Volatile anesthetics are used widely for achieving a state of unconsciousness, yet these agents are incompletely understood in their mechanisms of action and effects on neural development. There is mounting evidence that children exposed to anesthetic agents sustain lasting effects on learning and memory. The explanation for these behavioral changes remains elusive, although acute neuronal death after anesthesia is commonly believed to be a principal cause. Rodent models have shown that isoflurane exposure in newborns induces acute neuroapoptosis and long-term cognitive impairment. However, the assessment of predisposing factors is lacking. We investigated the role of sex by delivering isoflurane to postnatal day (P)7 male and female Sprague Dawley rats for 4 hours. Brain cell death was assessed 12 h later using FluoroJade C staining in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. Behavior was assessed separately using a series of object recognition tasks and a test of social memory beginning at P38. We found that isoflurane exposure significantly increased neuronal death in each brain region with no difference between sexes. Behavioral outcome was also equivalent in simple novel object recognition. However, only males were impaired in the recognition of objects in different locations and contexts. Males also exhibited deficient social memory while females were intact. The profound behavioral impairment in males relative to females, in spite of comparable cell death, suggests that males are more susceptible to long-term cognitive effects and this outcome may not be exclusively attributed to neuronal death.

Therapeutic applications of light emitting diode‐red light (LED‐RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED‐RL (≥160 J/cm2). In two phase I, single‐blind, dose escalation, randomized controlled trials, healthy subjects received LED‐RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160‐640 J/cm2 for all skin types (STARS 1, n = 60) and at 480‐640 J/cm2 for non‐Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose‐limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm2 in STARS 1 (n = 1) and 640 J/cm2 in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED‐RL is safe up to 320 J/cm2 for skin of color and 480 J/cm2 for non‐Hispanic Caucasian individuals. LED‐RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED‐RL for the treatment of various diseases.

BackgroundSkin 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/designThis 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.DiscussionThis 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 registrationClinicalTrials.gov NCT02630303. Registered on 9 December 2015. Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1518-7) contains supplementary material, which is available to authorized users.