Melatonin suppression by illumination of upper and lower visual fields

As a guide to optimizing the geometry of bright light treatment, 12 healthy subjects were studied three times in the laboratory from 11 p.m. to 2 a.m. On three evenings, in counterbalanced orders, subjects received 500 lux in the upper visual field, 500 lux in the lower visual field, or 5 lux while watching television. In the upper visual field, 500 lux significantly suppressed melatonin, as compared to 500 lux in the lower visual field or to 5 lux. In the lower visual field, 500 lux produced intermediate suppression of borderline significance. The results suggest that bright light treatment of depression or circadian phase disorders might be most effective when applied in the upper visual field.     

Quantal melatonin suppression by exposure to low intensity light in man

Plasma melatonin concentrations were examined following three relatively low intensities of artificial light. Six normal, healthy control subjects were all exposed to (a) 200 lux, (b) 400 lux and (c) 600 lux for a three hour duration from midnight to 0300 h. Blood was also collected on a control night where light intensity was less than 10 lux throughout. Significant suppression of melatonin was observed following light of 400 lux and 600 lux intensity when compared to the control night (p less than 0.05; Mann-Whitney U-test). 200 lux light did not produce a statistically significant melatonin suppression when compared with control samples. Each light intensity produced its own individual maximal melatonin suppression by one hour of exposure. Increased duration of exposure to the light had no further influence on melatonin plasma concentrations. These data confirm a dose response relationship between light and melatonin suppression, and indicate that there is no reciprocal relationship between the effects of light intensity and the duration of exposure on maximal melatonin suppression in man.     

Relationship between individual difference in melatonin suppression by light and habitual bedtime

The purpose of this study was to determine the relationship between individual difference in melatonin suppression by exposure to light and habitual bedtime. Seventeen healthy male students (mean age: 22.6+/-2.4 yr) volunteered to participate in the study. The subjects were exposed to light (1000 lx) for 2 hours from 2 hours before the time of peak salivary melatonin concentration. Two hours after exposure to the light, melatonin suppression had occurred in fifteen subjects. No significant correlation was found between the rate of melatonin suppression and habitual bedtime in the fifteen subjects in whom melatonin suppression occurred. However, the habitual bedtime of the two subjects in whom melatonin suppression did not occur was earlier than that of the other subjects. These results suggest that there are some people with very low sensitivity to light and that this may affect habitual bedtime.     

Splenic hypertrophy and extramedullary hematopoiesis induced in male Syrian hamsters by short photoperiod or melatonin injections and reversed by melatonin pellets or pinealectomy

Adult male Syrian hamsters either placed in a short photoperiod alone or kept in a long photoperiod and given daily afternoon injections of the pineal indole melatonin (25 micrograms) exhibited splenic hypertrophy and extramedullary hematopoiesis in addition to a marked regression in testicular weight. The testicular regression as well as the changes in spleen weight and histology could be prevented if the animals in short photoperiod were either pinealectomized or implanted subcutaneously with a pellet containing 1 mg melatonin. Female Syrian hamsters given afternoon injections of melatonin for 7 or 12 weeks had ovaries devoid of corpora lutea; additionally, these animals had reduced relative spleen weights compared to the control animals. In conclusion, it is apparent that spleen weight varies with the functional status of the gonads. Splenic hypertrophy accompanied by pineal-induced testicular regression in males may be related to splenic extramedullary hematopoiesis.     

Influence of eye colors of Caucasians and Asians on suppression of melatonin secretion by light

This experiment tested effects of human eye pigmentation depending on the ethnicity on suppression of nocturnal melatonin secretion by light. Ten healthy Caucasian males with blue, green, or light brown irises (light-eyed Caucasians) and 11 Asian males with dark brown irises (dark-eyed Asians) volunteered to participate in the study. The mean ages of the light-eyed Caucasians and dark-eyed Asians were 26.4 +/- 3.2 and 25.3 +/- 5.7 years, respectively. The subjects were exposed to light (1,000 lux) for 2 h at night. The starting time of exposure was set to 2 h before the time of peak salivary melatonin concentration of each subject, which was determined in a preliminary experiment. Salivary melatonin concentration and pupil size were measured before exposure to light and during exposure to light. The percentage of suppression of melatonin secretion by light was calculated. The percentage of suppression of melatonin secretion 2 h after the start of light exposure was significantly larger in light-eyed Caucasians (88.9 +/- 4.2%) than in dark-eyed Asians (73.4 +/- 20.0%) (P < 0.01). No significant difference was found between pupil sizes in light-eyed Caucasians and dark-eyed Asians. These results suggest that sensitivity of melatonin to light suppression is influenced by eye pigmentation and/or ethnicity.     

褪黑素抑制小鼠卵母细胞的体外成熟

目的:探讨褪黑素(MT)对小鼠卵母细胞的体外成熟的影响.方法:通过卵母细胞自发、次黄嘌呤(HX)阻滞和激素诱导成熟三种体外培养模型研究了褪黑素(MT)对小鼠卵母细胞体外成熟的影响.结果:①0.1 g/L、0.02g/L、0.004 g/L及0.0008 g/L浓度的MT均能显著抑制小鼠卵丘卵母细胞复合体(CEOs)自发成熟过程中第一极体(PB1)的释放(P＜0.01);②动力曲线分析表明,MT对自发成熟的CEOs的GVBD和PB1有显著的推后作用,与对照组相比,处理组的GVBD和PB1分别被推后8～10 h和3～4 h;③0.1 g/L和0.02 g/L两有效浓度的MT还能显著抑制促性腺激素(FSH)诱导的HX阻滞的CEOsGVBD的发生(P＜0.05),对PB1的排出虽有一定的抑制作用,但没有统计学意义;④MT和次黄嘌呤(HX)对CEOs的自发成熟有协同抑制作用(P＜0.01),但在裸卵(DO)自发成熟的阻滞中没有协同效应.结论:MT是调节哺乳动物卵母细胞成熟的重要激素之一,其作用机制可能是通过卵丘细胞实现的.     

Inconsistent suppression of nocturnal pineal melatonin synthesis and serum melatonin levels in rats exposed to pulsed DC magnetic fields

The purpose of these experiments was to determine whether the exposure of rats at night to pulsed DC magnetic fields (MF) would influence the nocturnal production and secretion of melatonin, as indicated by pineal N-acetyltransferase (NAT) activity (the rate limiting enzyme in melatonin production) and pineal and serum melatonin levels. By using a computer-driven exposure system, 15 experiments were conducted. MF exposure onset was always during the night, with the duration of exposure varying from 15 to 120 min. A variety of field strengths, ranging from 50 to 500 μT (0.5 to 5.0 G) were used with the bulk of the studies being conducted using a 100 μT (1.0 G) field. During the interval of DC MF exposure, the field was turned on and off at 1-s intervals with a rise/fall time constant of 5 ms. Because the studies were performed during the night, all procedures were carried out under weak red light (intensity of <5 μW/cm²). At the conclusion of each study, a blood sample and the pineal gland were collected for analysis of serum melatonin titers and pineal NAT and melatonin levels. The outcome of individual studies varied. Of the 23 cases in which pineal NAT activity, pineal melatonin, and serum melatonin levels were measured, the following results were obtained; in 5 cases (21.7%) pineal NAT activity was depressed, in 2 cases (8.7%) studies pineal melatonin levels were lowered, and in 10 cases (43.5%) serum melatonin concentrations were reduced. Never was there a measured rise in any of the end points that were considered in this study. The magnitudes of the reductions were not correlated with field strength (i.e., no dose-response relationships were apparent), and likewise the reductions could not be correlated with the season of the year (experiments conducted at 12-month intervals under identical exposure conditions yielded different results). Duration of exposure also seemed not to be a factor in the degree of melatonin suppression. The inconsistency of the results does not permit the conclusion that pineal melatonin production or release are routinely influenced by pulsed DC MF exposure. In the current series of studies, a suppression of serum melatonin sometimes occurred in the absence of any apparent change in the synthesis of this indoleamine within the pineal gland (no alteration in either pineal NAT activity or pineal melatonin levels). Because melatonin is a direct free radical scavenger, the drop in serum melatonin could theoretically be explained by an increased uptake of melatonin by tissues that were experiencing augmented levels of free radicals as a consequence of MF exposure. This hypothetical possibly requires additional experimental documentation. Bioelectromagnetics 19:318–329, 1998. © 1998 Wiley-Liss, Inc.     

No apparent suppression by insulin of in vivo skeletal muscle lipolysis in nonobese women

To investigate the antilipolytic effect of insulin in skeletal muscle and adipose tissue in vivo, the rates of glycerol release from the two tissues were compared in 10 nonobese women during a two-step euglycemic hyperinsulinemic clamp. Tissue interstitial glycerol levels were determined by microdialysis, and tissue blood flow was assessed with the (133)Xe clearance technique. Absolute rates of glycerol release were estimated according to Fick's principle. In both adipose tissue and muscle, glycerol levels decreased significantly already during the low insulin infusion rate. The fractional release of glycerol (difference between interstitial glycerol and arterialized venous plasma glycerol) was reduced by more than one-half in adipose tissue (P < 0.0001) in response to insulin, whereas it remained unaltered in skeletal muscle. Muscle blood flow rates increased by 60% (P < 0.02) during insulin infusion; in adipose tissue, blood flow rates did not change significantly in response to insulin. The basal rate of glycerol release from skeletal muscle amounted to approximately 15% of that from adipose tissue. After insulin infusion, the rate of adipose tissue glycerol release was markedly suppressed, whereas in skeletal muscle the rate of glycerol mobilization did not change significantly in response to insulin. It is concluded that insulin does not inhibit the rate of lipolysis in skeletal muscle of nonobese women.     

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

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.     

Immune recruitment or suppression by glycan engineering of endogenous and therapeutic antibodies

Human serum IgG contains multiple glycoforms which exhibit a range of binding properties to effector molecules such as cellular Fc receptors. Emerging knowledge of how the Fc glycans contribute to the antibody structure and effector functions has opened new avenues for the exploitation of defined antibody glycoforms in the treatment of diseases. Here, we review the structure and activity of antibody glycoforms and highlight developments in antibody glycoengineering by both the manipulation of the cellular glycosylation machinery and by chemoenzymatic synthesis. We discuss wide ranging applications of antibody glycoengineering in the treatment of cancer, autoimmunity and inflammation. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.     

Effectiveness of a red-visor cap for preventing light-induced melatonin suppression during simulated night work

Bright light at night improves the alertness of night workers. Melatonin suppression induced by light at night is, however, reported to be a possible risk factor for breast cancer. Short-wavelength light has a strong impact on melatonin suppression. A red-visor cap can cut the short-wavelength light from the upper visual field selectively with no adverse effects on visibility. The purpose of this study was to investigate the effects of a red-visor cap on light-induced melatonin suppression, performance, and sleepiness at night. Eleven healthy young male adults (mean age: 21.2±0.9 yr) volunteered to participate in this study. On the first day, the subjects spent time in dim light (<15 lx) from 20:00 to 03:00 to measure baseline data of nocturnal salivary melatonin concentration. On the second day, the subjects were exposed to light for four hours from 23:00 to 03:00 with a nonvisor cap (500 lx), red-visor cap (approx. 160 lx) and blue-visor cap (approx. 160 lx). Subjective sleepiness and performance of a psychomotor vigilance task (PVT) were also measured on the second day. Compared to salivary melatonin concentration under dim light, the decrease in melatonin concentration was significant in a nonvisor cap condition but was not significant in a red-visor cap condition. The percentages of melatonin suppression in the nonvisor cap and red-visor cap conditions at 4 hours after exposure to light were 52.6±22.4% and 7.7±3.3%, respectively. The red-visor cap had no adverse effect on performance of the PVT, brightness and visual comfort, though it tended to increase subjective sleepiness. These results suggest that a red-visor cap is effective in preventing melatonin suppression with no adverse effects on vigilance performance, brightness and visibility.     

Effects of day-time exposure to different light intensities on light-induced melatonin suppression at night

Background

Bright nocturnal light has been known to suppress melatonin secretion. However, bright light exposure during the day-time might reduce light-induced melatonin suppression (LIMS) at night. The effective proportion of day-time light to night-time light is unclear; however, only a few studies on accurately controlling both day- and night-time conditions have been conducted. This study aims to evaluate the effect of different day-time light intensities on LIMS.

Methods

Twelve male subjects between the ages of 19 and 23 years (mean ± S.D., 20.8 ± 1.1) gave informed consent to participate in this study. They were exposed to various light conditions (<10, 100, 300, 900 and 2700 lx) between the hours of 09:00 and 12:00 (day-time light conditions). They were then exposed to bright light (300 lx) again between 01:00 and 02:30 (night-time light exposure). They provided saliva samples before (00:55) and after night-time light exposure (02:30).

Results

A one-tailed paired t test yielded significant decrements of melatonin concentration after night-time light exposure under day-time dim, 100- and 300-lx light conditions. No significant differences exist in melatonin concentration between pre- and post-night-time light exposure under day-time 900- and 2700-lx light conditions.

Conclusions

Present findings suggest the amount of light exposure needed to prevent LIMS caused by ordinary nocturnal light in individuals who have a general life rhythm (sleep/wake schedule). These findings may be useful in implementing artificial light environments for humans in, for example, hospitals and underground shopping malls.     

Lack of cardiovascular or ventilatory effects of melatonin in rats

The cardiovascular and ventilatory effects of centrally and peripherally administered melatonin were examined in both normotensive rats (NTR) and in spontaneously hypertensive rats (SHR). In the experiments on anaesthetised NTR melatonin was administered intravenously at doses of 1, 10, and 100 mumol/kg, or intracerebroventricularly at doses of 0.01, 0.1, 1, and 10 mumol/kg. In the experiments on conscious SHR melatonin was administered orally at doses of approximately 2 mg per animal per day, or intracerebroventricularly at doses of 0.01, 0.1, 1, and 10 mumol/kg. Melatonin did not produce any significant cardiovascular or ventilatory effects in any of the experiments.     

Illumination of upper and middle visual fields produces equivalent suppression of melatonin in older volunteers

Bright light treatment has become an important method of treating depression and circadian rhythm sleep disorders. The efficacy of bright light treatment may be dependent upon the position of the light-source, as it determines the relative illumination in each portion of the visual field. This study compared illumination of upper and middle visual fields to determine whether melatonin suppression is different or equivalent. Thirteen older volunteers received three illumination conditions in counterbalanced orders: 1000 lux in the upper visual field, 1000 lux in the middle visual field, or dim diffuse illumination < 5 lux. A four-choice reaction time task was performed during tests to ensure eye direction and illumination of the intended portion of the visual field. Illumination in the upper and middle visual fields significantly suppressed melatonin compared to < 5 lux (p < 0.001). Melatonin suppression was not significantly different with upper or middle field illumination. These results indicate that bright light treatments placed above the eye level might be as effective as those requiring patients to look directly at the light source. Clinical comparative testing would be valuable. In addition, this study demonstrates that significant suppression of melatonin may be achieved through the use of bright light in healthy older volunteers.     

Hypersensitivity of melatonin suppression in response to light in patients with delayed sleep phase syndrome

Patients with delayed sleep phase syndrome (DSPS) experience a chronic mismatch between the usual daily schedule required by the individual's environment and their circadian sleep-wake pattern, resulting in major academic, work, and social problems. Although functional abnormalities of the circadian pacemaker system have been reported in patients with DSPS, the etiology of DSPS has not been fully elucidated. One hypothesis proposed to explain why patients with DSPS fail to synchronize their 24h sleep-wake cycle to their environment is that they might have reduced sensitivity to environmental time cues, most notably light-dark cycles. Therefore, we compared the sensitivity of melatonin suppression in response to light in patients with DSPS and normal control subjects. Fifteen patients with DSPS and age- and sex-matched healthy controls were studied. As the melatonin secretion rhythm in patients with DSPS was expected to be delayed compared to the controls, the time of peak melatonin secretion was determined in each subject in the first session. In the second session, each subject was exposed to light with an intensity of 1000 lux for 2h beginning 2h prior to his or her peak melatonin secretion. Melatonin was measured by radioimmunoassay in saliva sampled every 30 minutes during the period of light exposure. Suppression of the melatonin concentration in saliva was dependent on duration of light exposure. In addition, the suppressive effect of light on the melatonin concentration was significantly greater in patients with DSPS than in control subjects. The results suggest hypersensitivity to nighttime light exposure in patients with this syndrome. Our findings therefore suggest that evening light restriction is important for preventing patients with DSPS from developing a sleep phase delay. (Chronobiology International, 18(2), 263-271, 2001)     

Less exposure to daily ambient light in winter increases sensitivity of melatonin to light suppression

This study was carried out to examine the seasonal difference in the magnitude of the suppression of melatonin secretion induced by exposure to light in the late evening. The study was carried out in Akita (39 degrees North, 140 degrees East), in the northern part of Japan, where the duration of sunshine in winter is the shortest. Ten healthy male university students (mean age: 21.9+/-1.2 yrs) volunteered to participate twice in the study in winter (from January to February) and summer (from June to July) 2004. According to Japanese meteorological data, the duration of sunshine in Akita in the winter (50.5 h/month) is approximately one-third of that in summer (159.7 h/month). Beginning one week prior to the start of the experiment, the level of daily ambient light to which each subject was exposed was recorded every minute using a small light sensor that was attached to the subject's wrist. In the first experiment, saliva samples were collected every hour over a period of 24 h in a dark experimental room (<15 lux) to determine peak salivary melatonin concentration. The second experiment was conducted after the first experiment to determine the percentage of melatonin suppression induced by exposure to light. The starting time of exposure to light was set 2 h before the time of peak salivary melatonin concentration detected in the first experiment. The subjects were exposed to light (1000 lux) for 2 h using white fluorescent lamps (4200 K). The percentage of suppression of melatonin by light was calculated on the basis of the melatonin concentration determined before the start of exposure to light. The percentage of suppression of melatonin 2 h after the start of exposure to light was significantly greater in winter (66.6+/-18.4%) than summer (37.2+/-33.2%), p<0.01). The integrated level of daily ambient light from rising time to bedtime in summer was approximately twice that in winter. The results suggest that the increase in suppression of melatonin by light in winter is caused by less exposure to daily ambient light.