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G Kaya, N Saxer-Sekulic, A Kaya, O Sorg, A Boespflug, L Thomas, J H Saurat
BACKGROUND: Patients treated with vemurafenib for metastatic melanoma often develop skin lesions similar to those observed after exposure to dioxin-like compounds. We previously called these lesions MADISH (metabolizing acquired dioxin-induced skin hamartoma) when analysing a case of acute dioxin poisoning. OBJECTIVE: We performed a clinical trial aimed at comparing the skin lesions observed under vemurafenib treatment with MADISH in order to bring to light a possible cross-talk between vemurafenib and dioxin pathways...
March 24, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Pragya Kushwaha, Harish Kumar, Sandeep Kulkarni, Ashok Ghorpade
An 11-year-old boy presented with a 1-year history of multiple comedonal lesions distributed over his body. The lesions (Figure 1) were densely distributed throughout his body. Ophthalmologic examination revealed hyperpigmented conjunctival mucosae and enlarged meibomian glands (Figure 2). His nails were also hyperpigmented. In addition, he had been coughing and had a fever, each present for a month. Significant laboratory studies included mild anemia (hemoglobin 11.6 gm%) and leukocytosis of 20,800. A chest x-ray was suggestive of interstitial lung disease...
2017: Skinmed
Rainer Malisch, Michael S Denison, Heidelore Fiedler, Peter Fürst, Ron L A P Hoogenboom, Alexander Schaechtele, Dieter Schrenk, Martin van den Berg
Laboratory safety requires protecting personnel from chemical exposures. Working with stock solutions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) in routine analysis of feed and food with bioanalytical or physicochemical methods raises some concerns. Since PCDD/PCDFs are considered as possibly acutely toxic, the potential risks were evaluated to determine whether supervision of their use is necessary. Based on LD50 -data for oral or dermal intake, hazard classification of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a substance (category 1) and in commercially available TCDD standard solutions (category 4) is different...
October 2017: Chemosphere
Sang Yoon Do, Chul Gab Lee, Jae Yoon Kim, Young Hoon Moon, Min Sung Kim, In Ho Bae, Han Soo Song
BACKGROUND: In 2015, workers dismantling a fluorescent lamp factory in Korea were affected by mercury poisoning from exposure to mercury vapor. CASE PRESENTATION: Eighteen out of the 21 workers who participated in the demolition project presented with symptoms of poisoning and, of these, 10 had persistent symptoms even at 18 months after the initial exposure to mercury vapor. Early symptoms of 18 workers included a general skin rash, pruritus, myalgia, sleep disturbance, and cough and sputum production...
2017: Annals of Occupational and Environmental Medicine
Karl Walter Bock
Studies of TCDD toxicity stimulated identification of the responsible aryl hydrocarbon receptor (AHR), a multifunctional, ligand-activated transcription factor of the basic helix-loop-helix/Per-Arnt-Sim family. Accumulating evidence suggests a role of this receptor in homeostasis of stem/progenitor cells, in addition to its known role in xenobiotic metabolism. (1) Regulation of myelopoiesis is complex. As one example, AHR-mediated downregulation of human CD34+ progenitor differentiation to monocytes/macrophages is discussed...
April 6, 2017: Archives of Toxicology
Stephenie D Prokopec, Kathleen E Houlahan, Ren X Sun, John D Watson, Cindy Q Yao, Jamie Lee, Christine P'ng, Renee Pang, Alexander H Wu, Lauren C Chong, Ashley B Smith, Nicholas J Harding, Ivy D Moffat, Jere Lindén, Sanna Lensu, Allan B Okey, Raimo Pohjanvirta, Paul C Boutros
BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease...
January 13, 2017: BMC Genomics
Qiang Ju, Christos C Zouboulis
Endocrine-disrupting chemicals (EDCs) are exogenous compounds that have the ability to disrupt the production and actions of hormones through direct or indirect interaction with hormone receptors, thus acting as agonists or antagonists. Human health is affected after either individual occupation or dietary and environmental exposure to EDCs. On the other hand, skin is one of the largest organs of the body and its main function is protection from noxious substances. EDCs perturb the endocrine system, and they are also carcinogenic, immunotoxic, and hepatotoxic to human skin...
September 2016: Reviews in Endocrine & Metabolic Disorders
Karl Walter Bock
Despite decades of intensive research physiologic Ah receptor (AHR) functions are not yet elucidated. Challenges include marked species differences and dependence of AHR function on the cell type and cellular context. Hints to physiologic functions may be derived (i) from feedback loops between endogenous ligands and substrates of major target enzymes such as CYP1A1 and UGT1A1, and (ii) from dioxin toxicity in human individuals. For example, dioxin-mediated chloracne is probably due to dysregulated homeostasis of sebocyte stem/progenitor cells...
January 1, 2017: Biochemical Pharmacology
Karl Walter Bock
Target cells and molecular targets responsible for dioxin-mediated chloracne, the hallmark of dioxin toxicity, are reviewed. The dioxin TCDD accumulates in sebum, and thereby persistently activates the Ah receptor (AhR), expressed in bipotential stem/progenitor cells of the sebaceous gland. AhR operates in cooperation with other transcription factors including c-Myc, Blimp1 and ß-Catenin/TCF: c-Myc stimulates exit of stem cells from quiescence to proliferating sebocyte progenitors; Blimp1 is a major c-Myc repressor, and ß-Catenin/TCF represses sebaceous gland differentiation and stimulates differentiation to interfollicular epidermis...
July 15, 2016: Biochemical Pharmacology
Gabriella Fabbrocini, Gürkan Kaya, Patricia Caseiro Silverio, Valerio De Vita, Aysin Kaya, Fabienne Fontao, Olivier Sorg, Jean-Hilaire Saurat
BACKGROUND: Dioxins are persistent organic pollutants present in the environment. They exert their biological effects by binding to an intracellular receptor, the aryl hydrocarbon receptor (AhR). Activation of AhR leads to the induction of cytochrome p450 1A1 (CYP1A1). Expression of CYP1A1 in human skin is a key marker for AhR activation, and it may induce comedogenesis resulting in acne-like lesions known as chloracne/metabolising acquired dioxin-induced skin hamartomas (MADISH). The contribution of this pathway in patients seen in a busy acne clinic is unknown...
2015: Dermatology: International Journal for Clinical and Investigative Dermatology
Olivier Sorg
No abstract text is available yet for this article.
2015: Dermatology: International Journal for Clinical and Investigative Dermatology
Andrew T Patterson, Frances T Tian, Dirk M Elston, Benjamin H Kaffenberger
Many environmental acne disorders, including chloracne and oil acne, were previously thought to occur predominantly in occupational settings following polycyclic aromatic hydrocarbon exposure. Cigarette smoke has also been shown to contain a large number of these toxic polycyclic aromatic hydrocarbon components and strictly correlates with noninflammatory acneiform lesion development in postadolescent patients. We report a case of localized open comedones associated with occluded cigarette smoke exposure near the nasal cavity due to infrequently changed gauze following rhinectomy...
2015: Dermatology: International Journal for Clinical and Investigative Dermatology
Andrew T Patterson, Benjamin H Kaffenberger, Richard A Keller, Dirk M Elston
Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects...
January 2016: Journal of the American Academy of Dermatology
Azrina Azlan, Nurul Nadiah Mohamad Nasir, Norashikin Shamsudin, Hejar Abdul Rahman, Hock Eng Khoo, Muhammad Rizal Razman
BACKGROUND: Exposure to PCDD/PCDF (dioxin and furan) through consumption of fish and shellfish is closely related to the occurrence of skin diseases, such as chloracne and hyperpigmentation. This study aimed to determine the exposure of PCDD/PCDF and its congeners in fish and shellfish obtained from different regions of the Straits of Malacca among the fishing community. METHODS: The risk of fish and shellfish consumption and exposure to PCDD/PCDF among fishermen living in coastal areas of the Straits were evaluated based on a cross-sectional study involving face to face interviews, blood pressure and anthropometric measurements, and administration of food frequency questionnaires (FFQ)...
July 21, 2015: BMC Public Health
Rowland Noakes
The aryl hydrocarbon receptor (AHR) is a cytosolic receptor for low molecular weight molecules, of which the most widely recognized ligand is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the most widely recognized effect, chloracne. Adverse effects of manipulation were most recently and graphically demonstrated by the poisoning of Viktor Yushchenko during the Ukrainian presidential elections of 2004. However, recent research has revealed a receptor with wide-ranging, and at times, paradoxical actions. It was arguably among the first biological receptors to be utilized by dermatologists, dating from the time of topical tar preparations as a therapeutic agent...
2015: International Journal of Tryptophan Research: IJTR
Chirag Mandavia
The environmental toxin 2,3,7,8 tetrachlorodibenzo p-dioxin (TCDD) plays an important role in the development of chloracne. Chloracne is characterized by hyperkeratosis of the interfollicular squamous epithelium and metaplasia of sebaceous glands. Dysregulation of keratinocyte terminal differentiation leading to accelerated formation of the cornified envelope as a result of TCDD-mediated aryl hydrocarbon receptor (AHR) activation has been implicated as one of the molecular pathogenic mechanisms contributing to the development of chloracne...
March 2015: Medical Hypotheses
Philip R Cohen
INTRODUCTION: Sorafenib is an oral multikinase inhibitor that targets tumor cell angiogenesis and proliferation. Drug-associated cutaneous adverse events, such as alopecia and hand-foot skin reaction, occur frequently. Sorafenib-related side effects affecting hair, nails, and skin are summarized and the characteristics of sorafenib-treated patients who developed acneiform facial lesions are reviewed to present the clinical features of these individuals. CASE REPORT: A man with sorafenib-associated facial acneiform lesions mimicking those of chloracne is described...
March 2015: Dermatology and Therapy
P Ruiz, L L Aylward, M Mumtaz
Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (dioxin-like PCBs) are identified as a family or group of organic compounds known as 'dioxins' or dioxin-like chemicals (DLCs). The most toxic member of this group is 2,3,7,8-tetrachlorodibenzo-(p)-dioxin (TCDD). Historically, DLCs have caused a variety of negative human health effects, but a disfiguring skin condition known as chloracne is the only health effect reported consistently. As part of translational research to make computerized models accessible to health risk assessors, the Concentration- and Age-Dependent Model (CADM) for TCDD was recoded in the Berkeley Madonna simulation language...
2014: SAR and QSAR in Environmental Research
Nguan S Tan, Walter Wahli
The nuclear factor erythroid 2-related factor 2 (Nrf2) is best known for its role in resistance to oxidant stress. In this issue of EMBO Molecular Medicine, Nrf2-prolonged genetic activation is shown with devastating effects on skin homeostasis. The study provides novel molecular insights into poison-induced chloracne and metabolizing acquired dioxin-induced skin hamartomas or MADISH.
2014: EMBO Molecular Medicine
Matthias Schäfer, Ann-Helen Willrodt, Svitlana Kurinna, Andrea S Link, Hany Farwanah, Alexandra Geusau, Florian Gruber, Olivier Sorg, Aaron J Huebner, Dennis R Roop, Konrad Sandhoff, Jean-Hilaire Saurat, Erwin Tschachler, Marlon R Schneider, Lutz Langbein, Wilhelm Bloch, Hans-Dietmar Beer, Sabine Werner
The transcription factor Nrf2 is a key regulator of the cellular stress response, and pharmacological Nrf2 activation is a promising strategy for skin protection and cancer prevention. We show here that prolonged Nrf2 activation in keratinocytes causes sebaceous gland enlargement and seborrhea in mice due to upregulation of the growth factor epigen, which we identified as a novel Nrf2 target. This was accompanied by thickening and hyperkeratosis of hair follicle infundibula. These abnormalities caused dilatation of infundibula, hair loss, and cyst development upon aging...
2014: EMBO Molecular Medicine
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