Publications by authors named "George C Brainard"

48 Publications

Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers.

J Pineal Res 2021 Jun 12:e12752. Epub 2021 Jun 12.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, USA.

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n = 16 males, mean age ± SD = 23.4 ± 2.3 years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n = 25, 14 females, 36.3 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7 hours and -4.2 hours, respectively, compared to -6.6 hours and -4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.
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http://dx.doi.org/10.1111/jpi.12752DOI Listing
June 2021

Spectral sensitivity of circadian phase resetting, melatonin suppression and acute alerting effects of intermittent light exposure.

Biochem Pharmacol 2021 Mar 10:114504. Epub 2021 Mar 10.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.

Intermittent light (IML) pulses are more efficient per minute of exposure than continuous exposure in resetting the phase of the human circadian pacemaker. We assessed the spectral sensitivity in phase resetting, melatonin suppression and alertness induced by IML pulses. Twelve healthy young adults (6 females; mean age ± SD = 25.4 ± 3.6 years) were exposed to six monochromatic light pulses (2.8 × 10 photons/cm/s) over a 6.5 h window during the biological night. Six participants (3F) received 6 × 15-minute 460 nm (blue) pulses and six participants received 6 × 2-minute 555 nm (green) light pulses. Results were compared to historical data in 16 individuals who received continuous 460 nm (n = 8) or 555 nm (n = 8) light exposure using an identical protocol. As expected, long duration continuous 460 nm light exposure induced the largest total phase delay shifts, but intermittent 555 nm light induced the largest phase delay shifts per minute of the photic stimulus. Melatonin suppression was significantly higher under continuous light exposure compared to intermittent exposure patterns, and for 460 nm versus 555 nm exposure (under both light patterns). These data extend prior work showing a non-linear relationship between light exposure duration and phase resetting responses and illustrate the potential role of light wavelength, and therefore photoreceptor recruitment, in mediating these responses.
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http://dx.doi.org/10.1016/j.bcp.2021.114504DOI Listing
March 2021

Relevance of Electrical Light on Circadian, Neuroendocrine, and Neurobehavioral Regulation in Laboratory Animal Facilities.

ILAR J 2020 10;60(2):150-158

Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania.

Light is a key extrinsic factor to be considered in operations and design of animal room facilities. Over the past four decades, many studies on typical laboratory animal populations have demonstrated impacts on neuroendocrine, neurobehavioral, and circadian physiology. These effects are regulated independently from the defined physiology for the visual system. The range of physiological responses that oscillate with the 24 hour rhythm of the day include sleep and wakefulness, body temperature, hormonal secretion, and a wide range of other physiological parameters. Melatonin has been the chief neuroendocrine hormone studied, but acute light-induced effects on corticosterone as well as other hormones have also been observed. Within the last two decades, a new photosensory system in the mammalian eye has been discovered. A small set of retinal ganglion cells, previously thought to function as a visual output neuron, have been shown to be directly photosensitive and act differently from the classic photoreceptors of the visual system. Understanding the effects of light on mammalian physiology and behavior must take into account how the classical visual photoreceptors and the newly discovered ipRGC photoreceptor systems interact. Scientists and facility managers need to appreciate lighting impacts on circadian, neuroendocrine, and neurobehavioral regulation in order to improve lighting of laboratory facilities to foster optimum health and well-being of animals.
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http://dx.doi.org/10.1093/ilar/ilaa010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947598PMC
October 2020

Smart Lighting Clinical Testbed Pilot Study on Circadian Phase Advancement.

IEEE J Transl Eng Health Med 2019 30;7:3200110. Epub 2019 Aug 30.

4Internal MedicineUniversity of New MexicoAlbuquerqueNM87131USA.

Objective: Lighting is a strong synchronizer for circadian rhythms, which in turn drives a wide range of biological functions. The objective of our work is a) to construct a clinical in-patient testbed with smartİ lighting, and b) evaluate its feasibility for use in future clinical studies.

Methods: A feedback capable, variable spectrum lighting system was installed at the University of New Mexico Hospital. The system consists of variable spectrum lighting troffers, color sensors, occupancy sensors, and computing and communication infrastructure. We conducted a pilot study to demonstrate proof of principle, that 1) this new technology is capable of providing continuous lighting and sensing in an active clinical environment, 2) subject recruitment and retention is feasible for round-the-clock, multi-day studies, and 3) current techniques for circadian regulation can be deployed in this unique testbed. Unlike light box studies, only troffer-based lighting was used, and both lighting intensity and spectral content were varied.

Results: The hardware and software functioned seamlessly to gather biometric data and provide the desired lighting. Salivary samples that measure dim-light melatonin onset showed phase advancement for all three subjects.

Conclusion: We executed a five-day circadian rhythm study that varied intensity, spectrum, and timing of lighting as proof-of-concept or future clinical studies with troffer-based, variable spectrum lighting. Clinical Impact: The ability to perform circadian rhythm experiments in more realistic environments that do not overly constrain the subject is important for translating lighting research into practice, as well as for further research on the health impacts of lighting.
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http://dx.doi.org/10.1109/JTEHM.2019.2937957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075421PMC
August 2019

Menstrual phase-dependent differences in neurobehavioral performance: the role of temperature and the progesterone/estradiol ratio.

Sleep 2020 02;43(2)

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.

Study Objectives: Women in the luteal phase of the menstrual cycle exhibit better cognitive performance overnight than women in the follicular phase, although the mechanism is unknown. Given the link between core body temperature (CBT) and performance, one potential mechanism is the thermoregulatory role of progesterone (P4), estradiol (E2), and their ratio (P4/E2), which change across the menstrual cycle. We examined the role of P4/E2 in modulating performance during extended wake in premenopausal women. Additionally, we compared the acute effects of nighttime light exposure on performance, CBT, and hormones between the menstrual phases.

Methods: Participants were studied during a 50 h constant routine and a 6.5 h monochromatic nighttime light exposure. Participants were 16 healthy, naturally cycling women (eight follicular; eight luteal). Outcome measures included reaction time, attentional failures, self-reported sleepiness, CBT, melatonin, P4, and E2.

Results: As compared to women in the luteal phase, women in the follicular phase exhibited worse performance overnight. CBT was significantly associated with performance, P4, and P4/E2 but not with other sex hormones. Sex hormones were not directly related to performance. Light exposure that suppressed melatonin improved performance in the follicular phase (n = 4 per group) to levels observed during the luteal phase and increased CBT but without concomitant changes in P4/E2.

Conclusions: Our results underscore the importance of considering menstrual phase when assessing cognitive performance during sleep loss in women and indicate that these changes are driven predominantly by CBT. Furthermore, this study shows that vulnerability to sleep loss during the follicular phase may be resolved by exposure to light.
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http://dx.doi.org/10.1093/sleep/zsz227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457328PMC
February 2020

Influence of Daytime LED Light Exposure on Circadian Regulatory Dynamics of Metabolism and Physiology in Mice.

Comp Med 2019 10 20;69(5):350-373. Epub 2019 Sep 20.

Departments of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana.

Light is a potent biologic force that profoundly influences circadian, neuroendocrine, and neurobehavioral regulation in animals. Previously we examined the effects of light-phase exposure of rats to white light-emitting diodes (LED), which emit more light in the blue-appearing portion of the visible spectrum (465 to 485 nm) than do broad-spectrum cool white fluorescent (CWF) light, on the nighttime melatonin amplitude and circadian regulation of metabolism and physiology. In the current studies, we tested the hypothesis that exposure to blue-enriched LED light at day (bLAD), compared with CWF, promotes the circadian regulation of neuroendocrine, metabolic, and physiologic parameters that are associated with optimizing homeostatic regulation of health and wellbeing in 3 mouse strains commonly used in biomedical research (C3H [melatonin-producing], C57BL/6, and BALB/c [melatonin-non-producing]). Compared with male and female mice housed for 12 wk under 12:12-h light:dark (LD) cycles in CWF light, C3H mice in bLAD evinced 6-fold higher peak plasma melatonin levels at the middark phase; in addition, high melatonin levels were prolonged 2 to 3 h into the light phase. C57BL/6 and BALB/c strains did not produce nighttime pineal melatonin. Body growth rates; dietary and water intakes; circadian rhythms of arterial blood corticosterone, insulin, leptin, glucose, and lactic acid; pO₂ and pCO₂; fatty acids; and metabolic indicators (cAMP, DNA, tissue DNA H-thymidine incorporation, fat content) in major organ systems were significantly lower and activation of major metabolic signaling pathways (mTOR, GSK3β, and SIRT1) in skeletal muscle and liver were higher only in C3H mice in bLAD compared with CWF. These data show that exposure of C3H mice to bLAD compared with CWF has a marked positive effect on the circadian regulation of neuroendocrine, metabolic, and physiologic parameters associated with the promotion of animal health and wellbeing that may influence scientific outcomes. The absence of enhancement in amelatonic strains suggests hyperproduction of nighttime melatonin may be a key component of the physiology.
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http://dx.doi.org/10.30802/AALAS-CM-19-000001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807725PMC
October 2019

Effects of Daytime Exposure to Light from Blue-Enriched Light-Emitting Diodes on the Nighttime Melatonin Amplitude and Circadian Regulation of Rodent Metabolism and Physiology.

Comp Med 2016 ;66(5):373-383

Departments of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, Pennsylvania, USA.

Regular cycles of exposure to light and dark control pineal melatonin production and temporally coordinate circadian rhythms of metabolism and physiology in mammals. Previously we demonstrated that the peak circadian amplitude of nocturnal blood melatonin levels of rats were more than 6-fold higher after exposure to cool white fluorescent (CWF) light through blue-tinted (compared with clear) rodent cages. Here, we evaluated the effects of light-phase exposure of rats to white light-emitting diodes (LED), which emit light rich in the blue-appearing portion of the visible spectrum (465-485 nm), compared with standard broadspectrum CWF light, on melatonin levels during the subsequent dark phase and on plasma measures of metabolism and physiology. Compared with those in male rats under a 12:12-h light:dark cycle in CWF light, peak plasma melatonin levels at the middark phase (time, 2400) in rats under daytime LED light were over 7-fold higher, whereas midlight phase levels (1200) were low in both groups. Food and water intakes, body growth rate, and total fatty acid content of major metabolic tissues were markedly lower, whereas protein content was higher, in the LED group compared with CWF group. Circadian rhythms of arterial plasma levels of total fatty acids, glucose, lactic acid, pO, pCO, insulin, leptin, and corticosterone were generally lower in LED-exposed rats. Therefore, daytime exposure of rats to LED light with high blue emissions has a marked positive effect on the circadian regulation of neuroendocrine, metabolic, and physiologic parameters associated with the promotion of animal health and wellbeing and thus may influence scientific outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073062PMC
December 2017

The development of lighting countermeasures for sleep disruption and circadian misalignment during spaceflight.

Curr Opin Pulm Med 2016 11;22(6):535-44

aDepartment of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania bDivision of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital; Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts cDepartment of Psychology, University of California, San Diego, La Jolla, California, USA.

Purpose Of Review: The review addresses the development of a new solid-state lighting system for the International Space Station (ISS) that is intended to enhance the illumination of the working and living environment of astronauts and to improve sleep, circadian entrainment, and daytime alertness.

Recent Findings: Spaceflight missions often expose astronauts and mission support ground crews to atypical sleep-wake cycles and work schedules. A recent, extensive study describes the sleep characteristics and use of sleep-promoting pharmaceuticals in astronauts before, during, and after spaceflight. The acceptability, feasibility, and efficacy of the new ISS solid-state lighting systems are currently being tested in ground-based, analog studies. Installation of this lighting system on the ISS is scheduled to begin later this year. In-flight testing of this lighting system is planned to take place during ISS spaceflight expeditions.

Summary: If the new ISS lighting system is capable of improving circadian entrainment and sleep during spaceflight, it should enhance astronaut health, performance, well-being, and safety. Such an advance would open the door to future lighting applications for humans living on Earth.
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http://dx.doi.org/10.1097/MCP.0000000000000329DOI Listing
November 2016

Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth.

Comp Med 2015 Dec;65(6):473-85

Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.

Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462-484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake-metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681241PMC
December 2015

Short-wavelength enrichment of polychromatic light enhances human melatonin suppression potency.

J Pineal Res 2015 Apr;58(3):352-61

Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.

The basic goal of this research is to determine the best combination of light wavelengths for use as a lighting countermeasure for circadian and sleep disruption during space exploration, as well as for individuals living on Earth. Action spectra employing monochromatic light and selected monochromatic wavelength comparisons have shown that short-wavelength visible light in the blue-appearing portion of the spectrum is most potent for neuroendocrine, circadian, and neurobehavioral regulation. The studies presented here tested the hypothesis that broad spectrum, polychromatic fluorescent light enriched in the short-wavelength portion of the visible spectrum is more potent for pineal melatonin suppression in healthy men and women. A total of 24 subjects were tested across three separate experiments. Each experiment used a within-subjects study design that tested eight volunteers to establish the full-range fluence-response relationship between corneal light irradiance and nocturnal plasma melatonin suppression. Each experiment tested one of the three types of fluorescent lamps that differed in their relative emission of light in the short-wavelength end of the visible spectrum between 400 and 500 nm. A hazard analysis, based on national and international eye safety criteria, determined that all light exposures used in this study were safe. Each fluence-response curve demonstrated that increasing corneal irradiances of light evoked progressively increasing suppression of nocturnal melatonin. Comparison of these fluence-response curves supports the hypothesis that polychromatic fluorescent light is more potent for melatonin regulation when enriched in the short-wavelength spectrum.
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http://dx.doi.org/10.1111/jpi.12221DOI Listing
April 2015

The influence of red light exposure at night on circadian metabolism and physiology in Sprague-Dawley rats.

J Am Assoc Lab Anim Sci 2015 Jan;54(1):40-50

Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.

Early studies on rodents showed that short-term exposure to high-intensity light (> 70 lx) above 600 nm (red-appearing) influences circadian neuroendocrine and metabolic physiology. Here we addressed the hypothesis that long-term, low-intensity red light exposure at night (rLEN) from a 'safelight' emitting no light below approximately 620 nm disrupts the nocturnal circadian melatonin signal as well as circadian rhythms in circulating metabolites, related regulatory hormones, and physi- ologic parameters. Male Sprague-Dawley rats (n = 12 per group) were maintained on control 12:12-h light:dark (300 lx; lights on, 0600) or experimental 12:12 rLEN (8.1 lx) lighting regimens. After 1 wk, rats underwent 6 low-volume blood draws via cardiocentesis (0400, 0800, 1200, 1600, 2000, and 2400) over a 4-wk period to assess arterial plasma melatonin, total fatty acid, glucose, lactic acid, pO2, pCO2, insulin, leptin and corticosterone concentrations. Results revealed plasma melatonin levels (mean ± 1 SD) were high in the dark phase (197.5 ± 4.6 pg/mL) and low in the light phase (2.6 ± 1.2 pg/mL) of control condi- tions and significantly lower than controls under experimental conditions throughout the 24-h period (P < 0.001). Prominent circadian rhythms of plasma levels of total fatty acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were significantly (P < 0.05) disrupted under experimental conditions as compared with the corresponding entrained rhythms under control conditions. Therefore, chronic use of low-intensity rLEN from a common safelight disrupts the circadian organization of neuroendocrine, metabolic, and physiologic parameters indicative of animal health and wellbeing.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311741PMC
January 2015

Regulation of L1 expression and retrotransposition by melatonin and its receptor: implications for cancer risk associated with light exposure at night.

Nucleic Acids Res 2014 Jul 9;42(12):7694-707. Epub 2014 Jun 9.

Department of Structural and Cellular Biology, Tulane School of Medicine, Tulane Cancer Center, New Orleans, LA 70115, USA Tulane Center for Aging, New Orleans, LA 70112, USA

Expression of long interspersed element-1 (L1) is upregulated in many human malignancies. L1 can introduce genomic instability via insertional mutagenesis and DNA double-strand breaks, both of which may promote cancer. Light exposure at night, a recently recognized carcinogen, is associated with an increased risk of cancer in shift workers. We report that melatonin receptor 1 inhibits mobilization of L1 in cultured cells through downregulation of L1 mRNA and ORF1 protein. The addition of melatonin receptor antagonists abolishes the MT1 effect on retrotransposition in a dose-dependent manner. Furthermore, melatonin-rich, but not melatonin-poor, human blood collected at different times during the circadian cycle suppresses endogenous L1 mRNA during in situ perfusion of tissue-isolated xenografts of human cancer. Supplementation of human blood with exogenous melatonin or melatonin receptor antagonist during the in situ perfusion establishes a receptor-mediated action of melatonin on L1 expression. Combined tissue culture and in vivo data support that environmental light exposure of the host regulates expression of L1 elements in tumors. Our data imply that light-induced suppression of melatonin production in shift workers may increase L1-induced genomic instability in their genomes and suggest a possible connection between L1 activity and increased incidence of cancer associated with circadian disruption.
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http://dx.doi.org/10.1093/nar/gku503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081101PMC
July 2014

Breast cancer and circadian disruption from electric lighting in the modern world.

CA Cancer J Clin 2014 May-Jun;64(3):207-18. Epub 2013 Dec 24.

Professor, Department of Community Medicine, University of Connecticut Health Center, Farmington, CT.

Breast cancer is the leading cause of cancer death among women worldwide, and there is only a limited explanation of why. Risk is highest in the most industrialized countries but also is rising rapidly in the developing world. Known risk factors account for only a portion of the incidence in the high-risk populations, and there has been considerable speculation and many false leads on other possibly major determinants of risk, such as dietary fat. A hallmark of industrialization is the increasing use of electricity to light the night, both within the home and without. It has only recently become clear that this evolutionarily new and, thereby, unnatural exposure can disrupt human circadian rhythmicity, of which three salient features are melatonin production, sleep, and the circadian clock. A convergence of research in cells, rodents, and humans suggests that the health consequences of circadian disruption may be substantial. An innovative experimental model has shown that light at night markedly increases the growth of human breast cancer xenografts in rats. In humans, the theory that light exposure at night increases breast cancer risk leads to specific predictions that are being tested epidemiologically: evidence has accumulated on risk in shift workers, risk in blind women, and the impact of sleep duration on risk. If electric light at night does explain a portion of the breast cancer burden, then there are practical interventions that can be implemented, including more selective use of light and the adoption of recent advances in lighting technology and application.
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http://dx.doi.org/10.3322/caac.21218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038658PMC
August 2014

Diurnal spectral sensitivity of the acute alerting effects of light.

Sleep 2014 Feb 1;37(2):271-81. Epub 2014 Feb 1.

Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA ; Division of Sleep Medicine, Department of Medicine, Harvard Medical School, Boston, MA.

Study Objectives: Previous studies have demonstrated short-wavelength sensitivity for the acute alerting response to nocturnal light exposure. We assessed daytime spectral sensitivity in alertness, performance, and waking electroencephalogram (EEG).

Design: Between-subjects (n = 8 per group).

Setting: Inpatient intensive physiologic monitoring unit.

Participants: Sixteen healthy young adults (mean age ± standard deviation = 23.8 ± 2.7 y).

Interventions: Equal photon density exposure (2.8 × 10(13) photons/cm(2)/s) to monochromatic 460 nm (blue) or 555 nm (green) light for 6.5 h centered in the middle of the 16-h episode of wakefulness during the biological day. Results were compared retrospectively to 16 individuals who were administered the same light exposure during the night.

Measurements And Results: Daytime and nighttime 460-nm light exposure significantly improved auditory reaction time (P < 0.01 and P < 0.05, respectively) and reduced attentional lapses (P < 0.05), and improved EEG correlates of alertness compared to 555-nm exposure. Whereas subjective sleepiness ratings did not differ between the two spectral conditions during the daytime (P > 0.05), 460-nm light exposure at night significantly reduced subjective sleepiness compared to 555-nm light exposure at night (P < 0.05). Moreover, nighttime 460-nm exposure improved alertness to near-daytime levels.

Conclusions: The alerting effects of short-wavelength 460-nm light are mediated by counteracting both the circadian drive for sleepiness and homeostatic sleep pressure at night, but only via reducing the effects of homeostatic sleep pressure during the day.
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http://dx.doi.org/10.5665/sleep.3396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900613PMC
February 2014

Effect of different spectral transmittances through tinted animal cages on circadian metabolism and physiology in Sprague-Dawley rats.

J Am Assoc Lab Anim Sci 2014 Jan;53(1):44-51

Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, Louisiana, USA.

The suprachiasmatic nucleus is synchronized by the light:dark cycle and is the master biologic clock that serves as a pacemaker to regulate circadian rhythms. We explored the hypothesis that spectral transmittance (tint) of light through caging alters circadian rhythms of endocrine and metabolic plasma constituents in nonpigmented Sprague-Dawley rats. Rats (Crl:SD; n = 12 per group) were housed in a 12:12-h light:dark environment (300 lx; 123.0 μ W/cm(2); lights on, 0600) in either clear-, amber-, blue-, or red-tinted rodent cages. Blood was collected at 0400, 0800, 1200, 1600, 2000, and 2400 and measured for melatonin, total fatty acids, pH, glucose, lactic acid, corticosterone, insulin, and leptin. As expected, plasma melatonin levels were low during the light phase but higher during the dark phase in all groups; however, when compared with the clear-cage group, rats in amber-, blue-, and red-tinted cages had 29%, 74%, and 48%, respectively, greater total daily melatonin levels due to an increased duration and, in some cases, amplitude of the nocturnal melatonin signal. No differences were found in dietary and water intake, body growth rates, total fatty acids, pH, or glucose among groups. Disruptions in circadian rhythms, manifesting as alterations in phase timing, amplitude, or duration, occurred in the melatonin, lactic acid, corticosterone, insulin, and leptin levels of rats in tinted compared with clear cages. Therefore, the use of variously tinted animal cages significantly alters circadian rhythms in plasma measures of metabolism and physiology in laboratory rats, thus potentially altering the outcomes of scientific investigations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894647PMC
January 2014

Effect of spectral transmittance through red-tinted rodent cages on circadian metabolism and physiology in nude rats.

J Am Assoc Lab Anim Sci 2013 Nov;52(6):745-55

Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane, Louisiana, USA.

Light entrains normal circadian rhythms of physiology and metabolism in all mammals. Previous studies from our laboratory demonstrated that spectral transmittance (color) of light passing through cages affects these responses in rats. Here, we addressed the hypothesis that red tint alters the circadian nocturnal melatonin signal and circadian oscillation of other metabolic and physiologic functions. Female nude rats (Hsd:RH-Foxn1(rnu); n = 12 per group) were maintained on a 12:12-h light (300 lx; 123.0 μW/cm(2); lights on 0600):dark regimen in standard polycarbonate translucent clear or red-tinted cages. After 1 wk, rats underwent 6 low-volume blood draws via cardiocentesis over a 4-wk period. Plasma melatonin levels were low during the light phase (1.0 ± 0.2 pg/mL) in rats in both types of cages but were significantly lower in red-tinted (105.0 ± 2.4 pg/mL) compared with clear (154.8 ± 3.8 pg/mL) cages during the dark. Normal circadian rhythm of plasma total fatty acid was identical between groups. Although phase relationships of circadian rhythms in glucose, lactic acid, pO2, and pCO2 were identical between groups, the levels of these analytes were lower in rats in red-tinted compared with clear cages. Circadian rhythms of plasma corticosterone, insulin, and leptin were altered in terms of phasing, amplitude, and duration in rats in red-tinted compared with clear cages. These findings indicate that spectral transmittance through red-colored cages significantly affects circadian regulation of neuroendocrine, metabolic, and physiologic parameters, potentially influencing both laboratory animal health and wellbeing and scientific outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838609PMC
November 2013

Measuring and using light in the melanopsin age.

Trends Neurosci 2014 Jan 25;37(1):1-9. Epub 2013 Nov 25.

Department of Neurology, Thomas Jefferson University, Philidelphia, PA, USA. Electronic address:

Light is a potent stimulus for regulating circadian, hormonal, and behavioral systems. In addition, light therapy is effective for certain affective disorders, sleep problems, and circadian rhythm disruption. These biological and behavioral effects of light are influenced by a distinct photoreceptor in the eye, melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs), in addition to conventional rods and cones. We summarize the neurophysiology of this newly described sensory pathway and consider implications for the measurement, production, and application of light. A new light-measurement strategy taking account of the complex photoreceptive inputs to these non-visual responses is proposed for use by researchers, and simple suggestions for artificial/architectural lighting are provided for regulatory authorities, lighting manufacturers, designers, and engineers.
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http://dx.doi.org/10.1016/j.tins.2013.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699304PMC
January 2014

Insulin and IGF1 enhance IL-17-induced chemokine expression through a GSK3B-dependent mechanism: a new target for melatonin's anti-inflammatory action.

J Pineal Res 2013 Nov 20;55(4):377-87. Epub 2013 Aug 20.

Department of Structural & Cellular Biology, Tulane University Health Sciences Center, New Orleans, LA, USA.

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 in Gsk3b(-/-) mouse embryonic fibroblast (MEF) cells. IL-17 induced higher levels of Cxcl1 and Ccl20 in the Gsk3b(-/-) MEF cells, compared with 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 in 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.
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http://dx.doi.org/10.1111/jpi.12084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797167PMC
November 2013

Adverse health effects of nighttime lighting: comments on American Medical Association policy statement.

Am J Prev Med 2013 Sep;45(3):343-6

University of Connecticut Health Center, Farmington, Connecticut 06030-6325, USA.

The American Medical Association House of Delegates in June of 2012 adopted a policy statement on nighttime lighting and human health. This major policy statement summarizes the scientific evidence that nighttime electric light can disrupt circadian rhythms in humans and documents the rapidly advancing understanding from basic science of how disruption of circadian rhythmicity affects aspects of physiology with direct links to human health, such as cell cycle regulation, DNA damage response, and metabolism. The human evidence is also accumulating, with the strongest epidemiologic support for a link of circadian disruption from light at night to breast cancer. There are practical implications of the basic and epidemiologic science in the form of advancing lighting technologies that better accommodate human circadian rhythmicity.
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http://dx.doi.org/10.1016/j.amepre.2013.04.011DOI Listing
September 2013

Effects of spectral transmittance through standard laboratory cages on circadian metabolism and physiology in nude rats.

J Am Assoc Lab Anim Sci 2013 Mar;52(2):146-56

Department of Structural & Cellular Biology, Tulane University School of Medicine, Tulane, LA, USA.

Light is potent in circadian, neuroendocrine, and neurobehavioral regulation, thereby having profound influence on the health and wellbeing of all mammals, including laboratory animals. We hypothesized that the spectral quality of light transmitted through colored compared with clear standard rodent cages alters circadian production of melatonin and temporal coordination of normal metabolic and physiologic activities. Female nude rats (Hsd:RH-Foxn1(rnu); n = 6 per group) were maintained on a 12:12-h light:dark regimen (300 lx; lights on, 0600) in standard translucent clear, amber, or blue rodent cages; intensity and duration of lighting were identical for all groups. Rats were assessed for arterial blood levels of pO(2) and pCO(2), melatonin, total fatty acid, glucose, lactic acid, insulin, leptin, and corticosterone concentrations at 6 circadian time points. Normal circadian rhythms of arterial blood pO(2) and pCO(2) were different in rats housed in cages that were blue compared with amber or clear. Plasma melatonin levels (mean ± 1 SD) were low (1.0 ± 0.2 pg/mL) during the light phase in all groups but higher at nighttime in rats in blue cages (928.2 ± 39.5 pg/mL) compared with amber (256.8 ± 6.6 pg/mL) and clear (154.8 ± 9.3 pg/mL) cages. Plasma daily rhythms of total fatty acid, glucose, lactic acid, leptin, insulin, and corticosterone were disrupted in rats housed in blue or amber compared with clear cages. Temporal coordination of circadian rhythms of physiology and metabolism can be altered markedly by changes in the spectral quality of light transmitted through colored standard rodent cages.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624782PMC
March 2013

Melanopsin, photosensitive ganglion cells, and seasonal affective disorder.

Neurosci Biobehav Rev 2013 Mar 31;37(3):229-39. Epub 2012 Dec 31.

Department of Psychology, University of Pittsburgh, 3500 Sennott Square, 210 South Bouquet St., Pittsburgh, PA 15260, USA.

In two recent reports, melanopsin gene variations were associated with seasonal affective disorder (SAD), and in changes in the timing of sleep and activity in healthy individuals. New studies have deepened our understanding of the retinohypothalamic tract, which translates environmental light received by the retina into neural signals sent to a set of nonvisual nuclei in the brain that are responsible for functions other than sight including circadian, neuroendocrine and neurobehavioral regulation. Because this pathway mediates seasonal changes in physiology, behavior, and mood, individual variations in the pathway may explain why approximately 1-2% of the North American population develops mood disorders with a seasonal pattern (i.e., Major Depressive and Bipolar Disorders with a seasonal pattern, also known as seasonal affective disorder/SAD). Components of depression including mood changes, sleep patterns, appetite, and cognitive performance can be affected by the biological and behavioral responses to light. Specifically, variations in the gene sequence for the retinal photopigment, melanopsin, may be responsible for significant increased risk for mood disorders with a seasonal pattern, and may do so by leading to changes in activity and sleep timing in winter. The retinal sensitivity of SAD is hypothesized to be decreased compared to controls, and that further decrements in winter light levels may combine to trigger depression in winter. Here we outline steps for new research to address the possible role of melanopsin in seasonal affective disorder including chromatic pupillometry designed to measure the sensitivity of melanopsin containing retinal ganglion cells.
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http://dx.doi.org/10.1016/j.neubiorev.2012.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604141PMC
March 2013

Human phase response curve to a single 6.5 h pulse of short-wavelength light.

J Physiol 2013 Jan 22;591(1):353-63. Epub 2012 Oct 22.

Circadian Physiology Program, Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.

The photic resetting response of the human circadian pacemaker depends on the timing of exposure, and the direction and magnitude of the resulting shift is described by a phase response curve (PRC). Previous PRCs in humans have utilized high-intensity polychromatic white light. Given that the circadian photoreception system is maximally sensitive to short-wavelength visible light, the aim of the current study was to construct a PRC to blue (480 nm) light and compare it to a 10,000 lux white light PRC constructed previously using a similar protocol. Eighteen young healthy participants (18-30 years) were studied for 9-10 days in a time-free environment. The protocol included three baseline days followed by a constant routine (CR) to assess initial circadian phase. Following this CR, participants were exposed to a 6.5 h 480 nm light exposure (11.8 μW cm(-2), 11.2 lux) following mydriasis via a modified Ganzfeld dome. A second CR was conducted following the light exposure to re-assess circadian phase. Phase shifts were calculated from the difference in dim light melatonin onset (DLMO) between CRs. Exposure to 6.5 h of 480 nm light resets the circadian pacemaker according to a conventional type 1 PRC with fitted maximum delays and advances of -2.6 h and 1.3 h, respectively. The 480 nm PRC induced ∼75% of the response of the 10,000 lux white light PRC. These results may contribute to a re-evaluation of dosing guidelines for clinical light therapy and the use of light as a fatigue countermeasure.
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http://dx.doi.org/10.1113/jphysiol.2012.239046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630790PMC
January 2013

Learning to live on a Mars day: fatigue countermeasures during the Phoenix Mars Lander mission.

Sleep 2012 Oct 1;35(10):1423-35. Epub 2012 Oct 1.

Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

Study Objectives: To interact with the robotic Phoenix Mars Lander (PML) spacecraft, mission personnel were required to work on a Mars day (24.65 h) for 78 days. This alien schedule presents a challenge to Earth-bound circadian physiology and a potential risk to workplace performance and safety. We evaluated the acceptability, feasibility, and effectiveness of a fatigue management program to facilitate synchronization with the Mars day and alleviate circadian misalignment, sleep loss, and fatigue.

Design: Operational field study.

Setting: PML Science Operations Center.

Participants: Scientific and technical personnel supporting PML mission.

Interventions: Sleep and fatigue education was offered to all support personnel. A subset (n = 19) were offered a short-wavelength (blue) light panel to aid alertness and mitigate/reduce circadian desynchrony. They were assessed using a daily sleep/work diary, continuous wrist actigraphy, and regular performance tests. Subjects also completed 48-h urine collections biweekly for assessment of the circadian 6-sulphatoxymelatonin rhythm.

Measurements And Results: Most participants (87%) exhibited a circadian period consistent with adaptation to a Mars day. When synchronized, main sleep duration was 5.98 ± 0.94 h, but fell to 4.91 ± 1.22 h when misaligned (P < 0.001). Self-reported levels of fatigue and sleepiness also significantly increased when work was scheduled at an inappropriate circadian phase (P < 0.001). Prolonged wakefulness (≥ 21 h) was associated with a decline in performance and alertness (P < 0.03 and P < 0.0001, respectively).

Conclusions: The ability of the participants to adapt successfully to the Mars day suggests that future missions should utilize a similar circadian rhythm and fatigue management program to reduce the risk of sleepiness-related errors that jeopardize personnel safety and health during critical missions.
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http://dx.doi.org/10.5665/sleep.2128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443769PMC
October 2012

Circadian gating of epithelial-to-mesenchymal transition in breast cancer cells via melatonin-regulation of GSK3β.

Mol Endocrinol 2012 Nov 21;26(11):1808-20. Epub 2012 Sep 21.

Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.

Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3β (GSK3β), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhythm of GSK3β phosphorylation. Melatonin activates GSK3β by inhibiting the serine-threonine kinase Akt phosphorylation, inducing β-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3β activity and driving epithelial-to-mesenchymal transition in breast cancer patients.
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http://dx.doi.org/10.1210/me.2012-1071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487627PMC
November 2012

Blue light from light-emitting diodes elicits a dose-dependent suppression of melatonin in humans.

J Appl Physiol (1985) 2011 Mar 16;110(3):619-26. Epub 2010 Dec 16.

Dept. of Neurology, Thomas Jefferson Univ., Philadelphia, Pennsylvania 19107, USA.

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.
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http://dx.doi.org/10.1152/japplphysiol.01413.2009DOI Listing
March 2011

Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light.

Sci Transl Med 2010 May;2(31):31ra33

Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

In humans, modulation of circadian rhythms by light is thought to be mediated primarily by melanopsin-containing retinal ganglion cells, not rods or cones. Melanopsin cells are intrinsically blue light-sensitive but also receive input from visual photoreceptors. We therefore tested in humans whether cone photoreceptors contribute to the regulation of circadian and neuroendocrine light responses. Dose-response curves for melatonin suppression and circadian phase resetting were constructed in subjects exposed to blue (460 nm) or green (555 nm) light near the onset of nocturnal melatonin secretion. At the beginning of the intervention, 555-nm light was equally effective as 460-nm light at suppressing melatonin, suggesting a significant contribution from the three-cone visual system (lambda(max) = 555 nm). During the light exposure, however, the spectral sensitivity to 555-nm light decayed exponentially relative to 460-nm light. For phase-resetting responses, the effects of exposure to low-irradiance 555-nm light were too large relative to 460-nm light to be explained solely by the activation of melanopsin. Our findings suggest that cone photoreceptors contribute substantially to nonvisual responses at the beginning of a light exposure and at low irradiances, whereas melanopsin appears to be the primary circadian photopigment in response to long-duration light exposure and at high irradiances. These results suggest that light therapy for sleep disorders and other indications might be optimized by stimulating both photoreceptor systems.
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http://dx.doi.org/10.1126/scitranslmed.3000741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414925PMC
May 2010

Circadian stage-dependent inhibition of human breast cancer metabolism and growth by the nocturnal melatonin signal: consequences of its disruption by light at night in rats and women.

Integr Cancer Ther 2009 Dec;8(4):347-53

Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane University School of Medicine, New Orleans, LA 70112, USA.

The circadian production of melatonin by the pineal gland during the night provides an inhibitory signal to tissue-isolated steroid receptor SR+ and - MCF-7 human breast cancer xenografts in female nude rats. A pivotal mechanism for melatonin's anticancer effects in vivo involves a melatonin receptor-mediated inhibition of linoleic acid (LA) uptake and its metabolism to mitogenically active 13-hydroxyoctadecadienoic acid (13-HODE). Exposure of (SR-) xenograft-bearing rats to increasing intensities of polychromatic white light at night suppresses melatonin while increasing tumor growth rates, DNA content, [3H]thymidine incorporation into DNA, LA uptake, 13-HODE formation, cAMP levels and ERK1/2 activation a dose-dependent manner. Similar effects occur in SR- human breast cancer xenografts perfused in situ with melatonin-depleted blood from healthy female subjects after their exposure to a single bright intensity (2800 lux) of polychromatic light at night. Additionally, SR- human breast cancer xenografts exhibit robust circadian rhythms of LA uptake, 13-HODE formation and proliferative activity. Exposure of xenograft-bearing rats to dim light at night results in the complete elimination of these rhythms which culminates in unfettered, high rates of tumor metabolism and growth. The organization of tumor metabolism and growth within circadian time structure by the oncostatic melatonin signal helps create a balance between the cancer and its host that is disrupted by host exposure to light at night. This biological mechanism may partially explain the higher risk of breast and other cancers in women working rotating night shifts and possibly others who also experience prolonged exposure to light at night.
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http://dx.doi.org/10.1177/1534735409352320DOI Listing
December 2009

Sensitivity of the human circadian system to short-wavelength (420-nm) light.

J Biol Rhythms 2008 Oct;23(5):379-86

Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA.

The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female (n=14) and male (n=12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark exposure control night. In the other study, subjects (n=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 10(13) photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression (p<0.001) with a half-saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin (p<0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications.
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http://dx.doi.org/10.1177/0748730408323089DOI Listing
October 2008

Integrative medicine research at an academic medical center: patient characteristics and health-related quality-of-life outcomes.

J Altern Complement Med 2008 Jul;14(6):763-7

Duke Integrative Medicine, Duke University Medical Center, Durham, NC, USA.

Objective: To characterize patients seeking care at a university-based integrative medicine practice, and to assess short-term changes in health-related quality of life (HRQoL) associated with integrative medical treatment.

Design: Prospective, observational study.

Setting: This study was conducted at a large U.S. academic medical center affiliated with the Consortium of Academic Health Centers for Integrative Medicine.

Participants: Seven hundred and sixty-three (763) new patients with diverse medical conditions participated in the study. Mean age was 49 years (standard deviation = 16, range = 14-93). Two thirds of patients were women and three quarters were white. The most common International Classification of Diseases 9th Revision medical diagnoses were malaise and fatigue, myalgia and myositis, allergy, anxiety or depression, hypertension, malignant neoplasm of the breast, lumbago, and irritable bowel disease. Over half the sample had two or more comorbid medical conditions.

Outcome Measure: The Medical Outcomes Study 36-item Short-Form (SF-36) health survey was used to measure HRQoL at initial assessment and 3-months following integrative medicine consultation.

Results: Baseline SF-36 scores fell below the 25th percentile, indicating substantially compromised HRQoL. Physician-prescribed treatment modalities included anthroposophical medicine, nutritional medicine, Western herbs, homeopathy, nutritional counseling, and acupuncture. Three (3) month follow-up assessment revealed statistically significant improvements on all eight SF-36 subscales among survey respondents. HRQoL effect sizes ranged from 0.17 (Physical Functioning) to 0.41 (Social Functioning), with a mean of 0.30. HRQoL effects were consistent among demographic subgroups.

Conclusions: Integrative medical treatment at a university-based center is associated with significant increases in HRQoL for a medically diverse population with substantial comorbidity and functional limitations. Controlled studies that measure HRQoL and additional outcomes related to whole person health--physical, mental, social, and spiritual--are needed to determine the full therapeutic potential of integrative medicine, and to determine efficacy and cost-effectiveness relative to conventional medical care.
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http://dx.doi.org/10.1089/acm.2008.0114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153865PMC
July 2008

Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina.

Curr Biol 2007 Dec;17(24):2122-8

Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, London W6 8RF, United Kingdom.

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found that short-wavelength light preferentially suppressed melatonin, reset the circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of the photopic visual system. In an action spectrum for pupillary constriction, the female subject exhibited a peak spectral sensitivity (lambda(max)) of 480 nm, matching that of the pRGCs but not that of the rods and cones. This subject was also able to correctly report a threshold short-wavelength stimulus ( approximately 480 nm) but not other wavelengths. Collectively these data show that pRGCs contribute to both circadian physiology and rudimentary visual awareness in humans and challenge the assumption that rod- and cone-based photoreception mediate all "visual" responses to light.
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http://dx.doi.org/10.1016/j.cub.2007.11.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151130PMC
December 2007
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