Light suppresses melatonin in humans, with the strongest response occurring in the short-wavelength portion of the spectrum between 446 and 477 nm that appears blue. Blue monochromatic light has also been shown to be more effective than longer-wavelength light for enhancing alertness. Disturbed circadian rhythms and sleep loss have been described as risk factors for astronauts and NASA ground control workers, as well as civilians. Such disturbances can result in impaired alertness and diminished performance. Prior to exposing subjects to short-wavelength light from light-emitting diodes (LEDs) (peak λ = 469 nm; 1/2 peak bandwidth = 26 nm), the ocular safety exposure to the blue LED light was confirmed by an independent hazard analysis using the American Conference of Governmental Industrial Hygienists exposure limits. Subsequently, a fluence-response curve was developed for plasma melatonin suppression in healthy subjects (n = 8; mean age of 23.9 ± 0.5 years) exposed to a range of irradiances of blue LED light. Subjects with freely reactive pupils were exposed to light between 2:00 and 3:30 AM. Blood samples were collected before and after light exposures and quantified for melatonin. The results demonstrate that increasing irradiances of narrowband blue-appearing light can elicit increasing plasma melatonin suppression in healthy subjects (P < 0.0001). The data were fit to a sigmoidal fluence-response curve (R(2) = 0.99; ED(50) = 14.19 μW/cm(2)). A comparison of mean melatonin suppression with 40 μW/cm(2) from 4,000 K broadband white fluorescent light, currently used in most general lighting fixtures, suggests that narrow bandwidth blue LED light may be stronger than 4,000 K white fluorescent light for suppressing melatonin.
Obesity is a chronic inflammation with increased serum levels of insulin, insulin-like growth factor 1 (IGF1), and interleukin-17 (IL-17). The objective of this study was to test a hypothesis that insulin and IGF1 enhance IL-17-induced expression of inflammatory chemokines/cytokines through a glycogen synthase kinase 3β (GSK3B)-dependent mechanism, which can be inhibited by melatonin. We found that insulin/IGF1 and lithium chloride enhanced IL-17-induced expression of C-X-C motif ligand 1 (Cxcl1) and C-C motif ligand 20 (Ccl20) in the Gsk3b+/+ but not Gsk3b−/− mouse embryonic fibroblast (MEF) cells. IL-17 induced higher levels of Cxcl1 and Ccl20 in the Gsk3b−/− MEF cells, compared to the Gsk3b+/+ MEF cells. Insulin and IGF1 activated Akt to phosphorylate GSK3B at serine 9, thus inhibiting GSK3B activity. Melatonin inhibited Akt activation, thus decreasing P-GSK3B at serine 9 (i.e., increasing GSK3B activity) and subsequently inhibiting expression of Cxcl1 and Ccl20 that was induced either by IL-17 alone or by a combination of insulin and IL-17. Melatonin's inhibitory effects were only observed in the Gsk3b+/+ but not Gsk3b−/− MEF cells. Melatonin also inhibited expression of Cxcl1, Ccl20 and Il-6 that was induced by a combination of insulin and IL-17 in the mouse prostatic tissues. Further, nighttime human blood, which contained high physiologic levels of melatonin, decreased expression of Cxcl1, Ccl20 and Il-6 in the PC3 human prostate cancer xenograft tumors. Our data support our hypothesis and suggest that melatonin may be used to dampen IL-17-mediated inflammation that is enhanced by the increased levels of insulin and IGF1 in obesity.
Policy makers, payers, and the general public are increasingly focused on health care quality improvement. Measuring quality requires robust data systems that collect data over time, can be integrated with other systems, and can be analyzed easily for trends. The goal of this project was to study effective tools and strategies in the design and use of clinical registries with the potential to facilitate quality improvement, value-based purchasing, and public reporting on the quality of care. The research team worked with an expert panel to define characteristics of effectiveness, and studied examples of effective registries in cancer, cardiovascular care, maternity, and joint replacement. The research team found that effective registries were successful in 1 or more of 6 key areas: data standardization, transparency, accuracy/completeness of data, participation by providers, financial sustainability, and/or providing feedback to providers. The findings from this work can assist registry designers, sponsors, and researchers in implementing strategies to increase the use of clinical registries to improve patient care and outcomes.
Light at night (LAN), via its ability to suppress nocturnal circadian pineal melatonin production, has been associated with an increased risk of prostate, breast, and endometrial cancers reported in rotating night shift workers. In previous studies, we determined that melatonin's tumor growth inhibitory mechanism occurs via an MT1 melatonin receptor-mediated suppression of tumor cAMP leading to an inhibition of tumor linoleic acid (LA) uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). These events culminate in down-regulation of the epidermal growth factor and insulin-like growth factor-1 pathways. Tissue-isolated, androgen-independent PC3 human prostate tumor xenografts (n=3/group; 57 perfusions) perfused for 60 minutes in situ in male nude rats with melatonin-rich blood (> 100 pg/ml) collected from healthy adult, male subjects (n = 3) during the night were compared to those perfused with melatonin-deficient blood (< 10 pg/ml) collected during the daytime or nighttime following 90 minutes of ocular exposure to bright, white fluorescent light (2800 lux). Perfusion of tissue-isolated PC3 human prostate xenografts with human donor nighttime-collected, melatonin-rich blood samples resulted in substantial reductions (60 – 99%) in tumor cAMP levels, LA uptake, 13-HODE production, glucose uptake, O2 consumption and CO2 production, and [3H]thymidine incorporation into tumor DNA, compared to tumors perfused with daytime-collected or nighttime/light exposure-collected, melatonin-diminished blood samples. The activation of MEK, ERK 1/2, Akt, and glycogen synthase kinase-3β (GSK3β), was also markedly diminished in tumors perfused with melatonin-rich, nighttime-collected blood and stimulated in tumors perfused with melatonin-deficient blood collected after exposure to light at night. Tumor inhibitions by melatonin-rich blood were completely prevented by a non-selective MT1/MT2 melatonin receptor antagonist, forskolin, pertussis toxin, or 8-Bromo-cAMP. These results are the first to demonstrate that the nocturnal melatonin signal in blood collected from male human volunteers during the night suppresses signal transduction, metabolic and growth activity in tissue-isolated PC3 human prostate cancer xenografts via an MT1 melatonin receptor-mediated mechanism. These findings are also the first to show that blood collected from human subjects exposed to light at night markedly stimulates human prostate cancer growth, signal transduction and metabolic activity via suppression of the nocturnal circadian melatonin signal. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1324. doi:10.1158/1538-7445.AM2011-1324
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.