Neil Brody

Transcranial Red and Near Infrared Light Transmission in a Cadaveric Model

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.

Sirtuins in dermatology: applications for future research and therapeutics.

Sirtuins are a family of seven proteins in humans (SIRT1–SIRT7) that are involved in multiple cellular processes relevant to dermatology. The role of sirtuins in other organ systems is established. However, the importance of these proteins in dermatology is less defined. Recently, sirtuins gained international attention because of their role as “longevity proteins” that may extend and enhance human life. Sirtuins function in the cell via histone deacetylase and/or adenosine diphosphate ribosyltransferase enzymatic activity that target histone and non-histone substrates, including transcription regulators, tumor suppressors, structural proteins, DNA repair proteins, cell signaling proteins, transport proteins, and enzymes. Sirtuins are involved in cellular pathways related to skin structure and function, including aging, ultraviolet-induced photoaging, inflammation, epigenetics, cancer, and a variety of cellular functions including cell cycle, DNA repair and proliferation. This review highlights sirtuin-related cellular pathways, therapeutics and pharmacological targets in atopic dermatitis, bullous dermatoses, collagen vascular disorders, psoriasis, systemic lupus erythematosus, hypertrophic and keloid scars, cutaneous infections, and non-melanoma and melanoma skin cancer. Also discussed is the role of sirtuins in the following genodermatoses: ataxia telangiectasia, Cowden’s syndrome, dyskeratosis congenita, Rubenstein–Taybi, Werner syndrome, and xeroderma pigmentosum. The pathophysiology of these inherited diseases is not well understood, and sirtuin-related processes represent potential therapeutic targets for diseases lacking suitable alternative treatments. The goal of this review is to bring attention to the dermatology community, physicians, and scientists, the importance of sirtuins in dermatology and provide a foundation and impetus for future discussion, research and pharmacologic discovery.

Inhibition of fibroblast proliferation in vitro using red light-emitting diodes.

Background Red light is part of the visible light spectrum. The effects of light‐emitting diode (LED)‐generated red light on human skin are not well‐characterized. Objective To study the effect of red LED‐generated low‐level light therapy (LLLT) on fibroblast proliferation and viability in vitro. Methods and Materials Irradiation of normal human skin fibroblasts using red LED panels was performed in vitro, and modulation of proliferation and viability was quantified using trypan blue dye exclusion assay. Results Statistically significant decreases in cell proliferation were noted at the following fluences (time): 160 J/cm2 (30 minutes, 34 seconds), 320 J/cm2 (61 minutes, 07 seconds) and 640 J/cm2 (122 minutes, 14 seconds) (Figure 1). Irradiation at the 160‐ (98.5 ± 1.2%) and 320‐J/cm2 (98.0 ± 3.1%) doses did not significantly alter viability. Conclusion At certain fluences, red LLLT can effectively inhibit fibroblast proliferation in vitro without altering viability and holds promise for the treatment of scars and other proliferative skin diseases.

Inhibition of Fibroblast Proliferation In Vitro Using Low-Level Infrared Light-Emitting Diodes

Background Scars, including hypertrophic and keloidal‐type scars, may occur after burns, trauma, or surgery. Despite several treatment options available for scars, few effective, noninvasive modalities exist. Recently, a few small clinical studies revealed the possible benefit of red and infrared (IR) low‐level light therapy (LLLT) in scar treatment. One of the important features of scars is proliferation of dermal fibroblasts, but in vitro data regarding the effects of light‐emitting diode (LED)‐generated IR light on human skin fibroblasts is lacking. Objective To evaluate the effect of IR LLLT generated using LEDs on fibroblast proliferation and viability in vitro. Methods and Materials Irradiation of normal human skin fibroblasts using IR LED panels was performed in vitro, and modulation of proliferation and viability was quantified using Trypan blue dye exclusion assay. Results Fluences of 80, 160 and 320 J/cm2 resulted in statistically significantly less fibroblast proliferation than in controls, without statistically significantly less cellular viability. Conclusion IR LLLT can effectively inhibit fibroblast proliferation in vitro without altering viability and holds promise for the treatment of scars.

CUTANEOUS FUNGAL INFECTIONS INNOVATIVE TREATMENT SCHEDULES WITH SYSTEMIC AGENTS

Eungal infections were first identified during the early 19th century, primarily in the form of vaginal candidiasis and superficial mycoses, especially tinea capitis. As a result of the superficial nature of these infections, treatment focused on topical agents. This contrasted with the development of systemic agents ro treat bacterial infections that were potentially life-threatening. Not until fungi were identified as a source of invasive mycoses were systemic antifungal drugs developed. Even then, it has only been during the past two decades that safe and effective systemic agents were developed to treat superficial skin diseases and onychomycoses. The initial treatment options for mycoses, although effective, have several limitations: potassium iodide is only effective against sporotrichosis; amphotericin B is associated with toxicity and requires inpatient treatment; flucytosine resistance has limited its application to use with a concomitant agent; griseofulvin is effective only against dermatophytes, requires a long treatment course, and has a low cure rate; miconazole, although used as a topical agent for superficial infections, needs to be administered intravenously for systemic infections, thereby necessitating hospitalization. Eortunately, until recently, serious systemic mycotic infection was rare; however, the increased use of chemotherapy and radiation therapy, as well as the acquired immune deficiency syndrome (AIDS) epidemic, have all contributed to an increased risk for the development of a systemic mycosis and/or a chronic superficial mycosis. Consequently, new systemically active antifungal drugs have been developed that address the limitations of the traditional agents. These new antifungals include the first orally active imidazole, ketoconazole, the triazoles, itraconazole and fluconazole, and the allylamine, terbinafine.

Dihydroxyacetone and sunless tanning: Knowledge, myths, and current understanding

DHA: dihydroxyacetone FDA: US Food and Drug Administration S unless tanning products, which contain dihydroxyacetone (DHA), produce a relatively long-lasting simulated tan without the risks of photodamage. DHA is a sugar that interacts with proteins in the skin to form brown-colored products called melanoidins. This reaction is limited to the stratum corneum, and in vitro skin absorption studies have found no significant systemic absorption of DHA when applied topically to the skin. In this Commentary, we review current misconceptions among the lay media and general public about the established risks of DHA-containing sunless tanning products, as well as US Food and Drug Administration (FDA)-approved guidelines for their proper use. DHA is FDA-approved for topical application to the skin (eg, cream or lotion formulations), but it ‘‘should not be inhaled, ingested, or exposed to areas covered by mucous membranes’’ such as the area around the eye or on the lips. DHA is not approved for use in all-over spray tans, including at-home spray tans and misting from tanning booths, due to limited safety data on these applications. The Skin Cancer Foundation and the American Academy of Dermatology maintain that self-tanning, with concomitant sunscreen use, is safer than tanning by ultraviolet radiation. Irritant and allergic contact dermatitis are the most common side effects. On a cellular level, DHA has been shown to cause severe morphologic changes and damage to cell proliferation and growth in cultured keratinocytes. Another in vitro study found that DHAwasmutagenic in Salmonella typhimurium and DNA-damaging in Bacillus subtilis. However,

Important implications and new uses of ablative lasers in dermatology: fractional carbon dioxide laser prevention of skin cancer.

Carbon dioxide (CO2) and other ablative lasers have been used for decades in dermatology to resurface the epidermis and superficial dermis. Carbon dioxide lasers have been primarily used for aesthetic enhancement and skin rejuvenation through reduction of rhytides and other cutaneous manifestations of chronologic and ultraviolet (UV)-associated skin aging. Nonfractional CO2 lasers were largely replaced in physician offices with the introduction of fractional CO2 lasers approximately a decade ago. Fractional CO2 allowed for interrupted or “fractional” ablation of skin, interlacing microscopic treatment zones of ablated columns of tissue and untreated tissue. The premise of fractional ablative laser treatments is that they achieve excellent resurfacing aesthetic outcomes approaching nonfractional CO2 laser treatments with less “downtime” because of more rapid wound healing because of less tissue destroyed. This microwounding process alters the epidermal and dermal milieu, resulting in epidermal and dermal remodeling similar to nonfractional laser ablation through increased collagen production and other processes.

Laboratory tests to evaluate the immune system.

Susceptibility to infection, assessment of the stage and activity of a number of diseases, and the probability of developing certain classes of diseases depend on measuring and monitoring parameters of the immune system. A rather extensive series of laboratory examinations is now available to evaluate the immune system. These screening tests help to pinpoint malfunctions within the system. It is preferable not to exhaustively evaluate each patient, but to be aware of clinical symptomatology that suggests the appropriate laboratory evaluation (Table 1). This paper assumes that the reader has a grasp of basic immunology and goes on to discuss some laboratory tests currently available to assess various portions of the immune system. An attempt has been made to eliminate tests for which the technology is only available in a handful of laboratories. Greater details for laboratory techniques may be found in the references. References have been selected either as general and laboratory aids or to present data supporting utilization of a newer controversial technique. Where connotations are readily perceived in the text, they are the opinion of the author.

Reduction of Facial Redness with Resveratrol Added to Topical Product Containing Green Tea Polyphenols and Caffeine

BACKGROUND/OBJECTIVE Many topical formulations include antioxidants to improve the antioxidant capability of the skin. This study evaluated the ability of a unique combination of antioxidants including resveratrol, green tea polyphenols, and caffeine to reduce facial redness. METHODS Subjects (n=16) presenting with facial redness applied the resveratrol-enriched product twice daily to the entire face. Reduction in redness was evaluated by trained staff members and dermatology house staff officers. Evaluators compared clinical photographs and spectrally enhanced images taken before treatment and at 2-week intervals for up to 12 weeks. RESULTS 16 of 16 clinical images showed improvement and 13 of 16 spectrally enhanced images were improved. Reduction in facial redness continued to evolve over the duration of the study period but was generally detectable by 6 weeks of treatment. Adverse effects were not observed in any subject. CONCLUSION The skin product combination of resveratrol, green tea polyphenols, and caffeine safely reduces facial redness in most patients by 6 weeks of continuous treatment and may provide further improvement with additional treatment.