Search

Patients with xeroderma pigmentosum (XP) have a 1,000-fold increase in ultraviolet (UV)-induced skin cancers while trichothiodystrophy (TTD) patients, despite mutations in the same genes, ERCC2 (XPD) or ERCC3 (XPB), are cancer-free. Unlike XP cells, TTD cells have a nearly normal rate of removal of UV-induced 6-4 photoproducts (6-4PP) in their DNA and low levels of the basal transcription factor, TFIIH. We examined seven XP, TTD, and XP/TTD complex patients and identified mutations in the XPD gene. We discovered large differences in nucleotide excision repair (NER) protein recruitment to sites of localized UV damage in TTD cells compared to XP or normal cells. XPC protein was rapidly localized in all cells. XPC was redistributed in TTD, and normal cells by 3 hr postirradiation, but remained localized in XP cells at 24-hr postirradiation. In XP cells recruitment of other NER proteins (XPB, XPD, XPG, XPA, and XPF) was also delayed and persisted at 24 hr (p < 0.001). In TTD cells with defects in the XPD, XPB, or GTF2H5 (TTDA) genes, in contrast, recruitment of these NER proteins was reduced compared to normals at early time points (p < 0.001) and remained low at 24 hr postirradiation. These data indicate that in XP persistence of NER proteins at sites of unrepaired DNA damage is associated with greatly increased skin cancer risk possibly by blockage of translesion DNA synthesis. In contrast, in TTD, low levels of unstable TFIIH proteins do not accumulate at sites of unrepaired photoproducts and may permit normal translesion DNA synthesis without increased skin cancer.

Objective We sought to determine the interobserver reliability of the histopathologic diagnosis of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) (keratinocyte carcinomas) in the setting of a Department of Veteran Affairs multicenter chemoprevention study. Methods Interobserver concordance was assessed by blinded review of histopathologic slides by study dermatopathologists. Results Overall interobserver agreement between the two dermatopathogists was κ = 0.69 (95% confidence interval [CI] 0.67-0.69). The dermatopathologists' interobserver agreement was highest for basal cell carcinoma at κ = 0.88 (95% CI 0.84-0.91) and for a diagnostic category in the SCC-actinic keratosis spectrum at κ = 0.80 (95% CI 0.73-0.86). The largest disagreements between the two reference dermatopathologists were regarding the categories of invasive SCC at κ = 0.62 (95% CI 0.52-0.72), SCC in situ at κ = 0.42 (95% CI 0.29-0.56), and actinic keratosis at κ = 0.51 (95% CI 0.40-0.62). Agreement between the local pathologists and central reference dermatopathologists were similar to the agreement between the central dermatopathologists. The morphea subtype of basal cell carcinoma was the only reliably diagnosed subtype (κ = 0.79, 95% CI 0.51-1.00), and tumor depth was reliably measured. Limitations A limitation of this study was the use of only two reference dermatopathologists. Conclusion Because of the impact on physician decision making and patient care, researchers and clinicians need to be aware of reliability of histopathology results, particularly pertaining to the SCC and actinic keratosis spectrum.

Fibroelastolytic papulosis (FEP) consists of two dermatological conditions with clinical and histological similarities: pseudoxanthoma elasticum (PXE)-like papillary dermal elastolysis (PXE-PDE) and white fibrous papulosis of neck (WFPN). There is no effective documented treatment of FEP that we found in the published medical literature. We present a case of a Caucasian man with FEP who underwent fractionated carbon dioxide (CO2) laser treatment and achieved excellent cosmetic results and resolution of pruritus after three treatment sessions with no recurrence six-months post treatment.

Skin grafts are utilized in dermatology to reconstruct a defect secondary to surgery or trauma of the skin. Common indications for skin grafts include surgical removal of cutaneous malignancies, replacement of tissue after burns or lacerations, and hair transplantation in alopecia. Skin grafts may be cosmetically displeasing, functionally limiting, and significantly impact patient's quality-of-life. There is limited published data regarding skin graft revision to enhance aesthetics and function. Here, we present a case demonstrating excellent aesthetic and functional outcome after fractionated carbon dioxide (CO2) laser skin graft revision surgery and review of the medical literature on laser skin graft revision techniques.

Caffeine is a naturally occurring alkaloid. It is found in leaves, seeds, and fruits, and acts as a central nervous system stimulant and pesticide, killing insects that feed on the plants while rewarding pollinators. Caffeine is probably best known as a stimulant in coffee, tea, and other drinks. Over 80% of American adults consume coffee on a daily basis in order to avoid drowsiness, stay alert, and increase focus.1 In coffee, caffeine is extracted from the seed of the coffee plant, Coffea arabica, which is found natively in the mountains of Ethiopia. Caffeine may also be extracted from the tea leaves of Camellia sinensis, in addition to antioxidant polyphenols.

Dermal fillers are important for facial aesthetic enhancement as patients are favoring non-surgical procedures with minimal recovery time. Voluma is a volumizing hyaluronic acid filler, 20 mg/ml HA dermal filler, which was FDA-approved in 2013 as the first dermal filler for treatment of age-related volume loss in the midface.We sought to systematically review clinical studies and expert opinions of this 20 mg/ml HA dermal filler and to provide evidence-based recommendations and expert opinions.A search of the computerized bibliographic databases Medline, Embase, Embal, Biosis, SciSearch, Pascal, HCAPlus, IPA, and Dissertation Abstracts was performed on August 18th 2014.Thirteen articles met inclusion and were included in our review: clinical trials with this 20 mg/ml HA dermal filler (10) and expert opinions and questionnaire survey studies of experts (3). This 20 mg/ml HA dermal filler has shown consistent, favorable results for treatment of age-related facial volume loss, aesthetic enhancement, and HIV facial lipoatrophy.HA fillers are safe and effective with minimal recovery time and complications. Future studies with longer follow-up period and use of this 20 mg/ml HA dermal filler on areas other than midface may provide additional efficacy and safety outcomes.

Tattoo reactions can be clinically challenging to diagnose and treat. We present a case of a biopsy-proven granulomatous reaction to purple tattoo ink that clinically mimicked lichen planus. This reaction was successfully treated with one course of intralesional kenalog (ILK), with no recurrence six months after treatment. To our knowledge, this is the first report of a granulomatous tattoo reaction appearing clinically like lichen planus, and one of the few reports of a reaction to purple tattoo pigment. It highlights the importance of biopsying tattoo-related dermatoses prior to treatment in order to confirm the diagnosis. It also illustrates how a minimally invasive technique utilizing ILK to treat a granulomatous tattoo reaction can result in excellent dermatologic, cosmetic, and symptomatic outcomes. Based on this therapeutic success, we believe treatment with ILK injections should be attempted before more invasive modalities such as excision or laser therapy.

OnabotulinumtoxinA is one of the most widely used agents for cosmetic and medical treatment. Studies have shown that onabotulinumtoxinA is safe and effective with minimal adverse events, and is often well tolerated by patients. We present a patient who developed neuropathic pruritus five days after treatment with onabotulinumtoxinA for neuromuscular pain. This case highlights the treatment of pruritus associated with onabotulinumtoxinA and the therapeutic method to resolve the patient's pruritus.

HIV facial lipoatrophy (FLA) is characterized by facial volume loss. HIV FLA affects the facial contours of the cheeks, temples, and orbits, and is associated with social stigma. Although new highly active antiretroviral therapy medications are associated with less severe FLA, the prevalence of HIV FLA among treated individuals exceeds 50%. The goal of our systematic review is to examine published clinical studies involving the use of filler agents for aesthetic treatment of HIV FLA and to provide evidence-based recommendations based on published efficacy and safety data. A systematic review of the published literature was performed on July 1, 2015, on filler agents for aesthetic treatment of HIV FLA. Based on published studies, poly-L-lactic acid is the only filler agent with grade of recommendation: B. Other reviewed filler agents received grade of recommendation: C or D. Poly-L-lactic acid may be best for treatment over temples and cheeks, whereas calcium hydroxylapatite, with a Food and Drug Administration indication of subdermal implantation, may be best used deeply over bone for focal enhancement. Additional long-term randomized controlled trials are necessary to elucidate the advantages and disadvantages of fillers that have different biophysical properties, in conjunction with cost-effectiveness analysis, for treatment of HIV FLA.

Hailey-Hailey disease is a genetic disorder that affects flexural skin with scale, blisters, and maceration. Botulinum toxins have been previously used to treat Hailey-Hailey disease. Here, we present a patient who underwent one treatment of onabotulinumtoxinA and achieved excellent improvement that was sustained for three months post initial treatment.

Hyaluronic acid (HA) dermal fillers are effective and safe for correction of facial rhytides. A new volumizing HA filler, 20 mg/ml HA dermal filler (Juvéderm® Voluma®, Allergan Inc., Irvine, CA), is the only HA filler with a FDA indication for facial volumization due to age-related facial volume loss.Evaluate the biological properties, including biochemical, biophysical and rheological, of this new 20 mg/ml HA dermal filler and discuss the importance of these properties in clinical applications.A systematic search of the computerized bibliographic databases Medline, Embase, Embal, Biosis, SciSearch, Pascal, HCAPlus, IPA, and Dissertation Abstracts with key term "Voluma." Four articles on the biological properties of this new 20 mg/ ml HA dermal filler were suitable for inclusion in this review.Biological analysis of elasticity and viscosity values of this new 20 mg/ml HA dermal filler demonstrated intermediate properties in three studies and high in one study compared to other HA dermal fillers. This 20 mg/ml HA dermal filler retained the highest elasticity and viscosity values at temperature of 37°C. Histology demonstrated that this 20 mg/ml HA dermal filler has an intermediate pattern of distribution within the superficial and deep reticular dermis.This 20 mg/ml HA dermal filler demonstrated volumizing ability, and maintaining viscosity and free-flowing characteristics for easy injection, tissue lifting, and molding. We hope future research incorporates biological properties analysis of this HA dermal filler in clinical trials.

Tattoo allergies are often eczematous skin rashes that can be complicated by ulceration and infection. These allergies are difficult to resolve, sometimes requiring surgical or laser intervention, with varying success. Here we present a case of a 29-year-old woman with a serious skin allergic reaction to red tattoo ink that ulcerated and became secondarily infected. The patient expressed a desire to have the tattoo allergic reaction treated while preserving the cosmetic appearance of her tattoo for sentimental reasons. This case is being presented to provide an effective treatment algorithm for managing allergic tattoo reactions with ulceration and co-infection, while preserving the aesthetic integrity of the tattoo.

Sirtuins are a family of mammalian histone deacetylases that have been studied as possible antiaging epigenetic regulators and were shown more recently to be involved in many processes relating to the field of dermatology. Herein we describe the epigenetic roles that sirtuins play in dermatology. Research implicates sirtuin function is crucial to dermatological diseases including skin aging, inflammatory skin diseases, hyperproliferative disease, scarring, skin cancer, and skin-related inherited diseases. We will highlight the epigenetic basis for sirtuin function in various cellular processes and investigate the potential role of sirtuin modulation in the development of novel epigenetic therapies in dermatology.

The pathogenesis and maintenance of skin fibrosis is a result of complex interactions between a number of cellular pathways, cell types, and extracellular matrix molecules. miRNAs regulate these pathways and contribute to skin fibrosis through TGF-β signaling, ECM deposition, fibroblast proliferation and differentiation, and epithelial–mesenchymal transition (EMT). Some miRNAs up-regulate these processes and are known as profibrotic; others, known as antifibrotic, inhibit them, leading to skin fibrosis. miRNA therapies are aimed at either increasing the levels of antifibrotic miRNAs or decreasing those of profibrotic miRNAs. There are few effective treatments for fibrotic skin diseases, and we believe that future miRNA therapies might alter the management paradigm of skin fibrosis and improve patient outcomes and quality of life.

Blue light is part of the visible light spectrum that does not generate harmful DNA adducts associated with skin cancer and photoaging, and may represent a safer therapeutic modality for treatment of keloid scars and other fibrotic skin diseases. Our laboratory previously demonstrated that light-emitting diode (LED) red and infrared light inhibits proliferation of skin fibroblasts. Moreover, different wavelengths of light can produce different biological effects. Furthermore, the effects of LED blue light (LED-BL) on human skin fibroblasts are not well characterized. This study investigated the effects of LED-BL on human skin fibroblast proliferation, viability, migration speed, and reactive oxygen-species (ROS) generation.Irradiation of adult human skin fibroblasts using commercially-available LED-BL panels was performed in vitro, and modulation of proliferation and viability was quantified using the trypan blue dye exclusion assay, migratory speed was assessed using time-lapse video microscopy, and intracellular ROS generation was measured using the dihydrorhodamine flow cytometry assay. Statistical differences between groups were determined by ANOVA and Student's t-test.Human skin fibroblasts treated with LED-BL fluences of 5, 10, 15, 30, and 80 J/cm(2) demonstrated statistically significant dose-dependent decreases in relative proliferation of 8.4%, 29.1%, 33.8%, 51.7%, and 55.1%, respectively, compared to temperature and environment matched bench control plates, respectively. LED-BL fluences of 5, 30, 45, and 80 J/cm(2) decreased fibroblast migration speed to 95 ± 7.0% (P = 0.64), 81.3 ± 5.5% (P = 0.021), 48.5 ± 2.7% (P 0.0001), and 32.3 ± 1.9% (P 0.0001), respectively, relative to matched controls. LED fluences of 5, 10, 30, and 80 J/cm(2) resulted in statistically significant increases in reactive oxygen species of 110.4%, 116.6%, 127.5%, and 130%, respectively, relative to bench controls.At the fluences studied, LED-BL can inhibit adult human skin dermal fibroblast proliferation and migration speed, and is associated with increased reactive oxygen species generation in a dose-dependent manner without altering viability. LED-BL has the potential to contribute to the treatment of keloids and other fibrotic skin diseases and is worthy of further translational and clinical investigation.

Advanced melanoma presents a significant therapeutic challenge to clinicians. Many therapies for metastatic melanoma are limited by low response rates, severe toxicities, and/or relatively short response duration. Cancer immunotherapies that act as immune-checkpoint inhibitors to block the localized immune suppression mechanisms utilized by tumors are undergoing development and clinical trials. A clinically relevant immune escape mechanism in melanoma is the activation of the programmed cell death-1 (PD-1) receptor on infiltrating T cells. Activating PD-1 triggers an immune checkpoint resulting in inhibition of T cells directed against melanoma antigens and prevents the immune system from combating the melanoma. In Phase I clinical trials, two anti-PD1 therapies, Nivolumab and MK-3475, that block the PD-1 receptor to enable T cell killing have demonstrated objective tumor responses in patients with advanced melanoma. The purpose of this review is to present the available clinical evidence on anti-PD-1 and anti-PD-L1 immunotherapy for the treatment of advanced melanoma. We also discuss limitations associated with anti-PD-1 therapy. The blockade of the PD-1–PD-L1 pathway has shown promising results in clinical trials and has revolutionized melanoma immunotherapy.

Injectable poly-L-lactic acid (PLLA) is a biodegradable, biocompatible, synthetic polymer that acts as a scaffold to promote collagen formation and is FDA-approved for the correction of facial lipoatrophy in patients with human immunodeficiency virus (HIV) infection. The safety and efficacy of injectable PLLA for the treatment of HIV-associated facial lipoatrophy has been demonstrated in clinical studies and is accompanied by improvement in patient quality of life. Volumization of the mid-face is regarded as complex. The importance of respecting patient mid-face differences at rest and in motion was highlighted in a study that demonstrated effectiveness of silicone microdroplets (0.01 mL) in a depot manner to treat HIV patients with facial lipoatrophy. One of the challenges of facial volume rejuvenation with these techniques is preserving and enhancing dynamic facial movements after treatment. To address this challenge, we developed an injection technique termed "smile-and-fill." In this case series, we describe three patients treated by this technique to restore the malar aspect of the mid-face with improvement several months post-treatment.

Nevus anelasticus represents a rare entity that is most commonly classified as a connective tissue nevus. It typically presents before 20 years of age with asymmetrically distributed white-to-skin-toned or pink-to-red papules or plaques on the trunk and upper extremities. The lesion is defined histopathologically by the absence or degeneration of elastic fibers in the dermis. We report the case of a healthy 17-year-old female who presented with an asymptomatic slowly progressive plaque on the right inferior areola. Histopathologic examination showed the absence of elastic fibers in the papillary and upper reticular dermis and fragmented elastic tissue fibers in the deep reticular dermis. Although there is ongoing controversy regarding the nosology of this uncommon disorder, we propose that it is a distinct entity based on its histopathologic and clinical features.

Dermatofibromas are benign skin lesions that may be treated if symptomatic or for cosmetic concerns. We present a case of an African American woman with an enlarging, pruritic dermatofibroma on the thigh that was treated with fractionated carbon dioxide (CO2) laser three times approximately 5 weeks apart. Between laser treatments, topical corticosteroids were applied to the lesion for a total of 13 weeks. The dermatofibroma completely flattened and became asymptomatic within 1 month after the final laser treatment. We hypothesize that the fractionated CO2 laser ablated a portion of the stromal component of the lesion and introduced microscopic channels that facilitated deeper penetration of the topical corticosteroids into the lesion. This is the first reported case demonstrating the successful treatment of a symptomatic dermatofibroma using combination therapy with fractionated CO2 laser and topical corticosteroids.

Optical coherence tomography (OCT) is a non-invasive imaging modality that is transforming clinical diagnosis in dermatology and other medical fields. OCT provides a cross-sectional evaluation of the epidermis and dermis and allows in vivo imaging of skin collagen. Upregulated collagen content is a key feature of fibrotic skin diseases. These diseases are often managed by the practitioner’s subjective assessment of disease severity and response to therapies. The purpose of this review is to provide an overview of the principles of OCT and present available evidence on the ability of OCT to image skin collagen in vivo for the diagnosis and management of diseases characterized by skin fibrosis. We review OCT studies that characterize the collagen content in normal skin and fibrotic skin diseases including systemic sclerosis and hypertrophic scars secondary to burn, trauma, and other injury. We also highlight several limitations of OCT and suggest enhancements to improve OCT imaging of skin fibrosis. We conclude that OCT imaging has the potential to serve as an objective, non-invasive measure of collagen’s status and disease progression for use in both research trials and clinical practice. The future use of OCT imagining as a quantitative imaging biomarker of fibrosis will help identify fibrosis and facilitate clinical examination in monitoring response to treatment longitudinally without relying on serial biopsies. The use of OCT technology for quantification of fibrosis is in the formative stages and we foresee tremendous growth potential, similar to the ultrasound development paradigm that evolved over the past 30 years.

The number of skin cancers continues to rise, accounting for approximately 40% of all cancers reported in the United States and approximately 9,500 deaths per year. Studies have shown reactive oxygen species (ROS) type free radicals are linked to skin cancer and aging. Therefore, it is important for us to identify agents that have anti-oxidant properties to protect skin against free radical damage. The purpose of this research is to investigate the anti-oxidant properties of bisabolol, silymarin, and ectoin that are components from chamomile, milk thistle, and halophilic bacteria, respectively. We measured the ability of bisabolol, silymarin, and ectoin to modulate the hydrogen peroxide (H2O2)-induced upregulation of ROS free radicals in normal human skin fibroblasts in vitro. Using a flow cytometry-based assay, we demonstrated that varying concentrations of these natural components were able to inhibit upregulation of H2O2-generated free radicals in human skin fibroblasts in vitro. Our results indicate components of chamomile, milk thistle, and halophilic bacteria exhibit anti-oxidant capabilities and warrant further study in clinical trials to characterize their anti-cancer and anti-aging capabilities.

Fibrosis is characterized by the excessive deposition of extracellular matrix components eventually resulting in organ dysfunction and failure. In dermatology, fibrosis is the hallmark component of many skin diseases, including systemic sclerosis, graft-versus-host disease, hypertrophic scars, keloids, nephrogenic systemic fibrosis, porphyria cutanea tarda, restrictive dermopathy and other conditions. Fibrotic skin disorders may be debilitating and impair quality of life. There are few FDA-approved anti-fibrotic drugs; thus, research in this area is crucial in addressing this deficiency. Recent investigations elucidating the pathogenesis of skin fibrosis have implicated endogenous reactive oxygen species produced by the multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzyme complex. In this review, we discuss Nox enzymes and their role in skin fibrosis. An overview of the Nox enzyme family is presented and their role in the pathogenesis of skin fibrosis is discussed. The mechanisms by which Nox enzymes influence specific fibrotic skin disorders are also reviewed. Finally, we describe the therapeutic approaches to ameliorate skin fibrosis by directly targeting Nox enzymes with the use of statins, p47phox subunit modulators, or GKT137831, a competitive inhibitor of Nox enzymes. Nox enzymes can also be targeted indirectly via scavenging ROS with antioxidants. We believe that Nox modulators are worthy of further investigation and have the potential to transform the management of skin fibrosis by dermatologists.

Ingestion of raw or undercooked shiitake mushrooms is associated with a distinctive flagellate erythema. We describe a 61-year-old Caucasian man who presented with a pruritic, erythematous eruption of multiple linear streaks on the trunk and extremities starting 1 day after eating raw shiitake mushrooms. His symptoms and skin lesions resolved with minimal hyperpigmentation within approximately 1 week after treating with topical steroids and oral antihistamines. Skin biopsy showed non-specific findings, including a sparse perivascular and interstitial dermatitis as well as focal vacuolar interface changes. Our case illustrates that this condition is a visibly striking dermatitis with a self-limited course. The pathomechanism of the skin eruption remains unclear.

Oxidative damage by reactive oxygen species (ROS) plays a major role in aging and carcinogenesis. Little is known about either the effects of acute ROS in necrosis and inflammation of skin or the therapeutic agents for prevention and treatment. Previously, our laboratory identified caffeine as an inhibitor of hydrogen peroxide (H2O2)-generated lipid peroxidation products in human skin fibroblasts. Here, we study effects of caffeine on acute ROS-mediated necrosis. Human skin fibroblasts were incubated with caffeine, followed by H2O2 challenge. Flow cytometry was used to analyze cell morphology, counts, apoptosis and necrosis, and ROS. We found that caffeine protects from H2O2 cell damage at lower (0.01 mM) and intermediate (0.1 mM) doses. The beneficial effects of caffeine appear to be mediated by a mechanism other than antioxidant function.

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. It has been previously reported that lung GVHD severity directly correlates with the expansion of donor Th17 cells in the absence of IFN-γ. However, the consequence of Th17-associated lung GVHD in the presence of IFN-γ has not been well characterized. In the current study, T cells from IFN-γ receptor knockout (IFN-γR−/−) mice, capable of producing IFN-γ but unable to signal in response to IFN-γ, have been used to elucidate further the role of IFN-γ in GVHD. We found the transfer of donor T cells from either IFN-γR−/− or IFN-γ knockout (IFN-γ−/−) mice resulted in significant increases in donor Th17 cells in the lung. Marked increases in IL-4–producing Th2 cells infiltrating the lungs were also observed in the mice of donor IFN-γR−/− T cells. Notably, despite the presence of these cells, these mice did not show the severe immune-mediated histopathological lung injury observed in mice receiving donor IFN-γ−/− T cells. Increases in lung GVHD did occur in mice with donor IFN-γR−/− T cells when treated in vivo with anti–IFN-γ demonstrating that the cytokine has a protective role on host tissues in GVHD. A survival benefit from acute GVHD was also observed using donor cells from IFN-γR−/− T cells compared with control donors. Importantly, tumor-bearing mice receiving IFN-γR−/− T cells versus wild-type donor T cells displayed similar graft-versus-tumor (GVT) effects. These results demonstrate the critical role of IFN-γ on host tissues and cell effector functions in GVHD/GVT.

Oxidative damage by reactive oxygen species (ROS) plays a major role in skin aging, carcinogenesis and inflammation. Little is known about the protective effects of green tea extract (GTE) on toxic ROS-induced skin death. We use an in vitro model of normal human skin fibroblasts (AG13145) to study the effects of green tea extract (GTE) on hydrogen peroxide (H(2)O(2)) induced necrosis. Cell morphology, numbers, apoptosis, necrosis, and ROS were assessed by epifluorescence microscopy and flow cytometry. This study demonstrates that GTE protected from H(2)O(2)-induced necrosis in a dose-dependent manner, with highest dose GTE (100 ng/mL) resulting in the most protection from necrosis, as assessed by improved cell morphology, increased cell numbers, and decreased necrosis. The protective effects of GTE on H(2)O(2)-induced necrosis appear to be mediated directly by decreasing intracellular ROS. The present study suggests that pretreatment with high doses of GTE could protect from toxic ROS-induced injury of skin in the clinical setting. However, additional studies are necessary to determine the clinical utility of GTE for decreasing skin cell ROS, necrosis and inflammation.

The study of free radicals is particularly relevant in the context of human skin carcinogenesis and photoaging because of these oxidants' ability to induce DNA mutations and produce lipid peroxidation byproducts, including 4-hydroxy-2-nonenal (HNE). Therefore, it is important to identify and evaluate agents with the ability to modulate intracellular free radicals and HNE. The purpose of this research is to investigate the ability of antioxidants green tea polyphenols (GTPs) and caffeine, alone and in combination, to modulate the hydrogen peroxide (H2O2)-induced upregulation of reactive oxygen species (ROS) free radicals and HNE in normal human skin fibroblast WS-1 cells in vitro. GTPs and caffeine were selected for evaluation because these compounds have demonstrated antioxidative properties in various skin models. Furthermore, GTPs and caffeine share a close natural botanical association as caffeine is present in green tea, as well. Hydrogen peroxide is a well-known generator of free radicals that is produced during endogenous and UV-induced oxidation processes in human skin and was used to upregulate ROS and HNE in normal human fibroblast WS-1 cells. Using a flow cytometry-based assay, the results demonstrate that at 0.001% concentration, green tea polyphenols alone, and in combination with 0.1 mM caffeine, inhibited the upregulation of H2O2-generated free radicals and HNE in human skin fibroblasts in vitro. Caffeine alone demonstrated limited anti-oxidant properties.

The study of free radicals is particularly relevant in the context of human skin carcinogenesis and photoaging because of their ability to induce DNA mutations and damaging lipid peroxidation byproducts. Therefore, it is important to identify and evaluate agents with the ability to modulate intracellular free radicals. Significant interest exists in evaluating the chemotherapeutic and anti-oxidant properties of resveratrol (trans-3,4',5-trihydroxystilbene). Resveratrol is a phytoalexin, a naturally occurring compound derived from the skin of grapes and other plants. Resveratrol was selected for evaluation because of demonstrated chemopreventive and chemotherapeutic properties in a murine skin cancer model and other human cancer models through a variety of mechanisms. However, the intracellular anti-oxidant properties of resveratrol on free radicals in human skin cells in vitro is not well characterized. The purpose of this research is to investigate the ability of resveratrol to modulate the hydrogen peroxide-induced upregulation of reactive oxygen species (ROS) free radicals in normal human skin fibroblast cells in vitro. Hydrogen peroxide is a well known generator of free radicals that occurs during endogenous and UV-induced oxidation processes in the human skin and was used to upregulate ROS in normal human skin fibroblast cells. Using a flow cytometry-based assay, the results demonstrate highly significant (P0.001) dose-dependent reduction of intracellular hydrogen peroxide-upregulated ROS by resveratrol at 0.01%, 0.001% and 0.0001% concentrations in human skin fibroblasts in vitro.

Sweet's syndrome–like (Sweet's-like) neutrophilic panniculitis is usually idiopathic, but is frequently associated with hematologic, inflammatory, and immunologic disease. Drug-related cases of Sweet's syndrome have been reported. Of relevance, chemotherapy with the retinoid all- trans -retinoic acid (ATRA) infrequently induces Sweet's-like neutrophilic panniculitis that occurs concomitantly with neutrophilic differentiation. The pathologic features are limited to the adipose tissue or include both the dermis and the subcutaneous fat; the neutrophilic infiltrate can be observed in the lobules, the septae, or both. We present this case because of the unusual subcutaneous neutrophilic infiltrate consistent with Sweet's-like neutrophilic lobular panniculitis in a patient with acute promyelocytic leukemia receiving ATRA chemotherapy. This case highlights the important connection between ATRA and Sweet's syndrome.

BACKGROUND AND OBJECTIVE: Low level light therapy has garnered significant interest within the past decade. The exact molecular mechanisms of how red and near infrared light result in physiologic modulation are not fully understood. Heme moieties and copper within cells are red and near infrared light photoreceptors that induce the mitochondrial respiratory chain component cytochrome C oxidase, resulting in a cascade linked to cytoprotection and cellular metabolism. The copper centers in cytochrome C oxidase have a broad absorption range that peaks around 830 nm. Several in vitro and in vivo animal and human models exist that have demonstrated the benefits of red light and near infrared light for various conditions. Clinical applications for low level light therapy are varied. One study in particular demonstrated improved durable functional outcomes status post-stroke in patients treated with near infrared low level light therapy compared to sham treatment [1]. Despite previous data suggesting the beneficial effect in treating multiple conditions, including stroke, with low level light therapy, limited data exists that measures transmission in a human model. STUDY DESIGN/MATERIALS AND METHODS: To investigate this idea, we measured the transmission of near infrared light energy, using red light for purposes of comparison, through intact cadaver soft tissue, skull bones, and brain using a commercially available LED device at 830 nm and 633 nm. RESULTS: Our results demonstrate that near infrared measurably penetrates soft tissue, bone and brain parenchyma in the formalin preserved cadaveric model, in comparison to negligible red light transmission in the same conditions. CONCLUSION: These findings indicate that near infrared light can penetrate formalin fixed soft tissue, bone and brain and implicate that benefits observed in clinical studies are potentially related to direct action of near infrared light on neural tissue.

Background Skin fibrosis is involved in a variety of pathologic conditions ranging from scar formation secondary to surgery or trauma to immune-mediated processes. Skin fibrosis is a significant international health problem with an estimated incidence of greater than 100 million people affected per year worldwide with few effective treatment options available. Preliminary in vitro data generated by our research group suggests that red light can function as a stand-alone treatment for skin fibrosis. To our knowledge, no prior clinical trials have been performed to determine the safety of high-fluence (dose) light-emitting diode-red light (LED-RL) phototherapy. The goal of this study is to evaluate the safety of LED-RL fluences from 160 J/cm2 up to 640 J/cm2 in healthy subjects. Methods/design This is a single-blind, dose escalation, randomized controlled, phase I study to evaluate the safety of high-fluence LED-RL on human skin. The protocol for dose escalation requires subjects be enrolled sequentially in groups of five. Within each group, three subjects will be randomized to LED-RL phototherapy and two subjects randomized to mock therapy. Subjects in group 1 randomized to LED-RL phototherapy will receive the maximum recommended starting dose (160 J/cm2). LED-RL dose will be escalated in subsequent groups (320 J/cm2, 480 J/cm2 and 640 J/cm2). The maximally tolerated dose (MTD) is defined as the dose level below the dose producing unacceptable but reversible toxicity and is considered to be the upper limit of subject tolerance. After either a MTD has been established, or the study endpoint of 640 J/cm2 has been achieved, an additional 27 LED-RL phototherapy subjects (for a total of 30) and 18 mock therapy subjects (for a total of 20) (determined randomly) will be enrolled. Each subject will receive a total of nine procedures, three times per week for three consecutive weeks. Discussion This study may provide important safety information on the effects of high-fluence LED-RL phototherapy on human skin and help facilitate future phase II studies to evaluate the efficacy of high-fluence LED-RL as a potential noninvasive, safe, portable, at-home therapy for treatment of skin fibrosis. Trial registration ClinicalTrials.gov NCT02630303. Registered on 9 December 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1518-7) contains supplementary material, which is available to authorized users.

To the Editor: The global population of bedbugs that feed on humans (Cimex lectularius, Cimex hemipterus, and Leptocimex boueti) has undergone a significant resurgence since the late 1990s. Due to increased international travel and pesticide resistance, bedbugs once thought to be native to certain geographic locations have been found in other parts of the world. Bedbugs present a socioeconomic burden because they are costly to eradicate and infestations often recur. According to the US Environmental Protection Agency, bedbugs are ‘‘a pest of significant health importance,’’ and upwards of 45 disease pathogens have been reported in bedbugs. It stands to reason to ask if bedbugs might transmit human pathogens. We performed a literature review on August 6, 2015, and searched the computerizedmedical bibliographic databases PubMed, EMBASE, CINAHL, and Web of Science with the search terms: ‘‘bedbug’’ OR ‘‘cimex lectularius.’’ A total of 1790 articles were returned, and 12 articles were suitable for inclusion (clinical and laboratory published studies [1990 to 2015] investigating bedbugs as potential vectors of infectious disease) after screening of titles, abstracts, and/or full-text articles. These articles demonstrated that although bedbugs may carry pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and hepatitis B virus, and may be competent vectors of Bartonella quintana and Trypanosoma cruzi, there were no confirmed cases of human disease transmission. Previous reports suggest that, although a number of different disease pathogen species have been detected in or on bedbugs, there is a lack of definitive evidence that bedbugs transmit human pathogens. An important challenge for scientists is to determine the reason for this interesting finding.