excimer laser treatment is commonly used for localized vitiligo. However, treatment areas may potentially be missed with excimer laser treatment. We aimed to evaluate the effect of combinational treatment with NBUVB light and excimer laser on vitiligo. All patients were first treated with NBUVB; excimer laser was then applied in conjunction with NBUVB phototherapy due to a slow response or no further improvement with continuous NBUVB treatment alone. To minimize adverse effects, a fixed dose of NBUVB was administered, and the dose of excimer laser was increased based on patient response. Among 80 patients, 54 patients showed responses after combination with excimer laser; however, 26 patients (32.5%) showed no remarkable change after combination therapy. Of the 26 patients who showed no further response, 12 patients (46.1%) presented with vitiligo on the acral areas, which are known to the least responsive sites. Our study suggests that combined treatment of NBUVB and excimer laser in vitiligo may enhance the treatment response without remarkable side effects, therefore might also increase the compliance of the patients to the treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vitiligo on the face (image)

MedlinePlus

This is a picture of vitiligo on the face. Complete loss of melanin, the primary skin pigment, ... the same areas on both sides of the face -- symmetrically -- or it may be patchy -- asymmetrical. The ...

Effects of age of onset on disease characteristics in non-segmental vitiligo.

PubMed

Solak, Berna; Dikicier, Bahar Sevimli; Cosansu, Nur C; Erdem, Teoman

2017-03-01

In patients with vitiligo, the clinical and laboratory features of the disease may vary according to time of onset. This is addressed in the literature by only a few studies with conflicting results. The aim of this study was to determine the demographic and clinical features of patients with non-segmental vitiligo and to establish the association between vitiligo and autoimmune diseases with a focus on time of disease onset. A total of 224 vitiligo patients for whom complete medical records were available were evaluated retrospectively. Demographic data, scores on the Vitiligo Area Score Index (VASI), clinical features, vitiligo disease activity, repigmentation status, presence of any accompanying autoimmune disease, antinuclear antibody (ANA) titers, serum levels of glucose, thyroid-stimulating hormone (TSH), thyroxine (T4) hormone, anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-TG) were recorded. The prevalence of halo nevi was significantly higher (P < 0.001) among children than in other patient groups. The prevalence of leukotrichia was higher in adults with adult-onset disease than in either pediatric patients or adults with childhood-onset disease (P = 0.002). Both anti-TG and anti-TPO levels were significantly higher in adults with adult-onset disease than in pediatric patients and adult patients with childhood-onset disease. The prevalence of autoimmune disease was 22.2%. Anti-TG levels were significantly higher in patients with treatment-related repigmentation than in those without repigmentation. This study shows that clinical features and associations with autoimmune disease may vary according to the age of onset of vitiligo. © 2017 The International Society of Dermatology.

Analysis of Oxidative Stress Status, Catalase and Catechol-O-Methyltransferase Polymorphisms in Egyptian Vitiligo Patients

PubMed Central

Mehaney, Dina A.; Darwish, Hebatallah A.; Hegazy, Rehab A.; Nooh, Mohammed M.; Tawdy, Amira M.; Gawdat, Heba I.; El-Sawalhi, Maha M.

2014-01-01

Vitiligo is the most common depigmentation disorder of the skin. Oxidative stress is implicated as one of the probable events involved in vitiligo pathogenesis possibly contributing to melanocyte destruction. Evidence indicates that certain genes including those involved in oxidative stress and melanin synthesis are crucial for development of vitiligo. This study evaluates the oxidative stress status, the role of catalase (CAT) and catechol-O-Methyltransferase (COMT) gene polymorphisms in the etiology of generalized vitiligo in Egyptians. Total antioxidant capacity (TAC) and malondialdehyde (MDA) levels as well as CAT exon 9 T/C and COMT 158 G/A polymorphisms were determined in 89 patients and 90 age and sex-matched controls. Our results showed significantly lower TAC along with higher MDA levels in vitiligo patients compared with controls. Meanwhile, genotype and allele distributions of CAT and COMT polymorphisms in cases were not significantly different from those of controls. Moreover, we found no association between both polymorphisms and vitiligo susceptibility. In conclusion, the enhanced oxidative stress with the lack of association between CAT and COMT polymorphisms and susceptibility to vitiligo in our patients suggest that mutations in other genes related to the oxidative pathway might contribute to the etiology of generalized vitiligo in Egyptian population. PMID:24915010

Treatment adherence and beliefs about medicines among Egyptian vitiligo patients.

PubMed

Ali, Mostafa A Sayed; Abou-Taleb, Doaa A E; Mohamed, Refaat Ragheb

2016-11-01

Vitiligo is a chronic disorder of depigmentation that has different treatment modalities, but patients' nonadherence is common. This study aimed to assess the influence of patients' medication beliefs on patients' adherence to topical, oral medications, and phototherapy in vitiligo. Between September 2015 and February 2016, 260 patients with vitiligo were asked to fill in the Beliefs about Medicines Questionnaire (BMQ) to assess their beliefs about therapy for vitiligo. Their adherence to the therapy was examined using the 8-item Morisky Medication Adherence Scale (MMAS-8). The MMAS-8 scale and BMQ had good internal consistency (Cronbach's α = 0.78 and 0.66, respectively). Using Morisky's recommended cutoff point, 71% of patients were categorized as low or nonadherent to the scheduled therapy. Patients who perceived specific necessity of dermatological medicines significantly adhered to their therapy (OR 1.23; 95% CI 1.09, 1.38; p = 0.001) whereas patients who had specific concerns about the adverse effects exhibited significant low adherence (OR 0.65; 95% CI 0.56, 0.76; p < 0.001). Positive beliefs about the necessity of medications in vitiligo do not necessarily reflect high adherence. Patients' adherence behavior is a multidimensional and dynamic process. The prolonged course of treatment, its cost, and unsatisfactory outcomes influenced the patients' adherence. © 2016 Wiley Periodicals, Inc.

Screening of Glaucoma or Cataract Prevalence in Vitiligo Patients and Its Relationship With Periorbital Steroid Use.

PubMed

Khurrum, Huma; AlGhamdi, Khalid M; Osman, Essam

2016-01-01

There is scarce literature connecting vitiligo and primary open angle glaucoma (POAG). Most literature reports that secondary complications are a direct consequence of corticosteroid treatment of vitiligo. In this study, we aimed to investigate the prevalence of ocular problems in patients with vitiligo and to determine its association with periorbital topical corticosteroid use. A cross-sectional study was carried out on 90 patients with vitiligo. The Vitiligo European Task Force questionnaire was completed for each patient. A control group comprising 90 healthy individuals who did not have vitiligo and who were matched on age and gender was used for comparison. A complete ophthalmologic examination was performed. A family history of glaucoma and the use of topical steroids were recorded. Two (2/90, 2.2%) of the patients with vitiligo had glaucoma compared with none of the individuals in the control group (P = .25). Nineteen of the 90 patients with vitiligo used periorbital steroids, and of these patients, 10.5% (2/19) developed glaucoma. The duration of periorbital corticosteroid use was 4.50 ± 2.1 years. Eighty-nine percent (17/19) of the vitiligo patients who applied the potent topical corticosteroid (class I) clobetasol propionate to the periorbital area did not develop glaucoma. In contrast, glaucoma was not observed in 79% (71/90) of the vitiligo patients who did not use steroids. Cataract, uveitis, or fundus problems were not observed in either group. The study suggests that patients who have vitiligo and use topical steroids periorbitally do not have an increased risk of glaucoma or cataracts. Future studies that have a larger sample size and use a detailed steroid use protocol are needed. © The Author(s) 2015.

Lived Experience of Women Suffering from Vitiligo: A Phenomenological Study

ERIC Educational Resources Information Center

Borimnejad, Leili; Yekta, Zohreh Parsa; Nasrabadi, Alireza Nikbakht

2006-01-01

Vitiligo is a chronic skin disease, which through change of appearance and body image, exerts a devastating effect on people, especially women. The objective of this study is to explore lived experience of women with Vitiligo by the hermeneutic phenomenology method. The purposive sample consisted of 16 Iranian women. Data analysis followed…

The incidence of leukotrichia in segmental vitiligo: implication of poor response to medical treatment.

PubMed

Lee, Dong-Youn; Kim, Cho-Rok; Park, Ji-Hye; Lee, Joo-Heung

2011-08-01

  In vitiligo, the melanocyte of the hair follicle is one of the major sources for repigmentation. Segmental vitiligo seems to be often associated with white hairs. However, in the case of small vellus hairs, it is often difficult or impossible to detect hair color. Thus, the real incidence of leukotrichia in segmental vitiligo has not been known.   In this study, we investigated the existence of white hairs in the lesional skin of 82 patients with segmental vitiligo. When it was difficult to detect hair color with the naked eye or a magnifier, a digital microscope with 30× magnification was used.   Interestingly, all 82 patients showed leukotrichia in segmental vitiligo independent of age and disease duration. Some patients had more than 90% white hairs in the lesional skin, and they showed poor response to medical treatment.   Based on our results, a very high percentage of patients with segmental vitiligo may be associated with leukotrichia. Many white hairs in segmental vitiligo may contribute to the lack of response with medical treatment. The examination of hair color with a digital microscope may be very useful for the prediction of treatment outcome and decision of treatment modalities. © 2011 The International Society of Dermatology.

Prevalence of choroidal nevus and retinal pigment epithelial alterations in vitiligo patients.

PubMed

Fleissig, Efrat; Pavlovksy, Mor; Loewenstein, Anat; Zur, Dinah; Newman, Hadas; Keren, Shay; Goldenberg, Dafna; Bar-Ilan, Efrat; Goldstein, Michaella

2018-05-01

To investigate ocular manifestations in patients with vitiligo by multimodal imaging, including optical coherence tomography (OCT), color fundus photography, and fundus autofluorescence (FAF). In this prospective, observational clinical study, vitiligo patients underwent ophthalmologic and dermatologic clinical assessment and imaging by spectral-domain OCT, FAF, and color fundus imaging. Ocular echography was performed as indicated. Statistical analysis was performed using paired T test and Pearson correlation. A total of 61 eyes of 31 vitiligo patients were examined. Ocular findings consisted of choroidal nevi (n = 10, 32%), of which four (40%) were bilateral; two patients (6.5%) had a prominent choroidal pattern, two (6.5%) had hypopigmentary retinal pigment epithelium (RPE) lesions, and one (3.2%) had peripapillary atrophy of the RPE. Choroidal nevi were demonstrated only in eyes of patients with generalized vitiligo and were more common with upper body involvement (p = 0.02) and more prevalent in women (p = 0.02). Hypopigmentary lesions were detected in two patients and demonstrated on OCT as RPE atrophy and as photoreceptor/RPE changes. In this case series, vitiligo patients had a higher rate of choroidal nevi than previously reported. The hypopigmentary vitiliginous fundus lesions were depicted on OCT as photoreceptor and RPE atrophy. These findings may suggest the advisability of regular ocular monitoring for vitiligo patients.

Camouflage for vitiligo.

PubMed

Tanioka, Miki; Miyachi, Yoshiki

2009-01-01

Cosmetic camouflage is indispensable for patients with vitiligo and can result in an improvement of their quality of life. Recent cosmetic advances enabled camouflage to obtain a suitable color match and keep it waterproof. However, camouflage needs some techniques. Therefore, patient education through a camouflage lesson is required to enjoy camouflage. Here the authors introduced a few tips for suitable camouflage, which were devised through camouflage lessons.

Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea.

PubMed

Bae, Jung Min; Choi, Kwang Hyun; Jung, Han Mi; Kim, Sook Young; Kim, Miri; Kim, Gyung Moon; Yu, Dong Soo; Lee, Young Bok

2017-03-01

Subsequent vitiligo after hematopoietic stem cell transplantation (HSCT) has been described sporadically in case series. To investigate the incidence and risk factors of subsequent vitiligo after HSCT. A nationwide, population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2009 to 2013. All HSCT recipients who had undergone HSCT between 2010 and 2011 and not treatment for vitiligo in 2009 (to exclude preexisting active vitiligo) were included in the HSCT recipient group, and an age- and sex-matched control group without HSCT was also established. A total of 2747 HSCT recipients and 8241 controls were enrolled. Newly acquired vitiligo occurred in 1.06% of HSCT recipients between 2010 and 2013, and there was a significant increase (OR 3.130, 95% CI 1.859-5.271) in cases of vitiligo in HSCT recipients compared with controls (0.34%). Allogeneic HSCT (OR 5.593, 95% CI 1.628-19.213) and bone marrow-sourced stem cells (as compared with peripheral blood-sourced stem cells; OR 2.492, 95% CI 1.114-5.576) were independently associated with the development of vitiligo after HSCT. Medical record review was not available. Vitiligo developed at a significantly increased rate after HSCT compared with controls. Allogeneic HSCT and bone marrow-sourced stem cells were independent risk factors. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Biomarkers of disease activity in vitiligo: A systematic review.

PubMed

Speeckaert, R; Speeckaert, M; De Schepper, S; van Geel, N

2017-09-01

The pathophysiology of vitiligo is complex although recent research has discovered several markers which are linked to vitiligo and associated with disease activity. Besides providing insights into the driving mechanisms of vitiligo, these findings could reveal potential biomarkers. Activity markers can be used to monitor disease activity in clinical trials and may also be useful in daily practice. The aim of this systematic review was to document which factors have been associated with vitiligo activity in skin and blood. A second goal was to determine how well these factors are validated in terms of sensitivity and specificity as biomarkers to determine vitiligo activity. Both in skin (n=43) as in blood (n=66) an adequate number of studies fulfilled the predefined inclusion criteria. These studies used diverse methods and investigated a broad range of plausible biomarkers. Unfortunately, sensitivity and specificity analyses were scarce. In skin, simple histopathology with or without supplemental CD4 and CD8 stainings can still be considered as the gold standard, although more recently chemokine (C-X-C motif) ligand (CXCL) 9 and NLRP1 have demonstrated a good and possibly even better association with progressive disease. Regarding circulating biomarkers, cytokines (IL-1β, IL-17, IFN-γ, TGF-β), autoantibodies, oxidative stress markers, immune cells (Tregs), soluble CDs (sCD25, sCD27) and chemokines (CXCL9, CXCL10) are still competing. However, the two latter may be preferable as both chemokines and soluble CDs are easy to measure and the available studies display promising results. A large multicenter study could make more definitive statements regarding their sensitivity and specificity. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the Psychological Impacts of Asymptomatic and Symptomatic Cutaneous Diseases: Vitiligo and Atopic Dermatitis

PubMed Central

Noh, Seongmin; Kim, Miri; Park, Chang Ook; Hann, Seung-Kyung

2013-01-01

Background Vitiligo and atopic dermatitis (AD) are common dermatological disorders which may cause significant psychological and social distress leading to impaired quality of life (QoL) in patients. Objective We evaluated the degree of psychological stress and impairment of QoL in vitiligo patients as compared with AD patients and normal controls (NCs). Methods A total of 60 patients from each group and 60 NCs were enrolled. Five questionnaires on depression (Beck depression inventory, BDI), state anxiety (SA) and trait anxiety (TA), interaction anxiousness (IAS), private body consciousness (PBC) and dermatologic QoL were used. Results The vitiligo patients had a significantly higher level of TA (p<0.01), PBC (p<0.001) and impaired QoL (p<0.001) than NCs, but not BDI, SA and IAS. The AD patients had significantly higher scores for all five questionnaire items compared with NCs. In the comparison between the AD and vitiligo groups, all of the indexes except body consciousness were higher in AD patients than in vitiligo patients: BDI (p<0.01), SA (p<0.05), TA (p<0.001), IAS (p<0.01) and impaired QoL (p<0.001). Exposure of vitiligo lesions was not a significant variable in the analysis of the contribution of clinical variables of vitiligo on psychological stress and QoL. Conclusion Vitiligo, which is not accompanied by any symptoms, involves less psychological impact than AD, which is accompanied by itching. Compared to NCs, however, the elevated general anxiety and body consciousness in patients with vitiligo suggests that they may be more concerned with the aggravation of hypopigmented patches than difficulties in social interactions. PMID:24371393

Association of Angiotensin-Converting Enzyme ACE Gene Polymorphism with ACE Activity and Susceptibility to Vitiligo in Egyptian Population.

PubMed

Badran, Dahlia I; Nada, Hesham; Hassan, Ranya

2015-05-01

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with vitiligo in the Indians and Koreans, but not in those of English or Turkish background. We investigated the ACE (I/D) polymorphism in vitiligo patients for the first time in Egypt and compared serum ACE levels between vitiligo patients and controls. The present study was carried out in 100 vitiligo patients (40 males and 60 females) and in 100 healthy controls of an Egyptian population using the polymerase chain reaction genotyping method. The ACE genotype and allele frequency was significantly different between vitiligo patients and controls. Our results revealed a significant increase in the frequency of the ACE I allele (p=0.002; odds ratio: 1.99; 95% confidence intervals: 1.207-3.284) with an overrepresentation of I/D genotype in the vitiligo patient group. Furthermore, there was a significant difference between the segmental, nonsegmental, and focal vitiligo in ACE gene genotype distribution. Serum ACE levels were significantly increased in vitiligo patients compared to controls (p=0.034). This study suggests that, for the first time, ACE gene polymorphism confers susceptibility to vitiligo in the Egyptian population.

IL-33 circulating serum levels are increased in patients with non-segmental generalized vitiligo.

PubMed

Vaccaro, Mario; Cicero, Francesca; Mannucci, Carmen; Calapai, Gioacchino; Spatari, Giovanna; Barbuzza, Olga; Cannavò, Serafinella P; Gangemi, Sebastiano

2016-09-01

IL-33 is a recently identified cytokine, encoded by the IL-33 gene, which is a member of the IL-1 family that drives the production of T-helper-2 (Th-2)-associated cytokines. Serum levels of IL-33 have been reported to be up-regulated in various T-helper (Th)-1/Th-17-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel. To investigate whether cytokine imbalance plays a role in the pathogenesis of vitiligo, we performed a case-control association study by enzyme-linked immunosorbent assay of IL-33 in our patients. IL-33 serum levels were measured by a quantitative enzyme immunoassay technique in patients with non-segmental generalized vitiligo and compared with those of healthy controls. IL-33 serum levels in patients with vitiligo were significantly increased than those in healthy controls. There was a positive correlation of IL-33 serum levels with extension of vitiligo and disease activity. This study suggests a possible systemic role of IL-33 in the pathogenesis of vitiligo. Inhibiting IL-33 activity might be a novel therapeutic strategy in the treatment of autoimmune inflammatory disease, like vitiligo.

Tumor Necrosis Factor B (TNFB) Genetic Variants and Its Increased Expression Are Associated with Vitiligo Susceptibility

PubMed Central

Laddha, Naresh C.; Dwivedi, Mitesh; Gani, Amina R.; Mansuri, Mohmmad Shoab; Begum, Rasheedunnisa

2013-01-01

Genetic polymorphisms in TNFB are involved in the regulation of its expression and are found to be associated with various autoimmune diseases. The aim of the present study was to determine whether TNFB +252A/G (rs909253) and exon 3 C/A (rs1041981) polymorphisms are associated with vitiligo susceptibility, and expression of TNFB and ICAM1 affects the disease onset and progression. We have earlier reported the role of TNFA in autoimmune pathogenesis of vitiligo, and we now show the involvement of TNFB in vitiligo pathogenesis. The two polymorphisms investigated in the TNFB were in strong linkage disequilibrium and significantly associated with vitiligo. TNFB and ICAM1 transcripts were significantly increased in patients compared to controls. Active vitiligo patients showed significant increase in TNFB transcripts compared to stable vitiligo. The genotype-phenotype analysis revealed that TNFB expression levels were higher in patients with GG and AA genotypes as compared to controls. Patients with the early age of onset and female patients showed higher TNFB and ICAM1 expression. Overall, our findings suggest that the increased TNFB transcript levels in vitiligo patients could result, at least in part, from variations at the genetic level which in turn leads to increased ICAM1 expression. For the first time, we show that TNFB +252A/G and exon 3 C/A polymorphisms are associated with vitiligo susceptibility and influence the TNFB and ICAM1 expression. Moreover, the study also emphasizes influence of TNFB and ICAM1 on the disease progression, onset and gender bias for developing vitiligo. PMID:24312346

Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo.

PubMed

Karam, Rehab A; Zidan, Haidy E; Khater, Mohamed H

2017-08-01

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

Misbalanced CXCL12 and CCL5 Chemotactic Signals in Vitiligo Onset and Progression.

PubMed

Rezk, Ahmed F; Kemp, Daria Marley; El-Domyati, Moetaz; El-Din, Wael Hosam; Lee, Jason B; Uitto, Jouni; Igoucheva, Olga; Alexeev, Vitali

2017-05-01

Generalized nonsegmental vitiligo is often associated with the activation of melanocyte-specific autoimmunity. Because chemokines play an important role in the maintenance of immune responses, we examined chemotactic signatures in cultured vitiligo melanocytes and skin samples of early (≤2 months) and advanced (≥6 months) vitiligo. Analysis showed that melanocytes in early lesions have altered expression of several chemotaxis-associated molecules, including elevated secretion of CXCL12 and CCL5. Higher levels of these chemokines coincided with prominent infiltration of the skin with antigen presenting cells (APCs) and T cells. Most of the intralesional APCs expressed the CD86 maturation marker and co-localized with T cells, particularly in early vitiligo lesions. These observations were confirmed by in vivo animal studies showing preferential recruitment of APCs and T cells to CXCL12- and CCL5-expressing transplanted melanocytes, immunotargeting of the chemokine-positive cells, continuous loss of the pigment-producing cells from the epidermis, and development of vitiligo-like lesions. Taken together, our studies show that melanocyte-derived CXCL12 and CCL5 support APC and T-cell recruitment, antigen acquisition, and T-cell activation in early vitiligo and reinforce the role of melanocyte-derived CXCL12 and CCL5 in activation of melanocyte-specific immunity and suggest inhibition of these chemotactic axes as a strategy for vitiligo stabilization. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Fractional CO2 lasers contribute to the treatment of stable non-segmental vitiligo.

PubMed

Yuan, Jinping; Chen, Hongqiang; Yan, Ru; Cui, Shaoshan; Li, Yuan-Hong; Wu, Yan; Gao, Xing-Hua; Chen, Hong-Duo

2016-12-01

Stable non-segmental vitiligo is often resistant to conventional therapies. The purpose of this study was to investigate the effect of three types of fractional lasers in the treatment of stable non-segmental vitiligo. Twenty patients were enrolled in the study. The vitiligo lesions of each patient were divided into four treatment parts, and all parts were treated with narrowband ultraviolet-B (NB-UVB). Three of the four parts were respectively treated with three types of fractional lasers (two ablative 10,600-nm CO 2 lasers and one non-ablative 1,565-nm laser), followed by topical betamethasone solution application. The treatment period lasted six months. Efficacy and satisfaction were respectively assessed by dermatologists and patients. The ablative CO 2 lasers, in combination with topical betamethasone solution and NB-UVB, achieved marked to excellent improvement on white patches assessed by dermatologists. Patients showed high satisfaction scores for the treatments. The non-ablative 1,565-nm fractional laser did not provide any further benefit in the treatment of vitiligo. No severe adverse events developed for any of the treatments. The treatment protocol with ablative CO 2 lasers, in combination with topical betamethasone solution and NB-UVB, was suitable for stable non-segmental vitiligo. For vitiligo, the ablative fractional CO 2 laser is more effective than the non-ablative fractional laser.

Association of Leukotrichia in Vitiligo and Asp148Glu Polymorphism of Apurinic/Apyrimidinic Endonuclease 1.

PubMed

Aydin, A Fatih; Aydıngöz, İkbal Esen; Doğru-Abbasoğlu, Semra; Vural, Pervin; Uysal, Müjdat

2017-01-01

Oxidative stress and increased DNA damage have been implicated in the etiopathogenesis of vitiligo. Oxidative DNA damage is mainly repaired by the base excision repair (BER) pathway. We sought to determine whether polymorphisms in DNA repair genes may have a role in the pathogenesis of vitiligo. We conducted a study including 100 patients with vitiligo and age- and sex-matched 193 control subjects to examine the role of single-nucleotide polymorphisms of BER genes, human 8-oxoG DNA N-glycosylase 1 (codon 326), apurinic/apyrimidinic endonuclease 1 (APE1) (codon 148), and X-ray repair cross-complementing group 1 (codon 399) as risk factors for vitiligo. These polymorphisms were determined by quantitative real-time polymerase chain reaction and melting curve analysis. No significant association was observed between the variant alleles of studied genes and vitiligo. However, we showed that the presence of APE1 148Glu variant allele is associated with leukotrichia. This preliminary study suggests that APE1 (codon 148) polymorphism may play a role in vitiligo pathogenesis.

Incident alopecia areata and vitiligo in adult women with atopic dermatitis: Nurses' Health Study 2.

PubMed

Drucker, A M; Thompson, J M; Li, W-Q; Cho, E; Li, T; Guttman-Yassky, E; Qureshi, A A

2017-05-01

We aimed to determine the risk of alopecia areata (AA) and vitiligo associated with atopic dermatitis (AD) in a large cohort of US women, the Nurses' Health Study 2. We used logistic regression to calculate age- and multivariate-adjusted odds ratios to determine the risk of incident AA and vitiligo associated with AD diagnosed in or before 2009. A total of 87 406 and 87 447 participants were included in the AA and vitiligo analyses, respectively. A history of AD in 2009 was reported in 11% of participants. There were 147 incident cases of AA and 98 incident cases of vitiligo over 2 years of follow-up. AD was associated with increased risk of developing AA (OR 1.80, 95% CI 1.18-2.76) and vitiligo (OR 2.14, 95% CI 1.29-3.54) in multivariate models. In this study of US women, AD was associated with increased risk of incident vitiligo and AA in adulthood. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Understanding mechanisms of autoimmunity through translational research in vitiligo

PubMed Central

Strassner, James P; Harris, John E

2016-01-01

Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible. PMID:27764715

The psychosocial impact of vitiligo in Indian patients.

PubMed

Pahwa, Pooja; Mehta, Manju; Khaitan, Binod K; Sharma, Vinod K; Ramam, M

2013-01-01

Vitiligo has a special significance in Indian patients both because depigmentation is obvious on darker skin and the enormous stigma associated with the disease in the culture. This study was carried out to determine the beliefs about causation, aspects of the disease that cause concern, medical, and psychosocial needs of the patients, expectation from treatment and from the treating physician, and effects of disease on the patient's life. Semi-structured interviews were conducted in 50 patients with vitiligo. Purposive sampling was used to select subjects for the study. Each interview was recorded on an audio-cassette and transcripts were analyzed to identify significant issues and concerns. Patients had a range of concerns regarding their disease such as physical appearance, progression of white patches onto exposed skin and the whole body, ostracism, social restriction, dietary restrictions, difficulty in getting jobs, and they considered it to be a significant barrier to getting married. The condition was perceived to be a serious illness. Stigma and suicidal ideation was reported. While there were several misconceptions about the cause of vitiligo, most patients did not think their disease was contagious, heritable or related to leprosy. Multiple medical consultations were frequent. Complete repigmentation was strongly desired, but a lesser degree of repigmentation was acceptable if progression of disease could be arrested. The problems were perceived to be more severe in women. The disease imposed a significant financial burden. Addressing psychosocial factors is an important aspect of the management of vitiligo, particularly in patients from communities where the disease is greatly stigmatizing.

Correlation between vitiligo occurrence and clinical benefit in advanced melanoma patients treated with nivolumab: A multi-institutional retrospective study.

PubMed

Nakamura, Yasuhiro; Tanaka, Ryota; Asami, Yuri; Teramoto, Yukiko; Imamura, Taichi; Sato, Sayuri; Maruyama, Hiroshi; Fujisawa, Yasuhiro; Matsuya, Taisuke; Fujimoto, Manabu; Yamamoto, Akifumi

2017-02-01

Vitiligo is occasionally seen in melanoma patients. Although several studies indicate a correlation between vitiligo occurrence and clinical response in melanoma patients receiving immunotherapy, most studies have included heterogeneous patient and treatment settings. The aim of this study is to investigate the correlation between the occurrence of vitiligo and clinical benefit of nivolumab treatment in advanced melanoma patients. We retrospectively reviewed unresectable stage III or IV melanoma patients treated with nivolumab. Of 35 melanoma patients treated with nivolumab, 25.7% (9/35) developed vitiligo during treatment. The time from the start of nivolumab treatment to occurrence of vitiligo ranged 2-9 months (mean, 5.2). Of nine patients who developed vitiligo, two (22.2%) had a complete response to nivolumab and two (22.2%) had a partial response. The objective response rate was significantly higher in patients with vitiligo than in patients without vitiligo (4/9 [44.4%] vs 2/26 [7.7%]; P = 0.027). The mean time to vitiligo occurrence in patients achieving an objective response was significantly less than that in patients who showed no response (3.1 vs 6.8 months, P = 0.004). Vitiligo occurrence was significantly associated with prolonged progression-free and overall survival (hazard ratio, 0.24 and 0.16; 95% confidence interval, 0.11-0.55 and 0.03-0.79; P = 0.005, and 0.047, respectively). At the 20-week landmark analysis, however, vitiligo was not associated with a statistically significant overall survival benefit (P = 0.28). The occurrence of vitiligo during nivolumab treatment may be correlated with favorable clinical outcome. © 2016 Japanese Dermatological Association.

Altered E-Cadherin Levels and Distribution in Melanocytes Precede Clinical Manifestations of Vitiligo.

PubMed

Wagner, Roselyne Y; Luciani, Flavie; Cario-André, Muriel; Rubod, Alain; Petit, Valérie; Benzekri, Laila; Ezzedine, Khaled; Lepreux, Sébastien; Steingrimsson, Eirikur; Taieb, A; Gauthier, Yvon; Larue, Lionel; Delmas, Véronique

2015-07-01

Vitiligo is the most common depigmenting disorder resulting from the loss of melanocytes from the basal epidermal layer. The pathogenesis of the disease is likely multifactorial and involves autoimmune causes, as well as oxidative and mechanical stress. It is important to identify early events in vitiligo to clarify pathogenesis, improve diagnosis, and inform therapy. Here, we show that E-cadherin (Ecad), which mediates the adhesion between melanocytes and keratinocytes in the epidermis, is absent from or discontinuously distributed across melanocyte membranes of vitiligo patients long before clinical lesions appear. This abnormality is associated with the detachment of the melanocytes from the basal to the suprabasal layers in the epidermis. Using human epidermal reconstructed skin and mouse models with normal or defective Ecad expression in melanocytes, we demonstrated that Ecad is required for melanocyte adhesiveness to the basal layer under oxidative and mechanical stress, establishing a link between silent/preclinical, cell-autonomous defects in vitiligo melanocytes and known environmental stressors accelerating disease expression. Our results implicate a primary predisposing skin defect affecting melanocyte adhesiveness that, under stress conditions, leads to disappearance of melanocytes and clinical vitiligo. Melanocyte adhesiveness is thus a potential target for therapy aiming at disease stabilization.

Measurement properties of outcome measures for vitiligo. A systematic review.

PubMed

Vrijman, Charlotte; Linthorst Homan, May W; Limpens, Jacqueline; van der Veen, Wietze; Wolkerstorfer, Albert; Terwee, Caroline B; Spuls, Phyllis I

2012-11-01

OBJECTIVE To summarize and critically appraise the evidence on the measurement properties of clinician-, patient-, and observer-reported outcomes, measuring any construct of interest in patients with all types of vitiligo. DATA SOURCES Electronic databases including PubMed (1948 to July 2011), OVID EMBASE (1980 to July 2011), and CINAHL (EBSCOhost) (1982 to July 2011) were searched. STUDY SELECTION Two authors independently screened all records for eligibility. For inclusion, the study population had to include patients with vitiligo, for which outcome measures were developed or evaluated on their measurement properties. The initial search retrieved 1249 records, of which 14 articles met the inclusion criteria. DATA EXTRACTION Characteristics of the included instruments, study population, and results of the measurement properties were extracted. The Consensus-Based Standards for the Selection of Health Status Measurement Instruments (COSMIN) 4-point checklist, combined with quality criteria for measurement properties, was used to calculate the overall level of evidence per measurement property of each instrument. Independent extraction and assessment was performed by 2 authors. DATA SYNTHESIS Eleven different measurement instruments were identified. Strong evidence was found for a positive internal consistency of the Dermatology Life Quality Index. For other instruments, the evidence of measurement properties was limited or unknown. CONCLUSIONS Recommendations on the use of specific outcome measures for vitiligo should be formulated with caution because current evidence is insufficient owing to a low number of studies with poor methodological quality and unclear clinical relevance. To recommend outcome measures for vitiligo, further research on measurement properties of clinical relevant outcome measures for vitiligo according to COSMIN quality criteria is needed.

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

Association of Angiotensin-Converting Enzyme (ACE) Gene Polymorphism with Inflammation and Cellular Cytotoxicity in Vitiligo Patients.

PubMed

Rashed, Laila; Abdel Hay, Rania; Mahmoud, Rania; Hasan, Nermeen; Zahra, Amr; Fayez, Salwa

2015-01-01

Vitiligo is a disorder with profound heterogeneity in its aetio-pathophysiology. Angiotensin converting enzyme (ACE) plays an important role in the physiology of the vasculature, blood pressure and inflammation. An insertion/deletion (I/D) polymorphism of the ACE gene was reported be associated with the development of vitiligo. Our aim was to evaluate the ACE I/D polymorphism in vitiligo patients and controls. Our second aim was to find a possible association between ACE gene polymorphism and inflammatory mediators (as interleukin (IL)-6) and/or cellular cytotoxicity induced by serum nitrite (as a breakdown product of the cytotoxic nitric oxide) in vitiligo patients. This case-control study included 74 vitiligo patients and 75 apparently healthy controls. The distribution of ACE gene I/D genotype was investigated using PCR. Serum ACE, IL-6 and nitrite were measured by colorimetric method, ELISA and Griess assay respectively. The ACE allele frequency was significantly different between vitiligo patients and healthy controls (P = 0.026). However there was no significant difference between the ACE genotyping frequency in both groups (P = 0.115). There were statistically significant higher VIDA score (P = 0.007), and serum IL-6 (P < 0.001) in patients with the DD genotype when compared to other genotypes. Serum nitrite in patients with the DD genotype was significantly higher (P = 0.007) when compared to patients with II genotype. Serum levels of ACE, IL-6 and nitrite in vitiligo patients were statistically significantly higher than those in controls. As a conclusion, ACE gene polymorphism might grant susceptibility to develop vitiligo. Serum IL-6 and nitrite levels might have an important role in the pathogenesis of vitiligo. Targeting these two factors might have an implication in the treatment of some resistant cases.

Increased Tumor Necrosis Factor (TNF)-α and Its Promoter Polymorphisms Correlate with Disease Progression and Higher Susceptibility towards Vitiligo

PubMed Central

Laddha, Naresh C.; Dwivedi, Mitesh; Begum, Rasheedunnisa

2012-01-01

Abstract Tumor Necrosis Factor (TNF)-α, is a paracrine inhibitor of melanocytes, which plays a critical role in the pathogenesis of several autoimmune diseases including vitiligo, as abnormal immune responses have frequently been observed in vitiligo patients. Moreover, vitiligo patients show higher lesion levels of TNF-α. Genetic polymorphisms in the promoter region of TNF-α are involved in the regulation of its expression. The present study explores TNF-α promoter polymorphisms and correlates them with TNF-α transcript and protein levels in vitiligo patients and controls of Gujarat along with its effect on disease onset and progression. PCR-RFLP technique was used for genotyping of these polymorphisms in 977 vitiligo patients and 990 controls. TNF-α transcript and protein levels were measured by Real time PCR and ELISA respectively. The genotype and allele frequencies for the investigated polymorphisms were significantly associated with vitiligo patients. The study revealed significant increase in TNF-α transcript and protein levels in vitiligo patients compared to controls. In particular, haplotypes: AATCC, AACCT, AGTCT, GATCT, GATCC and AGCCT were found to increase the TNF-α levels in vitiligo patients. Analysis of TNF-α levels based on the gender and disease progression suggests that female patients and patients with active vitiligo had higher levels of TNF-α. Also, the TNF-α levels were high in patients with generalized vitiligo as compared to localized vitiligo. Age of onset analysis of the disease suggests that the haplotypes: AACAT, AACCT, AATCC and AATCT had a profound effect in the early onset of the disease. Moreover, the analysis suggests that female patients had an early onset of vitiligo. Overall, our results suggest that TNF-α promoter polymorphisms may be genetic risk factors for susceptibility and progression of the disease. The up-regulation of TNF-α transcript and protein levels in individuals with susceptible haplotypes advocates

Low 25-hydroxyvitamin D levels are associated with vitiligo: a systematic review and meta-analysis.

PubMed

Upala, Sikarin; Sanguankeo, Anawin

2016-07-01

Vitamin D deficiency is associated with a number of autoimmune diseases. We completed a meta-analysis of observational studies to establish whether there was a relationship between hypovitaminosis D and the autoimmune skin disease vitiligo. Comprehensive search was applied in the MEDLINE and EMBASE databases from their inception to December 2015. Inclusion criteria were observational studies that assessed 25-hydroxyvitamin D (25(OH)D) levels in adults with vitiligo. The main outcome was the mean difference in serum 25(OH)D level between patients with vitiligo and controls. Our search strategy identified 383 articles; seventeen studies met the criteria for full-length review and seven studies, containing the data of 1200 patients, were included in a random-effects model meta-analysis. The pooled mean difference in serum 25-hydroxyvitamin D concentration between patients with vitiligo and controls was -7.45 ng/ml (95% confidence interval, -12.99 to -1.91, P-value = 0.01). The between-study heterogeneity (I(2) ) was 96%, P = value<0.001. This meta-analysis identifies a significant relationship between low 25-hydroxyvitamin D levels and vitiligo, but does not prove causation. Our findings emphasize the importance of measuring 25-hydroxyvitamin D levels in patients with vitiligo. Further studies will be needed to establish whether vitamin D supplementation in this population improves the outcome of vitiligo. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity?

PubMed

Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen

2016-01-01

Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Multivariate Analysis of Factors Associated with the Koebner Phenomenon in Vitiligo: An Observational Study of 381 Patients

PubMed Central

Khurrum, Huma; Bedaiwi, Khalid M.; AlBalahi, Naif Meshael

2017-01-01

Background The Koebner phenomenon (KP) is a common entity observed in dermatological disorders. The reported incidence of KP in vitiligo varies widely. Although the KP is frequently observed in patients with viltiligo, the associated factors with KP has not been established yet. Objective The aim is to estimate the prevalence of KP in vitiligo patients and to investigate the associated factors with KP among vitiligo characteristics. Methods A cross-sectional observational study was conducted using 381 vitiligo patients. Demographic and clinical information was obtained via the completion of Vitiligo European Task Force (VETF) questionnaires. Patients with positive history of KP were extracted from this vitiligo database. Multivariate analysis was performed to assess associations with KP. Results The median age of cases was 24 years (range, 0.6~76). In total, 237 of the patients were male (62.2%). Vitiligo vulgaris was the most common type observed (152/381, 39.9%). Seventy-two percent (274/381) patients did not exhibit KP, whereas 28.1% (107/381) of patients exhibited this condition. Multivariable analysis showed the following to be independent factors with KP in patients with vitiligo: the progressive disease (odds ratio [OR], 1.82; 95% confidence interval [95% CI], 1.17~2.92; p=0.041), disease duration longer than 5 years (OR, 1.92; 95% CI, 1.22~2.11; p=0.003), and body surface area more than 2% (OR, 2.20; 95% CI, 1.26~3.24; p<0.001). Conclusion Our results suggest that KP may be used to evaluate disease activity and investigate different associations between the clinical profile and course of vitiligo. Further studies are needed to predict the relationship between KP and responsiveness to therapy. PMID:28566906

Multidisciplinary approach to R&D in vitiligo, a neglected skin disease.

PubMed

Valle, Yan; Lotti, Torello M; Hercogova, Jana; Schwartz, Robert A; Korobko, Igor V

2012-01-01

A global interest in therapies for neglected diseases is rising, but traditional biopharma research and development (R&D) process is prohibitively expensive to justify cost of their development. Vitiligo is a multifactorial orphan disease that affects at minimum 35 million people worldwide, yet no therapeutic solutions exist. The present authors describe a budget-minded pursuit of the new therapy development for vitiligo, which includes a multidiscipline collaboration and effective bridging between academic research, biobanking, and bioinformatics. The present authors anticipate that the present authors' "theoretically induced and empirically guided" discovery process will enable development of more leads, with a much greater probability of success and under tighter budgets compared with those of the biopharma company. Ultimately, the multidisciplinary approach described below facilitates the collaborative development of personalized treatments for different patient subpopulations in vitiligo and other neglected diseases. © 2012 Wiley Periodicals, Inc.

Analysis of Manganese Superoxide Dismutase and Glutathione Peroxidase 1 Gene Polymorphisms in Vitiligo.

PubMed

Seçkin, Havva Yıldız; Kalkan, Göknur; Bütün, İlknur; Akbaş, Ali; Baş, Yalçın; Karakuş, Nevin; Benli, İsmail

2016-08-01

Vitiligo is a hereditary/acquired progressive pigmentation disorder characterized by discoloration of skin as a result of melanocyte dysfunction. Recent studies have proposed that oxidant/antioxidant status plays an important role in vitiligo pathogenesis because of the toxic effects on melanocytes. In this study, we aimed to investigate possible associations of MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms with vitiligo with in Turkish population. The study group consists of 57 patients with vitiligo and 69 healthy controls. Genotyping is performed to identify MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms. The method used for genotyping was based on the PCR amplification and detection of polymorphisms by hybridization probes labeled with fluorescent dyes. Both the genotype and allele frequencies of MnSOD Ala-9Val (p = 0.817 and p = 0.553, respectively) and GPx1 Pro198Leu polymorphisms (p = 0.422 and p = 0.673, respectively) were not significantly different between vitiligo patients and the control group. Although no significant difference was found, this is the first report investigating the possible associations between the MnSOD Ala-9Val and GPx1 Pro198Leu polymorphisms in Turkish population. Further studies with large populations will be able to clarify the association better.

[MELATONIN CONCENTRATION IN THE BLOOD OF VITILIGO PATIENTS WITH STRESS IN ANAMNESIS].

PubMed

Tsiskarishvili, N I; Katsitadze, A; Tsiskarishvili, N V; Tsiskarishvil, Ts; Chitanava, L

2016-05-01

In recent years, despite some progress in the study of vitiligo many aspects of pathogenesis and treatment of this dermatosis remain unsolved or are highly controversial. It is believed that progression of disease is associated with a genetic predisposition, autoimmune processes and oxidative stress, but the concrete role of stress on the processes having place in the organism of vitiligo patients so far is not investigated. As we know, epiphysis is the main regulator of adaptation of the individual to the environment. An important product of secretion of the pineal gland is the hormone melatonin - a universal regulator of vital functions and biorhythms of the body. Psychoses, neuroses, depression, immunopathology are aspects of disturbances in circadian, seasonal and annual rhythms of the synthesis of this hormone. Clinical and experimental studies indicate that the hormone melatonin, which is one of the links in a stress defense mechanism of the body, has antioxidant and immunomodulatory properties. The purpose of this study was to determine plasma level of melatonin in the blood of vitiligo patients (with stress in anamnesis), depending on the clinical form and duration of the disease. 41 patients with vitiligo (16 with segmental and 25 with non-segmental form) with stress in anamnesis and duration of disease from several months to 20 years were under observation. The level of melatonin in the blood plasma was determined by ELISA (IBL - international - reagent), the results were expressed in units of pg/ml. According to the results of our study, 8 patients with segmental vitiligo had the normal level of plasma melatonin concentration (in the range of 20.2-31.1 pg/ml), in 2 cases - the level was near the norm (19.2 pg/ml). In the group of patients with non-segmental vitiligo, the level of melatonin was below the norm (12.5 pg/ml) and in 2 cases, the content of melatonin was very low - 4.05 pg / ml. Correlation analysis of melatonin levels with duration of disease

Hashimoto's thyroiditis could be secondary to vitiligo: the possibility of antigen crossover and oxidative stress between the two diseases.

PubMed

Gong, Qingli; Li, Xue; Gong, Qixing; Zhu, Wenyuan; Song, Guoxin; Lu, Yan

2016-05-01

Autoimmune thyroid diseases (AITDs) are often accompanied by vitiligo, and the sera of patients with vitiligo often demonstrate increased frequencies of thyroid autoantibodies. In this study, we investigated the expression of melanocyte-associated antigens in tissues from patients with Hashimoto's thyroiditis (HT) without vitiligo using immunohistochemistry. Tissues of HT without vitiligo, as well as normal thyroid tissues, were both negative for the expression of NKI/beteb, gp100, tyrosinase-related protein 1 (TRP1), HMB-45 and S100, whereas they were positive for the expression of tyrosinase-related protein 2 (TRP2), lysosome-associated membrane protein 1 (LAMP1) and CD69. Tyrosinase (TYR) was only detected in tissues of HT, and levels of LAMP1 and CD69 were higher in tissues of HT than in normal thyroid tissues (p < 0.005). These results suggest the possibility of antigen crossover and oxidative stress between vitiligo and HT that might represent an immunological basis for secondary HT associated with vitiligo.

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

Suction Blister Epidermal Grafting for Vitiligo Involving Angles of Lip: Experience of 112 Patients

PubMed Central

Kar, Bikash R.; Raj, Chinmoy

2018-01-01

Background: Lip vitiligo is usually resistant to medical modalities of treatment, and in all these cases, surgery offers a hope. Suction blister grafting (SBG) has been tried since long for lip vitiligo with high rate of success. There have been no long-term follow-up studies of patients with SBG at a difficult-to-treat site like angles of lip, which prompted us to conduct this study. Aims and Objectives: To assess the pigmentation rate and patient satisfaction of SBG on vitiligo involving angles of lip. Materials and Methods: This is a prospective study conducted on 112 patients with stable vitiligo involving angles of lip. SBG was carried out in all the patients using the standard procedure. Patients were advised to apply topical psoralen followed by sun exposure (PUVASOL) for 8–12 weeks after operation. The patients were followed up at 3, 6, 12, 18, and 24 months for assessment of pigmentation and overall satisfaction. Results: We found a pigmentation success rate of 83.7%, 84.9%, 85.7%, 78.3%, and 77.8% in the patients who were followed up at 3, 6, 12, 18, and 24 months, respectively. A total of 77.8% of patients who came for follow-up at the end of 24 months were very happy with the treatment. Discussion: Our data show clearance of vitiligo and persistence of pigmentation gained through SBG in 77.8% of cases at the end of 2 years as well as excellent patient satisfaction in the cohort of patients who followed up with us. Conclusion: SBG is an easy and cost-effective way of repigmentation of vitiligo involving angles of lip. PMID:29731587

A study of the free radical scavenging effects of Piper betle leaf extract in patients with vitiligo.

PubMed

Mitra, Sneha; Pati, Ayan Kumar; Manna, Alak; Ghosh, Arghyaprasun; Sen, Sumit; Chatterjee, Suparna; Chatterjee, Mitali

2017-01-01

Vitiligo is an idiopathic skin disease manifested by depigmented macules. It is characterised by melanocyte destruction, and redox imbalance is proposed to play a contributory role. The aim of this study was to analyze the effects of an ethanolic extract of Piper betle leaves on the generation of reactive oxygen species in erythrocytes sourced from vitiligo patients. The effect of Piper betle on the generation of reactive oxygen species in erythrocytes was measured by flow cytometry in patients with active and stable vitiligo versus healthy controls, using 5-(and-6)-chloromethyl-2'-7'-dichlorodihydrofluorescein diacetate. The generation of reactive oxygen species in erythrocytes was higher in patients with vitiligo (n = 23) compared to healthy controls (n = 18). The geometrical mean fluorescence channel was 23.05 ± 2.11 in patients versus 17.77 ± 1.79 in controls, P = 0.039. The levels of reactive oxygen species were higher in patients with active vitiligo. Treatment of erythrocytes with Piper betle in concentrations of 0.5 and 1.0 μg/ml significantly decreased the baseline levels of reactive oxygen species by 31.7% in healthy controls, and 47.6% and 44.3% in patients with active vitiligo, respectively. Piper betle effectively scavenged hydrogen peroxide, which was evident by a decrease in the geometrical mean fluorescence channel by 52.4% and 62.9% in healthy controls, and 45.0% and 57.0% in patients with active vitiligo. The study had a small sample size. Future studies should focus on evaluation of the antioxidant role of Piper betle at the lesional site. This pilot study indicates that patients with active vitiligo demonstrate enhanced generation of reactive oxygen species in erythrocytes, which was significantly reduced following ex vivo treatment with Piper betle.

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.

Evaluation of treatment response to autologous transplantation of noncultured melanocyte/keratinocyte cell suspension in patients with stable vitiligo.

PubMed

Ramos, Mariana Gontijo; Ramos, Daniel Gontijo; Ramos, Camila Gontijo

2017-01-01

Vitiligo is a chronic disease characterized by the appearance of achromic macules caused by melanocyte destruction. Surgical treatments with melanocyte transplantation can be used for stable vitiligo cases. To evaluate treatment response to the autologous transplantation of noncultured epidermal cell suspension in patients with stable vitiligo. Case series study in patients with stable vitiligo submitted to noncultured epidermal cell suspension transplantation and evaluated at least once, between 3 and 6 months after the procedure, to observe repigmentation and possible adverse effects. The maximum follow-up period for some patients was 24 months. Of the 20 patients who underwent 24 procedures, 25% showed an excellent rate of repigmentation, 50% good repigmentation, 15% regular, and 10% poor response. The best results were observed in face and neck lesions, while the worst in extremity lesions (88% and 33% of satisfactory responses, respectively). Patients with segmental vitiligo had a better response (84%) compared to non-segmental ones (63%). As side effects were observed hyperpigmentation of the treated area and the appearance of Koebner phenomenon in the donor area. Some limitations of the study included the small number of patients, a subjective evaluation, and the lack of long-term follow-up on the results. CONCLUSION: Noncultured epidermal cell suspension transplantation is efficient and well tolerated for stable vitiligo treatment, especially for segmental vitiligo on the face and neck.

Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure.

PubMed

Liu, Lucy Y; Strassner, James P; Refat, Maggi A; Harris, John E; King, Brett A

2017-10-01

Vitiligo is an autoimmune disease in which cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors. To evaluate the efficacy of the JAK 1/3 inhibitor tofacitinib in the treatment of vitiligo. This is a retrospective case series of 10 consecutive patients with vitiligo treated with tofacitinib. Severity of disease was assessed by body surface area of depigmentation. Ten consecutive patients were treated with tofacitinib. Five patients achieved some repigmentation at sites of either sunlight exposure or low-dose narrowband ultraviolet B phototherapy. Suction blister sampling revealed that the autoimmune response was inhibited during treatment in both responding and nonresponding lesions, suggesting that light rather than immunosuppression was primarily required for melanocyte regeneration. Limitations include the small size of the study population, retrospective nature of the study, and lack of a control group. Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low-level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A study of the association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo in Egyptian patients.

PubMed

Aly, Dalia Gamal; Salem, Samar Abdallah; Amr, Khalda Sayed; El-Hamid, Mahmoud Fawzy Abd

2018-01-01

The association of glutathione S-transferases M1/T1 (GSTM1/T1) null polymorphisms with vitiligo was proposed in several studies including two Egyptian studies with contradictory results. The aim here was to assess the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo in a larger sample of Egyptian patients with generalized vitiligo. This study included 122 vitiligo patients and 200 healthy controls that were age, and gender matched. Assessment of GSTM1/T1 gene polymorphisms was done using a multiplex polymerase chain reaction (PCR). Increased odds of generalized vitiligo was observed with the null genotypes of GSTM1 and GSTT1 polymorphisms (P<0.05). Controls with GSTM1 null/GSTT1+ heterozygosis presented with a 2.97 odds protection from having generalized vitiligo (OR=2.97, 95%CI=1.1-7.7) (P=0.02) compared with patients. Small sample size of patients. This study showed a significant trend towards an association with the combination of the GSTM1/GSTT1 double null polymorphism and generalized vitiligo. Individuals with GSTM1 null/GSTT1+ heterozygosis have a 2.97 odds protection from having generalized vitiligo compared with patients. It was is the first time, to our knowledge, that such an association has been reported.

A holistic review on the autoimmune disease vitiligo with emphasis on the causal factors.

PubMed

Patel, Seema; Rauf, Abdur; Khan, Haroon; Meher, Biswa Ranjan; Hassan, Syed Shams Ul

2017-08-01

Vitiligo is an idiopathic systemic autoimmune disease affecting skin, hair and oral mucosa. This genetic yet acquired disease characterized by melanin loss is a cause of morbidity across all races. Though thyroid disturbance has been recognized as a key trigger of this pathology, an array of other factors plays critical role in its manifestation. Multiple hormones (corticotropin-releasing hormone, adrenocorticotropic hormone, α-melanocyte-stimulating hormone, melatonin, calcitriol, testosterone, estrogen), genes (Human leukocyte antigen (HLA), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), Forkhead box D3 (FOXD3), Cluster of differentiation 117 (CD117), Estrogen receptor (ESR) 1, Cyclooxygenase-2 (COX2), Vitiligo-associated protein 1 (VIT1)), and lifestyle choices (stress, diet, cosmetic products, and medications) have been suspected as drivers of this disorder. The pathological mechanisms have been understood in recent times, with the aid of genomic studies; however a universally-effective therapy is yet to be achieved. This review discusses these under-investigated facets of vitiligo onset and progression; hence, it is expected to enrich vitiligo research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[EFFICACY OF COMBINED USE OF ANTIOXIDATIVE AND PHOTOTHERAPY IN THE TREATMENT OF VITILIGO].

PubMed

Tsiskarishvili, N I; Katsitadze, A; Tsiskarishvili, N V; Tsiskarishvili, Ts; Chitanava, L

2016-11-01

Despite of numerous investigations, carried out practically in all countries of the world for the study of vitiligo and the search for its new effective therapies, pathogenic mechanisms of vitiligo are still poorly understood, and the proposed treatments are not perfect. One of the most accepted theories of the pathogenesis of vitiligo is an oxidative stress theory, according to which a series of biochemical anomalies cause oxidative stress, leading to accumulation of melanocytotoxic substances and inhibition of natural processes of detoxification with subsequent destruction of melanocytes in vitiligo focus. On the other hand, the use of antioxidants in combination with ultraviolet therapy of dermatological diseases, has been theoretically proved by biophysical studies, according to which- the antioxidants inhibit the oxidation of products, formed in the skin after ultraviolet irradiation and greatly reduce erythema sensitivity (1.5-2 times). Due to this effect, the power of radiation exposure can be approximately increased many times. Based on the foregoing, the use of antioxidants during phototherapy of vitiligo pathogenetically is justified. The aim of the study was to evaluate the therapeutic efficacy of Se ACE in treatment of patients with various forms of vitiligo. 35 patients (23 women and 12 men) aged 18 to 40 years with duration of the pathological process from 2 months to 15 years were under observation. 17 of these were diagnosed with a form of non segmental vitiligo (NSV), 18- segmental vitiligo. In 11 patients onset of the disease was not connected with any other problem, 24 noted the appearance of white spots after stress. Vitiligo patients were divided into 2 groups: the study group and the group of comparison. The study group included 17 patients (9 women and 8 men) aged 18 to 40 years with duration of the disease from 2 months to 5 years. The comparison group consisted of 18 patients (10 women and 8 men). Distribution of patients in both groups was

Frontal Fibrosing Alopecia and Vitiligo: Coexistence or True Association?

PubMed

Katoulis, Alexandros C; Diamanti, Konstantina; Sgouros, Dimitrios; Liakou, Aikaterini I; Alevizou, Antigoni; Bozi, Evangelia; Damaskou, Vasileia; Panayiotides, Ioannis; Rigopoulos, Dimitrios

2017-01-01

Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia characterized by a progressive band-like recession of the frontotemporal hairline and frequent loss of the eyebrows. It predominantly affects postmenopausal women. Coexistence of FFA and vitiligo is rarely reported in the literature. We retrospectively studied 20 cases diagnosed with FFA in a 14-month period in our Department. Among them, there were 2 cases, a 72-year-old woman and a 48-year-old man, who developed FFA on preexisting vitiligo of the forehead. Anatomical colocalization of the two dermatoses supports the notion that a causal link may exist and their association may not be coincidental. We suggest that interrelated immunologic events and pathologic processes may underlie both these skin conditions.

Goodbye warts, hello vitiligo: Candida antigen-induced depigmentation.

PubMed

Wilmer, Erin N; Burkhart, Craig N; Morrell, Dean S

2013-01-01

Depigmentation after the use of topical immune modulators is a rare but reported event. Herein we present what is to our knowledge the first case of vitiligo at a site of Candida antigen injection. © 2012 Wiley Periodicals, Inc.

Nivolumab-induced vitiligo in a metastatic melanoma patient: A case report.

PubMed

Edmondson, Lindsay A; Smith, Leticia V; Mallik, Alka

2017-12-01

The programmed-death-1 inhibitors selectively block programmed-death-1 interaction with its receptor, which restores active T-cell response directed at tumor cells, inducing an anti-tumor effect. This nonspecific activation of the immune system can also lead to a wide spectrum of side effects. Nivolumab has been used effectively to prolong survival in patients with metastatic melanoma and is recommended as a category 1 agent for systemic therapy in metastatic or unresectable melanoma per the National Comprehensive Cancer Network guidelines. We present a case of a 64-year-old woman who began nivolumab therapy for metastatic melanoma. After six doses of nivolumab therapy, the patient experienced generalized hypopigmentation on her face, chest, back, arms, and lower extremities. Although vitiligo has been reported in as many as 10.7% of patients undergoing nivolumab therapy in some clinical trials, we believe this is the first case to describe the progression of nivolumab-induced vitiligo in a metastatic melanoma patient. This case provides significant insight into the onset, symptoms, development, and treatment options for patients experiencing vitiligo as a result of nivolumab therapy.

Survey and online discussion groups to develop a patient-rated outcome measure on acceptability of treatment response in vitiligo

PubMed Central

2014-01-01

Background Vitiligo is a chronic depigmenting skin disorder which affects around 0.5-1% of the world’s population. The outcome measures used most commonly in trials to judge treatment success focus on repigmentation. Patient-reported outcome measures of treatment success are rarely used, although recommendations have been made for their inclusion in vitiligo trials. This study aimed to evaluate the face validity of a new patient-reported outcome measure of treatment response, for use in future trials and clinical practice. Method An online survey to gather initial views on what constitutes treatment success for people with vitiligo or their parents/carers, followed by online discussion groups with patients to reach consensus on what constitutes treatment success for individuals with vitiligo, and how this can be assessed in the context of trials. Participants were recruited from an existing database of vitiligo patients and through posts on the social network sites Facebook and Twitter. Results A total of 202 survey responses were received, of which 37 were excluded and 165 analysed. Three main themes emerged as important in assessing treatment response: a) the match between vitiligo and normal skin (how well it blends in); b) how noticeable the vitiligo is and c) a reduction in the size of the white patches. The majority of respondents said they would consider 80% or more repigmentation to be a worthwhile treatment response after 9 months of treatment. Three online discussion groups involving 12 participants led to consensus that treatment success is best measured by asking patients how noticeable their vitiligo is after treatment. This was judged to be best answered using a 5-point Likert scale, on which a score of 4 or 5 represents treatment success. Conclusions This study represents the first step in developing a patient reported measure of treatment success in vitiligo trials. Further work is now needed to assess its construct validity and responsiveness to

Tumor necrosis factor-α -308G/A polymorphism is associated with active vitiligo vulgaris in a northeastern Mexican population

PubMed Central

SALINAS-SANTANDER, MAURICIO; DÍAZ-GARCÍA, DANIEL; ROJAS-MARTÍNEZ, AUGUSTO; CANTÚ-SALINAS, CRISTINA; SÁNCHEZ-DOMÍNGUEZ, CELIA; REYES-LÓPEZ, MIGUEL; CERDA-FLORES, RICARDO M.; OCAMPO-CANDIANI, JORGE; ORTIZ-LÓPEZ, ROCÍO

2012-01-01

Vitiligo is a skin disease characterized by depigmentation. Its etiopathogenesis is unclear, but it has been associated with autoimmune processes. Gene polymorphisms in the tumor necrosis factor-α (TNF-α) have been associated with several imflammatory diseases. In particular, the -308G/A polymorphism in the gene promoter region has been reported to be associated with increased plasma levels of TNF-α and with an increased risk to develop autoimmune diseases. To date, this polymorphism has not been associated with vitiligo. To assess a possible association between the TNF-α -308G/A and vitiligo vulgaris (VV), 198 vitiligo patients and 395 control subjects were recruited for the study. A complete demographic and clinical profile of each case was registered to analyze the possible risk factors of vitiligo. Genomic DNA isolated from peri pheral blood was subjected to PCR-RFLP for genotyping of the TNF-α -308G/A polymorphism. Causal associations were determined by χ2 test and their respective OR was assessed in a 2×2 contingency table. When population variables of type of vitiligo, gender, age of disease onset, and active disease status were considered, an association between active VV and the TNF-α GA genotype was found (P=0.0295, OR=2.0; 95% CI 1.01-3.93). All other variables were irrelevant to vitiligo. Our data suggest a possible association between the TNF-α -308 GA genotype and the active form of VV in a Mexican population. PMID:22969989

Vitiligo-inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8.

PubMed

Toosi, Siavash; Orlow, Seth J; Manga, Prashiela

2012-11-01

Vitiligo is characterized by depigmented skin patches caused by loss of epidermal melanocytes. Oxidative stress may have a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study, we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol and monobenzyl ether of hydroquinone, known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box-binding protein 1 (XBP1), is increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators IL6 and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while overexpression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity.

Vitiligo inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8

PubMed Central

Toosi, Siavash; Orlow, Seth J.; Manga, Prashiela

2012-01-01

Vitiligo is characterized by depigmented skin patches due to loss of epidermal melanocytes. Oxidative stress may play a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol (4-TBP) and monobenzyl ether of hydroquinone (MBEH), known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box binding protein 1 (XBP1), are increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators interleukin-6 (IL6) and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while over-expression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity. PMID:22696056

Selenium, zinc, copper, Cu/Zn ratio and total antioxidant status in the serum of vitiligo patients treated by narrow-band ultraviolet-B phototherapy.

PubMed

Wacewicz, Marta; Socha, Katarzyna; Soroczyńska, Jolanta; Niczyporuk, Marek; Aleksiejczuk, Piotr; Ostrowska, Jolanta; Borawska, Maria H

2018-03-01

Vitiligo is a chronic, depigmenting skin disorder, whose pathogenesis is still unknown. Narrow band ultraviolet-B (NB-UVB) is now one of the most widely used treatment of vitiligo. It was suggested that trace elements may play a role in pathogenesis of vitiligo. The aim of this study was to estimate the concentration of selenium (Se), zinc (Zn), copper (Cu) and Cu/Zn ratio as well as total antioxidant status (TAS) in the serum of patients with vitiligo. We assessed 50 patients with vitiligo and 58 healthy controls. Serum levels of Se, Zn and Cu were determined by the atomic absorption spectrometry method, and the Cu/Zn ratio was also calculated. TAS in serum was measured spectrophotometrically. Serum concentration of Se in patients with vitiligo before and after phototherapy was significantly lower as compared to the control group. Zn level in the serum of patients decreased significantly after phototherapy. We observed higher Cu/Zn ratio (p < .05) in examined patients than in the control group and after NB-UVB. We have found decrease in TAS in the serum of vitiligo patients after NB-UVB. The current study showed some disturbances in the serum levels of trace elements and total antioxidant status in vitiligo patients.

The effect of topical piperine combined with narrowband UVB on vitiligo treatment: A clinical trial study.

PubMed

Shafiee, Anoosh; Hoormand, Mahmood; Shahidi-Dadras, Mohammad; Abadi, Alireza

2018-05-21

Vitiligo is the most common acquired hypopigmentary disease in the community. Piperine as an herbal extract derived from black pepper has strong impact on the melanocyte proliferation and adverse side effects less than synthetic drugs such as corticosteroids. For the first time, this study was aimed to evaluate the effect of topical piperine combined with narrowband ultraviolet B (NB-UVB) on vitiligo treatment. In this double-blind clinical trial, 63 patients with facial vitiligo were randomly divided into 2 groups: treated with piperine (case) and placebo (control). Also, both groups received NB-UVB phototherapy every other day for 3 months. In the case group, 10 patients have burning sensation on their skin areas (p value = .002). Also, redness of the treated areas was observed in 6 patients (p value = .028). Both side effects were temporary. Regarding repigmentation at time intervals of 1, 2, and 3 months after treatment, its level in the case group was significantly higher than the control group (p value < .001). Based on our findings, the combination therapy with NB-UVB/topical piperine has more influence on facial vitiligo than that of NB-UVB alone. It could be concluded that the simultaneous use of NB-UVB and topical piperine has a remarkable effect on treatment of vitiligo. Copyright © 2018 John Wiley & Sons, Ltd.

Triple-combination treatment with oral α-lipoic acid, betamethasone injection, and NB-UVB for non-segmental progressive vitiligo.

PubMed

Li, Li; Li, Lu; Wu, Yan; Gao, Xing-Hua; Chen, Hong-Duo

2016-06-01

Vitiligo is an acquired depigmenting disease with uncertain etiopathogenesis and the treatment modalities need to be consistently updated. To evaluate a triple-combination treatment with oral α-lipoic acid (ALA), betamethasone injection, and narrowband ultraviolet B (NB-UVB) on vitiligo. Patients with non-segmental and progressive vitiligo lesions were randomly assigned to two groups. The treatment group and the control group were respectively treated with oral ALA and placebo, in combination with betamethasone injection and NB-UVB. The effectiveness and adverse events were evaluated by investigators and patients before and after treatment. Fifty non-segmental progressive vitiligo patients were enrolled in the study. The treatment period was 6 months. In treatment group, over 40% patients achieved > 50% improvement and ≥ 5 satisfaction score by 3-month therapy (M3). This percentage increased to 90% at M6. Treatment group achieved better efficacy than control group at M3, while no difference was seen at M6. The combined treatment with oral ALA, betamethasone injection, and NB-UVB was effective and safe on non-segmental progressive vitiligo. ALA could accelerate the initial response of repigmentation.

A double-blind, randomized trial of 0.05% betamethasone vs. topical catalase/dismutase superoxide in vitiligo.

PubMed

Sanclemente, G; Garcia, J J; Zuleta, J J; Diehl, C; Correa, C; Falabella, R

2008-11-01

Among all the topical immunomodulators, vitiligo's mainstay therapy includes topical corticosteroids. Many other non-immune theories have also been suggested for vitiligo's pathogenesis, but the role of oxidative stress has gained more importance in recent years. To compare the effect of topical 0.05% betamethasone vs. catalase/dismutase superoxide (C/DSO). Randomized, matched-paired, double-blind trial. Dermatology Section, University of Antioquia, Medellín, Colombia. Patients (aged > 18 years or between 12 and 18 years) with parent's informed consent, with stable or active bilateral vitiligo. Topical 0.05% betamethasone or C/DSO. Two lesions similar to each other in size were chosen. All assessments were made by two blinded investigators, and photographs were subjected to morphometry analysis. Skin repigmentation by digital morphometry. Twenty-five patients were enrolled in the study (21 women and 4 men). Mean age of participants was 40 years (range: 12-74 years). One patient on C/DSO experienced a mild local erythematous papular rash that self-resolved. At 4 months of therapy, there was no statistical difference on the percentage of repigmentation between betamethasone and C/DSO (5.63% +/- 27.9 vs. 3.22% +/- 25.8, respectively, P = 0.758). After 10 months of therapy, the percentage of skin repigmentation increased to 18.5 +/- 93.14% with betamethasone and to 12.4 +/- 59% with C/DSO, but again, we found no statistical differences (P = 0.79). Few studies have described objective methods to evaluate repigmentation among vitiligo patients. Digital morphometry provides an objective assessment of repigmentation in vitiligo. Objective vitiligo repigmentation with topical C/DSO at 10 months is similar to topical 0.05% betamethasone. Although a mild adverse effect was related to the use of C/DSO, such finding was not severe enough to discontinue treatment.

Positivity rates of antithyroid antibody, antinuclear antibody and thyroid peroxidase antibody in different types of vitiligo.

PubMed

Lim, H K; Bae, M I; Jeong, K H; Shin, M K; Lee, M-H

2016-04-01

Vitiligo is associated with various autoimmune disorders, and organ-specific autoantibodies are frequently found in patients with this disorder. Vitiligo is classically divided into segmental vitiligo (SV) and nonsegmental vitiligo (NSV), and it is believed that the pathogenesis differs between these two types. As the NSV type is related to an autoimmune mechanism, autoantibody detection rates are likely to be higher in the NSV type than in the segmental type; however, no comparative studies have been performed. To analyse the rates of autoantibody positivity according to the clinical features in patients with vitiligo. Rates of antithyroid antibody (Tg Ab), antinuclear antibody (ANA) and thyroid peroxidase antibody (TPO Ab) positivity were analysed and compared according to the sex, clinical type and age of onset of 807 patients with vitiligo. There were 106 patients with SV (13.1%) and 701 patients with NSV (86.9%). Tg Ab and ANA positivity did not differ between the SV and NSV types. A positive TPO Ab result was obtained in 16 patients with SV (15.1%) and 173 patients with NSV (24.7%). The TPO Ab positivity rate was significantly higher in NSV (χ² = 4.14, P < 0.05). The positivity rates of the three autoantibodies differed significantly according to age of onset (P = 0.001, P = 0.02 and P < 0.001 for Tg Ab, ANA and TPO Ab positivity, respectively). The TPO Ab positivity rate also showed a sex difference (P < 0.001). The positivity rates for the three autoantibodies showed differences according to age of onset and sex. The rates of Tg Ab and ANA positivity showed no significant differences according to clinical type, but the TPO Ab positivity rate was significantly different between SV and NSV. It appears likely that an autoimmune mechanism contributes to the pathogenesis of SV. © 2015 British Association of Dermatologists.

Stressful life events, social support, attachment security and alexithymia in vitiligo. A case-control study.

PubMed

Picardi, A; Pasquini, P; Cattaruzza, M S; Gaetano, P; Melchi, C F; Baliva, G; Camaioni, D; Tiago, A; Abeni, D; Biondi, M

2003-01-01

It has often been suggested that stress might trigger vitiligo. However, only one study supported this hypothesis, and no study explored the role of other personality or social factors. Out-patients experiencing a recent onset or exacerbation of vitiligo (n = 31) were compared with out-patients with skin conditions in which psychosomatic factors are commonly were regarded as negligible (n = 116). Stressful events during the last 12 months were assessed with Paykel's Interview for Recent Life Events. Attachment style, alexithymia and social support were assessed with the 'Experiences in Close Relationships' questionnaire, the Toronto Alexithymia Scale (TAS-20), and the Multidimensional Scale of Perceived Social Support, respectively. Cases and controls did not differ regarding the total number of events and the number of undesirable, uncontrollable or major events. Three or more uncontrollable events had occurred more frequently among cases than controls. Perceived social support was lower in cases than in controls. Cases scored higher than controls on anxious attachment, tended towards higher scores on avoidant attachment and were classified more often as insecure. Cases scored higher than controls on the TAS-20 and were classified more often as alexithymic or borderline alexithymic. The occurrence of many uncontrollable events, alexithymia and anxious attachment were associated with vitiligo also in multiple logistic regression analysis. These findings suggest that vulnerability to vitiligo is not increased by stressful events, except for many uncontrollable events. Alexithymia, insecure attachment and poor social support appear to increase susceptibility to vitiligo, possibly through deficits in emotion regulation or reduced ability to cope effectively with stress. Copyright 2003 S. Karger AG, Basel

Fabrication of anti-vitiligo ointment containing Psoralea corylifolia: in vitro and in vivo characterization.

PubMed

Hussain, Irshad; Hussain, Nisar; Manan, Abdul; Rashid, Abdur; Khan, Barkat; Bakhsh, Sattar

2016-01-01

Vitiligo is a repugnant and odious dermatological malady of the time. It has an detrimental impact on the pigmentation of the human skin as a result of the destruction of cutaneous melanocytes. It affects 1%-2% of the population worldwide. Different therapeutic regimens have been deployed to treat vitiligo, but none of them could stand alone to be stated as a perfect cure. Recently, a change has been observed through novel experimental-designed optimization leading to the development of an anti-vitiligo ointment containing Psoralea corylifolia (PC) seed powder. The aim of this study was to explore the clinical outcomes of ointment containing powdered seeds of PC. Guided by the protocol Response Surface Methodology, 13 formulations of concentration variance of permeation enhancers were prepared. The formulation fulfilling the required criteria (pH; temperature stability tests at 8°C±0.1°C, 25°C±0.1°C and 40°C±0.1°C; and the physical properties such as color, bleeding and rheology) was selected for clinical trials. Fourier transform infrared spectroscopy studies of seed powder of PC and selected formulation of the seed powder were performed. After obtaining informed consents and with prior approval of university and hospital ethical review boards, 20 patients (age range 25-65 years) were included in the present study. Formulations were applied on the affected body parts of patients, and some affected portion of the same patient was taken as control (self-control study design). The pigmentation of white spots of vitiligo was photographically evaluated before, during and after 12 weeks of treatment. Analysis of the measured values was performed using GraphPad Prism version 5 statistical software. A paired sample t -test was performed to observe variation between repigmented patches and white patches of self-control. Hydrophilic ointment (10% w/w) prepared with seed powder of PC was fabricated. The ointment was found effective for small circular white lesions

Topical treatment and combination approaches for vitiligo: new insights, new developments.

PubMed

Hossani-Madani, A R; Halder, R M

2010-02-01

Despite much research done involving elucidation of the pathogenesis of vitiligo, a precise cause is still not known. Prevalent hypotheses include the autoimmune, genetic, neural, self-destruction, growth factor deficiency, viral, and convergence theories, which have served as the basis for treatment formulation. Topical therapies have been a mainstay of vitiligo treatment, with or without phototherapy. Topical treatments used in the treatment of vitiligo include steroids, calcineurin inhibitors, vitamin D analogues, pseudocatalase, and depigmenting agents. Combination therapies are used to improve the success rate of repigmentation. In this article, we have examined randomized controlled trials utilizing topical treatments used as monotherapy or combination therapy. Although psoralen and khellin can be used as topical agents, used in conjunction with UV radiation, we have not included them in the review due to their inability to be used as monotherapy. We have also excluded less used or ineffective topical agents, such as melagenina, topical phenylalanine, topical L-DOPA, coal tar, anacarcin forte oil and topical minoxidil. According to current guidelines, a less than two month trial of potent or very potent topical corticosteroids or topical calcineurin inhibitors may be used for therapy of localized vitiligo (<20% skin surface area). Combinations of topical corticosteroids with excimer laser and UVA seem to be more effective than steroids alone. Pseudocatalase plus NB-UVB does not seem to be more effective than placebo with NB-UVB. Combinations of vitamin D analogues have varied efficacy based on which type is used and the type of UV light. Efficacy of calcineurin inhibitor combinations also vary based on the type used and UV light combined, with tacrolimus being more effective with excimer laser. Pimecrolimus has been effective with NB-UVB and excimer laser on facial lesions, and microdermabrasion on localized areas.

Long-term follow-up of patients undergoing autologous noncultured melanocyte-keratinocyte transplantation for vitiligo and other leukodermas.

PubMed

Silpa-Archa, Narumol; Griffith, James L; Huggins, Richard H; Henderson, Marsha D; Kerr, Holly A; Jacobsen, Gordon; Mulekar, Sanjeev V; Lim, Henry W; Hamzavi, Iltefat H

2017-08-01

Persistence of pigmentation after a melanocyte-keratinocyte transplantation procedure (MKTP) is an important consideration for efficacy. We sought to determine long-term repigmentation of MKTP in vitiligo and other leukodermas. A retrospective review of electronic medical records was conducted for all MKTPs performed at Henry Ford Hospital between January 2009 and April 2014. Repigmentation was assessed by a 5-point grading scale (poor to excellent) and Vitiligo Area Scoring Index (VASI). One hundred patients had MKTP performed at 236 anatomically-based lesions (ABLs); 63 patients with 157 ABLs had long-term data available (12-72 months; median, 24 months). Segmental vitiligo, nonsegmental vitiligo, and physical leukoderma demonstrated improvement in VASI scores: -75.6 ± 24.6%, -59.2 ± 36.6%, and -32.4 ± 33.5%, respectively. In vitiligo, at 24, 48, and 72 months after MKTP, 53%, 64%, and 53% of ABLs, respectively, maintained >75% repigmentation. Skin phototype, age, and anatomic location of ABLs had no significant effect on the outcome of treatment. Limitations of the study include the retrospective design with uncontrolled, postoperative adjuvant treatments and inconsistent compliance to scheduled follow-up evaluations. MKTP provides satisfactory long-term repigmentation in the majority of appropriately selected patients with leukoderma. MKTP can maintain repigmentation for at least 72 months. Copyright © 2017. Published by Elsevier Inc.

The psychosocial impact of acne, vitiligo, and psoriasis: a review

PubMed Central

Nguyen, Catherine M; Beroukhim, Kourosh; Danesh, Melissa J; Babikian, Aline; Koo, John; Leon, Argentina

2016-01-01

Introduction Chronic skin conditions have been well reported to affect a patient’s quality of life on multiple dimensions, including the psychosocial domain. Psychosocial is defined as the interrelation of social factors with an individual’s thoughts and behavior. The assessment of the psychosocial impact of skin disease on a patient can help direct the dermatologists’ treatment goals. To evaluate the psychosocial impact of skin disease, we conducted a review of the literature on three skin conditions with onsets at various stages of life: acne, vitiligo, and psoriasis. Methods A PubMed search was conducted in March 2015 using the terms “psychosocial” AND “acne”, “psychosocial” AND “vitiligo”, and “psychosocial” AND “psoriasis”. The results were limited to articles published in English in the past 5 years studying patients of all ages. Results and their references were evaluated for relevance according to their discussion of psychosocial qualities in their patients and the validity of psychosocial assessments. The search for acne yielded 51 results, and eleven were found to be relevant; vitiligo yielded 30 results with ten found to be relevant; and psoriasis yielded 70 results with seven found to be relevant. Results According to the articles evaluated, 19.2% of adolescent patients with acne were affected in their personal and social lives. Social phobia was present in 45% of patients with acne compared to 18% of control subjects. Race and sex played a role in self-consciousness and social perceptions of the disease. Vitiligo negatively affected marriage potential and caused relationship problems in >50% of patients. Psoriasis negatively affected multiple domains of life, including work, relationships, and social activities. Anxiety and depression affected not only psoriasis patients but also their cohabitants; up to 88% of cohabitants had an impaired quality of life. Conclusion Though all three skin conditions resulted in an increase

Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a Receptor-Dependent Mechanism.

PubMed

Liu, Jun; Xu, Yan; Lin, Tzu-Kai; Lv, Chengzhi; Elias, Peter M; Man, Mao-Qiang

2017-01-01

Though vitiligo is a common depigmentary disorder, it still represents a substantial therapeutic challenge. Therapeutic options are limited in part due to its uncertain etiology. Because recent studies suggest that histamine stimulates melanogenesis in vitro, we determined here whether topical histamine stimulates repigmentation in patients with stable, nonsegmental vitiligo. A total of 23 otherwise normal volunteers with vitiligo, including 14 males and 9 females aged 6-59 years (mean age 29.2 ± 2.8), were enrolled in this study. 1% histamine in distilled water was applied to the lesions twice daily for 5 weeks, while comparable lesions, treated with distilled water alone, served as the controls. The melanin index was measured on the uninvolved and lesional skin sites before and after 5 weeks of treatments using the melanin/erythema probe connected to a Courage-Khazaka MPA5 (Cologne, Germany). Changes in epidermal permeability barrier were also assessed at the same time point. To determine whether histamine-induced repigmentation is receptor-dependent, both ears of C57BL/6J mice were treated topically with 5% cimetidine, a histamine type 2 receptor (H2r) antagonist, twice daily for 10 days. One hour after each cimetidine application, the right ear was treated topically with 10% histamine, while vehicle alone was applied to the left ear. Changes in melanin index were measured 24 h after the last application of histamine and vehicle as described in the human study. In patients with vitiligo treated with vehicle alone for 5 weeks, the melanin index remained unchanged, while topical histamine treatment increased the melanin index by 38% (p < 0.001 vs. both vehicle and pretreatment), which was paralleled by a >60% reduction in lesion surface area. Moreover, topical histamine accelerated permeability barrier recovery. No adverse events were observed following histamine applications. In mice, topical histamine significantly increased the melanin index, while topical co

The Effect of Butin on the Vitiligo Mouse Model Induced by Hydroquinone.

PubMed

Huo, Shi-Xia; Wang, Qiong; Liu, Xin-Min; Ge, Chun-Hui; Gao, Li; Peng, Xiao-Ming; Yan, Ming

2017-05-01

Vernonia anthelmintica (L.) Willd has been traditionally used in the treatment of vitiligo in Uyghur medicine. This study used butin, the main component of V. anthelmintica, to study the influence on hydroquinone-induced vitiligo in mice. The animals were randomly divided into six groups: control, model, 8-methoxypsoralen (8-MOP, 4.25 mg/kg), and butin (0.425, 4.25, and 42.5 mg/kg) groups. The number of melanin-containing hair follicles, basal layer melanocytes, melanin-containing epidermal cells, the expression of tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1), the malondialdehyde (MDA), and cholinesterase (CHE) activity in serum were measured. Our results indicated that compared with the model group, the melanin-containing hair follicles, the expression of TYR and TRP-1 increased, the activity of CHE decreased after treatment with 8-MOP and all doses of butin (p < 0.05, p < 0.01), the basal layer melanocytes and melanin-containing epidermal cells increased significantly after treatment with butin 4.25 and 42.5 mg/kg (p < 0.05, p < 0.01), and the MDA activity decreased after using butin 4.25 and 42.5 mg/kg and 8-MOP (p < 0.05, p < 0.01). Our results support the use of butin on vitiligo, and its possible mechanisms may be related to increase the TYR and TRP-1 protein expression and decrease the activity of MDA and CHE in hydroquinone-induced vitiligo model in mice. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

PubMed Central

Shi, Q; Zhang, W; Guo, S; Jian, Z; Li, S; Li, K; Ge, R; Dai, W; Wang, G; Gao, T; Li, C

2016-01-01

Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo. PMID:26315342

Isolating RNA from precursor and mature melanocytes from human vitiligo and normal skin using laser capture microdissection.

PubMed

Goldstein, Nathaniel B; Koster, Maranke I; Hoaglin, Laura G; Wright, Michael J; Robinson, Steven E; Robinson, William A; Roop, Dennis R; Norris, David A; Birlea, Stanca A

2016-10-01

To characterize the gene expression profile of regenerated melanocytes in the narrow band UVB (NBUVB)-treated vitiligo epidermis and their precursors in the hair follicle, we present here a strategy of RNA isolation from in situ melanocytes using human frozen skin. We developed a rapid immunostaining protocol using the NKI-beteb antibody, which labels differentiated and precursor melanocytes, followed by fluorescent laser capture microdissection. This technique enabled the direct isolation, from melanocyte and adjacent keratinocyte populations, of satisfactory quality RNA that was successfully amplified and analysed by qRT-PCR. The melanocyte-specific gene transcripts TYR, DCT, TYRP1 and PMEL were significantly upregulated in our NBUVB-treated melanocyte samples as compared with the keratinocyte samples, while keratinocyte-specific genes (KRT5 and KRT14) were expressed significantly higher in the keratinocyte samples as compared with the melanocyte samples. Furthermore, in both NBUVB-treated vitiligo skin and normal skin, when bulge melanocytes were compared with epidermal melanocytes, we found significantly lower expression of melanocyte-specific genes and significantly higher expression of three melanocytic stem cell genes (SOX9, WIF1 and SFRP1), while ALCAM and ALDH1A1 transcripts did not show significant variation. We found significantly higher expression of melanocyte-specific genes in the epidermis of NBUVB-treated vitiligo, as compared to the normal skin. When comparing bulge melanocyte samples from untreated vitiligo, NBUVB-treated vitiligo and normal skin, we did not find significant differences in the expression of melanocyte-specific genes or melanocytic stem cell genes. These techniques offer valuable opportunities to study melanocytes and their precursors in vitiligo and other pigmentation disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations.

PubMed

Song, Pu; Li, Kai; Liu, Ling; Wang, Xiaowen; Jian, Zhe; Zhang, Weigang; Wang, Gang; Li, Chunying; Gao, Tianwen

2016-10-01

The nuclear factor erythroid-derived two-like 2-antioxidant response element (Nrf2-ARE) pathway and its downstream antioxidant enzyme heme oxygenase-1 (HMOX1 or HO-1) play essential roles in H2 O2 -induced oxidative damage in human melanocytes. However, the link between Nrf2 promoter polymorphisms and susceptibility to oxidative stress-related diseases such as vitiligo is unknown. This study evaluated the association of the Nrf2 and HO-1 genes polymorphisms with vitiligo susceptibility. In this case-control study of 1136 Han Chinese vitiligo patients and 1200 controls, Nrf2 (rs35652124 and rs6721961) and HO-1 (rs2071746) genes were genotyped by PCR-restriction fragment length polymorphism analysis. Overall, a significantly decreased risk of vitiligo was found to be associated with Nrf2 rs35652124 CC and combined (CT+CC) genotypes [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.83 and OR, 0.84, 95% CI 0.71-0.99, respectively], as well as among subgroups: female, onset age ≤20 and never smoker. We subsequently found that Nrf2 rs35652124 C allele had higher transcriptional activity in the luciferase reporter assay compared with Nrf2 rs35652124 T allele. Furthermore, we investigated serum HO-1 activity was associated with the rs35652124 CT+CC genotype and lower in patients than in controls (P = 0.024). Logistic regression analysis showed a dose-response relationship between lower vitiligo risk and increased HO-1 activity in rs35652124 CT+CC genotype carriers (Ptrend < 0.05). These findings indicate that the C allele of rs35652124 located in the promoter region of Nrf2 gene is associated with protective effect on vitiligo in a Han Chinese population. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Fractional Er:YAG laser assisting topical betamethasone solution in combination with NB-UVB for resistant non-segmental vitiligo.

PubMed

Yan, Ru; Yuan, Jinping; Chen, Hongqiang; Li, Yuan-Hong; Wu, Yan; Gao, Xing-Hua; Chen, Hong-Duo

2017-09-01

Resistant non-segmental vitiligo is difficult to be treated. Ablative erbium-YAG (Er:YAG) laser has been used in the treatment of vitiligo, but the ablation of entire epidermis frustrated the compliance of patients. The purpose of this study is to investigate the effects of fractional Er:YAG laser followed by topical betamethasone and narrow band ultraviolet B (NB-UVB) therapy in the treatment of resistant non-segmental vitiligo. The vitiligo lesions of each enrolled patient were divided into four treatment parts, which were all irradiated with NB-UVB. Three parts were, respectively, treated with low, medium, or high energy of Er:YAG laser, followed by topical betamethasone solution application. A control part was spared with laser treatment and topical betamethasone. The treatment period lasted 6 months. The efficacy was assessed by two blinded dermatologists. Treatment protocol with high energy of 1800 mJ/P of fractional Er:YAG laser followed by topical betamethasone solution and in combination with NB-UVB made 60% patients achieve marked to excellent improvement in white patches. The protocol with medium energy of 1200 mJ/P of laser assisted approximate 36% patients achieve such improvement. The two protocols, respectively, showed better efficacies than NB-UVB only protocol. However, fractional Er:YAG laser at low energy of 600 mJ/P did not provide such contributions to the treatment of vitiligo. The fractional Er:YAG laser in combination with topical betamethasone solution and NB-UVB was suitable for resistant non-segmental vitiligo. The energy of laser was preferred to be set at relatively high level.

The effect of latanoprost on vitiligo: a preliminary comparative study.

PubMed

Anbar, Tag S; El-Ammawi, Tarek S; Abdel-Rahman, Amal T; Hanna, Michel R

2015-01-01

Latanoprost (LT), a prostaglandin F 2alpha (PGF2a ) analogue used in the treatment of glaucoma, was found to induce skin pigmentation in guinea pigs in addition to its known periocular and iridal pigmentation side effects. This study aims to evaluate the efficacy of topical LT in the induction of skin repigmentation in patients with vitiligo and to compare its potency with narrow band ultraviolet (UV) B (NB-UVB). The result of their combination was also assessed. This study involved 22 patients with bilateral and symmetrical vitiligo lesions, stable for the last three months, divided into three groups: group I, to evaluate LT vs. placebo; group II, to evaluate LT vs. NB-UVB; and group III, to evaluate the effect of their combination. The response to treatment was evaluated by taking photographic records of the treated lesions with follow-up photography every two weeks. After three months, assessment of the degree and extent of repigmentation was performed. Follow-up assessment was done six months after termination of the trial for the persistence of pigmentation, recurrence, or development of any side effects. LT was found to be better than placebo and comparable with the NB-UVB in inducing skin repigmentation. This effect was enhanced by the addition of NB-UVB. LT could be a promising treatment for vitiligo, especially the periocular variant. Its effect on skin repigmentation could be enhanced by NB-UVB exposure. © 2014 The International Society of Dermatology.

A role for tyrosinase-related protein 1 in 4-tert-butylphenol-induced toxicity in melanocytes: Implications for vitiligo.

PubMed

Manga, Prashiela; Sheyn, David; Yang, Fan; Sarangarajan, Rangaprasad; Boissy, Raymond E

2006-11-01

Vitiligo presents with depigmented cutaneous lesions following localized melanocyte death. Multiple factors contribute to cell death, including genetically determined susceptibility to trauma, and environmental factors, such as exposure to 4-tert-butylphenol (4-TBP). We demonstrate that 4-TBP induces oxidative stress that is more readily overcome by melanocytes from normally pigmented individuals than from two individuals with vitiligo. The antioxidant catalase selectively and significantly reduced death of melanocytes derived from two individuals with vitiligo, indicating a role for oxidative stress in vitiligo pathogenesis. In normal melanocytes, oxidative stress results in reduced expression of microphthalmia-associated transcription factor (MITF). Melanocyte-stimulating hormone-induced expression of MITF protein caused increased sensitivity to 4-TBP, whereas sensitivity of melanomas correlated with MITF expression. MITF stimulates melanin synthesis by up-regulating expression of melanogenic enzymes such as tyrosinase-related protein-1 (Tyrp1). Although melanin content per se did not affect sensitivity to 4-TBP, expression of Tyrp1 significantly increased sensitivity. Melanocytes and melanomas that express functional Tyrp1 were significantly more sensitive to 4-TBP than Tyrp1-null cells. Thus, normal melanocytes respond to 4-TBP by reducing expression of MITF and Tyrp1. We hypothesize that melanocytes in vitiligo demonstrate reduced ability to withstand oxidative stress due, partly, to a disruption in MITF regulation of Tyrp1.

Clinical efficacy of a novel topical formulation for vitiligo: compared evaluation of different treatment modalities in 149 patients.

PubMed

Buggiani, Gionata; Tsampau, Dionigi; Hercogovà, Jana; Rossi, Riccardo; Brazzini, Benedetta; Lotti, Torello

2012-01-01

Current vitiligo treatments are not always satisfactory for both patients and dermatologists. Recently, combination therapies have been introduced in order to obtain better results and reduce risks in the management of the disease. Novel efficacious products are needed to improve the therapeutic possibilities of dermatologists in the respect of safety for the patients. The objective of the present study was to evaluate the effects of a novel topical in a gel formulation containing phenylalanine, cucumis melo extract, and acetyl cysteine in vitiligo. The present study used an open observational study to evaluate the efficacy and safety of the investigated product, given alone or in combination with 311-nm narrow band microphototherapy. Results were compared with those obtained treating a matched patient population with microphototherapy alone and with clobetasol propionate 0.05% ointment alone. One hundred forty-nine patients suffering from symmetrical vitiligo affecting less than 10% of the skin surface were evaluated. Patients affected by acral vitiligo only were excluded from the analysis. Treatment duration was scheduled for 12 weeks. Excellent repigmentation (>75%) was achieved by 38-73% of patients, depending on the treatment regimen. Mild to moderate side effects were observed only in patients treated with clobetasol 0.05% ointment. The tested gel formulation showed a good efficacy in improving vitiligo repigmentation. No side effects were observed. © 2012 Wiley Periodicals, Inc.

Comparison between the efficacy of microneedling combined with 5-fluorouracil vs microneedling with tacrolimus in the treatment of vitiligo.

PubMed

Mina, Mary; Elgarhy, Lamia; Al-Saeid, Hanan; Ibrahim, Zeinab

2018-03-12

Several treatment modalities had been used for the treatment of vitiligo, but the optimal treatment has not yet been identified. To study the efficacy of microneedling with 5-flurouracil vs its efficacy with tacrolimus in the treatment of vitiligo. Twenty-five patients with vitiligo were subjected to microneedling of 2 patches of vitiligo with dermapen, then application of 5-fluorouracil to 1 patch and tacrolimus on the other patch. This procedure was repeated every 2 weeks for every patient for maximum 6 months (12 sessions). The patients were followed up for 3 months after the last session. The overall repigmentation was significantly higher in 5-fluorouracil-treated patches compared with tacrolimus. Excellent improvement occurred in 48% of 5- flurouracil-treated patches while only in 16% of tacrolimus-treated patches. In the acral parts, 40% of the patches treated with 5-fluorouracil achieved excellent improvement (repigmentation >75%), while no patch in the acral parts achieved excellent improvement with tacrolimus. However, there was significant difference between the 2 drugs,regarding inflammation, ulceration, and hyperpigmentation which occurred with 5-fluorouracil. Microneedling combined with 5-fluorouracil or tacrolimus is safe and effective treatment of vitiligo. However, 5-fluorouracil achieved a greater percentage of repigmentation than tacrolimus particularly in the acral parts. © 2018 Wiley Periodicals, Inc.

Preliminary study on the treatment of vitiligo with carbon dioxide fractional laser together with tacrolimus.

PubMed

Chen, Wei; Zhou, Yuan; Huang, Fei-Ran; Luo, Dan; Wang, Da-Guang

2018-04-10

Tacrolimus is a conventional medication for the treatment of vitiligo, but the effect of a single medication is limited. This paper aims at observing the effects, adverse responses, and repigmentation results of the joint treatment of vitiligo by Carbon dioxide (CO 2 ) fractional laser together with tacrolimus. Forty-five patients with vitiligo were randomly divided into two groups: treatment (T) group and control (C) group, and each group was further divided into three subgroups (face, torso and limbs, and hand and foot) according to the location of the skin defect. Both groups used topical 0.1% tacrolimus cream, but the T group was given one CO 2 fractional laser treatment each month. We observed the clinical efficacy, adverse responses, and repigmentation results after 6 months. Compared to the C group, the T group showed better improvement in both objective and subjective assessments. When the treatment time was increased, the efficacy was also improved, and the repigmentation in the T group occured in three ways: perifollicular repigmentation, marginal repigmentation and diffuse repigmentation. There were three cases of isomorphic responses (2 cases in the rapid progression stage, one case in the progression stage), and 1 case formed scarring on the neck in the T group. The treatment of vitiligo by CO 2 fractional laser together with tacrolimus is significantly effective and is most suitable for patients in the progression stage. Patients in the rapid progression stage should use this approach with caution, and its efficacy was limited for patients in the stable stage. An extended course of treatment is helpful for the repigmentation of white patches. All three forms of repigmentation can occur in the joint treatment of vitiligo by CO 2 fractional laser together with tacrolimus. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Biology and genetics of oculocutaneous albinism and vitiligo - common pigmentation disorders in southern Africa.

PubMed

Manga, Prashiela; Kerr, Robyn; Ramsay, Michèle; Kromberg, Jennifer G R

2013-07-29

Pigmentation disorders span the genetic spectrum from single-gene autosomal recessive disorders such as oculocutaneous albinism (OCA), the autosomal dominant disorder piebaldism to X-linked ocular albinism and multifactorial vitiligo. OCA connotes a group of disorders that result in hypopigmented skin due to decreased melanin production in melanocytes and loss of visual acuity. There are four non-syndromic forms, OCA1-4, which are classified based on the gene that is mutated (tyrosinase, OCA2, tyrosinase-related protein 1 and SLC45A2, respectively). Despite the fact that multiple genes account for the various forms of OCA, the phenotypes of all four forms result from disruption in the maturation and trafficking of the enzyme tyrosinase. OCA2 is the most prevalent autosomal recessive disorder among southern African blacks, affecting 1/3 900 individuals; while OCA3, although rare, is most prevalent in southern Africa. Another common pigmentation disorder in southern Africa is vitiligo, which affects 1 - 2% of people worldwide. Vitiligo is a complex, acquired disorder in which melanocytes are destroyed due to an autoimmune response. The aetiology underlying this disorder is poorly understood, although recent genetic association studies have begun to shed light on the contributing factors. Pigmentation disorders have significant psychosocial implications and co-morbidities, yet therapies are still lacking. Recent progress in our understanding of the pathobiology of both albinism and vitiligo may herald novel treatment strategies for these disorders. 

Vitamin D status and the effects of oral vitamin D treatment in children with vitiligo: A prospective study.

PubMed

Karagüzel, Gülay; Sakarya, Nil P; Bahadır, Sevgi; Yaman, Selçuk; Ökten, Ayşenur

2016-10-01

Vitiligo is a pigmentary disorder and autoimmune pathogenesis seems most likely. Decreased vitamin D levels have been related to several autoimmune diseases. Little is known about the association of vitiligo and vitamin D. We aimed to evaluate serum 25-hydroxyvitamin D [25(OH)D] levels in children with vitiligo and to determine the efficacy of oral vitamin D therapy on the repigmentation of vitamin D deficient patients. Thirty patients aged 6-17 years with vitiligo and 30 sex- and age-matched apparently healthy controls were included in this prospective study. Size of the vitiligo representative area was estimated using the point counting method and blood samples were obtained at the beginning and month six. By the end of the study, all patients treated with topical tacrolimus for six months and the patients who were vitamin D deficient (n = 14) had been on combination treatment of oral vitamin D and topical tacrolimus. A dose of 1500 IU/day vitamin D was given if the serum 25(OH)D levels <20 ng/ml and 3000 IU/day was given if the levels <10 ng/ml for six months. Serum 25(OH)D levels were measured by high-performance liquid chromatography. Serum 25(OH)D levels of patients and controls were not significantly different (p > 0.05). Lesion size decreased from 66.1 ± 58.3 cm 2 to 48.0 ± 52.6 cm 2 after six months of treatment in patients who received combination treatment (p < 0.001) and increased in patients who received only topical therapy from 34.8 ± 48.1 cm 2 to 53.5 ± 64.9 cm 2 (p < 0.01). Although we did not determine decreased serum 25(OH)D levels in children with vitiligo, we showed that combination treatment with oral vitamin D and topical tacrolimus is more effective in reaching repigmentation than topical tacrolimus alone. Oral vitamin D supplementation might be useful for children with vitiligo who are also deficient in vitamin D. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd

A systematic review of the effectiveness of therapeutic interventions on quality of life (QoL) for adult vitiligo patients.

PubMed

Lert, Chua Tse; Fai, Chan Moon

Vitiligo is the most common pigmentation disorder. It is an acquired, progressive disorder, presenting with white macules that can appear anywhere on the skin. Presently, there is no cure for vitiligo. Although there are therapies targeted at improving its appearance, their effectiveness is limited. Without satisfactory solution to vitiligo, patients are permanently disfigured for life. Quality of life of vitiligo patients has been commonly found to be moderately impaired. Patients are chronically embarrassed and depressed. Stigmatisation is also common and cause marginalization. Hence, while vitiligo is not "life-threatening", it can be "life-ruining". Because current treatments are unsatisfactory in repigmenting the skin, the question of continuing treatment must also consider the benefits to quality of life, and that is the purpose of this review. The overall objective of this systematic review was to examine the effectiveness of therapeutic interventions, in terms of quality of life for adult patients with vitiligo. Types of studies - The review considered quantitative papers, including randomised controlled trials and quasi-experimental studies.Types of participants - Adult patients who have vitiligo from 18 to 75 years-old.Types of interventions - This review considered studies of current therapeutic interventions for vitiligo, including oral, topical, combination, camouflage, cognitive-behavioural therapy and grafting.Types of measured outcomes - Quality of life outcomes as measured by validated tools. The search aimed to find published studies and papers, limited to English language reports. A three-step search strategy was utilised: An initial limited search of MEDLINE and CINAHL was undertaken, followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe the article. A second search using all identified keywords and index terms were then undertaken. Search strategies were developed using terms that

Cellular stress and innate inflammation in organ-specific autoimmunity: lessons learned from vitiligo

PubMed Central

Harris, John E.

2015-01-01

Summary For decades, research in autoimmunity has focused primarily on immune contributions to disease. Yet recent studies report elevated levels of reactive oxygen species (ROS) and abnormal activation of the unfolded protein response (UPR) in cells targeted by autoimmunity, implicating cellular stress originating from the target tissue as a contributing factor. A better understanding of this contribution may help to answer important lingering questions in organ-specific autoimmunity, like what factors initiate disease, and what directs its tissue specificity. Vitiligo, an autoimmune disease of the skin, has been the focus of translational research for over 30 years, and both melanocyte stress and immune mechanisms have been thought to be mutually exclusive explanations for pathogenesis. Chemical-induced vitiligo is a unique clinical presentation that reflects the importance of environmental influences on autoimmunity, provides insight into a new paradigm linking cell stress to the immune response, and serves as a template for other autoimmune diseases. In this review I will discuss the evidence for cell stress contributions to a number of autoimmune diseases, the questions that remain, and how vitiligo, an underappreciated example of organ-specific autoimmunity, helps to answer them. PMID:26683142

A Comparison of Betamethasone Valerate 0.1% Cream Twice Daily Plus Oral Simvastatin Versus Betamethasone Valerate 0.1% Cream Alone in the Treatment of Vitiligo Patients.

PubMed

Iraji, Fariba; Banihashemi, Seyed Hossin; Faghihi, Gita; Shahmoradi, Zabihollah; Tajmirriahi, Nabet; Jazi, Safoura Bokaie

2017-01-01

Vitiligo, a common disorder of depigmentation, is often difficult to treat. Corticosteroids are known to be effective, but with modest results. Although simvastatin has been reported to be effective for immunorelated dermatologic disorders including vitiligo, controlled trials are lacking. This study was conducted to compare the efficacy of topical betamethasone valerate 0.1% cream (as a standard method of treatment for vitiligo) versus a combination of betamethasone valerate plus oral simvastatin in the treatment of vitiligo. Eighty-eight subjects with symmetric vitiligo who had body surface involvement up to 20% were divided randomly into two groups. Group A were treated with betamethasone valerate 01% cream twice daily and Group B with betamethasone valerate 01% cream twice daily and oral simvastatin 80 mg daily for 12 weeks. Finally, 46 patients completed treatment after 12 weeks in both groups. The results were evaluated by a blind dermatologist using Vitiligo Area Scoring Index (VASI) score at baseline, 4 th , 8 th , and 12 th week of treatment. In a similar way, subjective assessment performed by patients based on photo evaluation at the end of the study. Despite a continuous reduction in VASI score in both groups, according to both physician ( P = 0.13) and patient ( P = 0.374) assessment oral simvastatin was not statistically more effective than conventional treatment of vitiligo. This study indicates that oral simvastatin is not associated with significant impacts in the treatment of vitiligo as compared to other inflammatory dermatologic conditions such as psoriasis. Indeed, other studies should be initiated regarding exact molecular and cellular effects of statins in the treatment of vitiligo.

A Comparison of Betamethasone Valerate 0.1% Cream Twice Daily Plus Oral Simvastatin Versus Betamethasone Valerate 0.1% Cream Alone in the Treatment of Vitiligo Patients

PubMed Central

Iraji, Fariba; Banihashemi, Seyed Hossin; Faghihi, Gita; Shahmoradi, Zabihollah; Tajmirriahi, Nabet; Jazi, Safoura Bokaie

2017-01-01

Background: Vitiligo, a common disorder of depigmentation, is often difficult to treat. Corticosteroids are known to be effective, but with modest results. Although simvastatin has been reported to be effective for immunorelated dermatologic disorders including vitiligo, controlled trials are lacking. This study was conducted to compare the efficacy of topical betamethasone valerate 0.1% cream (as a standard method of treatment for vitiligo) versus a combination of betamethasone valerate plus oral simvastatin in the treatment of vitiligo. Materials and Methods: Eighty-eight subjects with symmetric vitiligo who had body surface involvement up to 20% were divided randomly into two groups. Group A were treated with betamethasone valerate 01% cream twice daily and Group B with betamethasone valerate 01% cream twice daily and oral simvastatin 80 mg daily for 12 weeks. Finally, 46 patients completed treatment after 12 weeks in both groups. The results were evaluated by a blind dermatologist using Vitiligo Area Scoring Index (VASI) score at baseline, 4th, 8th, and 12th week of treatment. In a similar way, subjective assessment performed by patients based on photo evaluation at the end of the study. Results: Despite a continuous reduction in VASI score in both groups, according to both physician (P = 0.13) and patient (P = 0.374) assessment oral simvastatin was not statistically more effective than conventional treatment of vitiligo. Conclusion: This study indicates that oral simvastatin is not associated with significant impacts in the treatment of vitiligo as compared to other inflammatory dermatologic conditions such as psoriasis. Indeed, other studies should be initiated regarding exact molecular and cellular effects of statins in the treatment of vitiligo. PMID:28516068

Quality of life in patients with vitiligo: an analysis of the dermatology life quality index outcome over the past two decades.

PubMed

Amer, Abdulrahman A A; Gao, Xing-Hua

2016-06-01

Vitiligo is one of the most important skin disorders that does not cause much physical impairment, but due to its disfiguring appearance, patients have disturbances in mental health and quality of life (QoL). The dermatology life quality index (DLQI), as one of the most specific QoL instruments, is now used widely for patients with vitiligo. The main objective of this review is to collect and present detailed information about issues and disturbances related to the QoL of patients with vitiligo by reviewing the DLQI studies worldwide in the past 20 years. The impact of vitiligo assessed by the DLQI varies according to the clinical and demographic characteristics of patients. In the majority of our reviewed studies, women showed more QoL impairment than men did, as did young patients compared to elderly ones, married women with vitiligo than singles, and patients with involvement on exposed sites than those on unexposed sites. Dark-skinned people showed more life quality effects than white people did. Dermatologists should pay particular attention to such patients who experience insufficient QoL, as they require more effort to cure their disease. © 2016 The International Society of Dermatology.

Potential emerging treatment in vitiligo using Er:YAG in combination with 5FU and clobetasol.

PubMed

Mokhtari, Fatemeh; Bostakian, Anis; Shahmoradi, Zabihollah; Jafari-Koshki, Tohid; Iraji, Fariba; Faghihi, Gita; Hosseini, Sayed Mohsen; Bafandeh, Behzad

2018-04-01

Vitiligo is a pigmentary disorder of skin affecting at least 1% of the world population of all races in both sexes. Its importance is mainly due to subsequent social and psychological problems rather than clinical complications. Various treatment choices are available for vitiligo; however, laser-based courses have shown to give more acceptable results. The aim of this trial was to evaluate the efficacy of Er:YAG laser as a supplementary medicine to topical 5FU and clobetasol in vitiligo patients. Two comparable vitiligo patches from 38 eligible patients were randomized to receive topical 5FU and clobetasol in control group and additional Er:YAG laser in intervention group. Major outcomes of interest were the size of patch and pigmentation score at randomization and 2 and 4 months after therapy. Final sample included 18 (47%) male patients and age of 35.66±8.04. The performance Er:YAG group was superior in all sites. Reduction in the size of patches was greater in Er:YAG group (p-value=.004). Also, this group showed a higher pigmentation scores in the trial period than control group (p-value<.001). Greater reduction in the size and increase in pigmentation score was seen in Er:YAG group especially for short periods after therapy and repeating laser sessions may help improving final outcomes. Er:AYG could help in reducing complications of long-term topical treatments, achieving faster response, and improving patient adherence. © 2017 Wiley Periodicals, Inc.

Disciplines and Professors of Astronomy in Undergraduate Physics Teachers Formation Courses in Brazilian Universities. (Spanish Title: Disciplinas y Profesores de Astronomia en los Cursos de Licenciatura en Física en Las Universidades Brasileñas.) Disciplinas e Professores de Astronomia Nos Cursos de Licenciatura em Física das Universidades Brasileiras

NASA Astrophysics Data System (ADS)

Roberto, Artur Justiniano, Jr.; Reis, Thiago Henrique; dos Reis Germinaro, Daniel

2014-12-01

This article is the result of a research on basic training in Astronomy in physics degrees that performed the ENADE 2011 national examination. The objective was to identify whether there are disciplines of Astronomy in these courses, whether are mandatory or optional, its workload and when it is offered. The relationship between astronomers, physics degrees and disciplines of Astronomy was investigated. To perform this research we examined the results of ENADE 2011 and also the census of Brazilian Astronomical Society. As a result it is observed that in only 15% of the courses there is a mandatory subject of Astronomy, and therefore there is a high probability that 85% of physics teachers trained in 2011 have not had any discipline of Astronomy during their graduation. In addition, the data collected in this study shows a low number of members of SAB (Sociedade Astronômica Brasileira) among the surveyed courses. We have verified that the presence of astronomers in a given university does not imply to have a mandatory discipline of Astronomy in physics degrees at the same university. Este artículo es el resultado de una investigación sobre la formación básica en Astronomía en los cursos de Profesorado en Física que hicieron el examen nacional ENADE 2011. El objetivo del trabajo fue identificar se existen disciplinas de Astronomía en estos cursos, si son obligatorias u optativas, cuál es su carga horaria y el semestre en que son ofrecidas. Se investigó también la correlación entre astrónomos, los cursos de licenciatura en Física y las disciplinas de Astronomía. Para realizar esta investigación se utilizaron los datos del ENADE 2011 y también del censo de la Astronomía brasileña. Como resultado, se observó que en solo 15% de los cursos existe una disciplina obligatoria de Astronomía y que existe una grande probabilidad de que 85% de los profesores de Física formados en el año de 2011 no hayan cursado ninguna disciplina de Astronomía durante su

Effect of narrow band ultraviolet B phototherapy as monotherapy or combination therapy for vitiligo: a meta-analysis.

PubMed

Li, Ronghua; Qiao, Meng; Wang, Xiaoyan; Zhao, Xintong; Sun, Qing

2017-01-01

The treatment of vitiligo is still one of the most difficult dermatological challenges, although there are many therapeutic options. Narrow band ultraviolet B (NB-UVB) phototherapy is considered to be a very important modality for generalized vitiligo. The aim of this study was to explore whether a combination of NB-UVB and topical agents would be superior to NB-UVB alone for treating vitiligo. We searched the electronic databases such as PUBMED, EMBASE, Cochrane Library, and Web of Science. The primary outcome was the proportion of ≥50% repigmentation (a clinical significance), and secondary outcome was the proportion of ≥75% repigmentation (an excellent response). Seven randomized controlled trials (RCTs) involving 240 patients (413 lesions) were included in this meta-analysis. The study showed no significant difference between NB-UVB combination therapy (NB-UVB and topical calcineurin inhibitor or vitamin D analogs) and NB-UVB monotherapy in the outcomes of ≥50% repigmentation and ≥75% repigmentation. However, lesions located on the face and neck had better results in ≥50% repigmentation (RR = 1.40, 95% CI 1.08-1.81) and ≥75% repigmentation (RR = 1.88, 95% CI 1.10-3.20) with NB-UVB and topical calcineurin inhibitor combination therapy vs. NB-UVB monotherapy. The meta-analysis suggested that adding neither topical calcineurin inhibitors nor topical vitamin-D3 analogs on NB-UVB can yield significantly superior outcomes than NB-UVB monotherapy for treatment of vitiligo. However, addition of topical calcineurin inhibitors to NB-UVB may increase treatment outcomes in vitiligo affecting face and neck. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hydrogen peroxide-mediated oxidative stress disrupts calcium binding on calmodulin: More evidence for oxidative stress in vitiligo

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

Schallreuter, K.U.; Gibbons, N.C.J.; Zothner, C.

Patients with acute vitiligo have low epidermal catalase expression/activities and accumulate 10{sup -3} M H{sub 2}O{sub 2}. One consequence of this severe oxidative stress is an altered calcium homeostasis in epidermal keratinocytes and melanocytes. Here, we show decreased epidermal calmodulin expression in acute vitiligo. Since 10{sup -3}M H{sub 2}O{sub 2} oxidises methionine and tryptophan residues in proteins, we examined calcium binding to calmodulin in the presence and absence of H{sub 2}O{sub 2} utilising {sup 45}calcium. The results showed that all four calcium atoms exchanged per molecule of calmodulin. Since oxidised calmodulin looses its ability to activate calcium ATPase, enzyme activitiesmore » were followed in full skin biopsies from lesional skin of patients with acute vitiligo (n = 6) and healthy controls (n = 6). The results yielded a 4-fold decrease of ATPase activities in the patients. Computer simulation of native and oxidised calmodulin confirmed the loss of all four calcium ions from their specific EF-hand domains. Taken together H{sub 2}O{sub 2}-mediated oxidation affects calcium binding in calmodulin leading to perturbed calcium homeostasis and perturbed L-phenylalanine-uptake in the epidermis of acute vitiligo.« less

Effect of combination of fractional CO2 laser and narrow-band ultraviolet B versus narrow-band ultraviolet B in the treatment of non-segmental vitiligo.

PubMed

El-Zawahry, Mohamed Bakr; Zaki, Naglaa Sameh; Wissa, Marian Youssry; Saleh, Marwah Adly

2017-12-01

The present study was designed to evaluate the effect of combining fractional CO 2 laser with narrow-band ultraviolet B (NB-UVB) versus NB-UVB in the treatment of non-segmental vitiligo. The study included 20 patients with non-segmental stable vitiligo. They were divided into two groups. Group I received a single session of fractional CO 2 laser therapy on the right side of the body followed by NB-UVB phototherapy twice per week for 8 weeks. Group II received a second session of fractional CO 2 laser therapy after 4 weeks from starting treatment with NB-UVB. The vitiligo lesions were assessed before treatment and after 8 weeks of treatment by VASI. At the end of the study period, the vitiligo area score index (VASI) in group I decreased insignificantly on both the right (-2.6%) and left (-16.4%) sides. In group II, VASI increased insignificantly on the right (+14.4%) and left (+2.5%) sides. Using Adobe Photoshop CS6 extended program to measure the area of vitiligo lesions, group I showed a decrease of -1.02 and -6.12% in the mean area percentage change of vitiligo lesions on the right and left sides, respectively. In group II the change was +9.84 and +9.13% on the right and left sides, respectively. In conclusion, combining fractional CO 2 laser with NB-UVB for the treatment of non-segmental vitiligo did not show any significant advantage over treatment with NB-UVB alone. Further study of this combination for longer durations in the treatment of vitiligo is recommended.

The effects of galangin on a mouse model of vitiligo induced by hydroquinone.

PubMed

Huo, Shi-Xia; Liu, Xin-Ming; Ge, Chun-Hui; Gao, Li; Peng, Xiao-Ming; Zhao, Ping-Ping; Yan, Ming

2014-10-01

Galangin, the main active component of Alpinia officinarum Hance, was tested in a mouse model of vitiligo induced in C57BL/6 mice by the topical application of 2 mL of 2.5% hydroquinone daily to shaved areas (2 × 2 cm) of dorsal skin for 60 days. Thirty days after the final application of hydroquinone, galangin (0.425, and 4.25 mg/kg) was administered orally for 30 days. The hair colour darkened when it grew back after treatment, and histological analysis showed that the number of melanin-containing hair follicles had increased after treatment with all doses of galangin groups and 8-methoxypsoralen (8-MOP, the positive control) compared with the untreated vitiligo group (p < 0.05). The number of skin basal layer melanocytes and melanin-containing epidermal cells had also increased significantly with the application of 4.25 mg/kg of galangin. The concentration of tyrosinase (TYR) in serum was found to have increased, whereas the content of malondialdehyde and the activity of cholinesterase had decreased after treatment with all doses of galangin and 8-MOP, compared with control (p < 0.05). The expression of TYR protein in treated areas of skin also increased with the application of 4.25 mg/kg galangin and 8-MOP. In conclusion, the results showed that galangin was able to improve vitiligo induced by hydroquinone in mice, with the activity related to concentrations of TYR, expression of TYR protein, activity of malondialdehyde and content of cholinesterase. Galangin may therefore be a potential candidate for the treatment of vitiligo, subject to further investigation. Copyright © 2014 John Wiley & Sons, Ltd.

A pilot comparative study of topical latanoprost and tacrolimus in combination with narrow-band ultraviolet B phototherapy and microneedling for the treatment of nonsegmental vitiligo.

PubMed

Korobko, Igor V; Lomonosov, Konstantin M

2016-11-01

Prostaglandins and their analogues are beneficial as topical agents in vitiligo treatment, yet neither of the previous study addressed their comparative efficiency with conventional topical agents used in vitiligo treatment. In this pilot (24 patients) left-right comparative study we addressed efficiency of prostaglandin F2α analogue latanoprost versus tacrolimus when combined with narrow-band ultraviolet B and microneedling in repigmentation of nonsegmental vitiligo lesions. Our results confirm potency of prostaglandins, in particular, that of latanoprost, in inducing repigmentation, with the efficiency being at least comparable to that of tacrolimus, while contribution of microneedling remains unclear. In summary, results of our study provide further evidences for justified use of prostaglandins, in particular, latanoprost, in vitiligo treatment. In turn, this warrants future studies on the topic aiming to conclusively introduce prostaglandin-based formulations as conventional agents for vitiligo management. © 2016 Wiley Periodicals, Inc.

The nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo-inducing phenol monobenzone.

PubMed

Arowojolu, Omotayo A; Orlow, Seth J; Elbuluk, Nada; Manga, Prashiela

2017-07-01

Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Spectrophotometer is useful for assessing vitiligo and chemical leukoderma severity by quantifying color difference with surrounding normally pigmented skin.

PubMed

Hayashi, M; Okamura, K; Araki, Y; Suzuki, M; Tanaka, T; Abe, Y; Nakano, S; Yoshizawa, J; Hozumi, Y; Inoie, M; Suzuki, T

2018-05-01

Acquired skin hypopigmentation has many etiologies, including autoimmune melanocyte destruction, skin aging, inflammation, and chemical exposure. Distinguishing lesions from normally pigmented skin is clinically important to precisely assess disease severity. However, no gold standard assessment method has been reported. We aimed to investigate whether spectrophotometers are useful for assessing vitiligo and rhododendrol (4-(4-hydroxyphenol)-2-butanol) (Rhododenol ® )-induced leukoderma disease severity by quantifying skin color. Mexameter ® MX18 and CM-700d spectrophotometer were used for assessing vitiligo/leukoderma by measuring melanin index, L*a*b* color space, and ΔE*ab value, which represents the color difference between two subjects and is calculated by the values of L*a*b*. MX18 and CM-700d can quantitatively distinguish vitiligo/leukoderma from normally pigmented skin based on melanin index. CM-700d consistently quantified the color of vitiligo/leukoderma lesions and surrounding normally pigmented skin in L*a*b* color spaces and ΔE*ab. ΔE*ab is well correlated with melanin index and clinical appearance. ΔE*ab has been frequently used in aesthetic dentistry; however, current study is the first to use it in the measurement of skin color. ΔE*ab seems to be a useful parameter to evaluate the color contrast between vitiligo/leukoderma and surrounding normally pigmented skin and can be used to evaluate disease severity and patient's quality of life. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

To what extent is quality of life impaired in vitiligo? A multicenter study on Italian patients using the dermatology life quality index.

PubMed

Ingordo, Vito; Cazzaniga, Simone; Medri, Matelda; Raone, Beatrice; Digiuseppe, Maria Donata; Musumeci, Maria Letizia; Romano, Ivana; Fai, Dario; Pellegrino, Michele; Pezzarossa, Enrico; Di Lernia, Vito; Peccerillo, Francesca; Battarra, Vincenzo Claudio; Sirna, Riccardo; Patrizi, Annalisa; Naldi, Luigi

2014-01-01

It is believed that vitiligo has an impact on the overall patient quality of life (QoL). To estimate QoL in a fairly large sample of Italian vitiligo patients by using the Dermatology Life Quality Index (DLQI) questionnaire. One hundred and sixty-one vitiligo patients referred to 9 dermatological centers were offered to participate by filling in the Italian version of the DLQI questionnaire. The mean total DLQI score was 4.3 (SD ±4.9; range: 0-22). In multivariate analysis, DLQI >5 was associated with female gender, stability of the disease over time and involvement of the face at disease onset. The impairment of QoL is overall limited in Italian vitiligo patients, especially if it is compared with results from other available studies. This could be due to cultural and ethnic characteristics of the sample.

Epidermal hydrogen peroxide is not increased in lesional and non-lesional skin of vitiligo.

PubMed

Zailaie, Mohammad Z

2017-01-01

It is widely believed that the loss of the epidermal melanocytes in vitiligo is basically due to excessive oxidative stress. Previous research work described abnormal elevation of the absolute concentration of the epidermal hydrogen peroxide (H 2 O 2 ) in lesional and non-lesional skin of vitiligo. Based on this finding, our primary research objective was to use this feature as a screening marker in individuals at a great risk of developing vitiligo. Ninety-six patients of non-segmental vitiligo (NSV) of varying durations, skin phototypes, and treatment modalities (psoralen UVA-, narrow band UVB-treated) were recruited for this study. Raman spectroscopic measurements, using an external probehead, of the lesional and non-lesional skin were obtained, and the resulting spectra were analyzed using the Opus software package of the MultiRam spectrometer and the intensity of the peak at 875 cm -1 that represents the absolute concentration of H 2 O 2 was calculated. Contrary to previous reports, in patients of skin phototype IV, the absolute concentrations of H 2 O 2 in non-lesional and lesional NSV of all groups were non-significantly decreased compared to normal control. In patients of NSV of skin phototype V, the decrease in the absolute concentrations of H 2 O 2 was not significant in the untreated group, and a slight non-significant increase in the NBUVB-treated group was noted. However, in the PUVA-treated group, the non-lesional skin demonstrated significant increase in the absolute concentration of H 2 O 2 , whereas the lesional skin showed only a slight non-significant increase compared to normal control. In NSV patients of skin phototype VI who were previously treated with PUVA, the non-lesional skin showed a slight non-significant increase in the absolute concentration of H 2 O 2 ; however, the lesional skin showed a marked significant decrease compared to normal control and the non-lesional skin. Thereof, one can conclude that the epidermal H 2 O 2 is not

Comprension de los conceptos de los enlaces ionico y covalente en estudiantes universitarios del primer curso de quimica general

NASA Astrophysics Data System (ADS)

Ballesteros Benavides, Maria Elvira

Para este trabajo utilizamos el estudio de casos cualitativo que se llevo a cabo en una universidad privada de Puerto Rico. Empleamos como unidad de analisis el concepto de enlace quimico, ionico y covalente. Los participantes fueron los estudiantes de la seccion nocturna del curso de Quimica General I. La investigacion se desarrollo por medio de dos entrevistas de persona a persona, observaciones de las expresiones no verbales y la hoja de identificacion de conceptos. Para la triangulacion tomamos en consideracion las preconcepciones erroneas, las concepciones alternativas y el mapa de conceptos de cada participante. Preparamos un mapa de conceptos para el enlace quimico validado por un comite de expertos. Tambien, elaboramos los mapas de conceptos de los participantes que sirvieron para varios propositos: conocer la estructura conceptual, expresar los logros, hacer comparaciones e identificar la presencia de concepciones alternativas. Entre los hallazgos encontramos que todos los participantes poseen conocimiento previo de los enlaces quimicos ionico y covalente y dentro de ese conocimiento existen preconcepciones erroneas mas numerosas para el enlace ionico. Al principio del semestre el 50% de los participantes demostraron tener "carencia fuerte de conceptos" tanto para el enlace ionico como para el covalente. Al finalizar el semestre encontramos en el 40% de los participantes concepciones alternativas tanto para el enlace ionico como para el covalente y el 90% no lograron distinguir un enlace del otro. Nuestras conclusiones fueron que los participantes sin distincion del aprovechamiento academico demostraron tener la tendencia de "carencia fuerte de conceptos" tanto para el enlace ionico como para el covalente, presentaron dificultad al integrar los conceptos de los enlaces quimicos ionico y covalente que se pusieron de manifiesto al dar los ejemplos. Las preconcepciones erroneas contribuyen en el desarrollo de las concepciones alternativas. Ademas, los

Quality of life in vitiligo patients.

PubMed

Teovska Mitrevska, Natasa; Eleftheriadou, Viktoria; Guarneri, Fabrizio

2012-01-01

Quality of life is defined by the World Health Organization as "individuals' perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns." Often overlooked in the past, it is nowadays considered, in a more holistic view of medicine, a decisive factor to understand the impact of diseases and improve the quality of medical care. Such evaluation is particularly relevant for dermatological diseases, because visibility of the lesions can significantly affect self-esteem and social relationships. Vitiligo represents an emblematic case: often disfiguring and located in visible areas, confused in the past (and, in many world regions, even in the present) with leprosy, often perceived by physicians as a harmless, purely cosmetic problem, it significantly decreases the quality of life of affected persons. After a brief overview on definition, usefulness and methods for the assessment of quality of life, the authors examine the peculiarities of its relationship with skin diseases, particularly vitiligo. The state of the art of knowledge and research in this field is presented, together with data showing usefulness and positive results of a multidisciplinary approach, which adequately keeps into account perceived quality of life, on patient's satisfaction, adherence to treatment protocols and, ultimately, better outcome of treatments. In this context, an important role can be played by support communities, groups of patients and dedicated associations and societies, connected through modern communication networks like the Internet. © 2012 Wiley Periodicals, Inc.

Evaluation of the effect and mechanism of action of local phenytoin in treatment of vitiligo.

PubMed

Abdou, Asmaa Gaber; Abdelwahed Gaber, Mohammed; Elnaidany, Nada Farag; Elnagar, Ayat

2017-01-01

There are many theories explaining vitiligo such as genetic, autoimmune, neural, free radicals, biochemical, intrinsic defect, melanocytorrhagy, and convergent theories. Phenytoin is a widely used anticonvulsant, which is used in cutaneous medicine for treatment of ulcers and epidermolysis bullosa. The aim of this study is to assess the effectiveness of topical phenytoin gel in the treatment of vitiligo patients and explaining the underlying mechanism using immunohistochemistry for evaluation of HMB45, CD4, and CD8. Only 9 patients out of 28 experienced response to phenytoin in the form of dull, white color change and light brown color. Post-phenytoin treatment biopsies showed decreased density of inflammation, increased melanin and increased HMB45 positive cells together with an increased number of CD4 positive lymphocytes and decreased number of CD8 positive lymphocytes. These observations did not reach significant level (P > 0.05). A high percentage of CD4 positive lymphocytes was significantly associated with a long duration of vitiligo (p = 0.03) and segmental vitiligo type (p = 0.02). The current study applied phenytoin as 2% concentrated gel for 3 months, which is a relatively short duration without observed side effects throughout the period. These results indicate that topical phenytoin of low concentrations may have beneficial effects through immunomodulatory activity by affecting CD4 and CD8 counts and subsequently the ratio between them. Further studies are recommended to combine phenytoin with other antivitiligo agents as local corticosteroids or phototherapy to clarify if it could potentiate their effects.

Fine-mapping analysis of the MHC region for vitiligo based on a new Han-MHC reference panel.

PubMed

Yang, Chao; Wu, Juan; Zhang, Xuelei; Wen, Leilei; Sun, Jingying; Cheng, Yuyan; Tang, Xianfa; Liang, Bo; Chen, Gang; Zhou, Fusheng; Cui, Yong; Zhang, Anping; Zhang, Xuejun; Zheng, Xiaodong; Yang, Sen; Sun, Liangdan

2018-03-30

Vitiligo is an immune-related disease with patchy depigmentation of skin and hair caused by selective destruction of melanocytes. In recent decades, many studies have shown the association between vitiligo and HLA genes; however, the results of Han Chinese are scarce. In this study, we performed a fine-mapping analysis of the MHC region in 2818 Han Chinese subjects through a widely used HLA imputation method with a newly built large-scale Han-MHC reference panel. Three new four-digit HLA alleles (HLA-DQB1 ∗ 02:02, HLA-DQA1 ∗ 02:01 and HLA-DPB1 ∗ 17:01) were identified to be associated with the risk of vitiligo, and four previously reported alleles were confirmed. Further conditional analysis revealed that two important variants, HLA-DQβ1 amino acid position 135 (OR = 1.79, P = 1.87 × 10 -11 ) and HLA-B amino acid positions 45-46 (OR = 1.44, P = 5.61 × 10 -11 ), conferred most of the MHC associations. Three-dimension ribbon models showed that the former is located within the β2 domain of the HLA-DQβ1 molecule, and the latter lies in the α1 domain of the HLA-B molecule, while both are involved in specific antigen presenting process. Finally, we summarized all significant signals in the MHC region to clarify their complex relationships, and 8.60% of phenotypic variance could be explained based on all reported variants in Han Chinese so far. Our findings highlight the complex genetic architecture of the MHC region for vitiligo in Han Chinese population and expand our understanding of the roles of HLA coding variants in the etiology of vitiligo. Copyright © 2018. Published by Elsevier B.V.

Differences in the melanosome distribution within the epidermal melanin units and its association with the impairing background of leukoderma in vitiligo and halo nevi: a retrospective study.

PubMed

Xiong, Xi-Xi; Ding, Gao-Zhong; Zhao, Wen-E; Li, Xue; Ling, Yu-Ting; Sun, Li; Gong, Qing-Li; Lu, Yan

2017-07-01

Skin color is determined by the number of melanin granules produced by melanocytes that are transferred to keratinocytes. Melanin synthesis and the distribution of melanosomes to keratinocytes within the epidermal melanin unit (EMU) within the skin of vitiligo patients have been poorly studied. The ultrastructure and distribution of melanosomes in melanocytes and surrounding keratinocytes in perilesional vitiligo and normal skin were investigated using transmission electron microscopy (TEM). Furthermore, we performed a quantitative analysis of melanosome distribution within the EMUs with scatter plot. Melanosome count within keratinocytes increased significantly compared with melanocytes in perilesional stable vitiligo (P < 0.001), perilesional halo nevi (P < 0.01) and the controls (P < 0.01), but not in perilesional active vitiligo. Furthermore, melanosome counts within melanocytes and their surrounding keratinocytes in perilesional active vitiligo skin decreased significantly compared with the other groups. In addition, taking the means-standard error of melanosome count within melanocytes and keratinocytes in healthy controls as a normal lower limit, EMUs were graded into 3 stages (I-III). Perilesional active vitiligo presented a significantly different constitution in stages compared to other groups (P < 0.001). The distribution and constitution of melanosomes were normal in halo nevi. Impaired melanin synthesis and melanosome transfer are involved in the pathogenesis of vitiligo. Active vitiligo varies in stages and in stage II, EMUs are slightly impaired, but can be resuscitated, providing a golden opportunity with the potential to achieve desired repigmentation with an appropriate therapeutic choice. Adverse milieu may also contribute to the low melanosome count in keratinocytes.

[Usefulness of corrective make-up in children with vitiligo coordinated by dermatology nursing].

PubMed

Padilla-España, Laura; Ramírez-López, Belén; Fernández-Sánchez, Encarnación

2014-01-01

There are certain skin disorders such as vitiligo, acne, vascular malformations and postoperative scars that can affect the quality of life of children and especially adolescents. It can become an obstacle to their psychosocial development. A review was conducted on 4 patients with vitiligo located on face, who took part in a camouflage treatment course from January to December 2012. The impact of the skin disorder on quality of life was assessed before and after the therapeutic make-up sessions. Corrective makeup can be a complementary, reproducible, cost-effective, non-invasive, and useful technique in the management of dermatological diseases that have a physical and emotional impact in childhood. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The first childhood case with coexisting Hashimoto thyroiditis, vitiligo and autoimmune hepatitis.

PubMed

Keskin, Melikşah; Savaş-Erdeve, Şenay; Özbay-Hoşnut, Ferda; Kurnaz, Erdal; Çetinkaya, Semra; Aycan, Zehra

2016-01-01

Hashimoto thyroiditis (HT) is the most common pediatric autoimmune endocrine disorder. It results in autoimmune-mediated thyroid gland destruction and is an organ-specific, typical autoimmune disease. The presence of antithyroid antibodies and the typical pattern on ultrasonography indicate the diagnosis. It is also frequently seen together with other autoimmune disorders including type 1 insulin-dependent diabetes, celiac disease, alopecia and vitiligo. Autoimmune hepatitis (AIH) is a chronic type of liver injury with an immune etiology that can frequently cause end-stage liver disease if left untreated. Autoimmune hepatitis patients may present with hepatitis, and the laboratory tests in the absence of other etiology usually reveal a positive immune serology together with elevated immunoglobulins and abnormal liver histology. It is interesting that HT and AIH are rarely seen together although both have an autoimmune etiology. 14-year-old male who was being followed-up for vitiligo presented with symptoms of a swelling at the neck and fatigue. He was diagnosed with HT after the tests and the liver enzymes were found to be high. The patient was also diagnosed with AIH after tests revealed that the liver enzyme elevation had continued for longer than six months. The thyroid functions and liver enzymes returned to normal and the symptoms decreased after sodium L-thyroxine replacement together with steroid and azathioprine treatment. We present this case as we believe it is the first pediatric patient diagnosed with HT, AIH and vitiligo.

An in-depth analysis identifies two new independent signals in 11q23.3 associated with vitiligo in the Chinese Han population.

PubMed

Zhao, Suli; Fang, Fang; Tang, Xianfa; Dou, Jinfa; Wang, Wenjun; Zheng, Xiaodong; Sun, Liangdan; Zhang, Anping

2017-10-01

Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. This study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population. We selected and genotyped 26 SNPs at 11q23.3 in an independent cohort including 2924 cases and 4048 controls using the Sequenom MassArray iPLEX ® system. Bonferroni adjustment was used for multiple comparisons and P value <1.92×10 -3 (0.05/26) was considered statistically significant. The A allele of rs613791 and G allele of rs523604 located in CXCR5 were observed to be significantly associated with vitiligo (OR=1.21, 95% CI: 1.11-1.31, P=1.20×10 -5 ; OR=1.14, 95% CI: 1.07-1.23, P=1.90×10 -4 , respectively). The C allele of rs638893 (a previously reported one) located upstream of DDX6 was also significantly associated with vitiligo (OR=1.25, 95% CI: 1.12-1.38, P=3.04×10 -5 ). The genotypes distribution of 3 SNPs also showed significant differences between case and control (rs613791: P=7.00×10 -6 , rs523604: P=4.00×10 -3 , rs638893: P=1.20×10 -5 , respectively). The two newly identified SNPs (rs613791 and rs523604) showed independent associations with vitiligo by linkage disequilibrium analysis and conditional logistic regression. The study identified two new independent signals in the associated locus 11q23.3 for vitiligo. The presence of multiple independent variants emphasizes an important role of this region in disease susceptibility. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Laser-assisted depigmentation for resistant vitiligo: a retrospective case series with long-term follow-up.

PubMed

Boukari, F; Lacour, J P; Ortonne, J P; Bahadoran, P; Passeron, T

2014-03-01

Blanching creams are used to depigment and to achieve uniform skin tone in widespread vitiligo. Length of the treatment and side-effects strongly limit their use in common practice. To assess the long-term efficacy and tolerance of Q-Switched (QS) lasers for depigmenting the remaining unaffected skin in vitiligo. Retrospective study of vitiligo patients treated with QS lasers in the Department of Dermatology of the University Hospital of Nice, France, from 2002 to 2011. Localizations and the percentage of body surface area of treated lesions, the total number of sessions and the possible relapses and side-effects, were analysed. Global satisfaction of the patients was evaluated on a visual analogical scale. Sixteen areas of normally pigmented skin were treated in six patients. The median number of sessions to achieve a complete depigmentation was 2 (1-6). The mean duration of follow-up was 36 months (19-120). One third of the patients had no relapse. A complete repigmentation was observed after 21 months in one patient; a 50% repigmentation was noted in one patient, 7 months after the end of the treatment. Two patients showed a minimal repigmentation (<25%), 18 months and 9 years after the first laser treatments. The repigmentations were effectively treated with a maintenance session. The mean total number of sessions performed during this period was 3 (1-20). Side-effects were limited to transient purpura and crusts. The satisfaction of the patients was excellent (mean 9/10). conclusions: QS lasers appear as an efficient and safe modality for depigmenting normal skin in vitiligo. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Percepcion de los profesores universitarios acerca del concepto cultura cientifica y de sus implicaciones en el nuevo bachillerato del Recinto de Rio Piedras de la Universidad de Puerto Rico

NASA Astrophysics Data System (ADS)

Ramos Pastrana, Nilsa

El Senado Academico del Recinto de Rio Piedras de la Universidad de Puerto Rico aprobo en el ano academico 2005-2006 la Certificacion 46, que contiene los lineamientos de un nuevo bachillerato. Este nuevo bachillerato introdujo cambios significativos en el curriculo tradicional. Entre ellos se encuentra la reduccion del componente de educacion general y el de Ciencias Biologicas en particular. La reduccion de creditos en el componente de Ciencias Biologicas ha obligado a reevaluar el concepto de cultura cientifica que desarrollan esos cursos. El proposito del estudio consistio en auscultar las percepciones de los profesores de las Facultades de Administracion de Empresas, Humanidades, Ciencias Sociales, Ciencias Naturales, Educacion y Estudios Generales del Recinto de Rio Piedras de la Universidad de Puerto Rico en torno al concepto de cultura cientifica, los contenidos disciplinares del curso de Ciencias Biologicas y la reduccion de creditos en el nuevo bachillerato. Las preguntas que guiaron la investigacion fueron: ¿cuales son las percepciones que tienen los profesores de las Facultades de Administracion de Empresas, Ciencias Sociales, Estudios Generales, Ciencias Naturales, Humanidades y Educacion, en torno al concepto de cultura cientifica y los contenidos disciplinares del curso de Ciencias Biologicas? ¿cuales son las percepciones que tienen los profesores de Ciencias Biologicas en torno al concepto cultura cientifica y los contenidos disciplinares del curso de Ciencias Biologicas? ¿existen diferencias significativas por facultad, genero, experiencia, rango y nombramiento en las percepciones que tienen los profesores del Recinto de Rio Piedras de la Universidad de Puerto Rico sobre los elementos que caracterizan la cultura cientifica y los contenidos biologicos que deben tener los egresados del Recinto? ¿que implicaciones curriculares tienen estos testimonios en el desarrollo del concepto de cultura cientifica en el nuevo bachillerato? Para realizar la

Development and in vitro assessment of psoralen and resveratrol co-loaded ultradeformable liposomes for the treatment of vitiligo.

PubMed

Doppalapudi, Sindhu; Mahira, Shaheen; Khan, Wahid

2017-09-01

Vitiligo is a de-pigmenting skin disorder characterized by white patches on skin due to partial or complete loss of melanocytes. Psoralen in combination with ultraviolet-A (PUVA) acts by stimulation of melanin content and tyrosinase activity in melanocytes. Resveratrol, a sirtuin activator and a potential anti-oxidant reduce oxidative stress which is one of the triggering factors for initiation of vitiligo. Despite their therapeutic activity, weak percutaneous permeability of psoralen and poor solubility of resveratrol hinders their effective topical administration. The aim of present study is to formulate ultradeformable liposomes (UDL) co-loaded with psoralen and resveratrol for evaluation of PUVA and anti-oxidant combination in vitiligo treatment. For this purpose, UDL composed of DC-Chol, cholesterol and sodium deoxy cholate were prepared for their co-delivery. Liposomal carriers were characterized and evaluated for their efficacy using B16F10 cell line. Free radical scavenging potential was also determined for these carriers by in vitro anti-oxidant assays. Optimal co-loaded UDL with particle size ranging from 120 to 130nm, zeta potential of +46.2mV, entrapment efficiency of 74.09% (psoralen) and 76.91% (resveratrol) were obtained. Compared to control, co-loaded UDL showed significant stimulation of melanin and tyrosinase activity with major contribution of psoralen. Further, co-loaded UDL also exhibited potential free radical scavenging activity where resveratrol played a key role. Hence, psoralen and resveratrol co-loaded UDL acts in vitiligo through dual mechanisms of action viz., stimulation of melanin and tyrosinase activity as well as by anti-oxidant activity. These findings indicate that psoralen and resveratrol co-loaded UDL has the promising therapeutic potential for the treatment of vitiligo. Copyright © 2017 Elsevier B.V. All rights reserved.

Combined therapy for resistant vitiligo lesions: NB-UVB, microneedling, and topical latanoprost, showed no enhanced efficacy compared to topical latanoprost and NB-UVB.

PubMed

Stanimirovic, Andrija; Kovacevic, Maja; Korobko, Igor; Šitum, Mirna; Lotti, Torello

2016-09-01

Vitiligo is depigmenting disorder of the skin and mucous membranes but despite various therapeutic options, complete and satisfactory treatment of vitiligo still remains a challenge. Therapeutic success also varies depending on the localization of lesions; hands and bony prominents are considered to be resistant to treatment. We investigated feasibility of treating resistant bilateral symmetrical vitiligo vulgaris and acrofacialis lesions with combination of narrowband UVB and topical prostaglandins (0.005% latanoprost solution) with or without Dermaroller 0.5 mm needle length-assisted microneedling. Frequency of repigmentation onset was generally low (37.8%) and pronounced repigmentation was infrequently seen (26-50% repigmentation in 20.8%, and >50% repigmentation in only 8.8% of repigmenting lesions). Our study, however, showed that latanoprost can be used in combination with NB-UVB phototherapy to induce repigmentation in some vitiligo lesions in resistant-to-treatment location, while addition of skin microneedling seems not to improve the treatment outcome and possibly needs modification. © 2016 Wiley Periodicals, Inc.

The efficacy of narrowband UVB treatment in pediatric vitiligo: a retrospective analysis of 26 cases.

PubMed

Yazici, Serkan; Günay, Berrin; Başkan, Emel Bülbül; Aydoğan, Kenan; Saricaoğlu, Hayriye; Tunali, Şükran

2017-04-18

Narrowband UVB (Nb UVB) treatment is commonly used for the management of psoriasis and atopic dermatitis, and is less often used for vitiligo in children. The aim of this study was to evaluate the efficacy and short-term safety of Nb UVB phototherapy in children diagnosed with vitiligo retrospectively. A total of 26 patients younger than 18 years with the diagnosis of vitiligo and managed with Nb UVB phototherapy as documented in archive records were evaluated. Clinical response was assessed according to repigmentation of the lesions: good response when there was more than 75% repigmentation, moderate response when there was 25%-74% repigmentation, poor response when repigmentation was less than 24%, and unresponsive when there was no pigmentation and new lesions occurred. A total of 26 patients received Nb UVB treatment; 14 were girls and 12 were boys. The age at onset of the disease varied between 2 and 18 years, with a mean age of onset of 10.07 ± 4.53 years. Repigmentation rate of >75% was detected in 45.4% of cases. Nb UVB phototherapy seems to be a well-tolerated effective and safe treatment option in children, especially those unresponsive to topical treatment and those with widespread lesions. However, long-term risks such as photocarcinogenesis and photoaging should kept in mind.

Transporter TAP1-637G and Immunoproteasome PSMB9-60H Variants Influence the Risk of Developing Vitiligo in the Saudi Population

PubMed Central

Elhawary, Nasser Attia; Bogari, Neda; Jiffri, Essam Hussien; Rashad, Mona; Fatani, Abdulhamid; Tayeb, Mohammed

2014-01-01

We evaluated whether TAP1-rs1135216 (p.637D>G) and PSMB9-rs17587 (p.60R>H) were significantly associated with the risk and severity of vitiligo among Saudi patients. One hundred seventy-two subjects were genotyped for the TAP1-rs1135216 and PSMB9-rs17587 variants using endonuclease digestions of amplified genomic DNA. The TAP1-rs1135216 and PSMB9-rs17587 mutant alleles were strongly associated with vitiligo, with odds ratios showing five fold and two fold risks (P < 0.0001 and P = 0.007, resp.). In TAP1-rs1135216, the 637G mutant allele was more frequent in cases (74%) than in healthy controls. In cases, the 60H mutant allele PSMB9-rs17587 was less frequent (42%) than the wild-type 60R allele (58%). Vitiligo vulgaris was the most common type of disease, associated with the DG (55%) and GG (46%) genotypes for rs1135216 and with the RH genotype (59%) for rs17587. The heterozygous 637DG and 60RH genotypes were each linked with active phenotypes in 64% of cases. In conclusion, the TAP1-rs1135216 and PSMB9-rs17587 variants are significantly associated with vitiligo, and even one copy of these mutant alleles can influence the risk among Saudis. Vitiligo vulgaris is associated with genotypes containing the mutant G and H alleles. PMID:25548428

Oral and topical L-phenylalanine, clobetasol propionate, and UVA/sunlight--a new study for the treatment of vitiligo.

PubMed

Camacho, Francisco; Mazuecos, José

2002-09-01

Vitiligo is a hypopigmented skin condition that usually requires a combination of treatment options. To demonstrate the effectiveness of topical and oral L-phenylalanine in combination with light plus 0.025% clobetasol propionate at night. We have performed an open trial on a group of 70 patients with evolutive vitiligo. Participants were treated with oral (100 mg/Kg/day) and topical (gel at 10%) L-phenylalanine, exposed to sunlight (spring-summer) or UVA lamps (autumn-winter), and given 0.025% clobetasol propionate at night. All patients were revisited every 6 months while in the study, with a maximum of 4 revisits. Biochemical studies were performed at the beginning of the treatment and at each revisit. Overall, 90.9% of participants showed improvement, with 68.5% of patients achieving an improvement of 75% or more. This 75% improvement rate was reached 87.9% of the time on the face, 60.4% on the trunk, and 54.6% on the limbs. However, there was a moderate response to the treatment in patients with focal and segmental vitiligo. There was a slight additional improvement in patients receiving UVA lamp light. No biochemical abnormalities were found in any patients. L-phenylalanine in combination with 0.025% clobetasol propionate and sunlight during sunny months or UVA lamps in winter, appears to improve evolutive vitiligo without side effects, and therefore is especially recommended on the face or for children.

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).

Autoimmune vitiligo does not require the ongoing priming of naïve CD8 T cells for disease progression or associated protection against melanoma1

PubMed Central

Byrne, Katelyn T.; Zhang, Peisheng; Steinberg, Shannon M.; Turk, Mary Jo

2014-01-01

Vitiligo is a CD8 T cell-mediated autoimmune disease that has been shown to promote the longevity of memory T cell responses to melanoma. However mechanisms whereby melanocyte/melanoma antigen-specific T cell responses are perpetuated in the context of vitiligo are not well understood. The present studies investigate the possible phenomenon of naïve T cell priming in hosts with melanoma-initiated, self-perpetuating, autoimmune vitiligo. Using naïve pmel (gp10025-33-specific) transgenic CD8 T cells, we demonstrate that autoimmune melanocyte destruction induces naive T cell proliferation in skin-draining lymph nodes, in an antigen-dependent fashion. These pmel T cells upregulate expression of CD44, P-selectin ligand, and granzyme B. However, they do not downregulate CD62L, nor do they acquire the ability to produce IFN-γ, indicating a lack of functional priming. Accordingly, adult thymectomized mice exhibit no reduction in the severity or kinetics of depigmentation or long-lived protection against melanoma, indicating that the continual priming of naïve T cells is not required for vitiligo or its associated anti-tumor immunity. Despite this, depletion of CD4 T cells during the course of vitiligo rescues the priming of naïve pmel T cells that are capable of producing IFN-γ and persisting as memory, suggesting an ongoing and dominant mechanism of suppression by regulatory T cells. This work reveals the complex regulation of self-reactive CD8 T cells in vitiligo, and demonstrates the overall poorly immunogenic nature of this autoimmune disease setting. PMID:24403535

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

PubMed Central

Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; van der Veen, JP Wietze; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W.; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R.; Santorico, Stephanie A; Spritz, Richard A

2016-01-01

Vitiligo is an autoimmune disease in which depigmented skin results from destruction of melanocytes1, with epidemiologic association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) in EUR subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new loci and 7 suggestive loci, most encoding immune and apoptotic regulators, some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight relationships to other autoimmune diseases and melanoma, and offer potential targets for treatment. PMID:27723757

La preparacion en ciencia de los candidatos a maestros del nivel elemental primario segun la reforma de la educacion cientifica en Puerto Rico: Una propuesta de secuencia curricular

NASA Astrophysics Data System (ADS)

Rodriguez Plaza, Evelyn

El proposito de esta investigacion fue identificar los componentes de la preparacion en ciencia que deben recibir los estudiantes del Bachillerato en Artes en Educacion Elemental, Nivel Primario, de acuerdo a los documentos que dirigen la reforma de la educacion cientifica en Puerto Rico. Tambien, se identificaron los componentes de los cursos que forman parte de la preparacion en ciencia de estos estudiantes. Se compararon los componentes de la preparacion en ciencia y los componentes de los cursos para determinar congruencias y discrepancias. Con los datos recopilados se identificaron los componentes de los cursos de una secuencia curricular para la preparacion en ciencia de los candidatos a maestros del nivel elemental primario. La secuencia curricular que se propone en esta investigacion incluye cursos de contenido cientifico y de metodologia en la ensenanza de la ciencia disenados para satisfacer las necesidades de los candidatos. Se recomienda que en los procesos para el diseno, la implantacion y la evaluacion de estos cursos participen profesores de ciencia, profesores de educacion y maestros del nivel elemental primario. Todos los cursos de la secuencia curricular deben tener un enfoque constructivista. Las experiencias educativas que se incluyan en los cursos deben aspirar a desarrollar en los candidatos los atributos de la cultura cientifica y actitudes positivas hacia la ciencia y hacia la ensenanza de esta disciplina. El modelaje por parte de los profesores que ensenen los cursos de la secuencia curricular es fundamental en el desarrollo profesional de los candidatos. Se recomienda que en los cursos de contenido cientifico se estudien los conceptos y los conocimientos cientificos que forman parte del curriculo de Kindergarten a tercer grado de forma integrada y con una profundidad universitaria. Estos cursos deben tener un enfoque interdisciplinario e incluir el estudio de la naturaleza de la ciencia y un componente de laboratorio para desarrollar los

Oxidative stress drives CD8+ T-cell skin trafficking in patients with vitiligo through CXCL16 upregulation by activating the unfolded protein response in keratinocytes.

PubMed

Li, Shuli; Zhu, Guannan; Yang, Yuqi; Jian, Zhe; Guo, Sen; Dai, Wei; Shi, Qiong; Ge, Rui; Ma, Jingjing; Liu, Ling; Li, Kai; Luan, Qi; Wang, Gang; Gao, Tianwen; Li, Chunying

2017-07-01

In patients with vitiligo, an increased reactive oxygen species (ROS) level has been proved to be a key player during disease initiation and progression in melanocytes. Nevertheless, little is known about the effects of ROS on other cells involved in the aberrant microenvironment, such as keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and was recently found to mediate homing of CD8 + T cells in human skin. We sought to explicate the effect of oxidative stress on human keratinocytes and its capacity to drive CD8 + T-cell trafficking through CXCL16 regulation. We first detected putative T-cell skin-homing chemokines and ROS in serum and lesions of patients with vitiligo. The production of candidate chemokines was detected by using quantitative real-time PCR and ELISA in keratinocytes exposed to H 2 O 2 . Furthermore, the involved mediators were analyzed by using quantitative real-time PCR, Western blotting, ELISA, and immunofluorescence. Next, we tested the chemotactic migration of CD8 + T cells from patients with vitiligo mediated by the CXCL16-CXCR6 pair using the transwell assay. CXCL16 expression increased and showed a positive correlation with oxidative stress levels in serum and lesions of patients with vitiligo. The H 2 O 2 -induced CXCL16 expression was due to the activation of 2 unfolded protein response pathways: kinase RNA (PKR)-like ER kinase-eukaryotic initiation factor 2α and inositol-requiring enzyme 1α-X-box binding protein 1. CXCL16 produced by stressed keratinocytes induced migration of CXCR6 + CD8 + T cells derived from patients with vitiligo. CXCR6 + CD8 + T-cell skin infiltration is accompanied by melanocyte loss in lesions of patients with vitiligo. Our study demonstrated that CXCL16-CXCR6 mediates CD8 + T-cell skin trafficking under oxidative stress in patients with vitiligo. The CXCL16 expression in human keratinocytes induced by ROS is, at least in part, caused by unfolded protein response

Association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and susceptibility to vitiligo: Systematic review and meta-analysis.

PubMed

Agarwal, Silky; Changotra, Harish

2017-01-01

Protein tyrosine phosphatase, non-receptor type 22 gene, which translates to lymphoid tyrosine phosphatase, is considered to be a susceptibility gene marker associated with several autoimmune diseases. Several studies have demonstrated the association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism with vitiligo. However, these studies showed conflicting results. Meta-analysis of the same was conducted earlier that included fewer number of publications in their study. We performed a meta-analysis of a total of seven studies consisting of 2094 cases and 3613 controls to evaluate the possible association of protein tyrosine phosphatase, non-receptor type 22 +1858C>T polymorphism with vitiligo susceptibility. We conducted a literature search in PubMed, Google Scholar and Dogpile for all published paper on protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and vitiligo risk till June 2016. Data analysis was performed by RevMan 5.3 and comprehensive meta-analysis v3.0 software. Meta-analysis showed an overall significant association of protein tyrosine phosphatase, non- receptor type 22 +1858C→T polymorphism with vitiligo in all models (allelic model [T vs. C]: odds ratio = 1.50, 95% confidence interval [1.32-1.71], P< 0.001; dominant model [TT + CT vs. CC]: odds ratio = 1.61, 95% confidence interval [1.16-2.24], P = 0.004; recessive model [TT vs. CT + CC]: odds ratio = 4.82, 95% confidence interval [1.11-20.92], P = 0.04; homozygous model [TT vs. CC]: odds ratio = 5.34, 95% confidence interval [1.23-23.24], P = 0.03; co-dominant model [CT vs. CC]: odds ratio = 1.52, 95% confidence interval [1.09-2.13], P = 0.01). No publication bias was detected in the funnel plot study. Limited ethnic-based studies, unable to satisfy data by gender or vitiligo-type are some limitations of the present meta-analysis. Stratifying data by ethnicity showed an association of protein tyrosine phosphatase, non-receptor type 22 +1858C�

A case-control study on association of proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1) polymorphisms and their transcript levels in vitiligo from Gujarat.

PubMed

Jadeja, Shahnawaz D; Mansuri, Mohmmad Shoab; Singh, Mala; Dwivedi, Mitesh; Laddha, Naresh C; Begum, Rasheedunnisa

2017-01-01

Autoimmunity has been implicated in the destruction of melanocytes from vitiligo skin. Major histocompatibility complex (MHC) class-II linked genes proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1), involved in antigen processing and presentation have been reported to be associated with several autoimmune diseases including vitiligo. To explore PSMB8 rs2071464 and TAP1 rs1135216 single nucleotide polymorphisms and to estimate the expression of PSMB8 and TAP1 in patients with vitiligo and unaffected controls from Gujarat. PSMB8 rs2071464 polymorphism was genotyped using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and TAP1 rs1135216 polymorphism was genotyped by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 378 patients with vitiligo and 509 controls. Transcript levels of PSMB8 and TAP1 were measured in the PBMCs of 91 patients and 96 controls by using qPCR. Protein levels of PSMB8 were also determined by Western blot analysis. The frequency of 'TT' genotype of PSMB8 polymorphism was significantly lowered in patients with generalized and active vitiligo (p = 0.019 and p = 0.005) as compared to controls suggesting its association with the activity of the disease. However, TAP1 polymorphism was not associated with vitiligo susceptibility. A significant decrease in expression of PSMB8 at both transcript level (p = 0.002) as well as protein level (p = 0.0460) was observed in vitiligo patients as compared to controls. No significant difference was observed between patients and controls for TAP1 transcripts (p = 0.553). Interestingly, individuals with the susceptible CC genotype of PSMB8 polymorphism showed significantly reduced PSMB8 transcript level as compared to that of CT and TT genotypes (p = 0.009 and p = 0.003 respectively). PSMB8 rs2071464 was associated with generalized and active vitiligo from Gujarat whereas TAP1 rs1135216 showed no association. The

Combination of Follicular and Epidermal Cell Suspension as a Novel Surgical Approach in Difficult-to-Treat Vitiligo: A Randomized Clinical Trial.

PubMed

Razmi T, Muhammed; Kumar, Ravinder; Rani, Seema; Kumaran, Sendhil M; Tanwar, Sushma; Parsad, Davinder

2018-03-01

Epidermal cell suspension (ECS) and follicular cell suspension (FCS) are successful surgical modalities for the treatment of stable vitiligo. However, repigmentation in generalized and acrofacial vitiligo and over acral or bony sites (eg, elbows, knees, iliac crests, and malleoli), which are difficult to treat, is challenging. To study the efficacy of transplanting a combination of autologous, noncultured ECS and FCS (ECS + FCS) compared with ECS alone in stable vitiligo. A prospective, observer-blinded, active-controlled, randomized clinical trial was conducted at a tertiary care hospital, with treatment administered as an outpatient procedure. Thirty participants who had stable vitiligo with symmetrical lesions were recruited between October 18, 2013, and October 28, 2016. All of the lesions were resistant to medical modalities with minimum lesional stability of 1 year. Intent-to-treat analysis was used. ECS + FCS was prepared by mixing equal amounts (in cell number) of FCS with ECS. After manual dermabrasion, ECS was applied to 1 lesion and ECS + FCS was applied to the anatomically based paired lesion of the same patient. No adjuvant treatment was given. Patients were followed up at 4, 8, and 16 weeks by a blinded observer and extent of repigmentation, color match, pattern of repigmentation, patient satisfaction and complications were noted. Both the visual and the computerized image analysis methods were used for outcome assessment. Cell suspensions were assessed post hoc for OCT4+ stem cell counts using flow cytometry; expression of stem cell factor and basic fibroblast growth factor was evaluated using quantitative relative messenger RNA expression. Of the 30 patients included in the study, 18 (60%) were women; mean (SD) age was 23.4 (6.4) years. Seventy-four percent of the lesions (62 of 84) were difficult-to-treat vitiligo. ECS + FCS showed superior repigmentation outcomes compared with ECS: extent (76% vs 57%, P < .001), rapidity (48

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes via Inhibition of JAK2: Its Implication for Vitiligo Treatment.

PubMed

Ning, Weixuan; Wang, Suiquan; Dong, Xiaowu; Liu, Dongyin; Fu, Lifang; Jin, Rong; Xu, Aie

2015-01-01

Vitiligo is an inflammatory skin disorder in which activated T cells play an important role in its onset and progression. Epigallocatechin-3-gallate (EGCG), the major chemical constituent of green tea, exhibits remarkable anti-oxidative and anti-inflammatory properties. EGCG administration has been confirmed to decrease the risk of vitiligo; however, the underlying mechanism is undetermined. In this study, we proved that EGCG directly inhibited the kinase activity of Janus kinase 2 (JAK2). In primary cultured human melanocytes, EGCG pre-treatment attenuated interferon (IFN)-γ-induced phosphorylation of JAK2 and its downstream signal transducer and activator of transcription (STAT)1 and STAT3 in a dose-dependent manner. We further examined the chemoattractant expression in melanocytes and demonstrated that EGCG significantly inhibited IFN-γ-induced expression of intracellular adhesion molecule (ICAM)-1, CXCL10, and monocyte chemotactic protein (MCP)-1 in human melanocytes. In addition, EGCG reduced the protein levels of the corresponding receptors including CD11a, CXCR3, and CCR2 in human T lymphocytes. As a consequence, adhesion of human T cells to melanocytes induced by IFN-γ was effectively suppressed by EGCG. Taken together, our results provided new evidence for the effectiveness of EGCG in vitiligo treatment and supported JAK2 as a molecular target for vitiligo medicine development.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

PubMed

Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; Wietze van der Veen, J P; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R; Santorico, Stephanie A; Spritz, Richard A

2016-11-01

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.

The effect of platelet-rich plasma on the outcome of short-term narrowband-ultraviolet B phototherapy in the treatment of vitiligo: a pilot study.

PubMed

Ibrahim, Zeinab A; El-Ashmawy, Amal A; El-Tatawy, Rania A; Sallam, Fersan A

2016-06-01

Narrowband - ultraviolet B (NB-UVB) is an emerging, effective, and safe therapy for vitiligo, but the treatment course often requires a long duration of time which may carry a potential risk for various side effects and patients' noncompliance. To explore the effect of platelet-rich plasma (PRP) injection on the outcome of short-term NB-UVB therapy for the patients with stable vitiligo. The study included 60 stable vitiligo patients with overall symmetrical lesions. For each patient, the left side of the body was treated with NB-UVB alone (control side) while the right side was treated with NB-UVB therapy in addition to intradermal injection of PRP, every 2 weeks for 4 months. There was statistically highly significant improvement in the repigmentation in the combination group(PRP plus NB-UVB) compared with NB-UVB group. Intradermal PRP injection in combination with NB-UVB could be considered as a simple, safe, tolerable, and cheap technique for treatment of vitiligo. It shortens the duration of NB-UVB therapy and is expected to increase patient compliance. Longer follow-up is needed. © 2015 Wiley Periodicals, Inc.

A case-control study on association of proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1) polymorphisms and their transcript levels in vitiligo from Gujarat

PubMed Central

Jadeja, Shahnawaz D.; Mansuri, Mohmmad Shoab; Singh, Mala; Dwivedi, Mitesh; Laddha, Naresh C.

2017-01-01

Background Autoimmunity has been implicated in the destruction of melanocytes from vitiligo skin. Major histocompatibility complex (MHC) class-II linked genes proteasome subunit beta 8 (PSMB8) and transporter associated with antigen processing 1 (TAP1), involved in antigen processing and presentation have been reported to be associated with several autoimmune diseases including vitiligo. Objectives To explore PSMB8 rs2071464 and TAP1 rs1135216 single nucleotide polymorphisms and to estimate the expression of PSMB8 and TAP1 in patients with vitiligo and unaffected controls from Gujarat. Methods PSMB8 rs2071464 polymorphism was genotyped using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) and TAP1 rs1135216 polymorphism was genotyped by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 378 patients with vitiligo and 509 controls. Transcript levels of PSMB8 and TAP1 were measured in the PBMCs of 91 patients and 96 controls by using qPCR. Protein levels of PSMB8 were also determined by Western blot analysis. Results The frequency of ‘TT’ genotype of PSMB8 polymorphism was significantly lowered in patients with generalized and active vitiligo (p = 0.019 and p = 0.005) as compared to controls suggesting its association with the activity of the disease. However, TAP1 polymorphism was not associated with vitiligo susceptibility. A significant decrease in expression of PSMB8 at both transcript level (p = 0.002) as well as protein level (p = 0.0460) was observed in vitiligo patients as compared to controls. No significant difference was observed between patients and controls for TAP1 transcripts (p = 0.553). Interestingly, individuals with the susceptible CC genotype of PSMB8 polymorphism showed significantly reduced PSMB8 transcript level as compared to that of CT and TT genotypes (p = 0.009 and p = 0.003 respectively). Conclusions PSMB8 rs2071464 was associated with generalized and active vitiligo from

Association of Neuropeptide Y (NPY), Interleukin-1B (IL1B) Genetic Variants and Correlation of IL1B Transcript Levels with Vitiligo Susceptibility

PubMed Central

Laddha, Naresh C.; Dwivedi, Mitesh; Mansuri, Mohmmad Shoab; Singh, Mala; Patel, Hetanshi H.; Agarwal, Nishtha; Shah, Anish M.; Begum, Rasheedunnisa

2014-01-01

Background Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. NPY plays an important role in induction of immune response by acting on a variety of immune cells. NPY synthesis and release is governed by IL1B. Moreover, genetic variability in IL1B is reported to be associated with elevated NPY levels. Objectives Aim of the present study was to explore NPY promoter −399T/C (rs16147) and exon2 +1128T/C (rs16139) polymorphisms as well as IL1B promoter −511C/T (rs16944) polymorphism and to correlate IL1B transcript levels with vitiligo. Methods PCR-RFLP method was used to genotype NPY -399T/C SNP in 454 patients and 1226 controls; +1128T/C SNP in 575 patients and 1279 controls and IL1B −511C/T SNP in 448 patients and 785 controls from Gujarat. IL1B transcript levels in blood were also assessed in 105 controls and 95 patients using real-time PCR. Results Genotype and allele frequencies for NPY −399T/C, +1128T/C and IL1B −511C/T SNPs differed significantly (p<0.0001, p<0.0001; p = 0.0161, p = 0.0035 and p<0.0001, p<0.0001) between patients and controls. ‘TC’ haplotype containing minor alleles of NPY polymorphisms was significantly higher in patients and increased the risk of vitiligo by 2.3 fold (p<0.0001). Transcript levels of IL1B were significantly higher, in patients compared to controls (p = 0.0029), in patients with active than stable vitiligo (p = 0.015), also in female patients than male patients (p = 0.026). Genotype-phenotype correlation showed moderate association of IL1B -511C/T polymorphism with higher IL1B transcript levels. Trend analysis revealed significant difference between patients and controls for IL1B transcript levels with respect to different genotypes. Conclusion Our results suggest that NPY −399T/C, +1128T/C and IL1B −511C/T polymorphisms are associated with vitiligo and IL1B −511C/T SNP influences its transcript levels leading to increased risk for vitiligo in

The therapeutic effects of a topical tretinoin and corticosteroid combination for vitiligo: a placebo-controlled, paired-comparison, left-right study.

PubMed

Kwon, Hyok Bu; Choi, Yunseok; Kim, Hwa Jung; Lee, Ai-Young

2013-04-01

Topical all-trans-retinoic acid (tretinoin) prevents skin atrophy induced by long-term use of topical corticosteroids, without abrogating their anti-inflammatory effects. The goal of this study was to determine the efficacy of tretinoin plus topical corticosteroids (tretinoin plus) for repigmentation in patients with vitiligo. A placebo-controlled, paired-comparison, left-right study was conducted for a period of 6 months on tretinoin plus and the vehicle plus the same topical corticosteroid (vehicle plus) treatment in 50 patients diagnosed with generalized vitiligo. Clinical responses were assessed using the computerized analysis, and the results were compared with the visual analysis. The percentage agreement between the 2 analyses was 91.8%. Among 49 participants who successfully completed this study, 27 (55%) showed a better response to tretinoin plus than to vehicle plus. The improved response was noted at an early stage of treatment, during the first 3 months in 60% of patients. Combined therapy with tretinoin plus topical corticosteroids is safe and effective and provides another option for treatment of patients with vitiligo.

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.

Comparison of efficacy and side-effect profile of oral PUVA vs. oral PUVA sol in the treatment of vitiligo: a 36-week prospective study.

PubMed

Singh, S; Khandpur, S; Sharma, V K; Ramam, M

2013-11-01

Both Oral PUVA and PUVA sol have been successfully used in vitiligo treatment. However, there is paucity of studies comparing the two therapies, especially under subtropical conditions of abundant sunlight where PUVA sol is more feasible. To compare the efficacy and side effects of oral PUVA versus oral PUVA sol therapy in generalized vitiligo. Comparative prospective clinical trial conducted on consecutive patients of generalized vitiligo. Response to treatment was assessed using change in Lund & Browder (L & B) score for assessment of reduction in body surface area of involvement, patient global assessment (PGA) of improvement in vitiligo, investigator's global assessment (IGA) of extent of repigmentation, and quality of life (QOL) assessment using Tjioe et al questionnaire. Thirty five patients were recruited- 18 in PUVA and 17 in PUVA sol group. Mean percentage change in L & B score at 36 weeks was 46.4% in PUVA and 26.1% in PUVA sol group (P = 0.06), mean PGA score in PUVA was 4.58 ± 2.23 and in PUVA sol group was 6 ± 2.08 (P = 0.13), mean IGA score was 3.08 ± 1.68 in PUVA and 1.79 ± 0.57 in PUVA sol group (P = 0.11). QOL scores were significantly higher in PUVA group as compared to the PUVA sol group (P = 0.04). Side effects were comparable in two groups except for phototoxic side effects which were significantly more in PUVA group. PUVA is more efficacious than PUVA sol and also provides greater psychological benefit in treatment of generalized vitiligo but is associated with more phototoxic adverse effects. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Translation, cross-cultural adaptation and validation of the vitiligo-specific health-related quality of life instrument (VitiQoL) into Brazilian Portuguese.

PubMed

Boza, Juliana Catucci; Kundu, Roopal V; Fabbrin, Amanda; Horn, Roberta; Giongo, Natalia; Cestari, Tania Ferreira

2015-01-01

Vitiligo, although asymptomatic, highly compromises patients' quality of life (QoL). Therefore, an adequate evaluation of QoL is essential. Translation, cultural adaptation and validation of VitiQol (Vitiligo-specific health-related quality of life instrument) into Brazilian Portuguese. The study was conducted in two stages; the first stage was the translation and cultural/linguistic adaptation of the instrument; the second stage was the instrument's validation. The translated VitiQol showed high internal consistency (Cronbach alpha = 0.944) and high test-retest reliability and intraclass correlation coefficient=0.95 (CI 95% 0.86 - 0.98), p<0.001. There was no statistically significant difference between the means of the first completion of the VitiQoL questionnaire and the retest, p = 0.661. There was a significant correlation between VitiQoL and DLQI (r = 0.776, p <0.001) and also between VitiQoL-PB and subjects' assessment of the severity of their disease (r = 0.702, p <0.001). The impact of vitiligo on the QoL of Brazilian patients can be assessed by a specific questionnaire.

The role of systemic steroids and phototherapy in the treatment of stable vitiligo: a randomized controlled trial.

PubMed

El Mofty, Medhat; Essmat, Samia; Youssef, Randa; Sobeih, Sherine; Mahgoub, Doaa; Ossama, Sherine; Saad, Akmal; El Tawdy, Amira; Mashaly, Heba M; Saney, Iman; Helal, Rana; Shaker, Olfat

2016-11-01

Pathogenesis of vitiligo is believed to be multifactorial disease with a wide variety of therapeutic modalities. The aim of this work is to assess the efficacy of oral mini-pulse steroids (OMP) plus Nb-U.V.B in comparison to OMP alone and Nb-U.V.B alone in treating stable vitiligo. A prospective randomized controlled study including 45 patients categorized into three groups receiving therapy for 3 months; Group A received Nb-U.V.B plus OMP, Group B received OMP alone while Group C received Nb-U.V.B alone. Clinical assessment and PCR evaluation of bFGF, ICAM1, and ELISA for AMA were done. Patients receiving Nb-U.V.B plus OMP and using Nb-U.V.B alone gave statistically significant clinical response than those treated with OMP alone. Statistically significant rise of BFGF was noticed after treatment with Nb-U.V.B plus OMP and with Nb-U.V.B alone. Patients treated with OMP alone and with Nb-U.V.B alone showed statistically significant drop of ICAM-1 after therapy. NB-U.V.B plus OMP and Nb-U.V.B alone were found to be clinically superior over OMP alone in treating stable vitiligo patients, hence suggesting that adding OMP to Nb-U.V.B can maintain clinical and laboratory success for a longer period of time and with less relapse. © 2016 Wiley Periodicals, Inc.

Interleukin-22 participates in the inflammatory process of vitiligo

PubMed Central

Dong, Jinjin; An, Xiaohong; Zhong, Hui; Wang, Yichuan; Shang, Jing; Zhou, Jia

2017-01-01

Vitiligo is an acquired depigmentary skin inflammatory disorder. The pathogenesis of inflammatory skin disease involves the release of cytokines from keratinocytes, including interleukin (IL)-1β. IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. Among skin cell populations only keratinocytes are the major targets of IL-22. In the present study, we demonstrated that IL-22 promoting IL-1β secretion from keratinocytes via the Reactive oxygen species (ROS)-NOD-like receptor family, pyrin domain containing 3 (NLRP3)-caspase-1 pathway. It inhibited the expression of protease-activated receptor-2 (PAR-2) of keratinocytes. However, IL-22 had no direct effect on normal human foreskin-derived epidermal melanocytes (NHEM). Considering the closely connection between keratinocytes and melanocytes, and the ability of keratinocytes to produce a plethora of cytokines, in the present work, we examined whether IL-22 could regulate melanocytes functions by keratinocytes participation. Keratinocytes were exposed to IL-22 and the conditional medium was collected. The effect of conditional medium on melanocytes was studied. The expressions of relative proteins were assessed by western blot. Influence of conditional medium on NHEM migration was assessed by Transwell method and the apoptosis by flow cytometry analysis. The IL-22-treating keratinocytes conditional medium inhibited melanogenesis and restrained the expressions of Rab GTPases of NHEM. In addition, the conditional medium suppressed melanocytes migration and induced apoptosis. Our results collectively indicated that IL-22 may potentiate IL-1β-mediated skin inflammation and result in participating in the inflammatory pathogenesis of vitiligo. PMID:29312598

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

Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization.

PubMed

Birlea, Stanca A; Costin, Gertrude-E; Roop, Dennis R; Norris, David A

2017-07-01

Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin. Using an in-depth correlative analysis of multiple experimental and clinical data sets, we generated a modern molecular research platform that can be used as a working model for further research of vitiligo repigmentation. Our analysis emphasizes the active participation of defined molecular pathways that regulate the balance between stemness and differentiation states of melanocytes and keratinocytes: p53 and its downstream effectors controlling melanogenesis; Wnt/β-catenin with proliferative, migratory, and differentiation roles in different pigmentation systems; integrins, cadherins, tetraspanins, and metalloproteinases, with promigratory effects on melanocytes; TGF-β and its effector PAX3, which control differentiation. Our long-term goal is to design pharmacological compounds that can specifically activate melanocyte precursors in the hair follicle in order to obtain faster, better, and durable repigmentation. © 2016 Wiley Periodicals, Inc.

Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization

PubMed Central

Birlea, Stanca A.; Costin, Gertrude-E.; Roop, Dennis R.; Norris, David A.

2017-01-01

Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin. Using an in-depth correlative analysis of multiple experimental and clinical data sets, we generated a modern molecular research platform that can be used as a working model for further research of vitiligo repigmentation. Our analysis emphasizes the active participation of defined molecular pathways that regulate the balance between stemness and differentiation states of melanocytes and keratinocytes: p53 and its downstream effectors controlling melanogenesis; Wnt/β-catenin with proliferative, migratory, and differentiation roles in different pigmentation systems; integrins, cadherins, tetraspanins, and metalloproteinases, with promigratory effects on melanocytes; TGF-β and its effector PAX3, which control differentiation. Our long-term goal is to design pharmacological compounds that can specifically activate melanocyte precursors in the hair follicle in order to obtain faster, better, and durable repigmentation. PMID:28029168

Modelo de accesibilidad de conceptos matematicos aplicados en el curso de Astronomia Descriptiva para estudiantes con impedimentos visuales en la UPR

NASA Astrophysics Data System (ADS)

Isidro Villamizar, Gloria Maria

Este estudio utiliza metodologia de investigacion cualitativa, con el proposito de describir, analizar y evaluar los procesos de diseno y desarrollo de un modelo de accesibilidad que consiste en estrategias de ensenanza de las matematicas para estudiantes con impedimentos visuales matriculados en el curso de Astronomia Descriptiva en la UPR. Se utilizaron las siguientes estrategias para recopilar la informacion, 1) reflexiones de la investigadora en el proceso de diseno y desarrollo de las lecciones adaptadas, que se registraron en un diario reflexivo. 2) entrevista semiestructurada luego de haber trabajado las lecciones de aprendizaje adaptadas con los participantes. 3) observaciones y notas de la investigadora del trabajo de los participantes. Para obtener la informacion de los participantes se obtuvo los permisos institucionales necesarios; se seleccionaron los participantes y se validaron los instrumentos; se realizo el desarrollo de las lecciones adaptadas con los participantes; y finalmente, se analizo la informacion obtenida. El diseno de las lecciones de aprendizaje adaptadas se hizo siguiendo las recomendaciones curriculares de los temas de matematicas aplicados en el curso de Astronomia Descriptiva realizado por la investigadora durante su semestre de internado. El testimonio de las voces de los participantes se obtuvo del proceso de desarrollo de las lecciones de aprendizaje adaptadas de temas seleccionados de conceptos matematicos requeridos en el curso de Astronomia Descriptiva y de la entrevista semiestructurada con los participantes, luego de haber trabajado las lecciones de aprendizaje. Para el desarrollo de las lecciones de aprendizaje, se utilizaron materiales tactiles adaptados, materiales tactiles disenados y materiales disponibles comercialmente. Los textos de las lecciones se imprimieron en tinta y en Braille. Se exhorta a disenar y desarrollar estrategias de ensenanza accesibles, considerando como recursos para evaluar su efectividad a

Altered expression of four miRNA (miR-1238-3p, miR-202-3p, miR-630 and miR-766-3p) and their potential targets in peripheral blood from vitiligo patients.

PubMed

Shang, Zhiwei; Li, Hongwen

2017-10-01

Vitiligo is an acquired skin disease with pigmentary disorder. Autoimmune destruction of melanocytes is thought to be major factor in the etiology of vitiligo. miRNA-based regulators of gene expression have been reported to play crucial roles in autoimmune disease. Therefore, we attempt to profile the miRNA expressions and predict their potential targets, assessing the biological functions of differentially expressed miRNA. Total RNA was extracted from peripheral blood of vitiligo (experimental group, n = 5) and non-vitiligo (control group, n = 5) age-matched patients. Samples were hybridized to a miRNA array. Box, scatter and principal component analysis plots were performed, followed by unsupervised hierarchical clustering analysis to classify the samples. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was conducted for validation of microarray data. Three different databases, TargetScan, PITA and microRNA.org, were used to predict the potential target genes. Gene ontology (GO) annotation and pathway analysis were performed to assess the potential functions of predicted genes of identified miRNA. A total of 100 (29 upregulated and 71 downregulated) miRNA were filtered by volcano plot analysis. Four miRNA were validated by quantitative RT-PCR as significantly downregulated in the vitiligo group. The functions of predicted target genes associated with differentially expressed miRNA were assessed by GO analysis, showing that the GO term with most significantly enriched target genes was axon guidance, and that the axon guidance pathway was most significantly correlated with these miRNA. In conclusion, we identified four downregulated miRNA in vitiligo and assessed the potential functions of target genes related to these differentially expressed miRNA. © 2017 Japanese Dermatological Association.

Solar Physics Topics in High School: Analysis of a Course with Practical Activities at Dietrich Schiel Observatory. (Spanish Title: Temas de Física Solar Para Estudiantes de Escuelas Secundarias: un Análisis de un Curso con Enfoque Práctico en el Observatorio Dietrich Schiel.) Tópicos de Física Solar no Ensino Médio: Análise de um Curso com Atividades Práticas no Observatório Dietrich Schiel

NASA Astrophysics Data System (ADS)

Calbo Aroca, Silvia; Donizete Colombo, Pedro, Jr.; Celestino Silva, Cibelle

2012-12-01

This work analyses results obtained in a solar physics course for high school students promoted at the Dietrich Schiel Observatory of the University of São Paulo (USP). The course was elaborated by the authors with the intention of investigating student's concepts about the Sun, teaching topics of modern physics related to the Sun and providing students with knowledge about our star as well. The methodology of data gathering consisted of audio and video records of classes and of semi-structured interviews, and analysis of answers to written questionnaires. The results showed that most high school students conceived the Sun as made of fire, while sunspots were thought to be holes in the Sun. Even though some students did know that a spectrum is formed using a prism or diffraction grating, most of them ignored the nature of the observed spectral lines. Through the course, this topic was developed by means of a practical approach with solar and lamp spectra observations. The results obtained in the course point to the importance of science centers as partners in formal education. In this specific case, the Solar Room at the Dietrich Schiel Observatory is as a favorable environment for teaching modern physics in high school. Este artículo analiza los resultados obtenidos en un curso sobre la física solar, auspiciado por el Observatorio Dietrich Schiel de la USP para estudiantes de las escuelas secundarias. El curso fue diseñado por los autores con la intención de investigar las concepciones sobre el sol, enseñar temas relacionados con la física moderna del Sol y conocimientos generales sobre el astro rey. La metodología utilizada para la recolección de datos consistió en grabar, en audio y video, las clases, las entrevistas semi-estructuradas y las respuestas a los cuestionarios escritos. Los resultados mostraron que la mayoría de los participantes conciben el Sol como constituido por fuego y las manchas solares en la superficie solar como agujeros. Aunque

Depigmentation therapy in vitiligo universalis with topical 4-methoxyphenol and the Q-switched ruby laser.

PubMed

Njoo, M D; Vodegel, R M; Westerhof, W

2000-05-01

Monobenzylether of hydroquinone is used worldwide to remove residual pigment in patients with vitiligo universalis. Because of the side effects reported with this drug, the use of monobenzylether of hydroquinone has been restricted in The Netherlands. Our purpose was to evaluate the long-term effectiveness and safety of a combination therapy consisting of topical 4-methoxyphenol (4-MP) cream and Q-switched ruby (QSR) laser in 16 patients with vitiligo universalis. In a retrospective study, patient record forms were evaluated. Data were collected regarding history as well as physical and histologic examination. The patients came to the institute for a follow-up visit after a treatment-free period of 2 to 36 months. Thirteen patients received both therapies. Three patients only used the cream. None of the areas was treated by the cream and QSR laser at the same time. In 11 of the 16 patients (69%; 95% confidence interval [CI], 41%-89%) total depigmentation was achieved using the 4-MP cream. Onset of depigmentation was between 4 and 12 months. Four of the 5 patients who did not respond to the 4-MP cream had successful depigmentation with the QSR laser. Mild burning or itching was reported with the cream in 4 cases (25%). Of the 11 patients who responded to the 4-MP cream, 4 had recurrence of pigmentation (relapse rate of 36%; 95% CI, 11%-69%) after a treatment-free period of 2 to 36 months. In 9 of the 13 patients (69%; 95% CI, 39%-91%) total depigmentation was achieved after QSR laser therapy. Onset of depigmentation was between 7 and 14 days after the treatment. Three of the 4 unresponsive patients showed total depigmentation after application of the 4-MP cream. No side effects were observed. Of the 9 patients who responded to QSR laser therapy, 4 had recurrence of pigmentation (relapse rate of 44%; 95% CI, 14%-79%) after a treatment-free period of 2 to 18 months. These patients had a negative Koebner phenomenon. Depigmentation therapy using a 4-MP cream and/or QSR

Halo naevi, vitiligo and diffuse alopecia areata associated with tocilizumab therapy

PubMed Central

Nadesalingam, Kavitha; Goodfield, Mark; Emery, Paul

2016-01-01

We present a follow-up case report of a 33-year-old lady with juvenile onset arthritis who developed halo naevi while on treatment with tocilizumab. This case report describes the development of halo naevi, vitiligo and diffuse alopecia areata associated with tocilizumab therapy following infection with Methicillin-resistant Staphylococcus aureus (MRSA) and Panton–Valentine leukocidin positivity. This is the first case that describes these events and supports previous theories on cellular and humoral immunity as causative factors. The regression of melanocytes during treatment with tocilizumab could also implicate IL-6 and sIL-6R as future targets in the treatment of melanoma through its direct effect of melanocytic cytotoxicity, which supports previous studies. PMID:27516894

Integrating modern dermatology and Ayurveda in the treatment of vitiligo and lymphedema in India.

PubMed

Narahari, Saravu R; Ryan, Terence J; Bose, Kuthaje S; Prasanna, Kodimoole S; Aggithaya, Guruprasad M

2011-03-01

Globally, governments have recognized the growing popularity of Complementary and Alternative Medicines and the possibility of their combined use with biomedicine. Decisions within the Government of India have led to a conducive environment for conducting clinical studies, to achieve integration of more than one system of medicine, so that their combined benefits can be brought to bear on chronic, difficult-to-treat conditions. To develop integrative dermatology treatment protocols for patients with long-standing skin diseases who have received treatment from many centers. A team of doctors from modern dermatology, Ayurveda, yoga therapy, and homeopathy studied recruited patients to develop mutual orientation on each therapeutic system and a working knowledge of approach to their clinical diagnosis. Six-hundred thirty-eight patients affected by lower limb lymphedema requiring skin care as a major part of treatment were treated integrating modern dermatology and Ayurveda. Three-hundred eighty-one vitiligo patients were examined and treated to understand the clinical presentations and treatment options in Ayurveda. A two-step cluster analysis performed by SPSS Version 16 showed average volume reductions of 13.3% and 23% on day 14, 19.7% and 31.1% on day 45, and 23.4% and 39.7% on day 90 of treatment in small and large lymphedematous limbs. Inflammatory episodes before the onset on this treatment was reported by 79.5% of our lymphedema patients, and 9.4% reported this at the end of three months after our treatment. Among vitiligo patients, we found that 39.6% of patients had kapha, 39.8% pitta, 10.8% had vatha and 0.52% has tridoshaja presentation. There are over 100 treatment options available in Ayurveda to treat vitiligo. Each system of medicine recognizes the same disease albeit with minor difference in description. Skin care procedures like washing and emollients restore the barrier function and skin health. We have converged Ayurvedic skin care with that of

Mapping of melanin-concentrating hormone receptor 1 B cell epitopes predicts two major binding sites for vitiligo patient autoantibodies.

PubMed

Gavalas, Nikos G; Gottumukkala, Raju V S R K; Gawkrodger, David J; Watson, Philip F; Weetman, Anthony P; Kemp, E Helen

2009-05-01

The melanin-concentrating hormone receptor 1 (MCHR1) has been identified as a B cell autoantigen in vitiligo with antibodies to the receptor detectable in binding and function-blocking assays. Two epitope domains (amino acids 1-138 and 139-298) have been previously identified. In this study, we aimed to further define the epitope specificity of MCHR1 antibodies using phage-display technology and to identify the epitopes recognised by receptor antibodies detected in MCHR1 function-blocking assays. Antibody reactivity to MCHR1 peptides 51-80, 85-98, 154-158 and 254-260 was identified by phage-display and subsequently confirmed in phage ELISA in 2/12, 5/12, 3/12 and 6/12 of vitiligo patients, respectively. The results suggest that major autoantibody epitopes are localised in the 85-98 and 254-260 amino acid regions of MCHR1 with minor epitopes in amino acid sequences 51-80 and 154-158. Antibodies with MCHR1 function-blocking activity were determined to recognise epitope 254-260, this being the first epitope to be reported as a target site for antibodies that block the function of the receptor.

Treatment of vitiligo with a chimeric monoclonal antibody to CD20: a pilot study

PubMed Central

Ruiz-Argüelles, A; García-Carrasco, M; Jimenez-Brito, G; Sánchez-Sosa, S; Pérez-Romano, B; Garcés-Eisele, J; Camacho-Alarcón, C; Reyes-Núñez, V; Sandoval-Cruz, M; Mendoza-Pinto, C; López-Colombo, A

2013-01-01

Five patients with active disseminated vitiligo were given 1 g of a chimeric (murine/human) monoclonal antibody to CD20 in a single intravenous infusion and followed-up for 6 months. Three of the patients showed an overt clinical and histological improvement of the disease, one presented slight improvement and the remaining patient showed no changes. Improvement was neither associated with changes in laboratory parameters nor to a specific human leucocyte antigen D-related (HLA-DR) phenotype. We believe that these preliminary results are encouraging, and further clinical trials should be undertaken. An important aim should be the finding of a marker with a good response to this therapeutic approach. PMID:23815517

Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization, in vitro evaluation and preclinical assessment.

PubMed

Garg, Bhawna Jain; Garg, Neeraj K; Beg, Sarwar; Singh, Bhupinder; Katare, Om Prakash

2016-01-01

The present investigation aimed for the development and characterization of ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery and effective treatment against vitiligo. The ethosomes were prepared by central composite design (CCD) and characterized for various quality attributes like vesicle shape, size, zeta potential, lamellarity, drug entrapment and drug leaching. The optimized ethosomes were subsequently incorporated int Carbopol® 934 gel and characterized for drug content, rheological behavior, texture profile, in vitro release, ex vivo skin permeation and retention, skin photosensitization and histopathological examination. Ethosomes were found to be spherical and multilamellar in structures having nanometric size range with narrow size distribution, and high encapsulation efficiency. Ethosomal formulations showed significant skin permeation and accumulation in the epidermal and dermal layers. The fluorescence microscopy study using 123 Rhodamine exhibited enhanced permeation of the drug-loaded ethosomes in the deeper layers of skin. Also, the developed formulation showed insignificant phototoxicity and erythema vis-à-vis the conventional cream. The results were cross-validated using histopathological examination of skin segments. In a nutshell, the ethosomes-based hydrogel formulation was found to be a promising drug delivery system demonstrating enhanced percutaneous penetration of methoxsalen with reduced phototoxicity and erythema, thus leading to improved patient compliance for the treatment against vitiligo.

Clinical efficacy of Apamarga Kshara Yoga in the management of Shvitra (vitiligo)

PubMed Central

Jadav, Hasmukh R.; Galib, R.; Prajapati, Pradeep Kumar

2015-01-01

Introduction: Vitiligo is a progressive, idiopathic, pigmentation disorder of the skin, characterized by hypopigmented patches. This condition is compared with Shvitra in Ayurveda. Many Ayurvedic drugs are beneficial in such cases and Apamarga Kshara Yoga is one among them. Aim: To evaluate the efficacy of Apamarga Kshara Yoga in Lepa and ointment forms in the management of Shvitra. Materials and Methods: Total 50 patients of Shvitra were randomly grouped into two. Patients registered in Group A (n = 25) were treated with Apamarga Kshara Yoga Lepa and Group B (n = 25) with Apamarga Kshara Yoga ointment for 2 months. Rasayana Churna (3g) along with Honey and Ghee was given twice daily internally in the both groups. Results: Significant improvement was found in the symptoms of Shvitra with treatment in both the groups. The difference in between the groups was statistically insignificant. Conclusion: Both forms of Apamraga Kshara Yoga are effective in cases of Shvitra and can be good alternatives for contemporary medicines. PMID:27011717

Clinical efficacy of Apamarga Kshara Yoga in the management of Shvitra (vitiligo).

PubMed

Jadav, Hasmukh R; Galib, R; Prajapati, Pradeep Kumar

2015-01-01

Vitiligo is a progressive, idiopathic, pigmentation disorder of the skin, characterized by hypopigmented patches. This condition is compared with Shvitra in Ayurveda. Many Ayurvedic drugs are beneficial in such cases and Apamarga Kshara Yoga is one among them. To evaluate the efficacy of Apamarga Kshara Yoga in Lepa and ointment forms in the management of Shvitra. Total 50 patients of Shvitra were randomly grouped into two. Patients registered in Group A (n = 25) were treated with Apamarga Kshara Yoga Lepa and Group B (n = 25) with Apamarga Kshara Yoga ointment for 2 months. Rasayana Churna (3g) along with Honey and Ghee was given twice daily internally in the both groups. Significant improvement was found in the symptoms of Shvitra with treatment in both the groups. The difference in between the groups was statistically insignificant. Both forms of Apamraga Kshara Yoga are effective in cases of Shvitra and can be good alternatives for contemporary medicines.

Vitiligo and alopecia areata associated with subclinical/clinical hypothyroidism.

PubMed

Sehgal, Virendra N

2011-01-01

The parents of an 18-year-old woman had noticed white hair while combing their daughter's hair 12 years ago. They found tiny white spots on her scalp, but she was asymptomatic. The spots have since progressed. Examination of the affected skin on the scalp was marked by the presence of a chalky/ivory white macule, 8 to 10 cm in diameter, conforming to that of segmental (zosteriformis) vitiligo (Figure 1). The lesions were located on the temporoparietal region of the scalp. The hair over the macules was white (leukotrichia) and dry, coarse, and brittle. The patient's nails were thin and dull. Her thyroid profile revealed the following: triiodothyronine, 1.12 nmol/L (0.95-2.5 nmol/L); thyroxine, 69.21 nmol/L (60.0-120.0 nmol/L); and thyroid-stimulating hormone, 6.26 microIU/mL (0.25-5.00 microIU/mL), indicative of primary hypothyroidism. Liver and renal function tests were within normal limits. A lipid profile revealed the following: total lipids, 503.8 mg% (400-700 mg %); triglycerides, 123.0 mg % (160 mg %); cholesterol, 212.0 mg % (150-250 mg %); high-density lipoprotein, 43.1 mg % (30-63 mg %); and low-density lipoprotein, 144.3 mg % (50 mg %). Electrocardiographic findings were normal. History of tiredness, constipation, depression, sensitivity to cold, weight gain, muscle weakness, cramps, and increased menstrual flow supported the diagnosis. The patient was administered 100 microg of thyroxine once a day along with methoxsalen, the dose of which was calculated at 0.6 mg/kg to 0.7 mg/kg body weight per day given on alternate days, followed 2 hours later by exposure to UV-A (1 J/cm2) irradiation (psoralen-UV-A [PUVA]), supplemented by 1 mg of beta-methasone, 150 mg of levamisole on 2 consecutive days per week, and an antioxidant. During the course of 7 weeks, the macules (13 exposures) had become erythematous, with an appearance of perifollicular/ marginal pigmentation. Repeat examination showed a thyroid profile of total triiodothyronine (T3), 127.3 microg

Simplified Non-cultured Non-trypsinised Epidermal Cell Graft Technique Followed by Psoralen and Ultraviolet A Light Therapy for Stable Vitiligo

PubMed Central

Kachhawa, Dilip; Rao, Pankaj; Kalla, Gyaneshwar

2017-01-01

Background and Aims: Stable vitiligo can be treated by various surgical procedures. Non-cultured melanocyte grafting techniques were developed to overcome the time-consuming process of culture while at the same time providing acceptable results. All the techniques using non-cultured melanocyte transfer involve trypsinisation as an integral step. Jodhpur technique used by the author is autologous, non-cultured, non-trypsinised, epidermal cell grafting. Settings and Design: The study was conducted on patients visiting the dermatology outpatient department of a tertiary health centre in Western Rajasthan. Materials and Methods: At the donor site, mupirocin ointment was applied and dermabrasion was done with the help of micromotor dermabrader till pinpoint bleeding was seen. The paste-like material obtained by this procedure containing melanocytes and keratinocytes admixed with the ointment base was harvested with spatula and was subsequently spread over the recipient area. Recipient site was prepared in the same manner by dermabrasion. After 10 days, dressing at both sites was removed taking utmost care at the recipient site as there was a theoretical risk of dislodging epidermal cells. Results: In a study of 437 vitiligo patches, more than 75% re-pigmentation (excellent improvement) was seen in 41% of the patches. Lesions on thigh (100%), face (75%) and trunk (50%) showed maximal excellent improvement, whereas patches on joints and acral areas did not show much improvement. Conclusions: This technique is a simplified, cost effective, less time-consuming alternative to other techniques which involve tryspsinisation of melanocytes and at the same time provides satisfactory uniform pigmentation. PMID:28852293

Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.

PubMed

Dey-Rao, Rama; Sinha, Animesh A

2017-01-28

Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile. We used several in silico bioinformatics-based analyses to provide new insights into disease mechanisms and suggest novel targets for future therapy. Unsupervised clustering methods of the VL-blood dataset demonstrate a "disease-state"-specific set of co-expressed genes. Ontology enrichment analysis of 99 differentially expressed genes (DEGs) uncovers a down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis and catabolic processes in VL-blood. There is evidence for both type I and II interferon (IFN) playing a role in VL pathogenesis. We used interactome analysis to identify several key blood associated transcriptional factors (TFs) from within (STAT1, STAT6 and NF-kB), as well as "hidden" (CREB1, MYC, IRF4, IRF1, and TP53) from the dataset that potentially affect disease pathogenesis. The TFs overlap with our reported lesional-skin transcriptional circuitry, underscoring their potential importance to the disease. We also identify a shared VL-blood and -skin transcriptional "hot spot" that maps to chromosome 6, and includes three VL-blood dysregulated genes (PSMB8, PSMB9 and TAP1) described as potential VL-associated genetic susceptibility loci. Finally, we provide bioinformatics-based support for prioritizing dysregulated genes in VL-blood or skin as potential therapeutic targets. We examined the VL-blood transcriptome in context with our (previously published) VL-skin transcriptional profile to address

Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 1: Epidermal H2O2/ONOO(-)-mediated stress abrogates tryptophan hydroxylase and dopa decarboxylase activities, leading to low serotonin and melatonin levels.

PubMed

Schallreuter, Karin U; Salem, Mohamed A E L; Gibbons, Nick C J; Martinez, Aurora; Slominski, Radomir; Lüdemann, Jürgen; Rokos, Hartmut

2012-06-01

Vitiligo is characterized by a progressive loss of inherited skin color. The cause of the disease is still unknown. To date, there is accumulating in vivo and in vitro evidence for massive oxidative stress via hydrogen peroxide (H(2)O(2)) and peroxynitrite (ONOO(-)) in the skin of affected individuals. Autoimmune etiology is the favored theory. Since depletion of the essential amino acid L-tryptophan (Trp) affects immune response mechanisms, we here looked at epidermal Trp metabolism via tryptophan hydroxylase (TPH) with its downstream cascade, including serotonin and melatonin. Our in situ immunofluorescence and Western blot data reveal significantly lower TPH1 expression in patients with vitiligo. Expression is also low in melanocytes and keratinocytes under in vitro conditions. Although in vivo Fourier transform-Raman spectroscopy proves the presence of 5-hydroxytryptophan, epidermal TPH activity is completely absent. Regulation of TPH via microphthalmia-associated transcription factor and L-type calcium channels is severely affected. Moreover, dopa decarboxylase (DDC) expression is significantly lower, in association with decreased serotonin and melatonin levels. Computer simulation supports H(2)O(2)/ONOO(-)-mediated oxidation/nitration of TPH1 and DDC, affecting, in turn, enzyme functionality. Taken together, our data point to depletion of epidermal Trp by Fenton chemistry and exclude melatonin as a relevant contributor to epidermal redox balance and immune response in vitiligo.

Alkaptonuria in a boy with type 1 diabetes mellitus, vitiligo, autoimmune thyroiditis and immunoglobulin A deficiency - a case report.

PubMed

Hogendorf, Anna; Pietrzak, Iwona; Antosik, Karolina; Borowiec, Maciej; Młynarski, Wojciech

2016-01-01

We present a 15-year-old Caucasian boy with an exceptional coincidence of a rare monogenic metabolic disease - alkaptonuria (AKU) and a cluster of autoimmune disorders: type 1 diabetes (T1DM), autoimmune thyroiditis (AIT), vitiligo, insulin infusion induced lipoatrophy and immunoglobulin A deficiency (IgAD) Alkaptonuria and type 1 diabetes in a child, especially in such an interesting coincidence with other autoimmune conditions, has not been reported so far. Our investigation, including comprehensive genetic evaluation using next generation sequencing technology, shows that alkaptonuria and T1DM were independently inherited. We also show that alkaptonuria in its pre-ochronotic phase seems to have no effect on the course of diabetes. © Polish Society for Pediatric Endocrinology and Diabetology.

Diseno de una Actividad de Aprendizaje Basada en la Argumentacion Dialogica en un curso Virtual de Biotecnologia y su Incidencia en el Desarrollo de Competencias Cientificas

NASA Astrophysics Data System (ADS)

Ortiz Benavides, Fedra Lorena

El proposito de la investigacion fue evaluar la efectividad de una actividad de aprendizaje basado en la argumentacion dialogica en linea y su incidencia en el desarrollo de competencias cientificas. Se fundamenta en la teoria del aprendizaje socio cultural de Vigotsky (1984), los principios del diseno instruccional de la cognicion situada por Hung y Der-Thang (2001) y como estrategia se aplico la argumentacion dialogica utilizando el Modelo Argumentativo de Toulmin MAT (1984). El diseno experimental comparo dos grupos de estudiantes A y B en el curso virtual de Biotecnologia. El grupo A (experimental) desarrollo la discusion a partir de la estrategia disenada para este estudio y el grupo B (control) realizo la discusion desde las actividades tradicionales. El desarrollo de la competencia argumentativa se valoro con el instrumento de evaluacion para argumentacion dialogica en linea propuesta por Clark y Sampson (2008). La evaluacion de las competencias cientificas se realizo a partir de una postprueba. Los datos fueron analizados con pruebas estadisticas no parametricas. Los resultados de la investigacion, indicaron diferencias significativas en el nivel de la competencia argumental en el grupo experimental en comparacion al grupo control. Igualmente se demostro que existe una relacion positiva entre el nivel de desarrollo de la competencia argumentativa y el nivel de desarrollo de las competencias cientificas.

Earliest depiction of vitiligo in "Venus at a Mirror" (1615) by Peter Paul Rubens (1577-1640).

PubMed

Ashrafian, Hutan

2018-06-01

The 1615 painting of Venus at a Mirror by Peter Paul Rubens is considered a powerful example of the Flemish Baroque movement. Recently it has been identified that the Venus character in the image has a goitre, however on studying the image further, I note dermato-pathology in another of the painting's main characters; the dark-skinned female typically described as the Venus' maidservant who clearly demonstrates patches of skin pigment loss on her face and neck with a concurrent streak of white hair. Together these suggest the underlying diagnosis of vitiligo. There is also a goitre in this individual suggesting thyroid disease. This new finding may offer additional insight into the historical epidemiology of disease in northern Europe but also offers further understanding of the method, origin, and pathological associations of this prominent painting from a genius artist. © 2017 Wiley Periodicals, Inc.

Percutaneous penetration, melanin activation and toxicity evaluation of a phytotherapic formulation for vitiligo therapeutic.

PubMed

Truite, Cecília Valente Rodrigues; Philippsen, Gisele Strieder; Ueda-Nakamura, Tânia; Natali, Maria Raquel Marçal; Dias Filho, Benedito Prado; Bento, Antonio Carlos; Baesso, Mauro Luciano; Nakamura, Celso Vataru

2007-01-01

The aim of this work was to apply photoacoustic spectroscopy for the ex vivo determination of the penetration rate of a phytotherapic formulation for vitiligo therapeutic, with or without salicylic acid as the promoter agent. In addition, the compound toxicity and morphophysiology effects were evaluated for different concentrations of salicylic acid. The experiments were performed as a function of the period of time of treatment in a well-controlled group of rabbits. Toxic effects were not observed with any of the tested products. All formulations containing salicylic acid induced cutaneous reaction which was dose dependent. The histological analysis showed that the use of the medication was associated with an increased comedogenic effect in relation to the control group, regardless of salicylic acid concentration. Inflammatory reactions and acanthosis were observed only in the animals treated with formulations containing higher concentrations of salicylic acid, while none of these effects were detected with the use of the formulation containing 2.5% (wt/vol) of salicylic acid. Photoacoustic depth monitoring showed that both formulations, with or without salicylic acid, propagated through the skin up to the melanocytes region, suggesting that the transport of the active agent may occur through the epithelial structure without the need of using queratinolitic substances, which are known to induce side effects in the animals.

Estudio de la estructura logica utilizada en la ensenanza y el aprendizaje de los conceptos sobre el comportamiento de gases en el curso introductorio de quimica a nivel universitario

NASA Astrophysics Data System (ADS)

Costa Diaz, Agnes

El estudio que se presenta es de caracter cualitativo, un estudio multicasos donde se estudia la estructura logica utilizada por cuatro (4) profesores universitarios que ensenan el curso introductorio de quimica, en la planificacion, presentacion y evaluacion del tema sobre el comportamiento de los gases. Se utilizaron varias fuentes de informacion como: cuestionarios de profesores y estudiantes, entrevistas, grabaciones videomagnetofonicas, materiales didacticos y una prueba conceptual, entre otros. La informacion recopilada fue analizada de acuerdo al orden logico del contenido presentado, el estilo de ensenanza del profesor, las tecnicas y estrategias utilizadas para el desarrollo de destrezas de pensamiento, el ambiente fisico en el salon de clase y los instrumentos de evaluacion y avaluo. El estudio demuestra que lo que los profesores piensan y planifican para hacer sus presentaciones no necesariamente es lo que ocurre en el salon de clases. El desarrollo de destrezas de pensamiento, que constituye una prioridad de los profesores, no se elaboran efectivamente. El uso de las estrategias de resolucion de problemas numericos predomino. La participacion del estudiante en el salon de clases fue limitada y no se logro demostrar el desarrollo de las destrezas de pensamiento deseadas. Aunque los profesores tienen su propio estilo de ensenanza, el orden logico del contenido presentado en clase fue el mismo o siguio muy de cerca el orden establecido por el libro de texto. Los profesores utilizaron preferentemente la tiza y la pizarra para sus presentaciones y la dinamica en el salon de clases fue esencialmente tradicional. Los profesores hicieron su presentacion y los estudiantes copiaron pasivamente la informacion. Las evaluaciones de los estudiantes fueron esencialmente, pruebas escritas de seleccion multiple de acuerdo con el estilo en que se les enseno. El avaluo fue casi inexistente. La prueba conceptual administrada revela un aprendizaje pobre en los conceptos mas

Which plant for which skin disease? Part 2: Dermatophytes, chronic venous insufficiency, photoprotection, actinic keratoses, vitiligo, hair loss, cosmetic indications.

PubMed

Reuter, Juliane; Wölfle, Ute; Korting, Hans Christian; Schempp, Christoph

2010-11-01

This paper continues our review of scientifically evaluated plant extracts in dermatology. After plants effective against dermatophytes, botanicals with anti-edema effects in chronic venous insufficiency are discussed. There is good evidence from randomized clinical studies that plant extracts from grape vine leaves (Vitis vinifera), horse chestnut (Aesculus hippocastanum), sea pine (Pinus maritima) and butcher's broom (Ruscus aculeatus) can reduce edema in chronic venous insufficiency. Plant extracts from witch hazel (Hamamelis virginiana), green tea (Camellia sinensis), the fern Polypodium leucotomos and others contain antioxidant polyphenolic compounds that may protect the skin from sunburn and photoaging when administered topically or systemically. Extracts from the garden spurge (Euphorbia peplus) and from birch bark (Betula alba) have been shown to be effective in the treatment of actinic keratoses in phase II studies. Some plant extracts have also been investigated in the treatment of vitiligo, various forms of hair loss and pigmentation disorders, and in aesthetic dermatology. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

Computer and laboratory simulation in the teaching of neonatal nursing: innovation and impact on learning.

PubMed

Fonseca, Luciana Mara Monti; Aredes, Natália Del' Angelo; Fernandes, Ananda Maria; Batalha, Luís Manuel da Cunha; Apóstolo, Jorge Manuel Amado; Martins, José Carlos Amado; Rodrigues, Manuel Alves

2016-10-10

game e-Baby, software instrucional de semiologia e semiotécnica e simulação em laboratório. Para a avaliação do curso e caracterização dos estudantes utilizou-se instrumentos de coleta de dados desenvolvidos para este estudo. Utilizou-se estatística não paramétrica: Mann-Whitney e Wilcoxon. O uso de tecnologias digitais validadas e de simulação em laboratório evidenciou diferença estatisticamente significativa (p=0,001) na aprendizagem dos participantes. O curso foi avaliado como muito satisfatório pelos mesmos. A simulação em laboratório isoladamente não representou diferença significativa no aprendizado. a aprendizagem cognitiva dos participantes aumentou significativamente. Considera-se que o uso de tecnologia foi responsável por parte do sucesso do curso, denotando ser uma importante ferramenta de inovação didática e motivação da aprendizagem na área da saúde. evaluar el aprendizaje cognitivo de estudiantes de enfermería en evaluación clínica neonatal, a partir de un curso semipresencial, utilizando simulación por computador y en laboratorio; comparar el aprendizaje cognitivo de los estudiantes, entre grupo control y experimental, comprobando la simulación en el laboratorio; y evaluar el curso semipresencial extracurricular ofrecido sobre evaluación clínica del bebé pretérmino, de acuerdo a los estudiantes. estudio casi experimental con 14 estudiantes portugueses, conteniendo preprueba, prueba intermedia y postprueba. Las tecnologías ofrecidas en el curso fueron serious game e-Baby, programa de instrucción en semiología y semiotecnia, y simulación en laboratorio. Para la evaluación del curso y caracterización de los estudiantes se utilizaron instrumentos de recolección de datos desarrollados para este estudio. Se utilizó la estadística no-paramétrica de Mann-Whitney y Wilcoxon. el uso de tecnologías digitales validadas y de simulación en laboratorio evidenció diferencia estadísticamente significativa (p=0,001) en

Revision curricular a partir de un analisis comparativo de las discrepancias en los curriculos de una escuela de optometria en Puerto Rico con las competencias requeridas para las agencias de revalida y acreditacion 2004

NASA Astrophysics Data System (ADS)

Rivera Pacheco, Andres

El proposito de esta investigacion, un estudio cualitativo de caso, fue comparar y contrastar el curriculo vigente de la Escuela de Optometria de la UIAPR con las competencias y estandares requeridos por las agencias de acreditacion y de revalida. Con este proposito, decidimos realizar una revision y un analisis de documentos: el prontuario de cada uno de los cursos de los curriculos implantados en el 1993 y en el 2001; las competencias y estandares establecidos por las agencias de revalida y de acreditacion; y las estadisticas en las que se analiza el porcentaje de estudiantes que aprueban cada una de las partes de los examenes de revalida entre el 1998 al 2003. Se realizaron entrevistas dirigidas para dar apoyo y complementar la revision y el analisis de estos documentos. Los participantes de las entrevistas fueron tres estudiantes de la clase de optometria del 2004 (ultima clase del curriculo del 1993); tres estudiantes de la clase de optometria del 2005 (primera clase graduanda del curriculo vigente) y tres profesores y/o directores de los Departamentos de Ciencias Basicas, Ciencias Clinicas y Cuidado al Paciente. Esta investigacion se enmarco en el modelo de evaluacion curricular de discrepancia de Malcolm Provus y en el modelo de desarrollo basado en competencias. Uno de los hallazgos mas importantes del estudio es que los cambios que se implantaron al curriculo del 2001 no han logrado que los estudiantes mejoren su ejecucion en los examenes de revalida. Por otro lado, se encontro que el curriculo vigente atiende completamente los estandares de la practica de Optometria, pero no las competencias. Esta informacion fue validada mediante el uso de una tabla de cotejo para el analisis de los cursos y de la informacion obtenida de las entrevistas. El estudio determina y concluye que existen discrepancias entre los prontuarios de los cursos del curriculo y las competencias requeridas por la agencia de revalida. Segundo, que el Departamento de Ciencias Basicas es el

Modulation of T-Cell Activation in an Experimental Model of Mammary Carcinoma

DTIC Science & Technology

1999-07-01

depigmentation, reminiscent of the vitiligo that occurs in melanoma patients undergoing immunotherapy (3). In the transgenic prostate cancer model, we...extrusion in the hair follicles that is not observed in unaffected areas of the coat. This depigmentation is reminiscent of the vitiligo syndrome observed in...and a GM-CSF-expressing Vaccine. manuscript submitted. 3. Rosenberg, S.A., and D.E. White. 1996. Vitiligo in patients with melanoma: normal tissue

DEL phenotype.

PubMed

Kwon, Dong H; Sandler, S G; Flegel, Willy A

2017-09-01

DEL red blood cells (RBCs) type as D- by routine serologic methods and are transfused routinely, without being identified as expressing a very weak D antigen, to D- recipients. DEL RBCs are detected only by adsorption and elution of anti-D or by molecular methods. Most DEL phenotypes have been reported in population studies conducted in East Asia, although DEL phenotypes have been detected also among Caucasian individuals. Approximately 98 percent of DEL phenotypes in East Asians are associated with the RHD*DEL1 or RHD*01EL.01 allele. The prevalence of DEL phenotypes has been reported among D- Han Chinese (30%), Japanese (28%), and Korean (17%) populations. The prevalence of DEL phenotypes is significantly lower among D- Caucasian populations (0.1%). Among the 3-5 percent of African individuals who are D-, there are no reports of the DEL phenotype. Case reports from East Asia indicate that transfusion of DEL RBCs to D- recipients has been associated with D alloimmunization. East Asian immigrants constitute 2.1 percent of the 318.9 million persons residing in the United States, and an estimated 2.8 percent are blood donors. Using these statistics, we estimate that 68-683 units of DEL RBCs from donors of East Asian ancestry are transfused as D- annually in the United States. Given the reports from East Asia of D alloimmunization attributed to transfusion of DEL RBCs, one would expect an occasional report of D alloimmunization in the United States following transfusion of DEL RBCs to a D- recipient. If such cases do occur, the most likely reason that they are not detected is the absence of active post-transfusion monitoring for formation of anti-D.

Blepharoplasty

MedlinePlus

... Marks Sun-damaged Skin Tattoo Removal Varicose Veins Vitiligo Wrinkles Back Skin Treatments Back Ambulatory Phlebectomy Blepharoplasty ... Micropigmentation Back Migropigmentation for Burn Scars Migropigmentation for Vitiligo Back Microwave Thermolysis for Excessive Sweating Mohs Surgery ...

Wood lamp examination

MedlinePlus

... of the skin) Skin coloring changes, such as vitiligo Not all types of bacteria and fungi show ... confirm a fungal or bacterial infection or diagnose vitiligo. Your doctor may also be able to learn ...

Monitoring human melanocytic cell responses to piperine using multispectral imaging

NASA Astrophysics Data System (ADS)

Samatham, Ravikant; Phillips, Kevin G.; Sonka, Julia; Yelma, Aznegashe; Reddy, Neha; Vanka, Meenakshi; Thuillier, Philippe; Soumyanath, Amala; Jacques, Steven

2011-03-01

Vitiligo is a depigmentary disease characterized by melanocyte loss attributed most commonly to autoimmune mechanisms. Currently vitiligo has a high incidence (1% worldwide) but a poor set of treatment options. Piperine, a compound found in black pepper, is a potential treatment for the depigmentary skin disease vitiligo, due to its ability to stimulate mouse epidermal melanocyte proliferation in vitro and in vivo. The present study investigates the use of multispectral imaging and an image processing technique based on local contrast to quantify the stimulatory effects of piperine on human melanocyte proliferation in reconstructed epidermis. We demonstrate the ability of the imaging method to quantify increased pigmentation in response to piperine treatment. The quantization of melanocyte stimulation by the proposed imaging technique illustrates the potential use of this technology to quickly assess therapeutic responses of vitiligo tissue culture models to treatment non-invasively.

Uso de modelos mecânicos em curso informal de astronomia para deficientes visuais. Resgate de uma experiência

NASA Astrophysics Data System (ADS)

Tavares, E. T., Jr.; Klafke, J. C.

2003-08-01

O presente trabalho propõe-se a resgatar uma experiência que teve lugar no Planetário de São Paulo nos anos 60. Em 1962, o Sr. Acácio, então com 37 anos, deficiente visual desde os 27, passou a assistir às aulas ministradas pelo Prof. Aristóteles Orsini aos integrantes do corpo de servidores do Planetário. O Sr. Acácio era o único deficiente da turma e, embora possuísse conhecimentos básicos e relativamente avançados de matemática, enfrentava dificuldades na compreensão e acompanhamento da exposição, como também em estudos posteriores. Com o intuito de auxiliá-lo na superação desses problemas, o Prof. Orsini solicitou a construção de modelos mecânicos que, através do sentido do tato, permitissem o acompanhamento das aulas e a transposição do modelo para o "constructo" mental. Essa prática mostrou-se tão eficaz que facilitou sobejamente o aprendizado da matéria pelo sujeito. O Sr. Acácio passou a integrar o corpo de professores do Planetário/Escola Municipal de Astrofísica, tendo ficado responsável pelo curso de "Introdução à Astronomia" por vários anos. Além disso, a experiência foi tão bem sucedida que alguns dos modelos tiveram seus elementos constitutivos pintados diferencialmente para serem utilizados em cursos regulares do Planetário, tornando-se parte integrante do conjunto de recursos didáticos da instituição. É pensando nessa eficácia, tanto em seu objetivo original permitir o aprendizado de um deficiente visual quanto no subsidiário recurso didático sistemático da instituição que decidimos resgatar essa experiência. Estribados nela, acreditamos ser extremamente produtivo, em termos educacionais, o aperfeiçoamento dos modelos originais, agora resgatados e restaurados, e a criação de outros que pudessem ser utilizados no ensino dessa ciência a deficientes visuais.

Acerca del moho

EPA Pesticide Factsheets

El moho forma parte del medio ambiente natural. Afuera del hogar, el moho juega un papel en la naturaleza al desintegrar materias organicas tales como las hojas que se han caido o los arboles muertos. El moho puede crecer adentro del hogar cuando las espor

Produccion Gaseosa del Cometa Halley: Erupciones Y Fotodisociacion del Radical OH

NASA Astrophysics Data System (ADS)

Silva, A. M.; Mirabel, I. F.

1990-11-01

RESUMEN:En este trabajo informamos la detecci6n de 20 erupciones en la li'nea de =18cm (1667MHz) del radical OH en el Cometa Halley.Las observaciones incluyen todos los monitoreos existentes y se extienden desde 120 dias antes del perihelio hasta 90 dias despues.Se detectan bruscos crecimientos en el flujo medido,hasta un factor 1O,seguidos por decaimientos lentos asociados con la fotodisociaci6n del OH. Se obtuvieron valores para el tiempo de vida fotoquimico del OH y del H2O basandose en el modelo desarrollado previamente por Silva(1988). Esos tiempos de vida estan de acuerdo con predicciones teoricas y con las observaciones en el Ultravioleta, y los resultados, los que son fuertemente dependientes de la velocidad heliocentrica del Coineta (variando hasta un factor 6), han sido calculados para varios rangos de velocidad entre +28 y -28 km/seg. Key wo'L :

Vitiligo

MedlinePlus

... 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 Open Source Data Public Data Listing NIH... ...

Vitiligo

MedlinePlus

... Us Media contacts Advertising contacts AAD logo Advertising, marketing and sponsorships Legal notice Copyright © 2018 American Academy ... prohibited without prior written permission. AAD logo Advertising, marketing and sponsorships Legal notice Copyright © 2017 American Academy ...

Vitiligo

MedlinePlus

... Board Certification Grand Rounds Resident Awards AOCD Residency Leadership Award A.P. Ulbrich Resident Research Award Daniel Koprince Award Resident Research Paper Award Sponsors Corporate Members Exhibitors Information for Corporate ...

Vitiligo

MedlinePlus

... of Giving Governance By-Laws Committees Committee Service Conflict of Interest Policy Meeting Minutes Archive History Mission Statement Membership AOCD Membership Life Membership Membership Applications and Renewals Membership Benefits Fellows ...

Vitiligo

MedlinePlus

... eds. Treatment of Skin Disease: Comprehensive Therapeutic Strategies . 4th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 245. ... pigmentation. In: Patterson JW, ed. Weedon's Skin Pathology . 4th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2016:chap ...

Vitiligo

MedlinePlus

... required. Covermark and Dermablend are special drug store cosmetics that can be used to match most skin ... color, which can then be covered with the cosmetics. Sun-induced darkening of the surrounding normal skin ...

Vigilando la Calidad del Agua de los Grandes Rios de la Nacion: El Programa NASQAN del Rio Grande (Rio Bravo del Norte)

USGS Publications Warehouse

Lurry, Dee L.; Reutter, David C.; Wells, Frank C.; Rivera, M.C.; Munoz, A.

1998-01-01

La Oficina del Estudio Geologico de los Estados Unidos (U.S. Geological Survey, 0 USGS) ha monitoreado la calidad del agua de la cuenca del Rio Grande (Rio Bravo del Norte) desde 1995 como parte de la rediseiiada Red Nacional para Contabilizar la Calidad del Agua de los Rios (National Stream Quality Accounting Network, o NASOAN) (Hooper and others, 1997). EI programa NASOAN fue diseiiado para caracterizar las concentraciones y el transporte de sedimento y constituyentes quimicos seleccionados, encontrados en los grandes rios de los Estados Unidos - incluyendo el Misisipi, el Colorado y el Columbia, ademas del Rio Grande. En estas cuatro cuencas, el USGS opera actualmente (1998) una red de 40 puntos de muestreo pertenecientes a NASOAN, con un enfasis en cuantificar el flujo en masa (la cantidad de material que pasa por la estacion, expresado en toneladas por dial para cada constituyente. Aplicacando un enfoque consistente, basado en la cuantificacion de flujos en la cuenca del Rio Grande, el programa NASOAN esta generando la informacion necesaria para identificar fuentes regionales de diversos contaminantes, incluyendo sustancias qui micas agricolas y trazas elementos en la cuenca. EI efecto de las grandes reservas en el Rio Grande se puede observar segun los flujos de constituyentes discurren a 10 largo del rio. EI analisis de los flujos de constituyentes a escala de la cuenca proveera los medios para evaluar la influencia de la actividad humana sobre las condiciones de calidad del agua del Rio Grande.

Schmidt's syndrome: a rare cause of puberty menorrhagia.

PubMed

Sharma, J B; Tiwari, S; Gulati, N; Sharma, S

1990-12-01

Schmidt's syndrome, also known as polyglandular deficiency syndrome, is the presence of Addison's disease and hypothyrodism in a single patient. It is usually associated with other autoimmune disorders like vitiligo, diabetes mellitus, myasthenia gravis. A rare case of an 18-year-old girl having Schmidt's syndrome and vitiligo who presented with puberty menorrhagia is reported. A brief review of the literature is also given.

Radio-Observaciones del OH EN la Coma del Cometa Halley Desde EL Hemisferio Sur

NASA Astrophysics Data System (ADS)

Silva, A. M.; Bajaja, E.; Morras, R.; Cersosimo, J. C.; Martin, M. C.; Arnal, E. M.; Poppel, W. G. L.; Colomb, F. R.; Mazzaro, J.; Olalde, J. C.; Boriakoff, V.; Mirabel, I. F.

1987-05-01

Se utilizó una antena de 30 metros del Instituto Argentino de Radioastronomía para observaciones diarias Cf ebrero a abril de 1986) de la transición en 1667 MHz ( λ = 18 cm) del OH en la coma del cometa Halley. De las observaciones realizadas se concluye: 1) El número promedio de moléculas de OH en la coma durante 37 días de observación fue de (8.9±3.5)x1034 moléculas, lo que implica una tasa de producción promedio de OH de 1.8x1029 moléculas seg-1 y consecuentemente una pérdida de masa promedio de 17±6 toneladas seg-1 . Este valor está de acuerdo con las mediciones realizadas por las sondas Vega y Giotto. 2) El monitoreo desde el lAR revela la existencia de variaciones bruscas en los flujos de absorción del OH. Estas variaciones son consistentes con los modelos que representan la producción gaseosa a partir de ejecciones y/o desprendimientos discretos de materia congelada del núcleo. 3) Las variaciones en la densidad de flujo son consistentes con las estimaciones de los tiem- pos de vida medios del H2O y del OH en presencia del campo de radiación solar. 4) Se encuentra una correlación entre la intensidad del flujo absorbido y anisotropías en Ia dinamica de la coma.

Espectroscopia del Cometa Halley

NASA Astrophysics Data System (ADS)

Naranjo, O.; Fuenmayor, F.; Ferrin, L.; Bulka, P.; Mendoza, C.

1987-05-01

Se reportan observaciones espectroscópicas del cometa Halley. Los espectros fueron tomados usando el espectrógrafo del telescopio reflector de 1 metro del Observatorio Nacional de Venezuela. Se utilizó óptica azul, con una red de difracción de 600 lineas/min, obteniéndose una dispersión de 74.2 A/mm y una resolución de 2.5 A, en el rango espectral de 3500 a 6500 A. Seis placas fueron tomadas con emulsión IIa-O y dos con IIa-D. Los tiempos de exposición fueron entre 10 y 150 minutos. El cometa se encontraba entre 0.70 y 1.04 UA del Sol, y entre 1.28 y 0.73 UA de la Tierra. Las emisiones más prominentes en el espectro, son las del CN, C2, y C3. Otras emisiones detectadas corresponden a CH, NH2 y Na. Los espectros muestran un fuerte continuo, indicando un contenido significativo de polvo. Se detectó mayor intensidad del contínuo, en la dirección anti solar, lo cual es evidencia de la cola de polvo.

Hollow Threats: Why Coercive Diplomacy Fails

DTIC Science & Technology

2015-06-01

IDE from the Curso del Estado Mayor de las Fuerzas Armadas in Madrid, Spain. Maj Schore has a bachelor’s degree in Economics from the University...this element presupposes that the nature of a liberal democracy not only reduces its credibility to administer a severe level of hurt, but damages...of resistance increased Aidid’s ability to portray his forces as national liberators and augmented his support among the Somali people.40 This

Intertextual Sexual Politics: Illness and Desire in Enrique Gomez Carrillo's "Del amor", "del dolor y del vicio" and Aurora Caceres's "La rosa muerta"

ERIC Educational Resources Information Center

LaGreca, Nancy

2012-01-01

This study explores the intertextuality between Aurora Caceres's "La rosa muerta" (1914) and the novel "Del amor, del dolor y del vicio" (1898) by her ex-husband, Enrique Gomez Carrillo. Caceres strategically mentions Gomez Carrillo's novel in "La rosa muerta" to invite a reading of her work in dialogue with his. Both narratives follow the sexual…

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2010 CFR

2010-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Marina Del Rey, CA. 80.1118...

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2012 CFR

2012-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Marina Del Rey, CA. 80.1118...

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2013 CFR

2013-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Marina Del Rey, CA. 80.1118...

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2011 CFR

2011-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Marina Del Rey, CA. 80.1118...

33 CFR 80.1118 - Marina Del Rey, CA.

Code of Federal Regulations, 2014 CFR

2014-07-01

... NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Coast § 80.1118 Marina Del Rey, CA. (a) A line drawn from Marina Del Rey Breakwater South Light 1 to Marina Del Rey Light 4. (b) A line drawn from Marina Del Rey... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Marina Del Rey, CA. 80.1118...

Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort.

PubMed

Hwang, Shelley Ji Eun; Carlos, Giuliana; Wakade, Deepal; Byth, Karen; Kong, Benjamin Y; Chou, Shaun; Carlino, Matteo S; Kefford, Richard; Fernandez-Penas, Pablo

2016-03-01

Anti-programmed cell death (PD)-1 therapy is emerging as the backbone of new standard of care immunotherapy for metastatic melanoma. Immune-related cutaneous events are observed in these patients. We sought to describe cutaneous adverse events observed in patients with metastatic melanoma on anti-PD-1 therapy. We reviewed the clinical and histologic information of all patients treated with single-agent anti-PD-1 therapy for metastatic melanoma at Westmead Hospital, Sydney, Australia, from May 2012 to February 2015. Of the 82 patients included in the study, 34 had dermatology assessments. Forty (49%) developed a form of anti-PD-1-associated cutaneous adverse events. In all, 17% developed lichenoid reactions and eczema, and 15% developed vitiligo. An estimated 25% of patients were expected to develop their first lichenoid reactions within 8.3 months, and eczema and vitiligo within 10.3 months of therapy. These adverse events tend to appear together in patients on anti-PD-1 therapy. The study was from a single center and clinical information was reviewed retrospectively in patients not referred to dermatology. Anti-PD-1 therapy is associated with the development of immune-related cutaneous events. Lichenoid reactions, eczema, and vitiligo are the 3 most prevalent lesions observed in our population. There is a tendency for lichenoid reactions and eczema to occur with vitiligo. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Manual del McVCO 1999

USGS Publications Warehouse

McChesney, P.J.

1999-01-01

El McVCO es un generador de frecuencias basado en un microcontrolador que reemplaza al oscilador controlado por voltaje (VCO) utilizado en telemetría analógica de datos sísmicas. Acepta señales de baja potencia desde un sismómetro y produce una señal subportadora modulada en frecuencia adecuada para enlaces telefónicos o vía radio a un lugar remoto de recolección de datos. La frecuencia de la subportadora y la ganancia pueden ser seleccionadas mediante un interruptor. Tiene la opción de poder operar con dos canales para la observación con ganancia alta y baja. El McVCO fue diseñado con el propósito de mejorar la telemetría analógica de las señales dentro de la Pacific Northwest Seismograph Network (PNSN) (Red Sismográfica del Noroeste del Pacífico). Su desarrollo recibió el respaldo del Programa de Geofísica de la Universidad de Washington y del "Volcano Hazards and Earthquake Hazards programs of the United States Geological Survey (USGS) (Programa de Investigaciones de Riesgos Volcánicos y Programa de Investigaciones de Riesgos Sísmicos de los EEUU). Cientos de instrumentos se han construido e instalado. Además de utilizarlo el PNSN, el McVCO es usado por el Observatorio Vulcanológico de Alaska para monitorear los volcanes aleutianos y por el USGS Volcano Disaster Assistance Program (Programa de Ayuda en las Catástrofes Volcánicas del USGS) para responder a crisis volcánicas en otros países. Este manual cubre el funcionamiento del McVCO, es una referencia técnica para aquellos que necesitan saber con más detalle cómo funciona el McVCO, y cubre una serie de temas que requieren un trato explícito o que derivan del despliegue del instrumento.

Ácaros del mango

USDA-ARS?s Scientific Manuscript database

Los ácaros constituyen un grupo abundante y diverso que ocupa diferentes hábitats en árboles frutales y la estructura y disposición del follaje y ramas del mango, contribuyen significativamente a que se presente gran diversidad de ácaros benéficos y dañinos asociados a esta especie frutal. En Colomb...

Evaluation of Noise Effects in Auditory Function in Spanish Military Pilots

DTIC Science & Technology

2005-04-01

traumatismo sonoro crónico. Su incidencia en el medio aéreo. 131 Curso de Aptitud para el Ascenso a Comandante. Escuela Superior del E.A. Madrid 1991...FAYALA M.: Détèrorations audiométriques chez le pilote militaire en Tunisie. Méd. Aéro. Spat., Tome XXX, Nº 119 - 1991. [13] LORENTE J.: El...14] LORENTE J.M.: “Cambios auditivos en los pilotos de las Fuerzas Armadas. Revisión bibliográfica.” Revista Universitaria de Sanidad. Vol. 1, Núm. 1

Torres del Paine National Park

NASA Image and Video Library

2017-12-08

Grinding glaciers and granite peaks mingle in Chile’s Torres del Paine National Park. The Advanced Land Imager (ALI) on NASA’s Earth Observing-1 (EO-1) satellite captured this summertime image of the park on January 21, 2013. This image shows just a portion of the park, including Grey Glacier and the mountain range of Cordillera del Paine. The rivers of glacial ice in Torres del Paine National Park grind over bedrock, turning some of that rock to dust. Many of the glaciers terminate in freshwater lakes, which are rich with glacial flour that colors them brown to turquoise. Skinny rivers connect some of the lakes to each other (image upper and lower right). Cordillera del Paine rises between some of the wide glacial valleys. The compact mountain range is a combination of soaring peaks and small glaciers, most notably the Torres del Paine (Towers of Paine), three closely spaced peaks emblematic of the mountain range and the larger park. By human standards, the mountains of Cordillera del Paine are quite old. But compared to the Rocky Mountains (70 million years old), and the Appalachians (about 480 million years), the Cordillera del Paine are very young—only about 12 million years old. A study published in 2008 described how scientists used zircon crystals to estimate the age of Cordillera del Paine. The authors concluded that the mountain range was built in three pulses, creating a granite laccolith, or dome-shaped feature, more than 2,000 meters (7,000 feet) thick. NASA Earth Observatory image created by Jesse Allen and Robert Simmon, using Advanced Land Imager data from the NASA EO-1 team. Caption by Michon Scott. Instrument: EO-1 - ALI View more info: earthobservatory.nasa.gov/IOTD/view.php?id=80266 Credit: NASA Earth Observatory NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA�

Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.

PubMed

Donaldson, Scott H; Pilewski, Joseph M; Griese, Matthias; Cooke, Jon; Viswanathan, Lakshmi; Tullis, Elizabeth; Davies, Jane C; Lekstrom-Himes, Julie A; Wang, Linda T

2018-01-15

Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. To evaluate the safety and efficacy of tezacaftor monotherapy and of tezacaftor/ivacaftor combination therapy in subjects with cystic fibrosis homozygous for F508del or compound heterozygous for F508del and G551D. This was a randomized, placebo-controlled, double-blind, multicenter, phase 2 study (NCT01531673). Subjects homozygous for F508del received tezacaftor (10 to 150 mg) every day alone or in combination with ivacaftor (150 mg every 12 h) in a dose escalation phase, as well as in a dosage regimen testing phase. Subjects compound heterozygous for F508del and G551D, taking physician-prescribed ivacaftor, received tezacaftor (100 mg every day). Primary endpoints were safety through Day 56 and change in sweat chloride from baseline through Day 28. Secondary endpoints included change in percent predicted FEV 1 (ppFEV 1 ) from baseline through Day 28 and pharmacokinetics. The incidence of adverse events was similar across treatment arms. Tezacaftor (100 mg every day)/ivacaftor (150 mg every 12 h) resulted in a 6.04 mmol/L decrease in sweat chloride and 3.75 percentage point increase in ppFEV 1 in subjects homozygous for F508del, and a 7.02 mmol/L decrease in sweat chloride and 4.60 percentage point increase in ppFEV 1 in subjects compound heterozygous for F508del and G551D from baseline through Day 28 (P < 0.05 for all). These results support continued clinical development of tezacaftor (100 mg every day) in combination with ivacaftor (150 mg every 12 h) in subjects with cystic fibrosis. Clinical trial registered with www.clinicaltrials.gov (NCT01531673).

Kurt Gödels Brünner Verwandte

NASA Astrophysics Data System (ADS)

Müller, Dora

2007-11-01

The author of this memoir Dora Müller (born 1920) belongs - as well as Kurt Gödel-to the German minority playing an important role in the past life of Brno. The marriage of his son included her among the Gödels collaterals. She was chemist, but also pianist, historician, participant of antinacist movement and iniciator of Czech-German understanding after war. Following her personal experiences, remembrances of Gödels relatives and documental materials, she evokes the atmosphere of broader family milieu of Kurt Gödel.

The novel c.247_249delTTC (p.F83del) GJB2 mutation in a family with prelingual sensorineural deafness.

PubMed

Petersen, Michael B; Grigoriadou, Maria; Koutroumpe, Maria; Kokotas, Haris

2012-07-01

Non-syndromic hearing loss is one of the most common hereditary determined diseases in human, and the disease is a genetically heterogeneous disorder. Mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of non-syndromic recessive hearing impairment in many countries and are largely dependent on ethnic groups. Due to the high frequency of the c.35delG GJB2 mutation in the Greek population, we have previously suggested that Greek patients with sensorineural, non-syndromic deafness should be tested for the c.35delG mutation and the coding region of the GJB2 gene should be sequenced in c.35delG heterozygotes. Here we present on the clinical and molecular genetic evaluation of a family suffering from prelingual, sensorineural, non-syndromic deafness. A novel c.247_249delTTC (p.F83del) GJB2 mutation was detected in compound heterozygosity with the c.35delG GJB2 mutation in the proband and was later confirmed in the father, while the mother was homozygous for the c.35delG GJB2 mutation. We conclude that compound heterozygosity of the novel c.247_249delTTC (p.F83del) and the c.35delG mutations in the GJB2 gene was the cause of deafness in the proband and his father. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Estudio del CH interestelar

NASA Astrophysics Data System (ADS)

Olano, C.; Lemarchand, G.; Sanz, A. J.; Bava, J. A.

El objetivo principal de este proyecto consiste en el estudio de la distribución y abundancia del CH en nubes interestelares a través de la observación de las líneas hiperfinas del CH en 3,3 GHz. El CH es una molécula de amplia distribución en el espacio interestelar y una de las pocas especies que han sido observadas tanto con técnicas de radio como ópticas. Desde el punto de vista tecnológico se ha desarrollado un cabezal de receptor que permitirá la realización de observaciones polarimétricas en la frecuencia de 3,3 GHz, con una temperatura del sistema de 60 K y un ancho de banda de 140 MHz, y que será instalado en el foco primario de la antena parabólica del IAR. El cabezal del receptor es capaz de detectar señales polarizadas, separando las componentes de polarización circular derecha e izquierda. Para tal fin el cabezal consta de dos ramas receptoras que amplificarán la señal y la trasladarán a una frecuencia más baja (frecuencia intermedia), permitiendo de esa forma un mejor transporte de la señal a la sala de control para su posterior procesamiento. El receptor además de tener características polarimétricas, podrá ser usado en el continuo y en la línea, utilizando las ventajas observacionales y de procesamiento de señal que actualmente posee el IAR.

Características del viento en estrellas Be derivadas del perfil Hα

NASA Astrophysics Data System (ADS)

Rohrmann, R.; Cidale, L.

El estudio teórico de perfiles Hα y su variabilidad en estrellas Be ha sido frecuentemente desarrollado en base a modelos de envolturas circunestelares inhomogéneas, donde la geometría del material es responsable de la forma del perfil dependiendo de la dirección de observación. Nosotros damos una interpretación alternativa y proponemos que la mayoría de las propiedades de esta línea tienen origen en la base de un viento estelar y de una estructura cromosférica anexa a la fotósfera. Encontramos que típicos perfiles Hα en Be, como son los llamados pole-on y winebottle, pueden ser reproducidos cualitativamente sin recurrir a la existencia de una envoltura asimétrica. Analizamos como la línea Hα permite identificar la posible estructura del viento en la región donde éste se inicia.

Tierra del Fuego, Argentina, South America

NASA Technical Reports Server (NTRS)

1991-01-01

The Mitre Peninsula is the easternmost tip of Tierra del Fuego, Argentina, (54.5S, 65.5W). Early winter snow can be seen on this south tip of the Andes Mountains. These same mountains continue underwater to Antarctica. The Strait of Magellan, separating the South American mainland from Tierra del Fuego is off the scene to the north and west, but the Strait of LeMaire, separating Tierra del Fuego from the Isla de los Estados can be seen.

Unidades del paisaje de Puerto Rico: la influencia del clima, el substrato y la topografia

Treesearch

William Gould; Michael E. Jimenez; Gary Potts; Maya Quinones; Sebastian Martinuzzi

2008-01-01

El mapa de unidades del paisaje de Puerto Rico representa variaciones climaticas, topograficas y del substrato mediante la integracion de seis zonas climaticas (Ewel y Whitmore, 1973), seis substratos (Bawiec, 2001; USGS, 2005), cinco posiciones topograficas, o topoformas (Martinuzzi et al. 2007), y cuerpos de agua (USGS 2005). Los substratos representan el conjunto...

Analisis del contenido curricular de los Documentos Normativos del Programa de Ciencias en el area de biologia para la escuela superior del sistema de educacion publica de Puerto Rico: 1993-2012

NASA Astrophysics Data System (ADS)

Davila Montanez, Melissa

Esta investigacion de naturaleza cualitativa se ocupo de realizar un analisis de contenido documental de los Documentos Normativos del Programa de Ciencias en el area de biologia de la escuela superior del sistema de educacion publica de Puerto Rico del periodo 1993-2012. Los documentos analizados fueron: Guia Curricular, 1995; Marco Curricular, 2003; Estandares de Excelencia, 1996, 2000 y Estandares de Contenido y Expectativas de Grado, 2007. Se indago si hubo cambios en significados en los Componentes Estructurales: Naturaleza de la ciencia, Paradigmas para la ensenanza de la ciencia, Funcion del curriculo formal, Mision de la ensenanza de la ciencia; Contenidos, destrezas y competencias, Estrategias de ensenanza y Evaluacion/Assessment del aprendizaje. El analisis sugiere que no hubo cambios sustanciales en los significados de los Componentes Estructurales. Los documentos estudiados muestran mayormente caracteristicas similares, aunque los documentos mas recientes eran mas descriptivos, explicativos y especificos.

Estudio teórico del CO2. Orbitales de valencia y del ``core''

NASA Astrophysics Data System (ADS)

Olalla Gutiérrez, E.

Hemos calculado las intensidades de las transiciones E1 a los miembros de las series de Rydberg con origen en los orbitales ``no enlazantes'' del dióxido de carbono, especie de conocida relevancia atmosférica. Se han computado, asimismo, los continuos de fotoionización correspondientes a los distintos canales de ionización, representándolos como densidad espectral de fuerza de oscilador frente a la energía del fotón incidente; mostramos los resultados df/dE para la fotoionización total de esta especie en el intervalo 15-60 eV. Todos los cálculos se han llevado a cabo mediante la formulación Molecular del Método de los Orbitales de Defecto Cuántico, MQDO [1,2]. La calidad de los resultados que presentamos se ha evaluado en base a la comparación con los datos, tanto experimentales como teóricos, disponibles en la bibliografía. El acuerdo encontrado es altamente satisfactorio

Visiting the Gödel universe.

PubMed

Grave, Frank; Buser, Michael

2008-01-01

Visualization of general relativity illustrates aspects of Einstein's insights into the curved nature of space and time to the expert as well as the layperson. One of the most interesting models which came up with Einstein's theory was developed by Kurt Gödel in 1949. The Gödel universe is a valid solution of Einstein's field equations, making it a possible physical description of our universe. It offers remarkable features like the existence of an optical horizon beyond which time travel is possible. Although we know that our universe is not a Gödel universe, it is interesting to visualize physical aspects of a world model resulting from a theory which is highly confirmed in scientific history. Standard techniques to adopt an egocentric point of view in a relativistic world model have shortcomings with respect to the time needed to render an image as well as difficulties in applying a direct illumination model. In this paper we want to face both issues to reduce the gap between common visualization standards and relativistic visualization. We will introduce two techniques to speed up recalculation of images by means of preprocessing and lookup tables and to increase image quality through a special optimization applicable to the Gödel universe. The first technique allows the physicist to understand the different effects of general relativity faster and better by generating images from existing datasets interactively. By using the intrinsic symmetries of Gödel's spacetime which are expressed by the Killing vector field, we are able to reduce the necessary calculations to simple cases using the second technique. This even makes it feasible to account for a direct illumination model during the rendering process. Although the presented methods are applied to Gödel's universe, they can also be extended to other manifolds, for example light propagation in moving dielectric media. Therefore, other areas of research can benefit from these generic improvements.

Vitiligo (For Parents)

MedlinePlus

... Dealing With the Emotional Impact Print Whether fair, dark, or any shade in between, most kids have ... amount), but rather by how active they are. Dark-skinned people have cells that naturally produce a ...

Essays on Eclipses, Transits and Occultations as Teaching Tools in the Introductory Astronomy College Course. (Spanish Title: Ensayos sobre Eclipses, Tránsitos y Ocultaciones Como Herramientas de Enseñanza en el Curso Universitario Introductorio a la Astronomía.) Ensaios sobre Eclipses, Trânsitos e Ocultações Como Ferramentas de Ensino em um Curso Universitário Introdutório de Astromomia

NASA Astrophysics Data System (ADS)

Dcruz, Noella L.

2014-07-01

We occasionally include projects in our learner-centered introductory astronomy college course to enable non-science major students explore some astronomical concepts in more detail than otherwise. Such projects also highlight ongoing or upcoming astronomical events. We hope that students will feel more interested in astronomy through projects tied to astronomical events. In Spring 2012, we offered short essays focused on eclipses, transits and occultations to promote the rare transit of Venus that occurred on June 5th, 2012. We asked students to write two short essays from three that were offered. The essays contained descriptive and conceptual parts. They were meant to serve as teaching tools. 62% of 106 essays from 55 students earned A, B or C grades. 21% of 47 feedback survey respondents felt the essays increased their interest in astronomy. 49% of respondents felt that the essays were not educationally beneficial and should not be offered again. The most common written response to our survey indicated that students need more guidance and better preparation in writing successful essays. Since students found the conceptual parts of the essays difficult, in the future we will provide relevant activities prior to essay deadlines to help students create successful essays. Ocasionalmente, incluimos proyectos en nuestro curso de introducción a la astronomía universitario centrado en el alumno para permitir que los estudiantes de carreras no científicas exploren algunos conceptos astronómicos en más detalle que lo habitual. Estos proyectos también ponen en relevancia eventos astronómicos en curso o futuros. Esperamos que los estudiantes se sientan más interesados en la astronomía a través de proyectos vinculados a eventos astronómicos. En el período de primavera de 2012 (EUA), propusimos breves ensayos centrados en los eclipses, tránsitos y ocultaciones para promover el raro tránsito de Venus que se produjo el 5 de junio de 2012. Le pedimos a los

Extensión del Formalismo de Orbitales de Defecto Cuántico al tratamiento del efecto Stark (SQDO).

NASA Astrophysics Data System (ADS)

Menéndez, J. M.; Martín, I.; Velasco, A. M.

El estudio experimental de las interacciones de átomos Rydberg altamente excitados con campos eléctricos ha experimentado un creciente interés durante las dos últimas décadas debido, en gran medida, al desarrollo de nuevas técnicas para crear y estudiar átomos Rydberg en el laboratorio. Acompañando a estas nuevas técnicas experimentales, es necesario el desarrollo de modelos teóricos que nos permitan contrastar sus medidas y conocer mejor los fundamentos de los mismos. Desde el punto de vista teórico el conocimiento del desdoblamiento de los niveles energéticos de un átomo en función de la magnitud del campo eléctrico aplicado (lo que se conoce como mapa Stark) es el mejor punto de partida para la descripción del sistema y un prerrequisito fundamental para el cálculo de distintas propiedades atómicas en presencia del campo eléctrico tales como intensidades de transición, umbrales de ionización de campo eléctrico, tiempos de vida, posición y anchura de cruces evitados, etc. En este trabajo presentamos la adaptación del método de orbitales de defecto cuántico [1,2,3] al tratamiento del efecto Stark (SQDO) [4] y su aplicación al cálculo de los desdoblamientos energéticos y fuerzas de oscilador de estados Rydberg en los átomos de Li, Na y K. El propósito de este estudio es, por un lado, desarrollar métodos fiables para la determinación de propiedades atómicas en presencia de campos eléctricos y, por otro, mostrar la fiabilidad de las funciones de onda QDO en la descripción del efecto Stark en sistemas atómicos.

Gödel universes in string theory

NASA Astrophysics Data System (ADS)

Barrow, John D.; Dabrowski, Mariusz P.

1998-11-01

We show that homogeneous Gödel spacetimes need not contain closed timelike curves in low-energy-effective string theories. We find exact solutions for the Gödel metric in string theory for the full O(α') action including both dilaton and axion fields. The results are valid for bosonic, heterotic and super-strings. To first order in the inverse string tension α', these solutions display a simple relation between the angular velocity of the Gödel universe, Ω, and the inverse string tension of the form α'=1/Ω2 in the absence of the axion field. The generalization of this relationship is also found when the axion field is present.

Perfil dos Professores de Ciências Naturais do Recôncavo da Bahia - Alunos da Disciplina Terra e Universo no Curso de Ciências Naturais do Parfor

NASA Astrophysics Data System (ADS)

Lima, S. R.; Cerqueira Júnior, W.; Dutra, G.

2011-12-01

Este trabalho foi desenvolvido pelo projeto Astronomia no Recôncavo da Bahia, no Centro de Formação de Professores da Universidade Federal do Recôncavo da Bahia. Traçamos o perfil de um grupo de professores que lecionam conteúdos de Ciências Naturais no recôncavo, alunos do curso de Licenciatura em Ciências Naturais, oferecido dentro do Plano Nacional de Formação de Professores da Educação Básica. Nosso objetivo era avaliar se eles estão preparados para trabalhar conteúdos de Astronomia e identificar suas dificuldades. Os resultados serviram para orientar o professor da disciplina “Terra e Universo”, oferecida no segundo semestre de 2010. Durante a primeira aula da disciplina Terra e Universo, os alunos responderam a um questionário contendo questões abertas e fechadas, divididas em duas partes. A primeira procurando caracterizar profissionalmente os alunos enquanto professores da rede pública da região do Recôncavo Sul da Bahia e uma segunda parte procurando identificar conhecimentos básicos em Astronomia. Os resultados indicam uma predominância de professores do sexo feminino, com idade superior aos 40 anos, pardos e sem formação específica para o ensino de ciências. A maioria leciona há mais de 15 anos para turmas do 1º ao 5º ano, alguns lecionam para turmas de 6º ao 9º ano. Quase todos nunca participaram de um curso de formação continuada em Astronomia. Além disso, não estão habituados a ler revistas especializadas e nem livros com esta temática. Os que procuram ensinar temas voltados para a Astronomia têm, no livro didático, a maior fonte de informação sobre o assunto. As respostas também indicam uma deficiência em conteúdos básicos como a compreensão da esfericidade da Terra, noções de verticalidade e gravidade, incapacidade de identificar a Terra como um planeta, no Sistema Solar, em uma galáxia, no Universo. Estes resultados ressaltam a importância de disciplinas de Astronomia básica na formação dos

Calidad de Imagen del Telescopio UNAM212

NASA Astrophysics Data System (ADS)

Cobos, F. J.; Teiada de Vargas, C.

1987-05-01

El telescopio UNAM2l2, del Observatorio Astronómico Nacional, situado en la Sierra de San Pedro Mártir (Baja California, México), cumplira en un futuro muy cercano siete años de uso para fines de investigación astronómica. Aunque en este tiempo no se ha efectuado un estudio sistemático acerca de su comportamiento óptico y de los factores que influyen en la calidad de las imágenes, se han realizado pruebas diversas, estudios parciales y reuniones especificas, cuyos resultados no siempre se han difundido ampliamente y generalmente no se han presentado por escrito. Es por ello que hemos creido necesario intentar una recopilación de la información existente para poder con ella establecer un diagnóstjco que, aunque no sea definitivo, sirva de base para futuros trabajos tendientes a optimizar el comportamiento óptico del telescopio. Es evidente que un buen número de las conclusiones que se presentan son resultado del trabajo de muchas personas ó de esfuerzos colectivos. Asimismo, hemos tratado de localizar información bibliográfica que pueda ser de utilidad. Nuestro objetivo primordial ha consistido en centrarnos en la óptica del telescopio y su calidad, pero también se han considerado otros aspectos que puedan afectar las imágenes obtenidas tales como: celda del primario, `seeing' local y externo, flexiones posibles en la estructura mecánica del telescopio, etc.

Conservacion de truchas del Pacifico

Treesearch

Brooke E. Penaluna

2016-01-01

La historia de las truchas del Pacífico, pertenecientes al género Oncorhynchus, es una historia muy interesante que se basa en la persistencia y diversificación de sus especies debido, en gran parte, al dinamismo propio que existe en su medio ambiente. Desde el oeste de Norteamérica, extendiéndose hasta el este de Asia, las truchas del Pacífico han experimentado la...

Willingness to pay and quality of life in patients with rosacea.

PubMed

Beikert, F C; Langenbruch, A K; Radtke, M A; Augustin, M

2013-06-01

Rosacea is a chronic inflammatory dermatosis affecting >2% of the population. Willingness to pay (WTP) is a well established method which reflects the individual burden of disease. Evaluation of WTP and quality of life (QoL) in patients with rosacea. Nationwide postal survey on adult patients with rosacea affiliated with the German rosacea patient advocacy group. WTP was evaluated by three standardized items and compared to historical data on vitiligo (n = 1023). QoL was assessed using the Dermatology Life Quality Index (DLQI). Data from n = 475 rosacea patients (79.9% women, mean age 56.3, range 26-90) were analysed. On average, patients were willing to pay € 2880 (median € 500) for complete healing compared with € 7360 (median € 3000) in vitiligo. Relative WTP was higher in women; the highest sums were registered for the age group 21-30 years. The extent of facial involvement predicted a higher relative WTP, whereas WTP decreased with the duration of symptoms and age. Mean DLQI total score was 4.3 compared to 7.0 in vitiligo. In rosacea, the highest values were observed in patients <30 years. Severe QoL reductions (DLQI>10) were less frequent (11%) than in vitiligo (24.6%). The correlation between WTP and DLQI was significant (e.g. r = 0.249, P = 0.000 for relative WTP). Rosacea patients show a moderate WTP and average QoL reduction is mild. WTP proved to be a valid tool to assess patients' burden of disease. Patient education and the development of effective treatment options might still improve patients' satisfaction. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Morphology, geology and geochemistry of the "Salar del Gran Bajo del Gualicho" (Rio Negro, Argentina)

USGS Publications Warehouse

Angelucci, A.; Barbieri, M.; Brodtkorb, A.; Ciccacci, S.; Civitelli, G.; De Barrio, R.; Di, Filippo M.; Fredi, P.; Friedman, I.; Lombardi, S.; Schalamuk, A.I.; Toro, B.

1996-01-01

A multidisciplinary study of the Gran Bajo del Gualicho area (Rio Negro - Argentina) was carried out; the aim was to delineate its geological and geomorphological evolution and to estabilish the genesis of salts filling the depression. Climatic conditions were analized first to individuate their role in the present morphogenetic processes; moreover the main morphological features of present landscape were examined as well as the stratigraphy of the outcropping formations, and of the Gran Bajo del Gualicho Formation in particular. Finally, a possible geomorphological evolution of the studied area was traced. Geophysical analyses allowed to estabilish that the paleosurface shaped on the crystalline basement is strongly uneven and shows evidence of the strong tectonic phases it underwent. The result of isotope analyses confirmed that the salt deposits on the Gran Bajo del Gualicho bottom were produced by fresh water evaporation, while strontium isotope ratio suggested that such waters were responsible for solubilization of more ancient evaporitic deposits.

Nevado del Huila, Columbia

NASA Technical Reports Server (NTRS)

2007-01-01

Nevado del Huila Volcano in Colombia is actually a volcanic chain running north to south, capped by a glacier. With peaks ranging in height from 2,600 to 5,780 meters (8,530 to 18,960 feet), Nevado del Huila is a stratovolcano composed of alternating layers of hardened lava, solidified ash, and volcanic rocks. Its first recorded eruption occurred in the mid-sixteenth century. The long-dormant volcano erupted again in mid-April 2007. A few months before the eruption, the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite captured this image of Nevado del Huila, on February 23, 2007. In this image, the bright white area just east of the central summit is ice. Immediately west of the summit are bare rocks, appearing as blue-gray. West of those rocks, white reappears, but this patch of white results from clouds hovering in the nearby valley. In the east, the colors turn to brown (indicating bare rock) and bright green (indicating vegetation). ASTER photographed Nevado del Huila near the end of a long phase of quietude. On April 17, 2007, local authorities recorded seismic activity associated with rock fracturing on the volcano's central summit, according to the ReliefWeb Website. Activity intensified the following day with an eruption and mudflows, forcing thousands of nearby residents to evacuate. As the Associated Press reported, the eruption caused avalanches and floods that wiped away both houses and bridges. It marked the volcano's first recorded eruption since the Spanish colonized the area five centuries earlier. NASA image created by Jesse Allen, using data provided courtesy of the NASA/GSFC/MITI/ERSDAC/JAROS, and U.S./Japan ASTER Science Team.

Calidad del aire interior en las escuelas

EPA Pesticide Factsheets

EPA ha desarrollado el Programa de Herramientas de Calidad del Aire Interior para las Escuelas para reducir la exposición a los contaminantes ambientales en las mismas a través de la adopción voluntaria de las prácticas para manejar la calidad del aire int

May Gödel's Ideas Be Addressed Philosophically?

NASA Astrophysics Data System (ADS)

Dokulil, Miloš

2007-11-01

Gödel emphasised philosophy as an important tool in science. Much less is known about his religious background. We should bear in mind that our evaluational perspective differs very much from the one in which Gödel lived. He was personally sure that there must be another existence after death-an afterlife (''of unlimited life span''). As a ''Baptized Lutheran'' he did not include ''Trinity'' in his creed. He was also certain that mind is separate from matter. This text tries to include Libet's ''readiness potential'' into the debate concerning the specificity of the mind. Neither Gödel's identification of materialism with mechanism nor his vision of the ''spirit'' are a viable solution of the problem.

Autoimmune diseases in a Nigerian woman--a case report.

PubMed

Talabi, O A; Owolabi, M O; Osotimehin, B O

2003-12-01

Autoimmune diseases (AD) are conditions in which there is the development of antibodies against self cells/ organs. AD could either be organ-specific or non-organ specific (systemic) in clinical presentation. Commonly reported ADs includes: Myasthenia gravis, Hashimoto thyroiditis, Guillian-Barre syndrome, vitiligo, type 1 diabetes mellitus, Graves diseases, Goodpastures syndrome, pemphigus, rheumatoid arthritis, systemic lupus erythematosis, Addisons disease, multiple sclerosis, pernicious anaemia, autoimmune haemolytic anaemia, chronic active hepatitis, idiopathic thrombocytopenic purpura. There is paucity of locally documented information on the occurrence of AD in same patient in our environment. We therefore report the case of a 66 year old woman who presented at the University College Hospital (UCH), Ibadan, with a spectrum of the AD, Vitiligo, rheumatoid arthritis, myasthenia gravis, impaired glucose tolerance.

"Curso de Vulcanología General": Web-education efforts on volcanic hazards for the Latin American region from Mexico.

NASA Astrophysics Data System (ADS)

Delgado, Hugo

2016-04-01

Education of volcanic hazards is a never-ending task in countries where volcanoes erupt very frequently as they do in the Latin American region (LAR). Eleven countries in the LAR have active volcanoes within their territories and some volcanoes are located in between countries so the volcanic hazards associated to the eruption of those volcanoes affect more than one country. Besides, countries without volcanoes within their territory (i. e. Belize, Honduras or Brazil) can be impacted as well. Personnel working at several volcano observatories in the LAR need training in Volcanology and, more importantly, in Volcanic Hazards. Unfortunately, Volcanology is a discipline that is not taught at universities of some countries. Even worse, Earth Sciences are not even taught at high education centers in some countries of the LAR. Thus, there is an important need for the acquisition of volcanological knowledge by the personnel working at volcano observatories but there are no possibilities for them to study at their countries or they are impended for travel abroad for training. The international course: "Curso de Vulcanología General" taught from Mexico City at the Universidad Nacional Autónoma de México (UNAM) has been successfully implemented and has been active over the last five years. Nearly 700 students have participated in this course although only ~150 have been awarded the certificate UNAM grants to the students who have concluded the course successfully. This course has been sponsored by UNAM, ALVO (Latin American Volcanological Association) and IAVCEI (International Association of Volcanology and Chemistry of the Earth's Interior). More than 50 lecturers from LAR, Europe and US have been involved in these courses. Here, Reflections on the course, the opportunities sparkled, the educational tools, benefits, statistics and virtues of the course are presented.

Efecto del Programa de Entrenamiento “Manejo del Dolor” en la Documentación de Enfermería en el Expediente Electrónico

PubMed Central

Monsiváis, María Guadalupe Moreno; Guzmán, Ma. Guadalupe Interial; Flores, Paz Francisco Sauceda; Arreola, Leticia Vázquez

2012-01-01

Resumen En el presente trabajo se muestra la importancia de entrenar al personal de enfermería para mejorar la documentación en el expediente electrónico. Se eligió el manejo del dolor por ser un área prioritaria; una alta proporción de pacientes en período post operatorio cursa con dolor, por lo tanto, la documentación debe ser útil para la toma de decisiones clínicas. Se implementó un programa de entrenamiento denominado “Manejo del Dolor” dirigido al personal de enfermería. Se utilizó la tecnología de la información como herramienta para fortalecer el conocimiento con base en la revisión sistemática de la literatura; el personal de enfermería participante seleccionó la mejor evidencia; posteriormente se trabajó en la transferencia de este conocimiento a la práctica a través del diseño de un protocolo para el manejo del dolor. Se concluye que el conocimiento del manejo del dolor es fundamental para que enfermería documente con mayor precisión sus intervenciones. PMID:24199106

EL PROGRAMA CITI: UNA ALTERNATIVA PARA LA CAPACITACIÓN EN ÉTICA DE LA INVESTIGACIÓN EN AMÉRICA LATINA

PubMed Central

Litewka, Sergio; Goodman, Kenneth; Braunschweiger, y Paul

2011-01-01

El Programa CITI (Collaborative Institutional Training Initiative) es un curso basado en Internet y desarrollado por voluntarios, que brinda material educacional sobre protección de sujetos humanos en investigaciones biomédicas y de conducta, buenas prácticas clínicas, conducta responsable de la investigación y trato humanitario a animales de laboratorio. Es un esfuerzo conjunto del Fred Hutchinson Cancer Research Center y la Universidad de Miami. Con la colaboración de expertos locales, gran parte del contenido se ha adaptado para América Latina, se ha traducido al español y portugués y se han establecido acuerdos de colaboración con instituciones especializadas en bioética en Chile, Brasil, Costa Rica y Perú. Los autores presentan una metodología accesible para la capacitación en ética de la investigación y una justificación de su uso y difusión en América Latina PMID:21687817

PubMed

Litewka, Sergio; Goodman, Kenneth; Braunschweiger, Y Paul

2008-01-01

El Programa CITI (Collaborative Institutional Training Initiative) es un curso basado en Internet y desarrollado por voluntarios, que brinda material educacional sobre protección de sujetos humanos en investigaciones biomédicas y de conducta, buenas prácticas clínicas, conducta responsable de la investigación y trato humanitario a animales de laboratorio. Es un esfuerzo conjunto del Fred Hutchinson Cancer Research Center y la Universidad de Miami.Con la colaboración de expertos locales, gran parte del contenido se ha adaptado para América Latina, se ha traducido al español y portugués y se han establecido acuerdos de colaboración con instituciones especializadas en bioética en Chile, Brasil, Costa Rica y Perú. Los autores presentan una metodología accesible para la capacitación en ética de la investigación y una justificación de su uso y difusión en América Latina.

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Indian River Bay, Del. 110.65 Section 110.65 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing...

El Atlas del Bosque Nacional El Yunque

Treesearch

Maya Quiñones; Isabel K. Parés-Ramos; William A. Gould; Grizelle Gonzalez; Kathleen McGinley; Pedro. Ríos

2018-01-01

Esta publicación es un esfuerzo colaborativo entre el Instituto Internacional de Dasonomía Tropical y el Bosque Nacional El Yunque para proveer mapas y análisis de información espacial actualizados sobre una importante reserva natural en Puerto Rico y el único bosque tropical dentro del Sistema de Bosques Nacionales de los Estados Unidos. El Atlas del Bosque Nacional...

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Indian River Bay, Del. 110.65... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing... State highway bridge across Indian River Inlet; thence 174°, 600 feet; thence 264°, 800 feet; thence 354...

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Indian River Bay, Del. 110.65... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing... State highway bridge across Indian River Inlet; thence 174°, 600 feet; thence 264°, 800 feet; thence 354...

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Indian River Bay, Del. 110.65... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing... State highway bridge across Indian River Inlet; thence 174°, 600 feet; thence 264°, 800 feet; thence 354...

33 CFR 110.65 - Indian River Bay, Del.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Indian River Bay, Del. 110.65... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.65 Indian River Bay, Del. Beginning at a point bearing... State highway bridge across Indian River Inlet; thence 174°, 600 feet; thence 264°, 800 feet; thence 354...

The construction and validation of an instrument for the assessment of graduates of undergraduate nursing courses.

PubMed

Vieira, Maria Aparecida; Ohara, Conceição Vieira da Silva; Domenico, Edvane Birelo Lopes de

2016-06-14

especialistas enfermeiros, representantes de todas as regiões do país, com experiência em docência e pesquisa. A primeira rodada Delphi gerou alterações no primeiro instrumento, que foi reestruturado e submetido a nova rodada, com taxa de resposta de 94,44%. Na segunda rodada, validou-se o instrumento com alfa de Cronbach de 0,75. o instrumento final possui três dimensões relacionadas à caracterização do egresso, inserção no mercado de trabalho e avaliação do processo de formação profissional. Esse instrumento pode ser utilizado em território nacional por basear-se nas diretrizes curriculares e contribuir com o processo de regulação da qualidade dos cursos de graduação em enfermagem. construir un instrumento para evaluación de egresados de cursos de graduación en enfermería y validar ese instrumento a través del consenso de especialistas. estudo metodológico. Para la elaboración del instrumento, se realizó análisis documental y revisión de literatura. La validación se realizó por Conferencia Delphi, entre septiembre de 2012 y septiembre de 2013, de la cual participaron 36 especialistas de la Enfermería brasileña. Para el análisis de confiabilidad, se calculó el coeficiente alfa de Cronbach, la correlación ítem/total y el coeficiente de correlación de Pearson. el instrumento fue construido con la participación de especialistas enfermeros, representantes de todas las regiones del país, con experiencia en docencia e investigación. La primera rodada Delphi generó alteraciones en el primer instrumento, el que fue reestructurado y sometido a una nueva rodada, con tasa de respuesta de 94,44%. En la segunda rodada, se validó el instrumento con alfa de Cronbach de 0,75. el instrumento final posee tres dimensiones: caracterización del egresado, introducción en el mercado de trabajo y evaluación del proceso de formación profesional. El instrumento podrá ser utilizado en el territorio nacional por basarse en las directrices curriculares y

Genetics Home Reference: vitiligo

MedlinePlus

... PubMed or Free article on PubMed Central Smith AG, Sturm RA. Multiple genes and locus interactions in ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer.

PubMed

Lee, Soo Jung; Lee, Jeeyeon; Kim, Wan Wook; Jung, Jin Hyang; Park, Ho Yong; Park, Ji-Young; Chae, Yee Soo

2018-01-01

A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p < 0.036). Furthermore, a correlation was found between Del-1 expression and an aggressive histological grade, nuclear mitosis, and polymorphism, suggesting a possible role in tumor progression. In the survival analysis, a worse distant disease-free survival trend was noted for the group overexpressing Del-1. While all the investigated breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients. © 2018 S. Karger AG, Basel.

Forensic applicability of multi-allelic InDels with mononucleotide homopolymer structures.

PubMed

Zhang, Shu; Zhu, Qiang; Chen, Xiaogang; Zhao, Yuancun; Zhao, Xiaohong; Yang, Yiwen; Gao, Zehua; Fang, Ting; Wang, Yufang; Zhang, Ji

2018-04-27

Insertion/deletion polymorphisms (InDels), which possess the characteristics of low mutation rates and a short amplicon size, have been regarded as promising markers for forensic DNA analysis. InDels can be classified as bi-allelic or multi-allelic, depending on the number of alleles. Many studies have explored the use of bi-allelic InDels in forensic applications, such as individual identification and ancestry inference. However, multi-allelic InDels have received relatively little attention. In this study, InDels with 2-6 alleles and a minor allele frequency ≥0.01, in Chinese Southern Han (CHS), were retrieved from the 1000 Genomes Project Phase III. Based on the structural analysis of all retrieved InDels, 17 multi-allelic markers with mononucleotide homopolymer structures were selected and combined in one multiplex PCR reaction system. Sensitivity, species specificity and applicability in forensic case work of the multiplex were analyzed. A total of 218 unrelated individuals from a Chinese Han population were genotyped. The combined discriminatory power (CDP), the combined match probability (CMP) and the cumulative probability of exclusion (CPE) were 0.9999999999609, 3.91E-13 and 0.9956, respectively. The results demonstrated that this InDel multiplex panel was highly informative in the investigated population and most of the 26 populations of the 1000 Genomes Project. The data also suggested that multi-allelic InDel markers with monomeric base pair expansions are useful for forensic applications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Design, aerodynamics and autonomy of the DelFly.

PubMed

de Croon, G C H E; Groen, M A; De Wagter, C; Remes, B; Ruijsink, R; van Oudheusden, B W

2012-06-01

One of the major challenges in robotics is to develop a fly-like robot that can autonomously fly around in unknown environments. In this paper, we discuss the current state of the DelFly project, in which we follow a top-down approach to ever smaller and more autonomous ornithopters. The presented findings concerning the design, aerodynamics and autonomy of the DelFly illustrate some of the properties of the top-down approach, which allows the identification and resolution of issues that also play a role at smaller scales. A parametric variation of the wing stiffener layout produced a 5% more power-efficient wing. An experimental aerodynamic investigation revealed that this could be associated with an improved stiffness of the wing, while further providing evidence of the vortex development during the flap cycle. The presented experiments resulted in an improvement in the generated lift, allowing the inclusion of a yaw rate gyro, pressure sensor and microcontroller onboard the DelFly. The autonomy of the DelFly is expanded by achieving (1) an improved turning logic to obtain better vision-based obstacle avoidance performance in environments with varying texture and (2) successful onboard height control based on the pressure sensor.

Mejoras en la exactitud del reloj de ángulo horario del telescopio de 2,15 mts de CASLEO

NASA Astrophysics Data System (ADS)

Aballay, J. L.; Pereyra, P. F.; Marún, A. H.

Para aumentar la exactitud en el control del ángulo horario del telescopio, se está implementando el uso de un reloj con una precisión de 1/100 seg. En conjunto con el encoder que otorga la posición con un acierto de 0,012 seg. de arco, se podrá implementar otro dígito en el reloj de ángulo horario con la posibilidad de ver las décimas. Esto, sumado a la precisión ya lograda en declinación, permitirá realizar offsets con mayor exactitud.

Case Study: del Amo Bioventing

EPA Science Inventory

The attached presentation discusses the fundamentals of bioventing in the vadose zone. The basics of bioventing are presented. The experience to date with the del Amo Superfund Site is presented as a case study.

Comparative Study of the Gross Interpretation of Phototesting and Objective Measurement with Using a Spectrophotometer for Patients with Psoriasis and Vitiligo Treated with Narrow-band UVB

PubMed Central

Choi, Kyu-Won; Kim, Ki-Ho

2009-01-01

Background Determination of the minimal erythema dose (MED) is important for developing a phototherapy protocol and to diagnosis photosensitivity disorders. But obtaining a precise and reproducible MED is quite difficult because a phototest for erythema is based on subjective assessment. Objective The objective of our study was to compare the gross interpretation of a phototest and the objective measurement using a spectrophotometer for determining the parameters of cutaneous narrow-band UVB (NBUVB) therapy. Methods A total of 14 psoriasis and 10 vitiligo patients who receiving NBUVB phototherapy with skin types III and IV were selected for this study. To perform phototesting, ten sites on the skin of the back were vertically exposed to a series of 10 NBUVB doses among 14 doses between 340 and 1,400 mJ/cm2. We interpreted the gross findings of erythema and measured the L*a*b* values with using a spectrophotometer at each phototest spot and at the control skin. Also, we evaluate the relationship between the gross presentation and the spectrophotometric analysis by delta E for the assessment of the minimal perceptible erythema (MPE) and MED. Results For all the subjects, the MEDs were measured in the 490~1,000 mJ/cm2 range. The average of the colorimetric values for the control skin were L*: 64.8, a*: 7.9 and b*: 19.8. Among them, the L* value and MED value were shown to be inversely correlated, and as the L* value was decreased, the MED was increased. For the MPE, the delta E, which was the color difference of the normal skin and the phototest area, was within the range of 1.5~3.0 in 17 of the 21 patients, and 4 patients were within the range of 1.0~1.5. For the MED, among the 21 patients, the delta E of 17 patients was within the range of 3.0~6.0, and 4 patients were within the range of 6.0~12.0. Conclusion A spectrophotometer enables UV erythema to be assessed objectively and quantitatively, and this can compensate for the disadvantages of subjective gross

Comparative Study of the Gross Interpretation of Phototesting and Objective Measurement with Using a Spectrophotometer for Patients with Psoriasis and Vitiligo Treated with Narrow-band UVB.

PubMed

Choi, Kyu-Won; Kim, Ki-Ho; Kim, Young-Hun

2009-05-01

Determination of the minimal erythema dose (MED) is important for developing a phototherapy protocol and to diagnosis photosensitivity disorders. But obtaining a precise and reproducible MED is quite difficult because a phototest for erythema is based on subjective assessment. The objective of our study was to compare the gross interpretation of a phototest and the objective measurement using a spectrophotometer for determining the parameters of cutaneous narrow-band UVB (NBUVB) therapy. A total of 14 psoriasis and 10 vitiligo patients who receiving NBUVB phototherapy with skin types III and IV were selected for this study. To perform phototesting, ten sites on the skin of the back were vertically exposed to a series of 10 NBUVB doses among 14 doses between 340 and 1,400 mJ/cm(2). We interpreted the gross findings of erythema and measured the L*a*b* values with using a spectrophotometer at each phototest spot and at the control skin. Also, we evaluate the relationship between the gross presentation and the spectrophotometric analysis by delta E for the assessment of the minimal perceptible erythema (MPE) and MED. For all the subjects, the MEDs were measured in the 490~1,000 mJ/cm(2) range. The average of the colorimetric values for the control skin were L*: 64.8, a*: 7.9 and b*: 19.8. Among them, the L* value and MED value were shown to be inversely correlated, and as the L* value was decreased, the MED was increased. For the MPE, the delta E, which was the color difference of the normal skin and the phototest area, was within the range of 1.5~3.0 in 17 of the 21 patients, and 4 patients were within the range of 1.0~1.5. For the MED, among the 21 patients, the delta E of 17 patients was within the range of 3.0~6.0, and 4 patients were within the range of 6.0~12.0. A spectrophotometer enables UV erythema to be assessed objectively and quantitatively, and this can compensate for the disadvantages of subjective gross interpretation when determining the MED. Delta E is

Development of Halo Nevi in a Lung Cancer Patient: A Novel Immune-Related Cutaneous Event from Atezolizumab.

PubMed

Birnbaum, Mathew R; Ma, Michelle W; Casey, Michael A; Amin, Bijal D; Jacobson, Mark; Cheng, Haiying; McLellan, Beth N

2017-10-01

Immunotherapy-induced vitiligo is an immune-related adverse event (irAE) observed in metastatic melanoma patients treated with immune checkpoint inhibitors that target the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) pathways. To date, the development of leukoderma, poliosis, and halo nevi during immunotherapy has largely been reported in metastatic melanoma patients. We report a case of immunotherapy-induced leukoderma presenting as halo nevi in a patient with non-small cell lung cancer (NSCLC) treated with atezolizumab, a programmed cell death ligand (PD-L1) antibody. Immunotherapy-induced vitiligo in metastatic melanoma patients may be associated with improved survival, but it remains to be determined whether its occurrence in non-melanoma cancers has the same prognostic significance.

J Drugs Dermatol. 2017;16(10):1047-1049.

An evaluation of Delaware's DelTrac program : building an integrated transportation management system

DOT National Transportation Integrated Search

2004-06-01

The DelTrac deployment experience included both successes and unmet challenges. Programmatically, the DelTrac approach to managing ITS has been successful at creating a great deal of integration and cooperation between organizations at DelDOT. Stakeh...

El uso de la neuromodulación para el tratamiento del temblor

PubMed Central

Bendersky, Damián; Ajler, Pablo; Yampolsky, Claudio

2014-01-01

Introducción: El temblor puede ser un desorden incapacitante y el tratamiento de primera línea para estos pacientes es farmacológico. Sin embargo, este tratamiento puede llevar a una reducción satisfactoria del temblor en sólo el 50% de los pacientes con temblor esencial. La talamotomía era el tratamiento de elección para el temblor refractario al tratamiento médico hasta que comenzó a utilizarse la estimulación cerebral profunda (ECP) del núcleo ventral intermedio (Vim) del tálamo. En la actualidad, raramente se realiza la talamotomía. Métodos: Este artículo es una revisión no sistemática de las indicaciones, resultados, parámetros de programación y técnica quirúrgica de la ECP del Vim para el tratamiento del temblor. Resultados: Aunque los resultados clínicos son similares usando la talamotomía o la ECP del Vim, la primera causa más efectos adversos que la última. Además, la ECP puede ser usada bilateralmente, mientras que la talamotomía tiene un alto riesgo de causar disartria cuando se realiza de ambos lados. La ECP del Vim logró una adecuada mejoría del temblor en varias series de pacientes con temblor causado por temblor esencial, enfermedad de Parkinson o esclerosis múltiple. Además del Vim, hay otros blancos que están siendo usados por varios autores, tales como la zona incerta y las radiaciones prelemniscales. Conclusión: La ECP del Vim es un tratamiento útil para el temblor incapacitante refractario al tratamiento médico. Es esencial realizar una precisa selección de pacientes, así como utilizar una técnica quirúrgica correcta. Aún se desconoce el mejor blanco estereotáctico para el temblor, aunque el Vim es el más usado. PMID:25165613

CHEK2 1100delC and male breast cancer in the Netherlands.

PubMed

Wasielewski, Marijke; den Bakker, Michael A; van den Ouweland, Ans; Meijer-van Gelder, Marion E; Portengen, Henk; Klijn, Jan G M; Meijers-Heijboer, Hanne; Foekens, John A; Schutte, Mieke

2009-07-01

Mutations in the breast cancer susceptibility genes BRCA1, BRCA2, and CHEK2 are known risk factors for female breast cancer. Mutations in BRCA1 and BRCA2 also are associated with male breast cancer (MBC). Similarly, it had been suggested in the original CHEK2 identification report that the CHEK2 1100delC mutation confers an increased risk for MBC. Here, we have evaluated the risk of CHEK2 1100delC for MBC by genotyping CHEK2 1100delC in 23 familial and 71 unselected Dutch MBC cases. None of the 23 familial MBC cases carried the CHEK2 1100delC mutation. In contrast, CHEK2 1100delC was present in 3 of the 71 (4.2%) unselected MBC cases, which was significantly more prevalent than the 1.1% Dutch population frequency assessed in 1,692 individuals (P = 0.05, OR = 4.1, 95% CI 1.2-14.3). Our data suggest that, in the Netherlands, CHEK2 1100delC is associated with an increased risk for MBC.

Field measurements of del13C in ecosystem respiration

NASA Astrophysics Data System (ADS)

van Asperen, Hella; Sabbatini, Simone; Nicolini, Giacomo; Warneke, Thorsten; Papale, Dario; Notholt, Justus

2014-05-01

Stable carbon isotope del13C-measurements are extensively used to study ecological and biogeochemical processes in ecosystems. Above terrestrial ecosystems, atmospheric del13C can vary largely due to photosynthetic fractionation. Photosynthetic processes prefer the uptake of the lighter isotope 12C (in CO2), thereby enriching the atmosphere in 13C and depleting the ecosystem carbon. At night, when ecosystem respiratory fluxes are dominant, 13C-depleted CO2 is respired and thereby depletes the atmospheric del13C-content. Different ecosystems and different parts of one ecosystem (type of plant, leaves, and roots) fractionate and respire with a different del13C-ratio signature. By determining the del13C-signature of ecosystem respiration in temporal and spatial scale, an analysis can be made of the composition of respiratory sources of the ecosystem. A field study at a dry cropland after harvest (province of Viterbo, Lazio, Italy) was performed in the summer of 2013. A FTIR (Fourier Transform Infrared Spectrometer) was set up to continuously measure CO2-, CH4-, N2O-, CO- and del13C-concentrations. The FTIR was connected to 2 different flux measurements systems: a Flux Gradient system (sampling every half hour at 1.3m and 4.2m) and 2 flux chambers (measured every hour), providing a continuous data set of the biosphere-atmosphere gas fluxes and of the gas concentrations at different heights. Keeling plot intercept values of respiratory CO2, measured by the Flux Gradient system at night, were determined to be between -25‰ and -20‰. Keeling plot intercept values of respiratory CO2, measured by the flux chamber system, varied between -24‰ and -29‰, and showed a clear diurnal pattern, suggesting different (dominant) respiratory processes between day and night.

[Strengths and future of the Revista Médica del Instituto Mexicano del Seguro Social].

PubMed

Fajardo-Dolci, Germán

2014-01-01

The journals of medicine arose as a communication tool more than 200 years ago. At the beginning, their nature was local; later, their aim was to spread medical information along the nation; and, finally, they sought to reach the world distribution. The Revista Médica del Instituto Mexicano del Seguro Social was published for the first time 52 years ago, and it has walked its way from local to international distribution. This journal has 23 000 subscribers, it is included in Medline and it reached a 0.112 SCImago Journal Rank in 2012. Its website receives around 200 000 visits monthly and 45 % are foreign visits. In the future, the peer review system is going to be strengthened, and the journal is going to offer audio, video, and applications to reinforce interactive participation between authors, readers in order to reach modernity and draw young new attention.

Establishing the Empirical Relationship Between Non-Science Majoring Undergraduate Learners' Spatial Thinking Skills and Their Conceptual Astronomy Knowledge. (Spanish Title: Estableciendo Una Relación Empírica Entre el Razonamiento Espacial de los Estudiantes de Graduación de Carreras no Científicas y su Conocimento Conceptual de la Astronomía.) Estabelecendo Uma Relação Empírica Entre o RacioCínio Espacial dos Estudantes de Graduação EM Carreiras Não Científicas e Seu Conhecimento Conceitual da Astronomia

NASA Astrophysics Data System (ADS)

Heyer, Inge; Slater, Stephanie J.; Slater, Timothy F.

2013-12-01

The astronomy education community has tacitly assumed that learning astronomy is a conceptual domain resting upon spatial thinking skills. As a first step to formally identify an empirical relationship, undergraduate students in a non-major introductory astronomy survey class at a mediumsized, Ph.D. granting, mid-western US university were given pre- and post-astronomy conceptual diagnostics and spatial reasoning diagnostics, Instruments used were the "Test Of Astronomy Standards" and "What Do You Know?" Using only fully matched data for analysis, our sample consisted of 86 undergraduate non-science majors. Students' normalized gains for astronomy surveys were low at .26 and .13 respectively. Students' spatial thinking was measured using an instrument designed specifically for this study. Correlations between the astronomy instruments' pre- to post-course gain scores and the spatial assessment instrument show moderate to strong relationships suggesting the relationship between spatial reasoning and astronomy ability can explain about 25% of the variation in student achievement. La comunidad de educación en astronomía ha supuesto de forma tácita que el aprendizaje de la astronomía consiste en un dominio conceptual fundamentado en el razonamiento espacial. Como un primer paso para identificar formalmente una relación empírica entre estas dos cosas, utilizamos como muestra los estudantes de graduación de carreras no científicas de un curso experimental en una universidad norteamericana del medioeste de porte mediano con programa de Doctorado em curso, en el cual estos estudiantes se sometieron a un diagnóstico de razonamiento espacial y conceptos astronómicos antes e después del mismo. Las herramientas utilizadas fueron el Test Of Astronomy Standards (TOAST) y el cuestionario What do you know? Utilizando solo los datos completamente consistentes para este análisis, nuestra muestra consistió en 86 estudantes de graduación. Las mejoras, depués de

Pastoral del Nino: Bringing the Abundant Life to Paraguayan Children

ERIC Educational Resources Information Center

Austin, Ann Berghout; Aquino, Cyle; Burro, Elizabeth

2007-01-01

Pastoral del Nino is transforming children's lives in rural Paraguay. Part of Pastoral Social (Catholic Social Services), Pastoral del Nino's primary focus is to bring "vida en abundancia" (the abundant life) to families by ensuring that mothers survive childbirth and children reach their first birthdays. In addition, the organization…

Perk Ablation Ameliorates Myelination in S63del-Charcot–Marie–Tooth 1B Neuropathy

PubMed Central

Musner, Nicolò; Sidoli, Mariapaola; Zambroni, Desireè; Del Carro, Ubaldo; Ungaro, Daniela; D’Antonio, Maurizio; Feltri, Maria L.

2016-01-01

In peripheral nerves, P0 glycoprotein accounts for more than 20% of myelin protein content. P0 is synthesized by Schwann cells, processed in the endoplasmic reticulum (ER) and enters the secretory pathway. However, the mutant P0 with S63 deleted (P0S63del) accumulates in the ER lumen and induces a demyelinating neuropathy in Charcot–Marie–Tooth disease type 1B (CMT1B)–S63del mice. Accumulation of P0S63del in the ER triggers a persistent unfolded protein response. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER stress sensor that phosphorylates eukaryotic initiation factor 2 alpha (eIF2alpha) in order to attenuate protein synthesis. We have shown that increasing phosphophorylated-eIF2alpha (P-eIF2alpha) is a potent therapeutic strategy, improving myelination and motor function in S63del mice. Here, we explore the converse experiment: Perk haploinsufficiency reduces P-eIF2alpha in S63del nerves as expected, but surprisingly, ameliorates, rather than worsens S63del neuropathy. Motor performance and myelin abnormalities improved in S63del//Perk+/− compared with S63del mice. These data suggest that mechanisms other than protein translation might be involved in CMT1B/S63del neuropathy. In addition, Perk deficiency in other cells may contribute to demyelination in a non–Schwann-cell autonomous manner. PMID:27095827

[The role of psychological factors and psychiatric disorders in skin diseases].

PubMed

Kieć-Swierczyńska, Marta; Dudek, Bohdan; Krecisz, Beata; Swierczyńska-Machura, Dominika; Dudek, Wojciech; Garnczarek, Adrianna; Turczyn, Katarzyna

2006-01-01

In this paper, the relation between psychological factors and psychiatric disorders in patients with skin diseases is discussed. On the one hand psychological factors (stress, negative emotions) can influence the generation and aggravation of skin disorders (urticaria, atopic dermatitis, vitiligo), on the other hand psychological disorders can result in some skin diseases (psoriasis, atopic dermatitis). In the majority of cases the quality of life is poorly estimated by patients with skin problems. Psychodermatology is divided into three categories according to the relationship between skin diseases and mental disorders: 1) psychophysiologic disorders caused by skin diseases triggering different emotional states (stress), but not directly combined with mental disorders (psoriasis, eczema); 2) primary psychiatric disorders responsible for self-induced skin disorders (trichotillomania); and 3) secondary psychiatric disorders caused by disfiguring skin (ichthyosis, acne conglobata, vitiligo), which can lead to states of fear, depression or suicidal thoughts.

Multiplex pyrosequencing of InDel markers for forensic DNA analysis.

PubMed

Bus, Magdalena M; Karas, Ognjen; Allen, Marie

2016-12-01

The capillary electrophoresis (CE) technology is commonly used for fragment length separation of markers in forensic DNA analysis. In this study, pyrosequencing technology was used as an alternative and rapid tool for the analysis of biallelic InDel (insertion/deletion) markers for individual identification. The DNA typing is based on a subset of the InDel markers that are included in the Investigator ® DIPplex Kit, which are sequenced in a multiplex pyrosequencing analysis. To facilitate the analysis of degraded DNA, the polymerase chain reaction (PCR) fragments were kept short in the primer design. Samples from individuals of Swedish origin were genotyped using the pyrosequencing strategy and analysis of the Investigator ® DIPplex markers with CE. A comparison between the pyrosequencing and CE data revealed concordant results demonstrating a robust and correct genotyping by pyrosequencing. Using optimal marker combination and a directed dispensation strategy, five markers could be multiplexed and analyzed simultaneously. In this proof-of-principle study, we demonstrate that multiplex InDel pyrosequencing analysis is possible. However, further studies on degraded samples, lower DNA quantities, and mixtures will be required to fully optimize InDel analysis by pyrosequencing for forensic applications. Overall, although CE analysis is implemented in most forensic laboratories, multiplex InDel pyrosequencing offers a cost-effective alternative for some applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Trattamento del disturbo da uso di alcol da un punto di vista psicologico].

PubMed

Coriale, Giovanna; Fiorentino, Daniela; De Rosa, Francesca; Solombrino, Simona; Scalese, Bruna; Ciccarelli, Rosaria; Attilia, Fabio; Vitali, Mario; Musetti, Alessia; Fiore, Marco; Ceccanti, Mauro

2018-01-01

RIASSUNTO. L'elaborazione del piano di trattamento rappresenta un momento molto delicato e complesso del processo terapeutico del disturbo da abuso di alcol (DUA). È la fase in cui le informazioni raccolte da un'équipe di professionisti (medici, psicologi e assistenti sociali) (modello bio-psico-sociale del DUA) vengono messe insieme per decidere il percorso terapeutico più adatto. Per quanto riguarda la parte psicologica, è di notevole importanza scegliere un trattamento clinico in grado di ridurre al minimo la mancata adesione al trattamento e, per i soggetti che rimangono in trattamento, di garantirne l'efficacia. Se da una parte, le tecniche psicoanalitiche e comportamentali hanno fornito le basi della terapia psicologica dell'alcolismo, dall'altra, gli approcci basati sull'evidenza scientifica sono stati elaborati a partire dai principi del colloquio motivazionale e della terapia cognitivo-comportamentale. In questo articolo viene fornita una panoramica dei trattamenti che sono risultati più efficaci nel trattare il DUA e delle modalità temporali più adeguate per monitorare l'efficacia del trattamento.

Multi-InDel Analysis for Ancestry Inference of Sub-Populations in China

PubMed Central

Sun, Kuan; Ye, Yi; Luo, Tao; Hou, Yiping

2016-01-01

Ancestry inference is of great interest in diverse areas of scientific researches, including the forensic biology, medical genetics and anthropology. Various methods have been published for distinguishing populations. However, few reports refer to sub-populations (like ethnic groups) within Asian populations for the limitation of markers. Several InDel loci located very tightly in physical positions were treated as one marker by us, which is multi-InDel. The multi-InDel shows potential as Ancestry Inference Marker (AIM). In this study, we performed a genome-wide scan for multi-InDels as AIM. After examining the FST distributions in the 1000 Genomes Database, 12 candidates were selected and validated for eastern Asian populations. A multiplexed assay was developed as a panel to genotype 12 multi-InDel markers simultaneously. Ancestry component analysis with STRUCTURE and principal component analysis (PCA) were employed to estimate its capability for ancestry inference. Furthermore, ancestry assignments of trial individuals were conducted. It proved to be very effective when 210 samples from Han and Tibetan individuals in China were tested. The panel consisting of multi-InDel markers exhibited considerable potency in ancestry inference, and was suggested to be applied in forensic practices and genetic population studies. PMID:28004788

Observaciones del CH interestelar y el continuo en 3,3 GHz

NASA Astrophysics Data System (ADS)

Olano, C. A.; Combi, J. A.; Pöppel, W.; Benaglia, P.; Sanz, A. J.; Bava, J. A.

Se informa sobre el proyecto que se lleva a cabo en el IAR con el propósito de observar las líneas hiperfinas del estado fundamental del CH y el continuo en la banda de 3,3 GHz. El nuevo receptor construído en nuestro laboratorio para tal fin se instaló sobre uno de los radiotelescopios, funcionando conjuntamente con los sistemas de procesamiento actuales del IAR. Los resultados de las primeras observaciones, realizadas tanto en las líneas espectrales como en el continuo sobre fuentes conocidas, fueron satisfactorios.

[Diagnostics and treatment of polyglandular syndrome of adults].

PubMed

Larina, A A; Shapoval'iants, O S; Mazurina, N V; Troshina, E A

2012-01-01

Autoimmune polyendocrine syndromes (APS) are rare endocrinopathies characterized by the coexistence of at least two glandular autoimmune diseases. APS comprise a wide spectrum of autoimmune disorders and are divided into a very rare juvenile (APS type 1) and a more common adult type with (APS 2) or without adrenal failure (APS 3). The first clinical manifestations of APS 1 usually occur in childhood whereas APS 2 mostly occurs during the third and fourth decades of life. The third type has been described in adults that, contrary to types 1 and 2, does not involve the adrenal cortex. No clinical differences between types 2 and 3 have been described except the absence of adrenal failure. Type 4 APS is a rare syndrome characterized by the combination of autoimmune conditions not falling into the above categories. It consists of adrenal failure with one or more minor autoimmune disorders barring major components of type 1 and 2 APS. Usually, autoimmune polyendocrine syndrome of adults manifests itself as one of the major autoimmune diseases (such as adrenal failure, Grave's disease, or type 1 diabetes) and minor autoimmune disorders (vitiligo, alopecia) preceding the development of autoimmune deficiency of major endocrine glands. This article describes a patient with type 3 APS, who developed type 1 diabetes. Grave's disease and vitiligo. The development of the syndrome started from vitiligo in the chidhood. Moreover, the patient suffered primary sterility and presented with progressive diabetic nephropathy of autoimmune origin. It is concluded that patients with a single autoimmune component of polyendocrine syndrome should be screened to exclude other autoimmune endocrine disorders.

Chemical Leukoderma Associated with Methylphenidate Transdermal System: Data From the US Food and Drug Administration Adverse Event Reporting System.

PubMed

Cheng, Carmen; La Grenade, Lois; Diak, Ida-Lina; Brinker, Allen; Levin, Robert L

2017-01-01

To identify and characterize cases of chemical leukoderma, an underrecognized adverse event, associated with the methylphenidate transdermal system (MTS) reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS). We searched the Food and Drug Administration Adverse Event Reporting System for reports of chemical leukoderma associated with MTS, received by the Food and Drug Administration from April 6, 2006 to December 23, 2014. We identified 51 cases of chemical leukoderma reported with the use of MTS. The median age was 11 years; 43 cases reported leukoderma at or near the application site only, and 7 reported leukoderma at other parts of the body in addition to the application site; 1 case did not provide enough information to confirm the affected site. The time to onset ranged from 2 months to 4 years after the initiation of MTS. MTS was discontinued in 31 cases. Thirteen patients were prescribed treatment for repigmentation. Three cases reported continued spread of leukoderma after MTS was discontinued. Nineteen cases were diagnosed as vitiligo, including 5 cases reporting histologic features consistent with vitiligo. Leukoderma was persistent in all cases. The median follow-up interval after the discontinuation of MTS in 23 cases was 14 months. As outlined in recent changes to the prescribing information for MTS, health care professionals need to be aware of the potential risk of chemical leukoderma caused by MTS, especially given that chemical leukoderma is often misdiagnosed as idiopathic vitiligo. MTS should be discontinued at the earliest sign of pigment loss and other treatment options considered. Published by Elsevier Inc.

Genetic modifiers of CHEK2*1100delC-associated breast cancer risk.

PubMed

Muranen, Taru A; Greco, Dario; Blomqvist, Carl; Aittomäki, Kristiina; Khan, Sofia; Hogervorst, Frans; Verhoef, Senno; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Luben, Robert; Bojesen, Stig E; Nordestgaard, Børge G; Schoemaker, Minouk; Swerdlow, Anthony; García-Closas, Montserrat; Figueroa, Jonine; Dörk, Thilo; Bogdanova, Natalia V; Hall, Per; Li, Jingmei; Khusnutdinova, Elza; Bermisheva, Marina; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Investigators, Nbcs; Peto, Julian; Dos Santos Silva, Isabel; Couch, Fergus J; Olson, Janet E; Hillemans, Peter; Park-Simon, Tjoung-Won; Brauch, Hiltrud; Hamann, Ute; Burwinkel, Barbara; Marme, Frederik; Meindl, Alfons; Schmutzler, Rita K; Cox, Angela; Cross, Simon S; Sawyer, Elinor J; Tomlinson, Ian; Lambrechts, Diether; Moisse, Matthieu; Lindblom, Annika; Margolin, Sara; Hollestelle, Antoinette; Martens, John W M; Fasching, Peter A; Beckmann, Matthias W; Andrulis, Irene L; Knight, Julia A; Investigators, kConFab/Aocs; Anton-Culver, Hoda; Ziogas, Argyrios; Giles, Graham G; Milne, Roger L; Brenner, Hermann; Arndt, Volker; Mannermaa, Arto; Kosma, Veli-Matti; Chang-Claude, Jenny; Rudolph, Anja; Devilee, Peter; Seynaeve, Caroline; Hopper, John L; Southey, Melissa C; John, Esther M; Whittemore, Alice S; Bolla, Manjeet K; Wang, Qin; Michailidou, Kyriaki; Dennis, Joe; Easton, Douglas F; Schmidt, Marjanka K; Nevanlinna, Heli

2017-05-01

CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.21-2.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Genet Med advance online publication 06 October 2016.

The Cuernos del Paine mountains in Torres del Paine National Park, Chile, during NASA's AirSAR 2004 campaign

NASA Image and Video Library

2004-03-11

The Cuernos del Paine mountains in Torres del Paine National Park, Chile, during NASA's AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. Founded in 1959, Torres del Paine National Park encompasses 450,000 acres in the Patagonia region of Chile. This region is being studied by NASA using a DC-8 equipped with an Airborne Synthetic Aperture Radar (AirSAR) developed by scientists from NASA’s Jet Propulsion Laboratory. This is a very sensitive region that is important to scientists because the temperature has been consistently rising causing a subsequent melting of the region’s glaciers. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

Modelo semi-empírico de protuberancia solar a partir del diagnóstico de densidades

NASA Astrophysics Data System (ADS)

Cirigliano, D.; Vial, J. C.; Rovira, M.

A partir de la observación del espectro del quintuplete de C III alrededor de 1175 Å, se ha realizado el diagnóstico de la densidad y presión electrónica, basado en el cálculo del cociente de las intensidades observadas. Una vez establecida la densidad electrónica, y con el cálculo de las velocidades Doppler, hemos investigado el flujo de masa en la protuberancia en función de la temperatura. Estableciendo como hipótesis la conservación del número de partículas que ingresan y salen del cuerpo de la protuberancia, se investiga la variación del área de un tubo de flujo semi-empírico en función de la temperatura. A partir de dicho diagnóstico, se examina el comportamiento del radio del tubo magnético en función de la temperatura, los que dan cuenta de la abertura de las líneas de campo magnético que confinan el plasma y de la divergencia del campo magnético en diferentes alturas de la atmósfera solar.

Uso Del Condón en Adolescentes Nahuas, un Modelo Explicativo.

PubMed

Tirado, María de Los Ángeles Meneses; Benavides-Torres, Raquel A; Navarro, Sergio Meneses; de la Colina, Juan Antonio Doncel; Rodríguez, Dora Julia Onofre; Hernández, Francisco Javier Baéz

2018-03-01

En México, la población indígena supera los siete millones de habitantes, en Puebla el grupo más representativo es el Náhuatl. Sin embargo, las condiciones de vida, salud, educación y transporte son precarias para esta población. En los adolescentes, las responsabilidades como el matrimonio, la familia y los compromisos ante la comunidad, favorecen conductas de riesgo sexual que dificultan su desarrollo económico, social y reproductivo. El objetivo fue proponer un modelo explicativo del uso del condón en adolescentes nahuas. Método. Bajo el marco de la teoría social cognitiva, el concepto de valores culturales de Leininger y el proceso de la sustracción teórica, se desarrolló este artículo. Se muestran las relaciones del modelo con las proposiciones y los factores que influyen en el uso del condón para este grupo específico. Finalmente, el modelo explica las variables de interés, los niveles de abstracción y las relaciones entre sí en el contexto náhuatl. El siguiente paso será implementar los indicadores empíricos para conocer el grado de influencia de los factores personales y ambientales hacia el uso del condón en adolescentes nahuas. Resultados que aportarán información para el desarrollo del conocimiento en enfermería y la reducción de riesgo sexual de esta población.

Breast tumors from CHEK2 1100delC-mutation carriers: genomic landscape and clinical implications.

PubMed

Muranen, Taru A; Greco, Dario; Fagerholm, Rainer; Kilpivaara, Outi; Kämpjärvi, Kati; Aittomäki, Kristiina; Blomqvist, Carl; Heikkilä, Päivi; Borg, Ake; Nevanlinna, Heli

2011-09-20

Checkpoint kinase 2 (CHEK2) is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about twofold. We investigated gene copy-number aberrations and gene-expression profiles that are typical for breast tumors of CHEK2 1100delC-mutation carriers. In total, 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array-comparative genomic hybridization (aCGH) and gene-expression (GEX) experiments. After dimensionality reduction with CGHregions R package, CHEK2 1100delC-associated regions in the aCGH data were detected by the Wilcoxon rank-sum test. The linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by the bayesian method. We discovered four lost and three gained CHEK2 1100delC-related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2, and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3, and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors, nominating them as candidates for CHEK2 1100delC-associated tumor-progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM, and LRP1 on 12q13. Altogether, 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44, reduced expression levels.Our results suggest the WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC-mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC-associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. We have shown that copy-number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions, we identified

Breast tumors from CHEK2 1100delC-mutation carriers: genomic landscape and clinical implications

PubMed Central

2011-01-01

Introduction Checkpoint kinase 2 (CHEK2) is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about twofold. We investigated gene copy-number aberrations and gene-expression profiles that are typical for breast tumors of CHEK2 1100delC-mutation carriers. Methods In total, 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array-comparative genomic hybridization (aCGH) and gene-expression (GEX) experiments. After dimensionality reduction with CGHregions R package, CHEK2 1100delC-associated regions in the aCGH data were detected by the Wilcoxon rank-sum test. The linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by the bayesian method. Results We discovered four lost and three gained CHEK2 1100delC-related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2, and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3, and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors, nominating them as candidates for CHEK2 1100delC-associated tumor-progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM, and LRP1 on 12q13. Altogether, 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44, reduced expression levels. Our results suggest the WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC-mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC-associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions We have shown that copy-number aberrations of certain genomic regions are associated with CHEK2 mutation

Max Brödel: his art, legacy, and contributions to neurosurgery through medical illustration.

PubMed

Patel, Smruti K; Couldwell, William T; Liu, James K

2011-07-01

Max Brödel is considered the father of modern medical illustration. This report reviews his contributions to neurosurgery as a medical illustrator. Max Brödel, a young artist from Leipzig, Germany, was hired at Johns Hopkins Hospital in 1894, where he illustrated an operative textbook of gynecology for Howard A. Kelly. Although Brödel did not have any formal medical training, he quickly acquired knowledge of anatomy, pathology, physiology, and surgery. Brödel's extraordinary illustrations were characterized by an aerial perspective that conveyed the surgeon's operative viewpoint and precise surgical anatomy. He masterfully incorporated tissue realism with cross-sectional anatomy to accentuate concepts while maintaining topographical accuracy. Brödel's reputation spread quickly and resulted in collaborations with prominent surgeons, such as Cushing, Halsted, and Dandy. Cushing, who also possessed artistic talent, became a pupil of Brödel and remained a very close friend. In 1911, Brödel was appointed the director of the Department of Art as Applied to Medicine at Johns Hopkins, the first academic department of its kind in the world. For the next several decades, he trained generations of renowned medical illustrators. Just as Osler, Halsted, and Cushing passed their skills and knowledge to future leaders of medicine and surgery, Brödel did the same for the field of medical illustration. The advancement of neurosurgical education has been greatly facilitated by Max Brödel's artistic contributions. His unique ability to synthesize art and medicine resulted in timeless illustrations that remain indispensable to surgeons. The art produced by his legacy of illustrators continues to flourish in neurosurgical literature today.

Genetic modifiers of CHEK2*1100delC associated breast cancer risk

PubMed Central

Muranen, Taru A.; Greco, Dario; Blomqvist, Carl; Aittomäki, Kristiina; Khan, Sofia; Hogervorst, Frans; Verhoef, Senno; Pharoah, Paul D.P.; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Bojesen, Stig E.; Nordestgaard, Børge G.; Schoemaker, Minouk; Swerdlow, Anthony; García-Closas, Montserrat; Figueroa, Jonine; Dörk, Thilo; Bogdanova, Natalia V.; Hall, Per; Li, Jingmei; Khusnutdinova, Elza; Bermisheva, Marina; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Peto, Julian; dos Santos Silva, Isabel; Couch, Fergus J.; Olson, Janet E.; Hillemans, Peter; Park-Simon, Tjoung-Won; Brauch, Hiltrud; Hamann, Ute; Burwinkel, Barbara; Marme, Frederik; Meindl, Alfons; Schmutzler, Rita K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor J.; Tomlinson, Ian; Lambrechts, Diether; Moisse, Matthieu; Lindblom, Annika; Margolin, Sara; Hollestelle, Antoinette; Martens, John W.M.; Fasching, Peter A.; Beckmann, Matthias W.; Andrulis, Irene L.; Knight, Julia A.; Anton-Culver, Hoda; Ziogas, Argyrios; Giles, Graham G.; Milne, Roger L.; Brenner, Hermann; Arndt, Volker; Mannermaa, Arto; Kosma, Veli-Matti; Chang-Claude, Jenny; Rudolph, Anja; Devilee, Peter; Seynaeve, Caroline; Hopper, John L.; Southey, Melissa C.; John, Esther M.; Whittemore, Alice S.; Bolla, Manjeet K.; Wang, Qin; Michailidou, Kyriaki; Dennis, Joe; Easton, Douglas F.; Schmidt, Marjanka K.; Nevanlinna, Heli

2016-01-01

Purpose CHEK2*1100delC is a founder variant in European populations conferring a 2–3 fold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Methods With genotype data of 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. Results The PRS conferred an odds ratio (OR) of 1.59 [95% CI 1.21–2.09] per standard deviation for BC for CHEK2*1100delC carriers and 1.58 [1.55–1.62] for non-carriers. No evidence for deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 [0.86–4.78] for CHEK2*1100delC carriers placing them to the high risk category according to UK NICE guidelines. OR for the lowest quintile was 0.52 [0.16–1.74], indicating life-time risk close to population average. Conclusion Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify the carriers at a high life-time risk for clinical actions. PMID:27711073

Gödel metrics with chronology protection in Horndeski gravities

NASA Astrophysics Data System (ADS)

Geng, Wei-Jian; Li, Shou-Long; Lü, H.; Wei, Hao

2018-05-01

Gödel universe, one of the most interesting exact solutions predicted by General Relativity, describes a homogeneous rotating universe containing naked closed time-like curves (CTCs). It was shown that such CTCs are the consequence of the null energy condition in General Relativity. In this paper, we show that the Gödel-type metrics with chronology protection can emerge in Einstein-Horndeski gravity. We construct such exact solutions also in Einstein-Horndeski-Maxwell and Einstein-Horndeski-Proca theories.

Estrategia innovadora enfocada en parejas del mismo sexo para disminuir la infección del VIH en hombres Latinos

PubMed Central

Martinez, Omar; Wu, Elwin; Sandfort, Theo; Shultz, Andrew Z.; Capote, Jonathan; Chávez, Silvia; Moya, Eva; Dodge, Brian; Morales, Gabriel; Porras, Antonio; Ovejero, Hugo

2014-01-01

Resumen El VIH es un problema de salud importante dentro de la comunidad latina de los Estados Unidos. Gracias a los esfuerzos de prevención, los niveles de contagio entre los latinos se han mantenido estables por más de una década. Sin embargo, esta población sigue siendo afectada a niveles muy altos, en particular entre hombres que tienen sexo con hombres (HSH), de origen latino y que hablan principalmente el idioma español. Existen varios factores que contribuyen a la transmisión del VIH entre esta población, como son: el uso de drogas; la violencia dentro de la pareja; la presencia de infecciones de transmisión sexual; relaciones sexuales sin protección, dentro y fuera de la pareja; el evadir la búsqueda de recursos (prueba y tratamiento adecuado) por temor a ser discriminado o por su estatus migratorio; la escasez de recursos económicos o estado de pobreza y los patrones relacionados a la migración. En particular, Investigaciones Epidemiológicas de Comportamientos han determinado: cómo algunas dinámicas en parejas están directamente asociadas a los comportamientos sexuales de riesgos. En consecuencia, es necesaria mayor investigación para identificar esas dinámicas, y a su vez, realizar intervenciones dirigidas a la reducción de conductas de riesgo enfocadas en parejas de hombres del mismo sexo. En este escrito, se describe la importancia del uso de las relaciones de pareja como estrategia en la reducción de la trasmisión del VIH/SIDA en HSH de origen latino y que hablan principalmente el idioma español en los Estados Unidos. PMID:25580466

Photoacoustic measurement of epidermal melanin

NASA Astrophysics Data System (ADS)

Viator, John A.; Svaasand, Lars O.; Aguilar, Guillermo; Choi, Bernard; Nelson, J. Stuart

2003-06-01

Most dermatologic laser procedures must consider epidermal melanin, as it is a broadband optical absorber which affects subsurface fluence, effectively limiting the amount of light reaching the dermis and targeted chromophores. An accurate method for quantifying epidermal melanin content would aid clinicians in determining proper light dosage for therapeutic laser procedures. While epidermal melanin content has been quantified non-invasively using optical methods, there is currently no way to determine the melanin distribution in the epidermis. We have developed a photoacoustic probe that uses a Q-switched, frequency doubled Nd:YAG laser operating at 532nm to generate acoustic pulses in skin in vivo. The probe contained a piezoelectric element that detected photoacoustic waves which were then analyzed for epidermal melanin content, using a photoacoustic melanin index (PAMI). We tested 15 human subjects with skin types I--VI using the photoacoustic probe. We also present photoacoustic data for a human subject with vitiligo. Photoacoustic measurement showed melanin in the vitiligo subject was almost completely absent.

Determinacion de Caracteristicas Opticas del Telescopio OAN150

NASA Astrophysics Data System (ADS)

Galan, M. J.; Cobos, F. J.

1987-05-01

En el Observatorio de Calar Alto, en Almería, España, está ubicado un telescopio de 15O-cms de diámetro -construído por REOSC- perteneciente al Observatorio Astronómico Nacional, con sede en Madrid, España. La infraestructura técnica del OAN ha sido tradicionalmente débil y actualmente se está haciendo un esfuerzo por fortalecerla. Existe una información muy limitada del telescopio en general; de su óptica en particular se conocían los valores de los parámetros principales pero sin saber si éstos corresponden a valores teóricos ó de construcción. Por ello se consideró necesario iniciar una investigación para conocer en detalle los valores reales de las componentes ópticas del telescopio, obteniéndose algunos resultados de interés. El primario del telescopio OANl5O es aproximadamente F/3 y el siste ma en su conjunto es F/8.2, con su sistema corrector de campo. En términos generales, la imagen es satisfactoria en todo el campo y, sin sistema corrector, la imagen axial también es buena. En un futuro muy cercano se piensa diseñar instrumentación adicional para este telescopio. Conocer con mayor precisión sus características puede ser de gran utilidad para tal fin, pues se efectúan los cálculos considerando conjuntamente al telescopio y al instrumento.

Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells

PubMed Central

Stanton, Bruce A.; Coutermarsh, Bonita; Barnaby, Roxanna; Hogan, Deborah

2015-01-01

Background P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. Methods and Results F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. Conclusion The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials. PMID:26018799

Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells.

PubMed

Stanton, Bruce A; Coutermarsh, Bonita; Barnaby, Roxanna; Hogan, Deborah

2015-01-01

P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials.

Genomic profiling of CHEK2*1100delC-mutated breast carcinomas.

PubMed

Massink, Maarten P G; Kooi, Irsan E; Martens, John W M; Waisfisz, Quinten; Meijers-Heijboer, Hanne

2015-11-09

CHEK2*1100delC is a moderate-risk breast cancer susceptibility allele with a high prevalence in the Netherlands. We performed copy number and gene expression profiling to investigate whether CHEK2*1100delC breast cancers harbor characteristic genomic aberrations, as seen for BRCA1 mutated breast cancers. We performed high-resolution SNP array and gene expression profiling of 120 familial breast carcinomas selected from a larger cohort of 155 familial breast tumors, including BRCA1, BRCA2, and CHEK2 mutant tumors. Gene expression analyses based on a mRNA immune signature was used to identify samples with relative low amounts of tumor infiltrating lymphocytes (TILs), which were previously found to disturb tumor copy number and LOH (loss of heterozygosity) profiling. We specifically compared the genomic and gene expression profiles of CHEK2*1100delC breast cancers (n = 14) with BRCAX (familial non-BRCA1/BRCA2/CHEK2*1100delC mutated) breast cancers (n = 34) of the luminal intrinsic subtypes for which both SNP-array and gene expression data is available. High amounts of TILs were found in a relatively small number of luminal breast cancers as compared to breast cancers of the basal-like subtype. As expected, these samples mostly have very few copy number aberrations and no detectable regions of LOH. By unsupervised hierarchical clustering of copy number data we observed a great degree of heterogeneity amongst the CHEK2*1100delC breast cancers, comparable to the BRCAX breast cancers. Furthermore, copy number aberrations were mostly seen at low frequencies in both the CHEK2*1100delC and BRCAX group of breast cancers. However, supervised class comparison identified copy number loss of chromosomal arm 1p to be associated with CHEK2*1100delC status. In conclusion, in contrast to basal-like BRCA1 mutated breast cancers, no apparent specific somatic copy number aberration (CNA) profile for CHEK2*1100delC breast cancers was found. With the possible exception of copy

Summary of a Gas Transport Tracer Test in the Deep Cerros Del Rio Basalts, Mesita del Buey, Los Alamos NM.

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

Stauffer, Philip H.; Rahn, Thomas A.; Ortiz, John Philip

Here we describe results from a tracer test in the Cerros del Rio basalt beneath Mesita del Buey, Technical Area 54 (TA-54) at Los Alamos National Laboratory (LANL or the Laboratory). This report follows from plans outlined in our previous Tracer Test Work Plan (LANL 2016). These activities were conducted by LANL to further characterize subsurface properties of the Cerros del Rio basalts at Material Disposal Area (MDA) L (Figure 1.1-1). The work presented follows from the “Interim Measures Work Plan for Soil-Vapor Extraction of Volatile Organic Compounds from Material Disposal Area L, Technical Area 54, Revision 1,” submitted tomore » the New Mexico Environment Department (NMED) in September 2014 (LANL 2014). Remediation of the MDA L vapor plume by soil-vapor extraction (SVE) is recommended as part of the final remedy in the “Corrective Measures Evaluation Report for Material Disposal Area L, Solid Waste Management Unit 54-006, at Technical Area 54, Revision 2” to meet a remedial action objective of preventing groundwater from being impacted above a regulatory standard by the transport of volatile organic compounds (VOCs) to groundwater through soil vapor (LANL 2011).« less

Manipulating proteostasis to repair the F508del-CFTR defect in cystic fibrosis.

PubMed

Esposito, Speranza; Tosco, Antonella; Villella, Valeria R; Raia, Valeria; Kroemer, Guido; Maiuri, Luigi

2016-12-01

Cystic fibrosis (CF) is a lethal monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that entails the (diagnostic) increase in sweat electrolyte concentrations, progressive lung disease with chronic inflammation and recurrent bacterial infections, pancreatic insufficiency, and male infertility. Therapies aimed at restoring the CFTR defect have emerged. Thus, a small molecule which facilitates chloride channel opening, the potentiator Ivacaftor, has been approved for the treatment of CF patients bearing a particular class of rare CFTR mutations. However, small molecules that directly target the most common misfolded CFTR mutant, F508del, and improve its intracellular trafficking in vitro, have been less effective than expected when tested in CF patients, even in combination with Ivacaftor. Thus, new strategies are required to circumvent the F508del-CFTR defect. Airway and intestinal epithelial cells from CF patients bearing the F508del-CFTR mutation exhibit an impressive derangement of cellular proteostasis, with oxidative stress, overactivation of the tissue transglutaminase (TG2), and disabled autophagy. Proteostasis regulators such as cysteamine can rescue and stabilize a functional F508del-CFTR protein through suppressing TG2 activation and restoring autophagy in vivo in F508del-CFTR homozygous mice, in vitro in CF patient-derived cell lines, ex vivo in freshly collected primary patient's nasal cells, as well as in a pilot clinical trial involving homozygous F508del-CFTR patients. Here, we discuss how the therapeutic normalization of defective proteostasis can be harnessed for the treatment of CF patients with the F508del-CFTR mutation.

Esquizofrenia y trastorno en el consumo de sustancias: prevalencia y characterísticas sociodemográficas en la población Latina

PubMed Central

Jiménez-Castro, Lorena; Raventós-Vorst, Henriette; Escamilla, Michael

2012-01-01

El interés por comprender la co-morbilidad de la esquizofrenia y el trastorno en el uso de sustancias, ha aumentado debido al incremento de este diagnóstico, a los efectos negativos observados en el sujeto y a los costos en los servicios de salud. Este trastorno dual puede tener efectos dramáticos en el curso clínico del trastorno psicótico tales como: mayores recaídas, re-hospitalizaciones, síntomas más severos, no adherencia al tratamiento antipsicótico, cambios marcados del humor, aumento en el grado de hostilidad e ideación suicida, así como alteraciones en otras áreas del funcionamiento incluyendo violencia, victimización, indigencia y problemas legales. La literatura proveniente en particular de Estados Unidos y Europa sugiere que el rango de prevalencia para este diagnóstico puede oscilar entre el 10% hasta el 70%. En este estudio, revisamos la prevalencia del diagnóstico dual de esquizofrenia y trastorno en el uso sustancias, así como sus características sociodemográficas, con base en la literatura disponible alrededor del mundo dando énfasis en la poblacion latina. A pesar de que este diagnóstico es ampliamente aceptado, se conoce poco sobre su prevalencia en la población latina, sobre los factores ambientales, demográficos, clínicos y otras características de estos individuos. Un mejor conocimiento sobre este diagnóstico permitiría mejorar los métodos para la detección y adecuada valoración del trastorno en el uso de sustancias en personas con trastornos metales severos como la esquizofrenia. PMID:21404151

Estudio multifrecuencia del medio interestelar cercano a HD 192281

NASA Astrophysics Data System (ADS)

Arnal, E. M.; Cappa, C.; Cichowolski, S.; Pineault, S.; St-Louis, N.

Una de las causas que modifica la estructura y dinámica del medio interestelar es la acción que los vientos de las estrellas de gran masa ejercen sobre el mismo. En este trabajo, mediante el uso de datos interferométricos obtenidos en la banda de radio en la transición de 21-cm del Hidrógeno neutro y de imágenes de la emisión de continuo en las bandas de 408 y 1420 MHz, de imágenes HIRES del satélite IRAS en 60 y 100 micrones, y de observaciones de continuo obtenidas con radiotelescopios de disco simple en 2695, 4850 y 8350 MHz se ha realizado un estudio multifrecuencia de los efectos que los vientos estelares de HD 192281, una estrella de tipo espectral O5 Vn((f))p, han tenido sobre el medio interestelar que rodea a la misma.

Estudio multifrecuencia del medio interestelar cercano a HD 192281

NASA Astrophysics Data System (ADS)

Arnal, E. M.; Cappa, C. E.; Cichowolski, S.; Pineault, S.; St-Louis, N.

Una de las causas que modifica la estructura y dinámica del medio interestelar es la acción que los vientos de las estrellas de gran masa ejercen sobre el mismo. En este trabajo, mediante el uso de datos interferométricos obtenidos en la banda de radio en la transición de λ˜21-cm del hidrógeno neutro y de imágenes de la emisión de continuo en las bandas de 408 y 1420 MHz, de imágenes HIRES del satélite IRAS en 60 y 100μm, y de observaciones de continuo obtenidas con radiotelescopios de disco simple en 2695, 4850 y 8350 MHz se ha realizado un estudio multifrecuencia de los efectos que los vientos estelares de HD 192281, una estrella de tipo espectral O5,Vn((f))p, han tenido sobre el medio interestelar que rodea a la misma.

[La diagnosi del disturbo da uso di alcol dal punto di vista psicologico].

PubMed

Coriale, Giovanna; Fiorentino, Daniela; Porrari, Raffaella; Battagliese, Gemma; Capriglione, Ida; Cereatti, Federica; Iannuzzi, Silvia; Mauri, Benilde; Galli, Domenica; Fiore, Marco; Attilia, Maria Luisa; Ceccanti, Mauro

2018-01-01

RIASSUNTO. Il disturbo da uso di alcol (DUA) è uno dei disturbi psichiatrici più comuni nella popolazione generale. Il DUA è caratterizzato da un pattern di bere eccessivo, che si mantiene nonostante gli effetti negativi che l'alcol ha sul funzionamento lavorativo, sulla salute, sulle problematiche legali, sull'educazione e sulla vita sociale. Attualmente, il modello bio-psico-sociale è quello che spiega meglio il DUA. Infatti, molte ricerche hanno fornito evidenze su come il DUA sia una patologia multidimensionale. Variabili biologiche, psicologiche e socio-culturali entrano in gioco nell'eziologia, nella natura, nel mantenimento e nel cambiamento nel tempo del disturbo. La fase diagnostica è un momento importante del processo di cura, perché il successo del trattamento dipende in larga misura dall'esattezza e dall'adeguatezza della diagnosi. La diagnosi clinica si basa su una valutazione globale del funzionamento del paziente e utilizza il colloquio e gli strumenti psicometrici come mezzo di raccolta di informazioni. Questo articolo fornirà una panoramica delle dimensioni psicologiche più importanti da valutare e sui migliori strumenti psicometrici da usare per una diagnosi adeguata.

The Human 343delT HSPB5 Chaperone Associated with Early-onset Skeletal Myopathy Causes Defects in Protein Solubility*

PubMed Central

Mitzelfelt, Katie A.; Limphong, Pattraranee; Choi, Melinda J.; Kondrat, Frances D. L.; Lai, Shuping; Kolander, Kurt D.; Kwok, Wai-Meng; Dai, Qiang; Grzybowski, Michael N.; Zhang, Huali; Taylor, Graydon M.; Lui, Qiang; Thao, Mai T.; Hudson, Judith A.; Barresi, Rita; Bushby, Kate; Jungbluth, Heinz; Wraige, Elizabeth; Geurts, Aron M.; Benesch, Justin L. P.; Riedel, Michael; Christians, Elisabeth S.; Minella, Alex C.; Benjamin, Ivor J.

2016-01-01

Mutations of HSPB5 (also known as CRYAB or αB-crystallin), a bona fide heat shock protein and molecular chaperone encoded by the HSPB5 (crystallin, alpha B) gene, are linked to multisystem disorders featuring variable combinations of cataracts, cardiomyopathy, and skeletal myopathy. This study aimed to investigate the pathological mechanisms involved in an early-onset myofibrillar myopathy manifesting in a child harboring a homozygous recessive mutation in HSPB5, 343delT. To study HSPB5 343delT protein dynamics, we utilize model cell culture systems including induced pluripotent stem cells derived from the 343delT patient (343delT/343delT) along with isogenic, heterozygous, gene-corrected control cells (WT KI/343delT) and BHK21 cells, a cell line lacking endogenous HSPB5 expression. 343delT/343delT and WT KI/343delT-induced pluripotent stem cell-derived skeletal myotubes and cardiomyocytes did not express detectable levels of 343delT protein, contributable to the extreme insolubility of the mutant protein. Overexpression of HSPB5 343delT resulted in insoluble mutant protein aggregates and induction of a cellular stress response. Co-expression of 343delT with WT prevented visible aggregation of 343delT and improved its solubility. Additionally, in vitro refolding of 343delT in the presence of WT rescued its solubility. We demonstrate an interaction between WT and 343delT both in vitro and within cells. These data support a loss-of-function model for the myopathy observed in the patient because the insoluble mutant would be unavailable to perform normal functions of HSPB5, although additional gain-of-function effects of the mutant protein cannot be excluded. Additionally, our data highlight the solubilization of 343delT by WT, concordant with the recessive inheritance of the disease and absence of symptoms in carrier individuals. PMID:27226619

63. G.F.H., photographer July 30, 1932 DEL NORTE COUNTY, SECTION ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

63. G.F.H., photographer July 30, 1932 DEL NORTE COUNTY, SECTION A, HIGHWAY 1. 1-DN A #124, STA. 164=00 SHOWING DRAINAGE CONDITIONS, G.F.H., 7-30-32. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

Del(20q) in patients with chronic lymphocytic leukemia: A therapy-related abnormality involving lymphoid or myeloid cells

PubMed Central

Yin, C. Cameron; Tang, Guilin; Lu, Gary; Feng, Xiaoli; Keating, Michael J.; Medeiros, L. Jeffrey; Abruzzo, Lynne V.

2015-01-01

Del(20q), a common cytogenetic abnormality in myeloid neoplasms, is rare in chronic lymphocytic leukemia. We report 64 patients with chronic lymphocytic leukemia and del(20q), as the sole abnormality in 40, a stemline abnormality in 21, and a secondary abnormality in 3 cases. FISH analysis revealed an additional high-risk abnormality, del(11q) or del(17p), in 27/64 (42%) cases. In most cases, the leukemic cells showed atypical cytologic features, unmutated IGHV genes and ZAP70 positivity. The del(20q) was detected only after chemotherapy in all 27 cases with initial karyotypes available. With a median follow-up of 90 months, 30 patients (47%) died, most as a direct consequence of chronic lymphocytic leukemia. Eight patients developed a therapy-related myeloid neoplasm, seven with a complex karyotype. Combined morphologic and FISH analysis for del(20q) performed in 12 cases without morphologic evidence of a myeloid neoplasm localized the del(20q) to the chronic lymphocytic leukemia cells in 5 (42%) cases, and to myeloid/erythroid cells in 7 (58)% cases. The del(20q) was detected in myeloid cells in all 4 cases of myelodysplastic syndrome. In aggregate, these data indicate that chronic lymphocytic leukemia with del(20q) acquired after therapy is heterogeneous. In cases with morphologic evidence of dysplasia, the del(20q) likely resides in the myeloid lineage. However, in cases without morphologic evidence of dysplasia, the del(20q) may represent clonal evolution and disease progression. Combining morphologic analysis with FISH for del(20q) or performing FISH on immunomagnetically-selected subpopulations to localize the cell population with this abnormality may help guide patient management. PMID:25953391

Gene expression profiling assigns CHEK2 1100delC breast cancers to the luminal intrinsic subtypes.

PubMed

Nagel, Jord H A; Peeters, Justine K; Smid, Marcel; Sieuwerts, Anieta M; Wasielewski, Marijke; de Weerd, Vanja; Trapman-Jansen, Anita M A C; van den Ouweland, Ans; Brüggenwirth, Hennie; van I Jcken, Wilfred F J; Klijn, Jan G M; van der Spek, Peter J; Foekens, John A; Martens, John W M; Schutte, Mieke; Meijers-Heijboer, Hanne

2012-04-01

CHEK2 1100delC is a moderate-risk cancer susceptibility allele that confers a high breast cancer risk in a polygenic setting. Gene expression profiling of CHEK2 1100delC breast cancers may reveal clues to the nature of the polygenic CHEK2 model and its genes involved. Here, we report global gene expression profiles of a cohort of 155 familial breast cancers, including 26 CHEK2 1100delC mutant tumors. In line with previous work, all CHEK2 1100delC mutant tumors clustered among the hormone receptor-positive breast cancers. In the hormone receptor-positive subset, a 40-gene CHEK2 signature was subsequently defined that significantly associated with CHEK2 1100delC breast cancers. The identification of a CHEK2 gene signature implies an unexpected biological homogeneity among the CHEK2 1100delC breast cancers. In addition, all 26 CHEK2 1100delC tumors classified as luminal intrinsic subtype breast cancers, with 8 luminal A and 18 luminal B tumors. This biological make-up of CHEK2 1100delC breast cancers suggests that a relatively limited number of additional susceptibility alleles are involved in the polygenic CHEK2 model. Identification of these as-yet-unknown susceptibility alleles should be aided by clues from the 40-gene CHEK2 signature.

Eruptive Massive Vector Particles of 5-Dimensional Kerr-Gödel Spacetime

NASA Astrophysics Data System (ADS)

Övgün, A.; Sakalli, I.

2018-02-01

In this paper, we investigate Hawking radiation of massive spin-1 particles from 5-dimensional Kerr-Gödel spacetime. By applying the WKB approximation and the Hamilton-Jacobi ansatz to the relativistic Proca equation, we obtain the quantum tunneling rate of the massive vector particles. Using the obtained tunneling rate, we show how one impeccably computes the Hawking temperature of the 5-dimensional Kerr-Gödel spacetime.

Del(20q) in patients with chronic lymphocytic leukemia: a therapy-related abnormality involving lymphoid or myeloid cells.

PubMed

Yin, C Cameron; Tang, Guilin; Lu, Gary; Feng, Xiaoli; Keating, Michael J; Medeiros, L Jeffrey; Abruzzo, Lynne V

2015-08-01

Deletion 20q (Del(20q)), a common cytogenetic abnormality in myeloid neoplasms, is rare in chronic lymphocytic leukemia. We report 64 patients with chronic lymphocytic leukemia and del(20q), as the sole abnormality in 40, a stemline abnormality in 21, and a secondary abnormality in 3 cases. Fluorescence in situ hybridization (FISH) analysis revealed an additional high-risk abnormality, del(11q) or del(17p), in 25/64 (39%) cases. In most cases, the leukemic cells showed atypical cytologic features, unmutated IGHV (immunoglobulin heavy-chain variable region) genes, and ZAP70 positivity. The del(20q) was detected only after chemotherapy in all 27 cases with initial karyotypes available. With a median follow-up of 90 months, 30 patients (47%) died, most as a direct consequence of chronic lymphocytic leukemia. Eight patients developed a therapy-related myeloid neoplasm, seven with a complex karyotype. Combined morphologic and FISH analysis for del(20q) performed in 12 cases without morphologic evidence of a myeloid neoplasm localized the del(20q) to the chronic lymphocytic leukemia cells in 5 (42%) cases, and to myeloid/erythroid cells in 7 (58)% cases. The del(20q) was detected in myeloid cells in all 4 cases of myelodysplastic syndrome. In aggregate, these data indicate that chronic lymphocytic leukemia with del(20q) acquired after therapy is heterogeneous. In cases with morphologic evidence of dysplasia, the del(20q) likely resides in the myeloid lineage. However, in cases without morphologic evidence of dysplasia, the del(20q) may represent clonal evolution and disease progression. Combining morphologic analysis with FISH for del(20q) or performing FISH on immunomagnetically selected sub-populations to localize the cell population with this abnormality may help guide patient management.

62. R.L.T., photographer November 1, 1934 DEL NORTE COUNTY, SECTION ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

62. R.L.T., photographer November 1, 1934 DEL NORTE COUNTY, SECTION D, HIGHWAY 1. REDWOOD CLEARING ON EXISTING LINE, 1-DN-71-A #26, R.L.T. 11-1-34. Stamped office copy. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

60. C.J.T., photographer December 23, 1955 KLAMATH RIVER BRIDGE, DEL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

60. C.J.T., photographer December 23, 1955 KLAMATH RIVER BRIDGE, DEL NORTE COUNTY, SECTION A, HIGHWAY 1. DN-1-A #538, KLAMATH RIVER BR. FROM SO. END, 12/23/55, C.J.T. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

Inclusion of Astronomy Themes in an Inovative Approach of Informal Physics Teaching for High School Students. (Spanish Title: Inclusión de Temas Astronómicos en Uma Abordaje Innovadora de la Enseñanza Informal de Física Para Estudiantes de Secumdaria.) Inclusão de Temas Astronômicos Numa Abordagem Inovadora do Ensino Informal de Física Para Estudantes do Ensino Médio

NASA Astrophysics Data System (ADS)

Tiara Mota, Aline; de Morais Bonomini, Iracema Ariel; Meloni Martins Rosado, Ricardo

2009-12-01

The current work reports on an experience on Astronomy education at the Federal University of Itajubá through an extra-curricular course offered for High School students. This initiative was motivated by the low attention paid to the Astronomy subjects at this stage of the Brazilian Formal Education, in spite that the National Curricular Parameters (PCN and PCN+, in Brazil) point out the importance of their inclusion Este artículo relata una experiencia en la enseñanza de la astronomía efectuada en la Universidad Federal de Itajubá en la forma de un curso de extensión orientado para los estudiantes del colegio secundario. Esta iniciativa surgió de constatar la poca atención dada a la Astronomía en esta etapa de la Educación formal brasileña, a pesar que los Parámetros Curriculares Nacionales (PCN y PCN+, en Brasil) destacan la importancia de su inclusión. Este artigo relata uma experiência em ensino de Astronomia realizada na Universidade Federal de Itajubá na forma de um curso de extensão voltado para alunos do Ensino Médio. Esta iniciativa surgiu da pouca atenção que se dá à Astronomia nesta etapa da Educação embora os Parâmetros Curriculares Nacionais (PCN e PCN+) apontem a importância de sua inclusão.

Digitalización de diapositivas del Sol en H α

NASA Astrophysics Data System (ADS)

Missio, H.; Montenegro, C.; Montenegro, R.

El objetivo de este trabajo ha sido el de obtener imágenes digitalizadas de las diapositivas tomadas del Sol en luz de hidrógeno de la línea correspondiente a Hα, y de esta manera llegar a convertir las mismas a un archivo digital para poder ser tratadas luego por computadora y poder contabilizar con exactitud, mediante un programa adecuado para tal fin, las zonas activas del Sol en la imagen digitalizada. En principio, para llegar a esto se pensó en la utilización de medios accesibles, y como detector se utilizó un fototransistor ubicado dentro de un soporte rectangular sobre dos ejes de desplazamiento X e Y. Se han obtenido con este procedimiento imágenes de buena calidad, construídas a partir de tres datos digitalizados en cada barrido que aportan la posición X e Y y la intensidad del pixel en ese punto indicada en 255 tonos de grises.

CHEK2 (∗) 1100delC Mutation and Risk of Prostate Cancer.

PubMed

Hale, Victoria; Weischer, Maren; Park, Jong Y

2014-01-01

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 (∗)1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23-3.18) for unselected cases and 3.39 (1.78-6.47) for familial cases, indicating that CHEK2 (∗)1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2(∗)1100delC should be considered in men with a familial history of prostate cancer.

CHEK2 ∗1100delC Mutation and Risk of Prostate Cancer

PubMed Central

Park, Jong Y.

2014-01-01

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer. CHEK2 plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, of CHEK2 on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussed CHEK2 ∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating that CHEK2 ∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer. PMID:25431674

The Cuernos del Paine mountains in Torres del Paine National Park in Chile, photographed during NASA's AirSAR 2004 campaign

NASA Image and Video Library

2004-03-11

The Cuernos del Paine mountains in Torres del Paine National Park in Chile, photographed during NASA's AirSAR 2004 campaign. AirSAR 2004 is a three-week expedition in Central and South America by an international team of scientists that is using an all-weather imaging tool, called the Airborne Synthetic Aperture Radar (AirSAR), located onboard NASA's DC-8 airborne laboratory. Scientists from many parts of the world are combining ground research with NASA's AirSAR technology to improve and expand on the quality of research they are able to conduct. Founded in 1959, Torres del Paine National Park encompasses 450,000 acres in the Patagonia region of Chile. This region is being studied by NASA using a DC-8 equipped with an Airborne Synthetic Aperture Radar (AirSAR) developed by scientists from NASA’s Jet Propulsion Laboratory. This is a very sensitive region that is important to scientists because the temperature has been consistently rising causing a subsequent melting of the region’s glaciers. AirSAR will provide a baseline model and unprecedented mapping of the region. This data will make it possible to determine whether the warming trend is slowing, continuing or accelerating. AirSAR will also provide reliable information on ice shelf thickness to measure the contribution of the glaciers to sea level.

El ``Aula del Cel'': astronomy approaching high school

NASA Astrophysics Data System (ADS)

Ortiz-Gil, A.; Gómez Collado, M.; Gallego Calvente, A. T.

The “Aula del Cel” is a project carried out by the Astronomical Obsevatory of the University of Valencia, Spain. It offers high-school teachers a tool for teaching Astronomy to 10 to 17 year-old students. Different programs, experiments, and audiovisual presentations have been prepared by a team formed both by professional astronomers and teachers, and are offered in a format chosen to suit each particular age and curriculum group. Special sessions have been designed for students with special needs (for example blind or autistic children) in close contact with the pedagogical teams responsible for their education. Nearly three thousand students have already visited the “Aula del Cel” over the first six months that it has been offered to the school community.

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

PubMed Central

Huijts, Petra EA; Hollestelle, Antoinette; Balliu, Brunilda; Houwing-Duistermaat, Jeanine J; Meijers, Caro M; Blom, Jannet C; Ozturk, Bahar; Krol-Warmerdam, Elly MM; Wijnen, Juul; Berns, Els MJJ; Martens, John WM; Seynaeve, Caroline; Kiemeney, Lambertus A; van der Heijden, Henricus F; Tollenaar, Rob AEM; Devilee, Peter; van Asperen, Christi J

2014-01-01

The 1100delC mutation in the CHEK2 gene has a carrier frequency of up to 1.5% in individuals from North-West Europe. Women heterozygous for 1100delC have an increased breast cancer risk (odds ratio 2.7). To explore the prevalence and clinical consequences of 1100delC homozygosity in the Netherlands, we genotyped a sporadic breast cancer hospital-based cohort, a group of non-BRCA1/2 breast cancer families, and breast tumors from a tumor tissue bank. Three 1100delC homozygous patients were found in the cohort of 1434 sporadic breast cancer patients, suggesting an increased breast cancer risk for 1100delC homozygotes (odds ratio 3.4, 95% confidence interval 0.4–32.6, P=0.3). Another 1100delC homozygote was found in 592 individuals from 108 non-BRCA1/2 breast cancer families, and two more were found after testing 1706 breast tumors and confirming homozygosity on their wild-type DNA. Follow-up data was available for five homozygous patients, and remarkably, three of them had developed contralateral breast cancer. A possible relationship between 1100delC and lung cancer risk was investigated in 457 unrelated lung cancer patients but could not be confirmed. Due to the small number of 1100delC homozygotes identified, the breast cancer risk estimate associated with this genotype had limited accuracy but is probably higher than the risk in heterozygous females. Screening for CHEK2 1100delC could be beneficial in countries with a relatively high allele frequency. PMID:23652375

Primer registro para Peru del genero Nielsonia Young, 1977 (Hemiptera: Cicadellidae: Cicadellinae: Cicadellini)

USDA-ARS?s Scientific Manuscript database

En este articulo se reporta por primera vez para el Peru una especies del genero Nielsonia Young, 1977, de material procedente del Departamento de Tumbes. El genero ha sido reportada anteriormente de Ecuador, como unico registro para Sudamerica, y America Central. El unico especimen hembra encontra...

Ectopsocidae (Psocodea: 'Psocoptera') from Valle del Cauca and NNP Gorgona, Colombia.

PubMed

Manchola, Oscar Fernando Saenz; Obando, Ranulfo González; Aldrete, Alfonso N García

2014-04-14

The results of a survey of the psocid family Ectopsocidae in Valle del Cauca and NNP Gorgona, are here presented. Fifteen species were identified, in the genera Ectopsocus (14 species), and Ectopsocopsis (one species); four of the Ectopsocus species are new to science and are here described and illustrated. The male of E. thorntoni García Aldrete is here described. Records of Ectopsocopsis cryptomeriae (Enderlein), Ectopsocus briggsi McLachlan, E. californicus Banks, E. columbianus Badonnel, E. maindroni Badonnel, E. meridionalis Ribaga, E. pilosus Badonnel, E. richardsi Pearman, E. titschacki Jentsch, and E. vilhenai Badonnel, are provided. Ten species were found only in Valle del Cauca, two species were found only in the NNP Gorgona, and three species were found at both sites. The specimens studied are deposited in the Entomological Museum, Universidad del Valle, Santiago de Cali, Colombia (MUSENUV).

Desgarros del epitelio pigmentario de la retina: factores de riesgo, mecanismo y control terapéutico.

PubMed

Clemens, Christoph R; Eter, Nicole

2017-07-11

Los desgarros del epitelio pigmentario de la retina (EPR) se asocian en la mayoría de los casos con los desprendimientos vascularizados del EPR debido a una degeneración macular asociada a la edad (DMAE), y normalmente implican una pérdida adversa de la agudeza visual. Estudios recientes indican que ha habido un aumento en la incidencia de desgarros del EPR desde la introducción de fármacos anti-factor de crecimiento del endotelio vascular (anti-VEGF) así como una asociación temporal entre el desgarro y la inyección intravítrea. Dado que el número de pacientes con DMAE y el número de inyecciones anti-VEGF va en aumento, tanto la dificultad de prevenir desgarros del EPR como el tratamiento tras la formación de los desgarros han adquirido una mayor relevancia. De forma paralela, la evolución de la imagenología de la retina ha contribuido de manera significativa a comprender mejor el desarrollo de los desgarros del EPR en los últimos años. Esta revisión resume los conocimientos que se poseen actualmente sobre el desarrollo, los factores pronósticos y las estrategias terapéuticas de los desgarros del EPR antes y después de que estos se formen. © 2017 S. Karger AG, Basel.

Basic Concepts of Astronomy: a Methodological Proposal. (Spanish Title: Conceptos Básicos de Astronomía: Una Propuesta Metodológica.) Conceitos Básicos de Astronomia: Uma Proposta Metodológica

NASA Astrophysics Data System (ADS)

Darroz, Luiz Marcelo; Heineck, Renato; Samudio Pérez, Carlos Ariel

2011-12-01

In this report, the development of a methodological proposal which approaches basic concepts of astronomy-grounded pedagogically on Meaningful Learning is described. The proposal, which consists of four meetings, was developed by teachers and academics of the course of Professor in Physics of the University of Passo Fundo (UPF), through an extension course to a group of highschool students of a public school of the town of Passo Fundo, RS. The work was focused into basic concepts of astronomy. The signs of Meaningful Learning have been obtained by means of research and evaluation tools that were applied at the end of each meeting. The evaluation of the proposal has been conducted by means of a final questionnaire which was answered by the participants at the end ofthe development of activities. By means of the results obtained from the different instruments, and the comments made by the participants during the activities and by means of the high rates of approval obtained in the final questionnaire, we think that the proposal reached the established goals and it may be repeated with the certainty of success. En este relato se describe una propuesta de desarrollo metodológico que aborda conceptos básicos de astronomía fundamentada pedagógicamente en el Aprendizaje Significativo. La propuesta que comprende cuatro encuentros, fue desarrollada por profesores y académicos del curso de Licenciatura en Física de la Universidad de Passo Fundo (UPF), a través de un curso de extensión para un grupo de Liceo del 6º año de una Escuela Pública de la ciudad de Passo Fundo/RS. El trabajo tuvo como eje principal los "conceptos básicos de astronomía". Los indicios de Aprendizaje Significativo fueron obtenidos por instrumentos de pesquisa y evaluación, siempre aplicados después de cada encuentro. La evaluación de la propuesta fue hecha a través de un cuestionario final y contestado por los participantes al finalizar el desarrollo de actividades. Por los resultados

33 CFR 334.110 - Delaware Bay off Cape Henlopen, Del.; naval restricted area.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., Del.; naval restricted area. 334.110 Section 334.110 Navigation and Navigable Waters CORPS OF....110 Delaware Bay off Cape Henlopen, Del.; naval restricted area. (a) The area. Beginning at a point on... regulations in this section shall be enforced by the Commandant, Fourth Naval District, and such agencies as...

Modeling landscapes and past vegetation patterns of New Mexico's Rio Del Oso Valley

Treesearch

Richard D. Periman

2005-01-01

Humans have interacted with the landscape and ecosystem of New Mexico's Rio del Oso Valley for thousands of years. Throughout the Holocene, various cultures have dramatically affected and altered the Rio del Oso. An interdisciplinary research approach, incorporating geomorphology, paleobotany, archaeology, and history, provides a broad range of methodologies and...

El Alcalde José Carlos Aponte Dalmau del Municipio de Carolina es nombrado a formar parte del Comité Asesor de Gobiernos Locales de la EPA a nivel de todos los Estados Unidos

EPA Pesticide Factsheets

Comunicado de prensa de la EPA: El Alcalde José Carlos Aponte Dalmau del Municipio de Carolina es nombrado a formar parte del Comité Asesor de Gobiernos Locales de la EPA a nivel de todos los Estados Unidos

El bosque estatal del nuevo milenio antes y después del huracán Georges

Treesearch

A.E. Lugo; E. Román Nunci; M. Quinones; H. Marcano Vega; I. Vicéns

2005-01-01

We studied changes that occurred between 1997 and 2005 on a secondary wet subtropical urban forest in the University of Puerto Rico’s Botanical Garden (Bosque Estatal del Nuevo Milenio). Hurricane Georges passed south of the forest on November 21, 1998 with 127 km/h winds. The study consisted of identifying species in 40 plots of 254 m2 each, measuring the diameter at...

Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3β-C/EBPβ pathway.

PubMed

Maekawa, Tomoki; Hosur, Kavita; Abe, Toshiharu; Kantarci, Alpdogan; Ziogas, Athanasios; Wang, Baomei; Van Dyke, Thomas E; Chavakis, Triantafyllos; Hajishengallis, George

2015-09-16

Del-1 is an endothelial cell-secreted anti-inflammatory protein. In humans and mice, Del-1 expression is inversely related to that of IL-17, which inhibits Del-1 through hitherto unidentified mechanism(s). Here we show that IL-17 downregulates human endothelial cell expression of Del-1 by targeting a critical transcription factor, C/EBPβ. Specifically, IL-17 causes GSK-3β-dependent phosphorylation of C/EBPβ, which is associated with diminished C/EBPβ binding to the Del-1 promoter and suppressed Del-1 expression. This inhibitory action of IL-17 can be reversed at the GSK-3β level by PI3K/Akt signalling induced by D-resolvins. The biological relevance of this regulatory network is confirmed in a mouse model of inflammatory periodontitis. Intriguingly, resolvin-D1 (RvD1) confers protection against IL-17-driven periodontal bone loss in a Del-1-dependent manner, indicating an RvD1-Del-1 axis against IL-17-induced pathological inflammation. The dissection of signalling pathways regulating Del-1 expression provides potential targets to treat inflammatory diseases associated with diminished Del-1 expression, such as periodontitis and multiple sclerosis.

An unexpected effect of TNF-α on F508del-CFTR maturation and function

PubMed Central

Bitam, Sara; Urbach, Valérie; Sermet-Gaudelus, Isabelle; Hinzpeter, Alexandre; Edelman, Aleksander

2015-01-01

Cystic fibrosis (CF) is a multifactorial disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene ( CFTR), which encodes a cAMP-dependent Cl - channel. The most frequent mutation, F508del, leads to the synthesis of a prematurely degraded, otherwise partially functional protein. CFTR is expressed in many epithelia, with major consequences in the airways of patients with CF, characterized by both fluid transport abnormalities and persistent inflammatory responses. The relationship between the acute phase of inflammation and the expression of wild type (WT) CFTR or F508del-CFTR is poorly understood. The aim of the present study was to investigate this effect. The results show that 10 min exposure to TNF-alpha (0.5-50ng/ml) of F508del-CFTR-transfected HeLa cells and human bronchial cells expressing F508del-CFTR in primary culture (HBE) leads to the maturation of F508del-CFTR and induces CFTR chloride currents. The enhanced CFTR expression and function upon TNFα is sustained, in HBE cells, for at least 24 h. The underlying mechanism of action involves a protein kinase C (PKC) signaling pathway, and occurs through insertion of vesicles containing F508del-CFTR to the plasma membrane, with TNFα behaving as a corrector molecule. In conclusion, a novel and unexpected action of TNFα has been discovered and points to the importance of systematic studies on the roles of inflammatory mediators in the maturation of abnormally folded proteins in general and in the context of CF in particular. PMID:26594334

Weyl fermions in a family of Gödel-type geometries with a topological defect

NASA Astrophysics Data System (ADS)

Garcia, G. Q.; Oliveira, J. R. De S.; Furtado, C.

In this paper, we study Weyl fermions in a family of Gödel-type geometries in Einstein general relativity. We also consider that these solutions are embedded in a topological defect background. We solve the Weyl equation and find the energy eigenvalues and eigenspinors for all three cases of Gödel-type geometries where a topological defect is passing through them. We show that the presence of a topological defect in these geometries contributes to the modification of the spectrum of energy. The energy zero modes for all three cases of the Gödel geometries are discussed.

General nonextremal rotating charged Gödel black holes in minimal five-dimensional gauged supergravity.

PubMed

Wu, Shuang-Qing

2008-03-28

I present the general exact solutions for nonextremal rotating charged black holes in the Gödel universe of five-dimensional minimal supergravity theory. They are uniquely characterized by four nontrivial parameters: namely, the mass m, the charge q, the Kerr equal rotation parameter a, and the Gödel parameter j. I calculate the conserved energy, angular momenta, and charge for the solutions and show that they completely satisfy the first law of black hole thermodynamics. I also study the symmetry and separability of the Hamilton-Jacobi and the massive Klein-Gordon equations in these Einstein-Maxwell-Chern-Simons-Gödel black hole backgrounds.

La implantacion del enfoque constructivista en el aula de ciencia: Estudio de caso multiple

NASA Astrophysics Data System (ADS)

Arroyo Betancourt, Luz I.

Esta investigacion estudia la implantacion del enfoque constructivista en tres aulas de ciencia del contexto puertorriqueno. Se auscultaron las practicas educativas que utilizan maestras consideradas constructivistas y la correspondencia de sus practicas educativas con los elementos esenciales de la didactica que proponen los teoricos de los planteamientos constructivistas. Se ausculto, ademas, a que vision del enfoque constructivista responden las expresiones de las maestras acerca de su practica educativa y como compara con su quehacer, a la luz de los elementos esenciales de las visiones constructivistas piagetiana, social y radical. Se utilizo el diseno de estudio descriptivo de caso multiple. El estudio se baso en entrevistas a profundidad, revision de documentos y observacion no participativa a la sala de clases. El contexto fueron tres escuelas publicas de la Region Educativa de San Juan, una elemental, una intermedia y una superior. Los resultados confirmaron que la transicion hacia el enfoque constructivista es un proceso que toma tiempo, dedicacion y la participacion en adiestramientos y readiestramientos acerca del nuevo enfoque. Las maestras coinciden en la mayoria de las practicas educativas que utilizan para implantar el enfoque constructivista de ensenanza y difieren en algunas debido, probablemente, a que han tenido que adaptarlas a los correspondientes niveles de ensenanza: elemental, intermedio y superior. Dos de las maestras planifican por conceptos generadores, mientras que una de ellas planifica siguiendo la guia que recibe del Departamento de Educacion. Difieren ademas, en el enfasis que confieren al inquirir cientifico. Con relacion a la correspondencia entre la vision manifestada por las maestras a la luz de las visiones piagetiana, social y radical, aparentemente, las preguntas del protocolo de entrevistas no lograron evocar la informacion con suficiente profundidad, por lo que la investigadora tuvo que inferir las visiones de las

Estimaciones de Prevalencia del VIH por Género y Grupo de Riesgo en Tijuana, México: 2006

PubMed Central

Iñiguez-Stevens, Esmeralda; Brouwer, Kimberly C.; Hogg, Robert S.; Patterson, Thomas L.; Lozada, Remedios; Magis-Rodriguez, Carlos; Elder, John P.; Viani, Rolando M.; Strathdee, Steffanie A.

2010-01-01

OBJETIVO Estimar la prevalencia del VIH en adultos de 15-49 años de edad en Tijuana, México - en la población general y en subgrupos de riesgo en el 2006. METODOS Se obtuvieron datos demográficos del censo Mexicano del 2005, y la prevalencia del VIH se obtuvo de la literatura. Se construyó un modelo de prevalencia del VIH para la población general y de acuerdo al género. El análisis de sensibilidad consistió en estimar errores estándar del promedio-ponderado de la prevalencia del VIH y tomar derivados parciales con respecto a cada parámetro. RESULTADOS La prevalencia del VIH es 0.54%(N = 4,347) (Rango: 0.22%–0.86%, (N = 1,750–6,944)). Esto sugiere que 0.85%(Rango: 0.39%–1.31%) de los hombres y 0.22%(Rango: 0.04%–0.40%) de las mujeres podrían ser VIH-positivos. Los hombres que tienen sexo con hombres (HSH), las trabajadoras sexuales usuarias de drogas inyectables (MTS-UDI), MTS-noUDI, mujeres UDI, y los hombres UDI contribuyeron las proporciones más elevadas de personas infectadas por el VIH. CONCLUSIONES El número de adultos VIH-positivos entre subgrupos de riesgo en la población de Tijuana es considerable, marcando la necesidad de enforcar las intervenciones de prevención en sus necesidades específicas. El presente modelo estima que hasta 1 en cada 116 adultos podrían ser VIH-positivos. PMID:19685824

An evening at "La Clinica del Pueblo".

PubMed

Shefsky, M L

1986-01-01

This article describes a typical evening at the Clinica del Pueblo in the Hispanic neighborhood of Adams-Morgan in Washington, D.c. The Clinical del Pueblo began operating in 1983 in response to the urgen medical needs of Central American refugees arriving in the Washington D.c. area. The refugees bring with them severe trauma, fear, and health problems caused by the civil was and exacerbated by inadequate or non-existant health services. Approximately 80,000 Salvadoran refugees live in the area. They do not receive adequate health care for 3 reasons. 1) Because the US goverment is unwilling to recognize them as true refugees, they live with the constant threat of deportatin back to the violence from which they have fled. 2) Refugees lack the ability to pay for private care. 3) Langauage and culture create frightening barriers to health care for the refugees. For those who do seek care, these barriers can lead to the inadequate or incomplete diagnoses and poor compliance and follow-up. Plenty International and the Central American Refugee Center responded to these problems by organizing a free clinic to provide not only medical care but also a training course for volunteers. The director of the clinic organizes the course, the classes are taught by a variety of people including the clinic's volunteer physicians, nurses, and public health educators as well as graduates of previus training courses and people from the wider community. The services of the clinic reach only a small portion of the population in need. However, the fact that free medical services are now available to some Central American refugees make the Clinica del Pueblo an important program.

The novel complex allele [A238V;F508del] of the CFTR gene: clinical phenotype and possible implications for cystic fibrosis etiological therapies.

PubMed

Diana, Anna; Polizzi, Angela Maria; Santostasi, Teresa; Ratclif, Luigi; Pantaleo, Maria Giuseppina; Leonetti, Giuseppina; Iusco, Danila Rosa; Gallo, Crescenzio; Conese, Massimo; Manca, Antonio

2016-06-01

Few mutations in cis have been annotated for F508del homozygous patients. Southern Italy patients who at a first analysis appeared homozygous for the F508del mutation (n=63) or compound heterozygous for the F508del and another mutation in the cystic fibrosis transmembrane conductance regulator gene (n=155) were searched for the A238V mutation in exon 6. The allelic frequency of the complex allele [A238V;F508del] was 0.04. When the whole data set was used (comprised also of 56 F508del/F508del and 34 F508del/other mutation controls), no differences reached the statistical significance in the clinical parameters, except chloride concentrations which were lower in [A238V;F508del]/other mutation compared with F508del/other mutation (P=0.03). The two study groups presented less complications than the control groups. Within the minimal data set (34 F508del/F508del, 27 F508del/other mutation, 4 [A238V;F508del]/F508del cases and 5 [A238V;F508del]/other mutation cases); that is, presenting all the variables in each patient, forced expiratory volume in 1 s and forced vital capacity presented a trend to lower levels in the study groups in comparison with the F508del/F508del group, and C-reactive protein approximated statistically significant higher levels in the [A238V;F508del]/other mutation as compared with F508del/F508del patients (P=0.09). The analysis of statistical dependence among the variables showed a significant anticorrelation between chloride and body mass index in the [A238V;F508del]/other mutation group. In conclusion, the complex allele [A238V;F508del] seems to be associated with less general complications than in the control groups, on the other hand possibly giving a worse pulmonary phenotype and higher systemic/local inflammatory response. These findings have implications for the correct recruitment and clinical response of F508del patients in the clinical trials testing the new etiological drugs for cystic fibrosis.

Comportamiento del Helio en estrellas químicamente peculiares

NASA Astrophysics Data System (ADS)

Malaroda, S. M.; López García, Z.; Leone, F.; Catalano, F.

Las estrellas químicamente peculiares (CP) se caracterizan por tener deficiencias y sobreabundancias de algunos elementos químicos de hasta 106 veces la abundancia solar. Además presentan variaciones en las líneas espectrales. Se piensa que ello se debe a que los campos magnéticos presentes en este tipo de estrellas son principalmente dipolares, con un eje de simetría diferente del eje de rotación. La distribución de los elementos sobreabundantes y deficientes no es homogénea sobre la superficie estelar y las variaciones observadas serían una consecuencia directa de la rotación estelar. Entre los elementos con abundancia anómala se encuentra el Helio, cuyas líneas tienen intensidades que no son consistentes con una abundancia normal, que no puede ser determinada del modo usual, o sea, considerando una atmósfera con composición solar. Con el fin de determinar la abundancia de este elemento, se inició un estudio de estrellas anómalas de Helio, Hew y He strong. Además se determinarán las abundancias de otros elementos anómalos como ser el Si, Cr, Mg, Mn y Fe. Las mismas se determinan del modo tradicional, o sea: a) medida de los anchos equivalentes de las líneas de los distintos elementos analizados; b) adopción de la temperatura efectiva, gravedad y abundancia del Helio; c) cálculo del modelo de atmósfera d) comparación con las observaciones y reinicio de un proceso iterativo hasta lograr un acuerdo entre todos los parámetros analizados. Las observaciones se llevaron a cabo en el Complejo Astronómico El Leoncito. Se observaron setenta y ocho estrellas anómalas de Helio. En este momento se está procediendo a calcular las abundancias correspondientes a los distintos elementos químicos. Para ello se hace uso de los modelos de Kurucz, ATLAS9. Los cálculos NLTE de las líneas de Helio se llevan a cabo con el programa MULTI y se compararán con los realizados con el programa WIDTH9 de Kurucz (LTE), con el objeto de resaltar la importancia de

Misura de Massa e Larghezza degli Stati $$x_1$$ e $$x_2$$ del Charmonio Formati in Interazioni $$p - \\bar{p}$$

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

Pallavicini, Marco

1995-01-01

Oggetto di questa tesi è la misura di alcune caratteristiche fisiche ( massa, larghezza, e larghezza parziale in p - p) degli stati 3 Pi e 3 A del charmonio, - overo del sistema legato di un quark "charm" e del suo antiquark-, nell'ambito dell'esperimento E-760, installato nell'accumulatore di antiprotoni del Fermilab (U.S.A).

Archivo de placas astrométricas del Observatorio de La Plata

NASA Astrophysics Data System (ADS)

di Sisto, R.; Orellana, R. B.

Se ha realizado una base de datos con las placas fotográficas obtenidas con el Astrográfico del Observatorio de La Plata. Se han clasificado un total de 3000 placas obtenidas para asteroides y cometas. El acceso a la base de datos se hará por FTP y la misma contendrá la siguiente información: fecha y tiempo de exposición, coordenadas del centro de placa, tipo de emulsión fotográfica, estado de la placa, objeto fotografiado.

Gonadal dysgenesis, Turner syndrome with 46,XX,del(18p)3

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

Telvi, L.; Ion, R.; Bernheim, A.

1994-09-01

The authors report a case of a female infant with gonadal dysgenesis, clinical features of Turner syndrome and a de novo del(18p). The factors controlling gonadal dysgenesis and Turner syndrome are unknown to date. The genes involved could be located not only on X chromosome but also on autosomes. The present case suggests that one of these genes is situated on the short arm of chromosome 18. We conclude that patients with del(18p) syndrome should be evaluated for gonadal dysgenesis.

Mejoras en el apuntado del telescopio de 2,15 mts de CASLEO

NASA Astrophysics Data System (ADS)

Aballay, J. L.; Casagrande, A. R.; Pereyra, P. F.; Marún, A. H.

Con el objeto de optimizar el funcionamiento del telescopio de 2,15 mts. de CASLEO, se están eliminando los motores de calar, de guía y mecánica asociada. Para ésto, se están diseñando dos electrónicas que gobernarán, solamente, el motor de slew y el de tracking. Con el control del motor de slew se realizarán las funciones de slew y calar, controlando desde una PC la placa que maneja las rampas de velocidad. De este modo, el movimiento será programado y por lo tanto, más suave y preciso. Con el control del motor de tracking, a través de un generador de frecuencias programable desde una PC, se proveerá los movimientos necesarios para el tracking y guía.

[Recommendations to improve the scientific communication process in the Revista Médica del IMSS].

PubMed

Álvarez, Ivón

2016-01-01

In order to improve the position of the Revista Médica del Instituto Mexicano del Seguro Social among the different journals, in this editorial we enumerate a series of recommendations to ameliorate the practices of the different actors who participate in the scientific communication process of this journal.

Electromagnetically Inferred Structure of the Caja del Rio Plateau, New Mexico

NASA Astrophysics Data System (ADS)

Layton, M. E.; Speed, C.; Shukla, M.; Vila, A.; Chon, E.; Kitamikado, C.; Feucht, D. W.; Bedrosian, P.; Pellerin, L.

2016-12-01

Magnetotelluric (MT) and transient electromagnetic (TEM) data were acquired by students from the Summer of Applied Geophysical Experience (SAGE) to construct structural models in and around the Caja del Rio Plateau, New Mexico. The Caja del Rio is located on the La Bajada-Jemez constriction that separates the Española and Santa Domingo basins in the Rio Grande Rift. The Rio Grande Rift, the result of tectonic extensional forces, extends approximately north-south across northern New Mexico. MT data collected in 2016 were merged with that from previous years to make up an 11 km north line and a 16 km south line extending from the west side of the Caja Del Rio to the east off the plateau in the Old Buckman Road area. The resistivity distributions revealed in one-dimensional (1-D) and two-dimensional (2-D) inverse models show some robust features. Models of the north are interpreted as a top resistive layer (<500m) of Tertiary volcanoclastic rock, to a central conductive layer (600-200m) of Mesozoic and Paleozoic sediments of the Santa Fe group to crystalline basement rock. Models for the south line show low resistivity for the first 3 to 5 km and then transitions into higher resistivity values consistent with the models for the north line. At a period of 100 seconds induction arrows (Parkinson's convention) point in the northwest direction towards the conductive Valles Caldera. The MT models are consistent with geologic interpretations of the stratigraphic units. In addition, models disclose an additional conductive layer below the basement that we interpret as the mid-crustal conductor. Transient electromagnetic (TEM) data were collected in seven locations atop the Caja del Rio plateau in an attempt to identify the basal contact of the Cerros del Rio volcanic field, which, in turn, allow for the thickness of these basaltic and andesitic deposits to be mapped across the plateau. One-dimensional inverse models produced from the TEM data were aligned and interpreted

Field Measurements of Respiratory Del13CO2 and Photodegradation

NASA Astrophysics Data System (ADS)

van Asperen, H.; Sabbatini, S.; Nicolini, G.; Warneke, T.; Papale, D.; Notholt, J.

2014-12-01

Carbon decomposition dynamics have been studied in a variety of ecosystems and its variation can mostly be explained in terms of environmental variables (e.g. temperature and precipitation). However, carbon dynamics in arid, water limited regions have shown to be very different and are still largely unknown. Several studies have indicated the importance of photodegradation, the direct breakdown of organic matter by sunlight, in these arid regions. A FTIR (Fourier Transform Infrared Spectrometer) was set up to continuously measure concentrations of CO2, CH4, N2O, CO as well as del13C in CO2. The FTIR was connected to 2 different flux measurement systems: a Flux Gradient system and 2 flux chambers, providing a continuous data set of gas concentrations and biosphere-atmosphere gas fluxes at different heights and scales. Field measurements showed photodegradation induced carbon fluxes. Also, respiratory del13CO2 was determined by use of Keeling plots, and was determined to vary between -25‰ and -21‰. A clear diurnal pattern in respiratory del13CO2 was found, suggesting either different (dominant) respiratory processes between day and night or the effect of diffusive fractionation.

Ecos del Cosmos: A radio astroexperience at the Universitat de Valencia

NASA Astrophysics Data System (ADS)

Marco, E.; Ballesteros, F. J.; Ortiz-Gil, A.

2017-03-01

During the last three years Ecos del Cosmos has been a radio program dedicated to spreading astronomical hot news to the Universitat de València community and beyond, and also topics of general astronomical interest. To do this, this program by Ràdio Universitat has conducted live interviews with researchers, explored relationships of astronomy with humanities and society, performed contests and explained in a simple way the main monthly ephemerides. A version of Ecos del Cosmos was broadcasted in the Onda Cero’s summer program ''Jelo en verano''conducted by Arturo Tellez.

Pier Diego Siccardi (1880-1917) and the "Clinica del Lavoro" in the trench warfare.

PubMed

Riva, Michele Augusto; Caramella, Michela; Turato, Massimo; Cesana, Giancarlo

2017-12-14

The year 2017 marks the centenary of the death of the Italian scientist Pier Diego Siccardi (1880-1917), one of Luigi Devoto's assistants at the "Clinica del Lavoro" in Milan. To commemorate Siccardi and to describe the activities of the physicians of the "Clinica del Lavoro" during World War I. A comprehensive analysis was conducted on scientific papers written by Pier Diego Siccardi and by other physicians belonging to the Clinica del Lavoro, in the period 1915-1918. During the Great War, the Clinica del Lavoro became a military hospital, even though it indirectly maintained a role in Occupational Health, assisting women who had started to work to replace the men sent to the front. Devoto and his assistants were drafted as Army doctors, but continued their research activities while at the front; focusing on the diseases that affected the soldiers, mainly infections. Bleeding fevers and jaundice were endemic among Italian troops, but their etiology was unknown. Pier Diego Siccardi identified this syndrome as an infection caused by a spirochete, and was the first one to isolate the infectious agent. Siccardi prematurely died of the same disease as a consequence of a laboratory accident, which provided further confirmation for his research. The heroic life of Siccardi and his tragic death testify the important activities of the scientists of the "Clinica del Lavoro" in the years of the Great War.

DelPhiPKa web server: predicting pKa of proteins, RNAs and DNAs.

PubMed

Wang, Lin; Zhang, Min; Alexov, Emil

2016-02-15

A new pKa prediction web server is released, which implements DelPhi Gaussian dielectric function to calculate electrostatic potentials generated by charges of biomolecules. Topology parameters are extended to include atomic information of nucleotides of RNA and DNA, which extends the capability of pKa calculations beyond proteins. The web server allows the end-user to protonate the biomolecule at particular pH based on calculated pKa values and provides the downloadable file in PQR format. Several tests are performed to benchmark the accuracy and speed of the protocol. The web server follows a client-server architecture built on PHP and HTML and utilizes DelPhiPKa program. The computation is performed on the Palmetto supercomputer cluster and results/download links are given back to the end-user via http protocol. The web server takes advantage of MPI parallel implementation in DelPhiPKa and can run a single job on up to 24 CPUs. The DelPhiPKa web server is available at http://compbio.clemson.edu/pka_webserver. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility.

PubMed

Xiang, He-ping; Geng, Xiao-ping; Ge, Wei-wei; Li, He

2011-11-01

Cell cycle checkpoint kinase 2 (CHEK2) gene has been inconsistently associated with colorectal cancer (CRC), particularly the 1100delC variant. To generate large-scale evidence on whether the CHEK2 1100delC variant is associated with CRC susceptibility we have conducted a meta-analysis. Data were collected from the following electronic databases: PubMed, Excerpta Medica Database and Chinese Biomedical Literature Database, with the last report up to November 2010. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. We evaluated the contrast of carriers versus non-carriers. Meta-analysis was performed in a fixed/random effect model by using the software Review Manager 4.2. A total of six studies including 4194 cases and 10,010 controls based on the search criteria were involved in this meta-analysis. A significant association of the CHEK2 1100delC variant with unselected CRC was found (OR=2.11, 95% CI=1.41-3.16, P=0.0003). We also found an association of the CHEK2 1100delC variant with familial CRC (OR=2.80, 95% CI=1.74-4.51, P<0.0001). However, the association was not established for sporadic CRC (OR=1.45, 95% CI=0.49-4.30, P=0.50). This meta-analysis demonstrates that the CHEK2 1100delC variant may be an important CRC-predisposing gene, which increases CRC risk. Copyright © 2011. Published by Elsevier Ltd.

DelPhiForce web server: electrostatic forces and energy calculations and visualization.

PubMed

Li, Lin; Jia, Zhe; Peng, Yunhui; Chakravorty, Arghya; Sun, Lexuan; Alexov, Emil

2017-11-15

Electrostatic force is an essential component of the total force acting between atoms and macromolecules. Therefore, accurate calculations of electrostatic forces are crucial for revealing the mechanisms of many biological processes. We developed a DelPhiForce web server to calculate and visualize the electrostatic forces at molecular level. DelPhiForce web server enables modeling of electrostatic forces on individual atoms, residues, domains and molecules, and generates an output that can be visualized by VMD software. Here we demonstrate the usage of the server for various biological problems including protein-cofactor, domain-domain, protein-protein, protein-DNA and protein-RNA interactions. The DelPhiForce web server is available at: http://compbio.clemson.edu/delphi-force. delphi@clemson.edu. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

DelPhi web server v2: incorporating atomic-style geometrical figures into the computational protocol.

PubMed

Smith, Nicholas; Witham, Shawn; Sarkar, Subhra; Zhang, Jie; Li, Lin; Li, Chuan; Alexov, Emil

2012-06-15

A new edition of the DelPhi web server, DelPhi web server v2, is released to include atomic presentation of geometrical figures. These geometrical objects can be used to model nano-size objects together with real biological macromolecules. The position and size of the object can be manipulated by the user in real time until desired results are achieved. The server fixes structural defects, adds hydrogen atoms and calculates electrostatic energies and the corresponding electrostatic potential and ionic distributions. The web server follows a client-server architecture built on PHP and HTML and utilizes DelPhi software. The computation is carried out on supercomputer cluster and results are given back to the user via http protocol, including the ability to visualize the structure and corresponding electrostatic potential via Jmol implementation. The DelPhi web server is available from http://compbio.clemson.edu/delphi_webserver.

A Proposal for the Consolidation of Dermatology Services of Walter Reed Army Medical Center and the National Naval Medical Center

DTIC Science & Technology

1999-08-01

This includes the treatment of common skin conditions such as acne, dermatitis, psoriasis, vitiligo or alopecia to the more complex laser surgeries and...Phototherapy, Laser Surgery, Pediatric Dermatology, HIV Dermatology, Patch Testing, MOHS Micrographic Surgery, and Dermatologic Surgery. The entire...Dermatology Service is located on the first floor of the hospital. Minor surgical and MOHS Micrographic Surgery, ultraviolet treatment, and laser surgery

Los plaguicidas y la contaminacion del medio ambiente Venezolano

USGS Publications Warehouse

Stickel, L.F.; Stickel, W.H.

1972-01-01

RESUMEN DE RECOMENDACIONES Recomendaciones para el Programa de Investigacion: 1. Establecer un sistema de muestreo biologico para detectar los niveles tendencias de los productos quimicos toxicos en un peque?o numero de si tios representativos. 2. Mantener continua vigilancia de la contaminacion ambiental, mediante la seleccion acertadamente dirigida de las zonas afectadas y de las fuentes de contaminacion. 3. Realizar estudios acerca de las poblaciones de animales silvestres, y del exito de los procesos reproductivos de las especies o grupos clayes de animales que se consideran mas gravemente afectados. 4. Preparar recomendaciones para una accion gubernamental de proteccion al hombre, a la fauna silvestre y al medio ambiente. Recomendaciones para la Accion Administrativa: 1. Establecer limites a la tolerancia de los residuos de plaguicidas en los alimentos. Constituye una medida clave para disminuir la contaminacion ambiental. 2. Establecer normas de calidad del agua para las corrientes, represas, la gos y otros cuerpos. Es la segunda medida clave para reducir la contaminacion del ambiente 3. Exigir un tratamiento adecuado de los efluentes industriales, especialmente antes de que se construyan las nuevas plantas. 4. Exigir a los agricultores que en el uso de plaguicidas sigan los consejos tecnicos autorizados y negar a los vendedores el derecho a recomendar productos por su cuenta. 5. Tomar medidas para recoger y eliminar los recipientes y sobrantes de los plaguicidas.

CHEK2 c.1100delC allele is rarely identified in Greek breast cancer cases.

PubMed

Apostolou, Paraskevi; Fostira, Florentia; Papamentzelopoulou, Myrto; Michelli, Maria; Panopoulos, Christos; Fountzilas, George; Konstantopoulou, Irene; Voutsinas, Gerassimos E; Yannoukakos, Drakoulis

2015-04-01

The CHEK2 gene encodes a protein kinase that plays a crucial role in maintenance of genomic integrity and the DNA repair mechanism. CHEK2 germline mutations are associated with increased risk of breast cancer and other malignancies. From a clinical perspective, the most significant mutation identified is the c.1100delC mutation, which is associated with an approximately 25% lifetime breast cancer risk. The distribution of this mutation shows wide geographical variation; it is more prevalent in the Northern European countries and less common, or even absent, in Southern Europe. In order to estimate the frequency of the CHEK2 c.1100delC mutation in Greek breast cancer patients, we genotyped 2,449 patients (2,408 females and 41 males), which was the largest series ever tested for c.1100delC. The mean age of female and male breast cancer diagnosis was 49 and 59 years, respectively. All patients had previously tested negative for the Greek BRCA1 founder and recurrent mutations. The CHEK2 c.1100delC mutation was detected in 0.16% (4 of 2,408) of females, all of whom were diagnosed with breast cancer before the age of 50 years. Only one c.1100delC carrier was reported with breast cancer family history. The present study indicates that the CHEK2 c.1100delC mutation does not contribute substantially to hereditary breast cancer in patients of Greek descent. Copyright © 2015 Elsevier Inc. All rights reserved.

Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations

PubMed Central

Laitman, Yael; Feng, Bing-Jian; Zamir, Itay M; Weitzel, Jeffrey N; Duncan, Paul; Port, Danielle; Thirthagiri, Eswary; Teo, Soo-Hwang; Evans, Gareth; Latif, Ayse; Newman, William G; Gershoni-Baruch, Ruth; Zidan, Jamal; Shimon-Paluch, Shani; Goldgar, David; Friedman, Eitan

2013-01-01

The 185delAG* BRCA1 mutation is encountered primarily in Jewish Ashkenazi and Iraqi individuals, and sporadically in non-Jews. Previous studies estimated that this is a founder mutation in Jewish mutation carriers that arose before the dispersion of Jews in the Diaspora ∼2500 years ago. The aim of this study was to assess the haplotype in ethnically diverse 185delAG* BRCA1 mutation carriers, and to estimate the age at which the mutation arose. Ethnically diverse Jewish and non-Jewish 185delAG*BRCA1 mutation carriers and their relatives were genotyped using 15 microsatellite markers and three SNPs spanning 12.5 MB, encompassing the BRCA1 gene locus. Estimation of mutation age was based on a subset of 11 markers spanning a region of ∼5 MB, using a previously developed algorithm applying the maximum likelihood method. Overall, 188 participants (154 carriers and 34 noncarriers) from 115 families were included: Ashkenazi, Iraq, Kuchin-Indians, Syria, Turkey, Iran, Tunisia, Bulgaria, non-Jewish English, non-Jewish Malaysian, and Hispanics. Haplotype analysis indicated that the 185delAG mutation arose 750–1500 years ago. In Ashkenazim, it is a founder mutation that arose 61 generations ago, and with a small group of founder mutations was introduced into the Hispanic population (conversos) ∼650 years ago, and into the Iraqi–Jewish community ∼450 years ago. The 185delAG mutation in the non-Jewish populations in Malaysia and the UK arose at least twice independently. We conclude that the 185delAG* BRCA1 mutation resides on a common haplotype among Ashkenazi Jews, and arose about 61 generations ago and arose independently at least twice in non-Jews. PMID:22763381

Detecting a hierarchical genetic population structure via Multi-InDel markers on the X chromosome

PubMed Central

Fan, Guang Yao; Ye, Yi; Hou, Yi Ping

2016-01-01

Detecting population structure and estimating individual biogeographical ancestry are very important in population genetics studies, biomedical research and forensics. Single-nucleotide polymorphism (SNP) has long been considered to be a primary ancestry-informative marker (AIM), but it is constrained by complex and time-consuming genotyping protocols. Following up on our previous study, we propose that a multi-insertion-deletion polymorphism (Multi-InDel) with multiple haplotypes can be useful in ancestry inference and hierarchical genetic population structures. A validation study for the X chromosome Multi-InDel marker (X-Multi-InDel) as a novel AIM was conducted. Genetic polymorphisms and genetic distances among three Chinese populations and 14 worldwide populations obtained from the 1000 Genomes database were analyzed. A Bayesian clustering method (STRUCTURE) was used to discern the continental origins of Europe, East Asia, and Africa. A minimal panel of ten X-Multi-InDels was verified to be sufficient to distinguish human ancestries from three major continental regions with nearly the same efficiency of the earlier panel with 21 insertion-deletion AIMs. Along with the development of more X-Multi-InDels, an approach using this novel marker has the potential for broad applicability as a cost-effective tool toward more accurate determinations of individual biogeographical ancestry and population stratification. PMID:27535707

[The Revista Médica del IMSS in the 2017 Healthcare Book Fair].

PubMed

Ramiro-H, Manuel; Acosta-Pérez, L; Cruz-Aranda, J E; García-Damián, J J; Miguel-Reyes, R; González-Martínez, R

2017-01-01

On August, the second edition of the Healthcare Book Fair took place, sponsored by the Facultad de Medicina of UNAM. Again, the Revista Médica del Instituto Mexicano del Seguro Social participated with a stand where we promoted it, talked about the different indexes where our journal is included, explained its objective and scope, and finally talked about its nature as an open access journal, which is aimed to the clinical staff of the different health institutions of our country.

Resultados del relevamiento de HI en el Cielo Austral: 3. Relevamiento de Nubes de Alta Velocidad

NASA Astrophysics Data System (ADS)

Morras, R.; Bajaja, E.; Arnal, E. M.; Pöppel, W. G. L.

Los resultados del relevamiento de HI del Hemisferio Austral fueron reprocesados con el fin de incrementar su sensibilidad. Así, se utilizó esta nueva base de datos con el fin de obtener un nuevo relevamiento de Nubes de Alta Velocidad en el cielo austral. El ruido r.m.s. alcanzado es de 0.015-0.020 K, con una resolución espectral de 8 km/seg. El cubrimiento espacial del relevamiento mejora en un factor 16 al realizado por Bajaja et al (1985).

[La Medicina del Lavoro: 100 volumes].

PubMed

Zocchetti, C

2009-01-01

With these pages La Medicina del Lavoro starts its 100th volume, so we have yet another historical occasion to celebrate the oldest occupational health journal in the world that is still publishing. Over the last few years we have had many occasions to celebrate, for example several anniversaries of the Journal (the 80th volume in 1989, 90 years in 1992, 100 years in 2001); the centenary of the foundation of the Clinica del Lavoro "Luigi Devoto" of Milan in 2001; the celebration of the 300 years' anniversary of the publication of De Morbis Artificum Diatriba by Bernardino Ramazzini, and we obviously hope to continue for many years to come in this positive outlook. One hundred volumes makes for a very large collection, with the highs and lows ofthe Journal's history (here we mean the variations in number of pages and physical size of the Journal). It is thanks to the Editors-in-chief(there have been very few so we can cite them all: Luigi Devoto, 1901-1936; Luigi Preti, 1936-1941; Enrico Vigliani, 1943-1992; e Vito Foà, 1992 to the present); the contributors who in various ways and with varying degrees of commitment but always with an exceptional personal participation, that it has been possible to reach 100 volumes, starting with C. Moreschi who, along with Luigi Devoto, was the first and sole editor at the Journal's foundation; up to the present extended and impressive editorial board; the printers (from the first. Tipografia Cooperativa, Via dei Molini in Pavia, to the latest: Casa Editrice Mattioli in Fidenza); the sponsors, including the most evident who, via advertising (rather limited as a matter offact), directly gave information about themselves, but also those who have often been or are behind the scenes, ensuring fundamental support which is not visible; content. articles, news, events, reports, ideas, opinions, photographs, tables, numbers... etc, which are really impossible to sum up. But the true collection which, for obvious reasons, cannot be

Relevamiento total del hemisferio sur celeste en la frecuencia de 1420 MHz

NASA Astrophysics Data System (ADS)

Bava, J. A.; Colomb, F. R.; Hurrel, E.; Larrarte, J. J.; Sanz, A. J.; Testori, J. C.; Reich, P.; Reich, W.; Wielebinski, R.

En el presente artículo se describe el relevamiento del cielo en el Hemisferio Sur Celeste en la frecuencia de 1420 MHz para declinaciones δ<= -19o realizado con la Antena II de 30 metros de diámetro del IAR. Este relevamiento posee igual sensibilidad (3xr.m.s=50 mK) que el realizado en el Hemisferio Norte con el radiotelescopio de 25 metros de Stockert de la Universidad de Bonn, operado por el Max-Planck Institute für Radioastronomie ( Reich W., 1982, A&ASS 48, 219; Reich P. and Reich W., 1986, A&ASS 63, 205). Con los datos obtenidos por ambos radiotelescopios se posee una base de datos de todo el cielo en esta frecuencia. En esta publicación presentamos los detalles del sistema receptor, técnicas de observación y reducción de datos, calibración y discusión de los errores en los resultados.

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

PubMed Central

Stefano, Daniela De; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; Gregorio, Fabiola De; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; Rosa, Giuseppe De; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

2014-01-01

Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in CftrF508del homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation. PMID:25350163

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation.

PubMed

De Stefano, Daniela; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; De Gregorio, Fabiola; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; De Rosa, Giuseppe; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

2014-01-01

Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in Cftr(F508del) homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.

Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis.

PubMed

Marson, Fernando Augusto de Lima; Bertuzzo, Carmen Silvia; Ribeiro, Maria Ângela Gonçalves de Oliveira; Ribeiro, Antônio Fernando; Ribeiro, José Dirceu

2013-01-01

To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmembrane conductance regulator gene as a first step in the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with various clinical variables. We evaluated 180 CF patients regarding the F508del mutation. The clinical data were obtained from the medical records of the patients and from interviews with their parents or legal guardians. Of the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0 [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del homozygous (G2). All three groups showed associations with the clinical variables. Homozygosis was associated with younger patients, younger age at CF diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA), as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients were older; first experienced clinical symptoms, digestive disease, and pulmonary disease at an older age; were older at CF diagnosis and at first PA isolation; and had a lower prevalence of PI and meconium ileus, as well as of colonization by NMPA, mucoid PA, and Burkholderia cepacia. In G1 patients, values were intermediate for age at CF diagnosis; age at first PA isolation, first pulmonary symptoms, and first clinical manifestations; MPA colonization; and OR for PI. The identification of F508del in 63.9% of the patients studied showed that this can be a useful tool as a first step in the genetic diagnosis of CF. The F508del genotype was associated with clinical severity of the disease, especially with the variables related to CF onset.

Identificación de los miembros del cúmulo NGC 2516

NASA Astrophysics Data System (ADS)

de Elía, G. C.; Orellana, R. B.

El cúmulo abierto NGC 2516 (α = 7h 58m y δ = -60o 45') tiene una edad de, aproximadamente, 150 Myr. El análisis de este sistema es particularmente importante en el Hemisferio Sur debido a su abundancia de estrellas peculiares y muy estudiado aplicando técnicas fotométricas, pero muy poco analizado desde el punto de vista astrométrico. A partir de una placa obtenida en el Observatorio Astronómico de La Plata y observaciones más actuales, nos hemos abocado al estudio de los movimientos propios de este cúmulo con el fin de determinar la pertenencia al mismo de las estrellas del campo de dicho cúmulo. Luego de llevar a cabo la determinación de los movimientos propios de todas las estrellas a partir de las posiciones obtenidas de la placa existente en el Observatorio de La Plata de 1914 y leídas con la MAMA en París, las observaciones realizadas con el círculo meridiano de San Fernando que se encuentra en el Observatorio Félix Aguilar de San Juan y las posiciones existentes en los catálogos AC 2000, Tycho, USNO y UCAC, programamos el método de Vasilevsky y Sanders para determinar la pertenencia de las estrellas de la región al cúmulo en cuestión. En un paso posterior, se realizó una modificación al método anterior para la determinación de los miembros. En esta modificación se consideró la densidad de las estrellas del cúmulo y la densidad de estrellas de campo. Esto permitió evaluar la pertenencia, no sólo a partir del movimiento propio de las estrellas, sino también a partir de la posición de las mismas con respecto al centro del cúmulo. También se consideró la dependencia de los parámetros con la magnitud. Los resultados así obtenidos fueron comparados con otras investigaciones de movimientos propios de la región del cúmulo. El movimiento propio absoluto del cúmulo fue comparado con el obtenido a partir de los catálogos estelares. Se encontró que los resultados coincidían para estrellas brillantes (magnitud más brillante que

Alfabetización en Astronomía de docentes de Educación Primaria y de Educación Secundaria en La Plata

NASA Astrophysics Data System (ADS)

De Biasi, M. S.; Orellana, R. B.

2014-10-01

La educación de este siglo tiene como uno de sus retos alcanzar la alfabetización cientfica de todos los ciudadanos para que comprendan y tomen decisiones sobre el mundo natural y sus cambios originados por la actividad humana utilizando el conocimiento científico. En esta misión los docentes de los niveles obligatorios de enseñanza juegan un papel clave por su rol de agentes multiplicadores del conocimiento. Se requiere, entonces de una adecuada alfabetización en ciencias de los docentes o, como mínimo, que dominen los temas científicos a enseñar. En el campo de la Astronomía, numerosas investigaciones han señalado que maestros de primaria y estudiantes de profesorados poseen una escasa formación en estos temas (Camino 1995 y 1999, Gangui 2010), que frecuentemente presentan a los alumnos concepciones alternativas o no científicas de los fenómenos astronómicos cotidianos (Kriner 2004, Vega Navarro 2007, Gangui et al 2010); a lo que se suma la presentación confusa o errónea de algunos temas astronómicos en los textos escolares (Kriner 2004). Desde 2011, la Facultad de Ciencias Astronómicas y Geofísicas, UNLP, ofrece un curso de capacitación destinado a fortalecer y actualizar los contenidos académicos y didácticos de los docentes del distrito La Plata utilizando diversas estrategias didácticas. Los contenidos comprenden los temas astronómicos de los diseños curriculares vigentes. La evaluación diagnóstica de los conocimientos previos de los docentes cursantes sobre los contenidos de mayor presencia en los diseños curriculares mostró resultados similares a las investigaciones arriba mencionadas. Referente a los movimientos de la Tierra, en promedio, el 54% poseía conceptos erróneos y el 16% no los sabía; con referencia a la Luna el 56% poseía conceptos erróneos y un 4% no los sabía. Los resultados del curso mostraron que el 95% de los docentes revirtió sus conceptos previos erróneos, que adquirió criterios para la búsqueda de

Tofacitinib, an Oral Janus Kinase Inhibitor: Perspectives in Dermatology.

PubMed

Kostovic, Kresimir; Gulin, Sandra J; Mokos, Zrinka B; Ceovic, Romana

2017-05-31

Tofacitinib (formerly known as CP-690,550, CP690550, tasocitinib), a novel selective immunosuppressant, is a small molecule classified as Janus kinase inhibitor. The aim of this review article is to present updated data summary on the tofacitinib in the field of dermatology. We undertook a structured search of bibliographic databases for peer-reviewed scientific articles, including review articles, original research articles as well as case report articles based on inclusion/exclusion criteria. Technical reports on tofacitinib from U.S. Food and Drug Administration and European Medical Agency were also included. Forty-three papers were included in this review. We report current data on tofacitinib chemical properties, pharmacology, non-clinical toxicity, as well as efficacy and safety in potential new indications in dermatology: psoriasis, alopecia areata, vitiligo, atopic dermatitis and nail dystrophy associated with alopecia areata. JAK/STAT pathway has an important role in the pathogenesis of psoriasis, alopecia areata, atopic dermatitis, and vitiligo. Despite encouraging efficacy, due to concerns about the overall safety profile of tofacitinib, additional studies will have to determine the adequate risk-to-benefit ratio. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Inflammatory bowel disease is associated with an increased risk of inflammatory skin diseases: A population-based cross-sectional study.

PubMed

Kim, Miri; Choi, Kwang Hyun; Hwang, Se Won; Lee, Young Bok; Park, Hyun Jeong; Bae, Jung Min

2017-01-01

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract attributed to aberrant activity of the immune system. Increasing evidence suggests that patients with IBD are at an increased risk of inflammatory skin diseases (ISDs). We sought to clarify the association between IBD and ISDs using a nationwide health claims database maintained in Korea. We interrogated Korean health claim database data from 2009 to 2013. We enrolled all patients with IBD, and age- and sex-matched control subjects, and evaluated the risks of ISDs, including psoriasis, rosacea, and atopic dermatitis, and the risks of autoimmune skin diseases, including vitiligo and alopecia areata. We used multivariable logistic regression to this end. ISDs including rosacea, psoriasis, and atopic dermatitis were significantly associated with IBD, whereas the associations between IBD and autoimmune skin diseases including vitiligo and alopecia areata were less marked or nonexistent. Ulcerative colitis and Crohn's disease were both associated with ISDs. We were unable to distinguish phenotypes and severities of skin diseases. IBD was significantly associated with ISDs, but less so or not at all with autoimmune skin diseases. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Modeling visibility in the Paso del Norte (PDN) Region

NASA Astrophysics Data System (ADS)

Medina Calderon, Richard

Poor visibility is a subject of growing public concern throughout the U.S, and an active area of research. Its societal impacts on air quality, aviation transport and traffic are significant. Aerosols play a fundamental role in the attenuation of solar radiation, and also affect visibility. The scattering and extinction coefficients of aerosol particles in the Paso del Norte Region have been calculated using the T- matrix model in conjunction with a laser particle counter. Inter-comparison of the model's results of the scattering and absorption coefficients against the corresponding data from a Photoacustic extinctiometer instrument (which measures in-situ absorption and scattering coefficients of aerosol particles) shows excellent agreement. In addition, the volume-weighted method is used to determine the composite index of refraction which is representative of the aerosols for the Paso del Norte Region to obtain information of the type of aerosol particles present in the Region. The Single Scattering Albedo has also been retrieved using this methodology to obtain further insight into the type of aerosols present on a given day. Finally, the Koschmieder equation has been used to calculate the visual range or visibility, and was correlated with the PM2.5 and PM10 particle concentration present in the Region. Our methodology will allow a better understanding of the size and type of aerosol particles that are most detrimental to the visibility for the Paso Del Norte Region.

Highly preferential association of NonF508del CF mutations with the M470 allele.

PubMed

Ciminelli, B M; Bonizzato, A; Bombieri, C; Pompei, F; Gabaldo, M; Ciccacci, C; Begnini, A; Holubova, A; Zorzi, P; Piskackova, T; Macek, M; Castellani, C; Modiano, G; Pignatti, P F

2007-01-01

On the basis of previous findings on random individuals, we hypothesized a preferential association of CF causing mutations with the M allele of the M470V polymorphic site of the CFTR gene. We have determined the M/V-CF mutation haplotype in a series of 201 North East Italian and 73 Czech CF patients who were not F508del homozygotes, as F508del was already known to be fully associated with the M allele. Out of 358 not F508del CF genes, 84 carried the V allele and 274 the less common M allele. In the N-E Italian population, MM subjects have a risk of carrying a CF causing mutation 6.9x greater than VV subjects when F508del is excluded and 15.4x when F508del is included. In the Czech population a similar, although less pronounced, association is observed. Besides the possible biological significance of this association, the possibility of exploiting it for a pilot screening program has been explored in a local North East Italian population for which CF patients were characterized for their CF mutation. General M470V genotyping followed by common CF mutation screening limited to couples in which each partner carries at least one M allele would need testing only 39% of the couples, which contribute 89% of the total risk, with a cost benefit.

Age- and Tumor Subtype–Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers

PubMed Central

Hogervorst, Frans; van Hien, Richard; Cornelissen, Sten; Broeks, Annegien; Adank, Muriel A.; Meijers, Hanne; Waisfisz, Quinten; Hollestelle, Antoinette; Schutte, Mieke; van den Ouweland, Ans; Hooning, Maartje; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Antoniou, Antonis C.; Arndt, Volker; Bermisheva, Marina; Bogdanova, Natalia V.; Bolla, Manjeet K.; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Dunning, Alison M.; Fasching, Peter A.; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G.; Haeberle, Lothar; Hall, Per; Hillemanns, Peter; Hopper, John L.; Jakubowska, Anna; John, Esther M.; Jones, Michael; Khusnutdinova, Elza; Knight, Julia A.; Kosma, Veli-Matti; Kristensen, Vessela; Lee, Andrew; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Margolin, Sara; Meindl, Alfons; Milne, Roger L.; Muranen, Taru A.; Newcomb, Polly A.; Offit, Kenneth; Park-Simon, Tjoung-Won; Peto, Julian; Pharoah, Paul D.P.; Robson, Mark; Rudolph, Anja; Sawyer, Elinor J.; Schmutzler, Rita K.; Seynaeve, Caroline; Soens, Julie; Southey, Melissa C.; Spurdle, Amanda B.; Surowy, Harald; Swerdlow, Anthony; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Trentham-Dietz, Amy; Vachon, Celine; Wang, Qin; Whittemore, Alice S.; Ziogas, Argyrios; van der Kolk, Lizet; Nevanlinna, Heli; Dörk, Thilo; Bojesen, Stig; Easton, Douglas F.

2016-01-01

Purpose CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. Patients and Methods CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. Results Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center–based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10−20). The OR was higher for estrogen receptor (ER)–positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10−21]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10−4). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. Conclusion These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into

Estudio fenomenologico del conocimiento curricular y conocimiento de contenido en maestros de matematica a nivel secundario

NASA Astrophysics Data System (ADS)

Cardona Tomassini, Ivan Javier

En esta investigacion se estudio el fenomeno del conocimiento de contenido y el conocimiento curricular de maestros de matermaticas y como estos dos componentes se reflejan en su conocimiento pedagogico del contenido. El conocimiento de contenido es el conocimiento que tienen los maestros de los contenidos de una disciplina y sobre la estructura de su organizacion (Shulman, 1986). El conocimiento curricular es el conocimiento que los maestros poseen sobre los componentes de un curriculo disenado para ensenar un topico de una materia especifica a un nivel particular, la variedad de instrumentos instruccionales disponibles para implementar el mismo y como utilizar los instrumentos curriculares disponibles (Ball & Bass, 2003; Choppin, 2009; Hill, Rowan, & Ball, 2005). Este estudio se enmarca en el paradigma cualitativo, teniendo como diseno el estudio fenomenologico (Lucca y Berrios, 2009; McMillan, 2004). Los participantes fueron seis maestros de matermaticas del nivel superior (10mo a 12mo grado). Al momento de la investigacion los participantes ensenaban en escuelas publicas o privadas de Puerto Rico. Para recolectar la informacion se utilizo un grupo focal en donde los maestros resolvieron seis ejercicios matematicos y posteriormente reflexionaron en forma grupal sobre las soluciones. Tambien se realizo un analisis de documentos de planificacion y se llevaron a cabo entrevistas semiestructuradas. Se exploraron los contenidos relacionados a la ecuacion de una recta, rectas verticales y horizontales, suma y multiplicacion de polinomios, resolucion de ecuaciones cuadraticas y distancia entre dos puntos del plano cartesiano. Los resultados muestran que los participantes tienen dominio procesal de los contenidos correspondientes a las rectas verticales y horizontales, la suma y multiplicacion de polinomios, el calculo distancia entre dos puntos del plano cartesiano. Sin embargo, se noto cierta dificultad en la explicacion conceptual de los contenidos relacionados a la

Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers.

PubMed

Schmidt, Marjanka K; Hogervorst, Frans; van Hien, Richard; Cornelissen, Sten; Broeks, Annegien; Adank, Muriel A; Meijers, Hanne; Waisfisz, Quinten; Hollestelle, Antoinette; Schutte, Mieke; van den Ouweland, Ans; Hooning, Maartje; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Antoniou, Antonis C; Arndt, Volker; Bermisheva, Marina; Bogdanova, Natalia V; Bolla, Manjeet K; Brauch, Hiltrud; Brenner, Hermann; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Dunning, Alison M; Fasching, Peter A; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G; Haeberle, Lothar; Hall, Per; Hillemanns, Peter; Hopper, John L; Jakubowska, Anna; John, Esther M; Jones, Michael; Khusnutdinova, Elza; Knight, Julia A; Kosma, Veli-Matti; Kristensen, Vessela; Lee, Andrew; Lindblom, Annika; Lubinski, Jan; Mannermaa, Arto; Margolin, Sara; Meindl, Alfons; Milne, Roger L; Muranen, Taru A; Newcomb, Polly A; Offit, Kenneth; Park-Simon, Tjoung-Won; Peto, Julian; Pharoah, Paul D P; Robson, Mark; Rudolph, Anja; Sawyer, Elinor J; Schmutzler, Rita K; Seynaeve, Caroline; Soens, Julie; Southey, Melissa C; Spurdle, Amanda B; Surowy, Harald; Swerdlow, Anthony; Tollenaar, Rob A E M; Tomlinson, Ian; Trentham-Dietz, Amy; Vachon, Celine; Wang, Qin; Whittemore, Alice S; Ziogas, Argyrios; van der Kolk, Lizet; Nevanlinna, Heli; Dörk, Thilo; Bojesen, Stig; Easton, Douglas F

2016-08-10

CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center-based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10(-20)). The OR was higher for estrogen receptor (ER)-positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10(-21)]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10(-4)). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up. © 2016

Effect of the F508del genotype on outcomes of endoscopic sinus surgery in children with cystic fibrosis.

PubMed

Do, Bao Anh Julie; Lands, Larry C; Saint-Martin, Christine; Mascarella, Marco A; Manoukian, John J; Daniel, Sam J; Nguyen, Lily H P

2014-07-01

Numerous authors have sought to describe genotype-phenotype correlations in cystic fibrosis (CF), notably to pancreatic insufficiency and lung disease. However, few studies have focused on the association between the F508del genotype and response to sinus surgery. The objective of this study is to assess the effect of the F508del genotype on sinonasal disease severity and outcomes following functional endoscopic sinus surgery (FESS) in a pediatric population. A retrospective chart review of 153 children with CF seen at a tertiary care pediatric hospital from 1995 to 2008 was performed. Patients were classified into one of three groups according to F508del genotype, either as homozygous, heterozygous or not carrying a F508del mutation. The sinonasal disease phenotype of the three groups was compared based on clinical and radiological findings, extent of endoscopic sinus surgery and rate of revision surgery. The relationship between the F508del genotype and pancreatic insufficiency was confirmed (p<0.05). There was no association between the F508del genotype and increased need for FESS (p=0.75). Moreover, no association was established between F508del homozygosity and presence of nasal polyps, Lund-Mackay score, extent of surgery or length of postoperative hospitalization. The rates of revision surgery did not differ significantly among the three genotypes analyzed (p=0.59). There is no clear association between the F508del genotype and an increased need for FESS, extent of surgery, or revision surgery. Given the phenotypic variability of sinonasal disease in patients with CF, a prospective study is needed to better understand outcomes following FESS and the contribution of gene modifiers to this effect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Seventy years of medicine in the Instituto Mexicano del Seguro Social].

PubMed

Fajardo-Ortiz, Guillermo

2014-01-01

The purpose of these lines is to remember and refer some of the historical landmarks in the evolution of the medical services of the Instituto Mexicano del Seguro Social (IMSS, according to its initials in Spanish) since it was founded, in 1943. We also want to bring to the reader's attention that the dimensions and impacts on health that IMSS has achieved, throughout its history, have strengthened the citizenship, as well as social sustainability. Also, those impacts have determined the creation and the reinforcement of human capital in México. Throughout this concise balance, all the controversy surrounding the foundation of the Institute is being recalled (the protest in the Mexico City Zócalo, or the attack to an hospital in San Ángel -a neighborhood located in the Southwest of Mexico City-), as well as the way the IMSS incorporated several words into the vocabulary of Mexicans. We also remember the previous antecedent of the Revista Médica del Instituto Mexicano del Seguro Social, as well as the Revista de Enfermería, and the emblematic Archives of Medical Research. The IMSS has 70 years of achievements, seven decades covered.

Medición de densidades medias de meteoritos: test del método de inmersión

NASA Astrophysics Data System (ADS)

Steren, G.

Se evaluó una técnica simple para medir las densidades medias de meteoritos, basada en el Método de Arquímedes y que utiliza cuentas de vidrio de 40μ en lugar de un fluído esto presenta la ventaja de no ser intrusivo ni químicamente reactivo (D.Britt and G.Consolmagno, 1996, B.A.A.S.28,1106). El estudio, realizado en junio de este año por participantes de la VI Escuela de Verano del Observatorio del Vaticano, empleó 37 muestras de la colección del Observatorio del Vaticano, de las cuales 26 eran Condritas, 1 Pallasita y 1 Howardita; algunas de ellas ya habian sido estudiadas por otras técnicas aunque también se incluyeron muestras no estudiadas anteriormente.

Cutaneous signs of thyroid disease.

PubMed

Mullin, G E; Eastern, J S

1986-10-01

Hyperactivity of the sympathetic nervous system produces many of the skin changes of hyperthyroidism, while the hypometabolic state and the accumulation of mucopolysaccharides in the dermis are responsible for hypothyroid cutaneous manifestations. Acropachy, atopic eczema, localized myxedema and nail changes are associated with thyrotoxicosis. Vitiligo may be seen in all three thyroid diseases of autoimmune origin. Hyperpigmentation, pruritus and urticaria are associated with hyperthyroidism.

A chemical corrector modifies the channel function of F508del-CFTR.

PubMed

Kim Chiaw, Patrick; Wellhauser, Leigh; Huan, Ling Jun; Ramjeesingh, Mohabir; Bear, Christine E

2010-09-01

The deletion of Phe-508 (F508del) constitutes the most prevalent cystic fibrosis-causing mutation. This mutation leads to cystic fibrosis transmembrane conductance regulator (CFTR) misfolding and retention in the endoplasmic reticulum and altered channel activity in mammalian cells. This folding defect can however be partially overcome by growing cells expressing this mutant protein at low (27 degrees C) temperature. Chemical "correctors" have been identified that are also effective in rescuing the biosynthetic defect in F508del-CFTR, thereby permitting its functional expression at the cell surface. The mechanism of action of chemical correctors remains unclear, but it has been suggested that certain correctors [including 4-cyclohexyloxy-2-(1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl)-quinazoline (VRT-325)] may act to promote trafficking by interacting directly with the mutant protein. To test this hypothesis, we assessed the effect of VRT-325 addition on the channel activity of F508del-CFTR after its surface expression had been "rescued" by low temperature. It is noteworthy that short-term pretreatment with VRT-325 [but not with an inactive analog, 4-hydroxy-2-(1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl)-quinazoline (VRT-186)], caused a modest but significant inhibition of cAMP-mediated halide flux. Furthermore, VRT-325 decreased the apparent ATP affinity of purified and reconstituted F508del-CFTR in our ATPase activity assay, an effect that may account for the decrease in channel activity by temperature-rescued F508del-CFTR. These findings suggest that biosynthetic rescue mediated by VRT-325 may be conferred (at least in part) by direct modification of the structure of the mutant protein, leading to a decrease in its ATP-dependent conformational dynamics. Therefore, the challenge for therapy discovery will be the design of small molecules that bind to promote biosynthetic maturation of the major mutant without compromising its activity in

Autoantibodies to human tryptophan hydroxylase and aromatic L-amino acid decarboxylase.

PubMed

Dal Pra, Chiara; Chen, Shu; Betterle, Corrado; Zanchetta, Renato; McGrath, Vivienne; Furmaniak, Jadwiga; Rees Smith, Bernard

2004-03-01

To assess the prevalence of autoantibodies (Abs) to tryptophan hydroxylase (TPH) and aromatic l-amino acid decarboxylase (AADC) in patients with different autoimmune diseases and to analyse their respective epitopes. TPH and AADC Abs were measured in an immunoprecipitation assay using (35)S-labelled full-length and fragments of TPH and AADC. Patients with different autoimmune adrenal diseases (n=84), non-adrenal autoimmune diseases (n=37), idiopathic vitiligo (n=8) and 56 healthy blood donors were studied. Fourteen of twenty-three (61%) of patients with autoimmune polyglandular syndrome (APS) type I and 1/34 (3%) of patients with isolated Addison's disease (AD) were positive for TPH Abs. None of the patients with APS type II (n=27), coeliac disease (n=10), autoimmune thyroid disease (AITD) (n=11), type 1 diabetes mellitus (DM) (n=16) or idiopathic vitiligo (n=8) was positive for TPH Abs. AADC Abs were detected in 12/23 (52%) patients with APS type I, in 1/29 (3%) patients with APS type II and 1/34 (3%) patients with isolated AD. None of the patients with coeliac disease, type 1 DM, AITD or idiopathic vitiligo was positive for AADC Abs. TPH Abs were found to interact with the C-terminal amino acids (aa) 308-423, central aa 164-205 and N-terminal aa 1-105 of the TPH molecule. AADC Ab binding epitopes were within the C-terminal aa 382-483, the central aa 243-381 and the N-terminal aa 1-167. Our study suggests that TPH Abs and AADC Abs react with several different epitopes and that different epitopes are recognized by different sera. The prevalence of TPH Abs and AADC Abs in patients with APS type I in our study is in agreement with previous reports. TPH Abs and AADC Abs were found very rarely in patients with other forms of autoimmune adrenal disease and were not detected in patients with non-adrenal autoimmune diseases.

DK phocomelia phenotype (von Voss-Cherstvoy syndrome) caused by somatic mosaicism for del(13q).

PubMed

Bamforth, J S; Lin, C C

1997-12-31

DK phocomelia (von Voss-Cherstvoy syndrome) is a rare condition characterized by radial ray defects, occipital encephalocoele, and urogenital abnormalities. Lubinsky et al. [1994: Am J Med Genet 52:272-278] pointed out similarities between this and the del(13q) syndrome. To date, all reported cases of DK phocomelia have been apparently normal chromosomally. We report on a case of DK phocomelia in which the proposita had normal lymphocyte chromosomes, but was mosaic in fibroblasts for del(13)(q12). Fibroblast chromosomes studies on other cases of DK phocomelia have not been reported: this raises the possibility that some cases of DK phocomelia may be somatic mosaics for del(13)(q12).

Cirugía de los trastornos del comportamiento: el estado del arte

PubMed Central

Yampolsky, Claudio; Bendersky, Damián

2014-01-01

Introducción: La cirugía de los trastornos del comportamiento (CTC) se está convirtiendo en un tratamiento más común desde el desarrollo de la neuromodulación. Métodos: Este artículo es una revisión no sistemática de la historia, indicaciones actuales, técnicas y blancos quirúrgicos de la CTC. Dividimos su historia en 3 eras: la primera comienza en los inicios de la psicocirugía y termina con el desarrollo de las tícnicas estereotácticas, cuando comienza la segunda era. Ésta se caracteriza por la realización de lesiones estereotácticas. Nos encontramos transitando la tercera era, que comienza cuando la estimulación cerebral profunda (ECP) comienza a ser usada en CTC. Resultados: A pesar de los errores graves cometidos en el pasado, hoy en día, la CTC está renaciendo. Los trastornos psiquiátricos que se más frecuentemente se tratan con cirugía son: depresión refractaria, trastorno obsesivo-compulsivo y síndrome de Tourette. Además, algunos pacientes con agresividad fueron tratados quirúrgicamente. Hay varios blancos estereotácticos descriptos para estos trastornos. La estimulación vagal puede ser usada también para depresión. Conclusión: Los resultados de la ECP en estos trastornos parecen alentadores. Sin embargo, se necesitan más estudios randomizados para establecer la efectividad de la CTC. Debe tenerse en cuenta que una apropiada selección de pacientes nos ayudará a realizar un procedimiento más seguro así como también a lograr mejores resultados quirúrgicos, conduciendo a la CTC a ser más aceptada por psiquiatras, pacientes y sus familias. Se necesita mayor investigación en varios temas como: fisiopatología de los trastornos del comportamiento, indicaciones de CTC y nuevos blancos quirúrgicos. PMID:25165612

Excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive familial breast cancer cases.

PubMed

Adank, Muriel A; Verhoef, Senno; Oldenburg, Rogier A; Schmidt, Marjanka K; Hooning, Maartje J; Martens, John W M; Broeks, Annegien; Rookus, Matti; Waisfisz, Quinten; Witte, Birgit I; Jonker, Marianne A; Meijers-Heijboer, Hanne

2013-05-01

The CHEK2∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2∗1100delC mutation within a familial non-BRCA1/2 breast cancer setting. Cancer incidences were compared between first degree relatives of 107 familial breast cancer patients positive for the CHEK2∗1100delC mutation (CHEK2 positive families) and first degree relatives of 314 familial breast cancer patients without the CHEK2∗1100delC mutation (CHEK2 negative families). All families were derived from the same pool of familial non-BRCA1/2 breast cancer families (n=2554). Medical information of 2188 first degree relatives of these families was analysed for cancer risk. CHEK2∗1100delC status of relatives was unknown. Increased breast cancer risk (hazard ratio (HR) 2.0 (95% confidence interval (CI): 1.4-2.7), p<0.001) was observed in sisters of CHEK2∗1100delC positive index cases compared to sisters of CHEK2∗1100delC negative index cases. HR was 1.6 (95% CI: 1.0-2.4) for mothers of CHEK2 positive versus negative index cases (p=0.041). For second primary breast cancers HR was increased in CHEK2∗1100delC positive index cases (HR 2.1, 95% CI: 1.3-3.3, p=0.003) and their sisters (HR 2.6, 95% CI: 1.1-6.1, p=0.025). There is an excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive non-BRCA1/2 familial breast cancer patients compared to non-CHEK2∗1100delC familial breast cancer relatives. Genotyping for the CHEK2∗1100delC mutation in a familial breast cancer setting contributes to optimal clinical surveillance in countries in which this mutation is prevalent. Carriers and female relatives are eligible for stringent breast surveillance programs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Species identification in forensic samples using the SPInDel approach: A GHEP-ISFG inter-laboratory collaborative exercise.

PubMed

Alves, Cíntia; Pereira, Rui; Prieto, Lourdes; Aler, Mercedes; Amaral, Cesar R L; Arévalo, Cristina; Berardi, Gabriela; Di Rocco, Florencia; Caputo, Mariela; Carmona, Cristian Hernandez; Catelli, Laura; Costa, Heloísa Afonso; Coufalova, Pavla; Furfuro, Sandra; García, Óscar; Gaviria, Anibal; Goios, Ana; Gómez, Juan José Builes; Hernández, Alexis; Hernández, Eva Del Carmen Betancor; Miranda, Luís; Parra, David; Pedrosa, Susana; Porto, Maria João Anjos; Rebelo, Maria de Lurdes; Spirito, Matteo; Torres, María Del Carmen Villalobos; Amorim, António; Pereira, Filipe

2017-05-01

DNA is a powerful tool available for forensic investigations requiring identification of species. However, it is necessary to develop and validate methods able to produce results in degraded and or low quality DNA samples with the high standards obligatory in forensic research. Here, we describe a voluntary collaborative exercise to test the recently developed Species Identification by Insertions/Deletions (SPInDel) method. The SPInDel kit allows the identification of species by the generation of numeric profiles combining the lengths of six mitochondrial ribosomal RNA (rRNA) gene regions amplified in a single reaction followed by capillary electrophoresis. The exercise was organized during 2014 by a Working Commission of the Spanish and Portuguese-Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG), created in 2013. The 24 participating laboratories from 10 countries were asked to identify the species in 11 DNA samples from previous GHEP-ISFG proficiency tests using a SPInDel primer mix and control samples of the 10 target species. A computer software was also provided to the participants to assist the analyses of the results. All samples were correctly identified by 22 of the 24 laboratories, including samples with low amounts of DNA (hair shafts) and mixtures of saliva and blood. Correct species identifications were obtained in 238 of the 241 (98.8%) reported SPInDel profiles. Two laboratories were responsible for the three cases of misclassifications. The SPInDel was efficient in the identification of species in mixtures considering that only a single laboratory failed to detect a mixture in one sample. This result suggests that SPInDel is a valid method for mixture analyses without the need for DNA sequencing, with the advantage of identifying more than one species in a single reaction. The low frequency of wrong (5.0%) and missing (2.1%) alleles did not interfere with the correct species identification, which demonstrated the

Rescue of murine F508del CFTR activity in native intestine by low temperature and proteasome inhibitors.

PubMed

Wilke, Martina; Bot, Alice; Jorna, Huub; Scholte, Bob J; de Jonge, Hugo R

2012-01-01

Most patients with Cystic Fibrosis (CF) carry at least one allele with the F508del mutation, resulting in a CFTR chloride channel protein with a processing, gating and stability defect, but with substantial residual activity when correctly sorted to the apical membranes of epithelial cells. New therapies are therefore aimed at improving the folding and trafficking of F508del CFTR, (CFTR correctors) or at enhancing the open probability of the CFTR chloride channel (CFTR potentiators). Preventing premature breakdown of F508del CFTR is an alternative or additional strategy, which is investigated in this study. We established an ex vivo assay for murine F508del CFTR rescue in native intestinal epithelium that can be used as a pre-clinical test for candidate therapeutics. Overnight incubation of muscle stripped ileum in modified William's E medium at low temperature (26°C), and 4 h or 6 h incubation at 37°C with different proteasome inhibitors (PI: ALLN, MG-132, epoxomicin, PS341/bortezomib) resulted in fifty to hundred percent respectively of the wild type CFTR mediated chloride secretion (forskolin induced short-circuit current). The functional rescue was accompanied by enhanced expression of the murine F508del CFTR protein at the apical surface of intestinal crypts and a gain in the amount of complex-glycosylated CFTR (band C) up to 20% of WT levels. Sustained rescue in the presence of brefeldin A shows the involvement of a post-Golgi compartment in murine F508del CFTR degradation, as was shown earlier for its human counterpart. Our data show that proteasome inhibitors are promising candidate compounds for improving rescue of human F508del CFTR function, in combination with available correctors and potentiators.

CHEK2*1100delC and risk of malignant melanoma: Danish and German studies and meta-analysis.

PubMed

Weischer, Maren; Heerfordt, Ida M; Bojesen, Stig E; Eigentler, Thomas; Garbe, Claus; Röcken, Martin; Hölmich, Lisbet Rosenkrantz; Schmidt, Henrik; Klyver, Helle; Bastholt, Lars; Nordestgaard, Børge G

2012-02-01

It is possible that reduced function of DNA repair and cell-cycle control genes increases the individual susceptibility to malignant melanoma. As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated with increased risk of malignant melanoma. First, we performed case-control studies of 1,152 Danish and 752 German individuals with malignant melanoma compared with 9,142 Danish and 3,718 German controls. Second, we performed a meta-analysis of CHEK2*1100delC and malignant melanoma, involving 2,619 cases and 17,481 controls. Third, we examined the risk of malignant melanoma associated with CHEK2*1100delC heterozygosity in an analysis stratified for sun exposure, as well as for subtype and location on the body. The odds ratios for malignant melanoma for CHEK2(*)1100del heterozygotes compared with those for noncarriers were 2.01 (95% confidence interval (CI), 1.03-3.91) in Danes, 1.42 (95% CI, 0.46-4.31) in Germans, and 1.79 (95% CI, 1.02-3.17) in Danes and Germans combined. In a meta-analysis, the odds ratio of malignant melanoma for CHEK2*1100delC heterozygotes compared with that for noncarriers was 1.81 (95% CI, 1.07-3.05). Stratifications did not alter these results. CHEK2*1100delC heterozygotes have a twofold risk of malignant melanoma compared with noncarriers.

Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America.

PubMed

Iniesta, Maria D; Gorin, Michael A; Chien, Ling-Chen; Thomas, Samantha M; Milliron, Kara J; Douglas, Julie A; Merajver, Sofia D

2010-10-15

The CHEK2*1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries; the frequency may be much lower in North America. In this study, our aim was to determine the frequency of CHEK2*1100delC in members of breast cancer families who tested negative for a deleterious mutation in BRCA1/2 at the University of Michigan Comprehensive Cancer Center. We genotyped 102 members from 90 families for CHEK2*1100delC. Most of these families had several cases of breast cancer or ovarian cancer (or both), as well as multiple members with other cancer types in a single lineage. No CHEK2*1100delC mutations were detected in any of the 102 individuals, including 51 women diagnosed with breast cancer at an early age (<45 years), 8 women with bilateral breast cancer, 3 men with breast cancer, and 8 women with ovarian cancer. Our data are consistent with the reported very low frequency of CHEK2*1100delC mutations in North American populations (compared with Northern Europe), rendering CHEK2*1100delC such an unlikely culprit in BRCA1/2 negative families that routine testing of these families appears unwarranted. Copyright © 2010 Elsevier Inc. All rights reserved.

Mini-mastoidectomía para anastomosis hipogloso-facial con sección parcial del nervio hipogloso

PubMed Central

Campero, Álvaro; Ajler, Pablo; Socolovsky, Mariano; Martins, Carolina; Rhoton, Albert

2012-01-01

Introducción: La anastomosis hipogloso-facial es la técnica de elección para la reparación de la parálisis facial cuando no se dispone de un cabo proximal sano del nervio facial. La técnica de anastomosis mediante fresado mastoideo y sección parcial del hipogloso minimiza la atrofia lingual sin sacrificar resultados a nivel facial. Método: La porción mastoidea del nervio facial transcurre por la pared anterior de la AM, a un promedio de 18+/-3 mm de profundidad respecto de la pared lateral. Se debe reconocer la cresta supramastoidea, desde la cual se marca una línea vertical paralela al eje mayor de la AM, 1 cm por detrás de la pared posterior del CAE El fresado se comienza desde la línea medio mastoidea hasta la pared posterior del CAE. Una vez encontrado el nervio facial en el tercio medio del canal mastoideo, el mismo es seguido hacia proximal y distal. Resultados: El abordaje descripto permite acceder al nervio facial intratemporal en su porción mastoidea, y efectuar un fresado óseo sin poner en riesgo al nervio o a estructuras vasculares cercanas. Se trata de un procedimiento técnicamente más sencillo que los abordajes amplios habitualmente utilizados al hueso temporal; no obstante su uso debe ser restringido mayormente a la anastomosis hipogloso-facial. Conclusión: Esta es una técnica relativamente sencilla, que puede ser reproducida por cirujanos sin mayor experiencia en el tema, luego de su paso por el laboratorio de anatomía. PMID:23596555

Reproductive biology of the Del Norte salamander (Plethodon elongatus).

Treesearch

Clara A. Wheeler; Hartwell H. Welsh Jr.; Lisa M. Ollivier

2013-01-01

We examined seasonal reproductive patterns of the Del Norte Salamander, Plethodon elongatus, in mixed conifer and hardwood forests of northwestern California and southwestern Oregon. Seasonal size differences in reproductive structures suggested that maximum spermatogenic activity occurred during the late summer, with spermatozoa transfer to the...

New records of fishes at Isla del Coco, Costa Rica

USGS Publications Warehouse

Garrison, V.H.

1996-01-01

Isla del Coco lies at 5 degrees 32'N latitude, 87 degrees 04'W longitude and is the sole peak of the Cocos Ridge exposed above sea level. This isolated island formed approximately 2 million years ago. It rises 575 m above the surface of the sea and covers 46 km2 (Castillo et aI., 1988). Five hundred km to the NNE is Costa Rica; 630 km SSW are the Galapagos Islands; 650 km to the E is Isla Malpelo, Colombia; and approximately 8,000 km W lie the Line Islands. Costa Rica claimed Isla del Coco in 1832 and declared it a National Park in 1978. The area of the park was increased to include the adjacent waters 5 km offshore in 1984 and 25 km offshore in 1991.

The CHEK2 del5395 is a founder mutation without direct effects for cancer risk in the latvian population.

PubMed

Plonis, J; Kalniete, D; Nakazawa-Miklasevica, M; Irmejs, A; Vjaters, E; Gardovskis, J; Miklasevics, E

2015-12-01

Our objective was to determine: 1) whether the checkpoint kinase 2 ( CHEK2 ) del5395 (g.27417113-27422508 del, NC_000022.11) is a founder mutation in the Latvian population, 2) if there is an association between CHEK2 del5395 mutation and cancer risk, and 3) and whether the CHEK2 del5395 mutation impacts cancer predisposition in Chernobyl disaster liquidators (the civil and military personnel who were called upon to deal with consequences of the 1986 nuclear disaster) as well as geriatric populations. We recruited 438 breast cancer patients, 568 colorectal cancer patients, 399 ovarian cancer patients, 419 prostate cancer patients, 526 healthy blood donors, 480 Chernobyl disaster liquidators and 444 geriatric cancer-free participants. DNA samples were isolated from blood samples and subjected to multiplex polymerase chain reaction (PCR). The truncation of del5395 was estimated by fragment size of the multiplex PCR.All groups were compared to the healthy blood donors using Fisher's exact test. All p values were two-sided and the odds ratios (OR) calculated by two-by-two table. In cancer groups, the del5395 mutation was most frequently observed in the ovarian cancer group (1.00%, OR = 1.32). In control groups, the del5395 mutation was most frequent (0.76%) in the healthy donors, which exceeded its frequency in the Chernobyl liquidators group and the geriatric group by 0.01 and 0.08%, respectively. For all groups, the OR appeared to be >1 only in ovarian cancer patients. However, OR rates showed no statistical significance in either cancer or control groups, with the p value fluctuating within the range of 0.39-1.00. The CHEK2 gene del5395 is a founder mutation in the Latvian population, which, however, does not have a direct impact on genetic predisposition toward colorectal, breast, ovarian and prostate cancer.

Seguridad del paciente en Radioterapia Intraoperatoria: Impacto de los elementos controlados por el Radiofisico

NASA Astrophysics Data System (ADS)

Tarjuelo, Juan Lopez

Introduccion: En la administracion de la radioterapia intervienen profesionales y equipos de tratamiento, por lo que existe el riesgo de error y se precisa que dicho equipamiento funcione conforme a lo esperado. A los radiofisicos les corresponde participar en las actividades de garantia o aseguramiento de la calidad, incluyendo el control de calidad de los equipos, y en la evaluacion de los riesgos asociados. La radioterapia intraoperatoria (RIO) es una tecnica radioterapica de intensificacion de dosis, altamente selectiva, dirigida a volumenes anatomicos restringidos durante el tratamiento quirurgico oncologico, basada en la administracion de una dosis absorbida alta por medio de un haz de electrones tras el examen visual directo del lecho tumoral. Como incorporar los ultimos avances en el refuerzo de la seguridad en radioterapia es una tarea ambiciosa y compleja, resulta mas concreta y de inmediata aplicacion su introduccion en la RIO. El objetivo es analizar los elementos que reducen los riesgos y aumentan la seguridad en la RIO y su dosimetria, y valorar la funcion del radiofisico en esta labor. Material y metodos: Se emplearon el planificador Radiance de GMV y el acelerador lineal de los tratamientos de RIO Elekta Precise, controlado con el verificador diario de haces Daily QA Check 1090 y medido con las camaras de ionizacion PPC 40, FC65-G y FC65-P de PTW-Freiburg, a su vez verificadas con fuentes radiactivas adecuadas de estroncio-90 modelos CDP y CDC de IBA Dosimetry. Se realizo un analisis de modos de fallo y efectos (failure mode and effect analysis, FMEA) con el fin de identificar los elementos que forman la RIO y aplicar las herramientas necesarias para la minimizacion de los riesgos y la mejora de la seguridad en la tecnica. Se estudiaron las verificaciones diarias de dicho acelerador Precise con el control estadistico de procesos (statistical process control, SPC) y se simularon intervenciones para devolverlo al estado llamado en control. El SPC

Association Between CHEK2*1100delC and Breast Cancer: A Systematic Review and Meta-Analysis.

PubMed

Liang, Mingming; Zhang, Yun; Sun, Chenyu; Rizeq, Feras Kamel; Min, Min; Shi, Tingting; Sun, Yehuan