Light-emitting diodes and cool white fluorescent light similarly suppress pineal gland melatonin and maintain retinal function and morphology in the rat.

BACKGROUND AND PURPOSE: A novel light-emitting diode (LED) light source for use in animal-habitat lighting was evaluated. METHODS: The LED was evaluated by comparing its effectiveness with that of cool white fluorescent light (CWF) in suppressing pineal gland melatonin content and maintaining normal retinal physiology, as evaluated by use of electroretinography (ERG), and morphology. RESULTS: Pineal melatonin concentration was equally suppressed by LED and CWF light at five light illuminances (100, 40, 10, 1, and 0.1 lux). There were no significant differences in melatonin suppression between LED and CWF light, compared with values for unexposed controls. There were no differences in ERG a-wave implicit times and amplitudes or b-wave implicit times and amplitudes between 100-lux LED-exposed rats and 100-lux CWF-exposed rats. Results of retinal histologic examination indicated no differences in retinal thickness, rod outer segment length, and number of rod nuclei between rats exposed to 100-lux LED and 100-lux CWF for 14 days. Furthermore, in all eyes, the retinal pigmented epithelium was intact and not vacuolated, whereas rod outer segments were of normal thickness. CONCLUSION: LED light does not cause retinal damage and can suppress pineal melatonin content at intensities similar to CWF light intensities.

Effects of housing density on mouse physiology and behavior in the NASA Animal Enclosure Module simulators.

Space flight studies using the Animal Enclosure Module (AEM) make it possible to investigate the role of microgravity on animal physiology and behavior. In this study, we compared the health and well-being of mice housed at different densities in AEM simulators (AEMS), to vivarium shoebox (control) cages (VSBC). A stress assessment battery (SAB) of measures was developed to evaluate mouse health and well-being, and to determine if any of the population sizes resulted in a stressful environment. The SAB was based, in part, on recommendations of a NASA Workshop on Rodent Cage Sizing. It includes: 1) General assessment of appearance, 2) Behavioral assessment (video), 3) Food and water consumption, 4) Body weight changes, 5) Thymus, adrenal, spleen, heart and kidney weights, 6) Plasma corticosterone concentration, 7) Total plasma protein concentration, 8) Total blood leukocyte count, 9) Differential leukocyte count: neutrophil/lymphocyte ratio; eosinophil count, 10) Gastric histology.

New findings regarding light intensity and its effects as a zeitgeber in the Sprague-Dawley rat.

Circadian rhythmicities are oscillations of physiological cycles designed to create temporal organization. Circadian rhythms ensure that physiological mechanisms are expressed in proper relationship to each other and the 24 hour day. Light is the main zeitgeber ("time giver") for biological clocks. The daily variations in light intensity from dawn to dusk, and seasonally due to the rotation of the earth, act upon organisms to give them photoperiodic information. This entrainment allows them to vary biologically to prepare for reproduction, hibernation, migration and the daily adaptations necessary for survival. In most mammals, the suprachiasmatic nucleus of the anterior hypothalamus has been implicated as the central diving mechanism of circadian rhythmicity. The photic input from the retina, via the retino-hypothalamic tract, and modulation from the pineal gland help regulate the clock. In this study we investigated the effects of low light intensity on the circadian system of the Sprague-Dawley rat. A series of light intensity experiments were conducted to determine if a light level of 0.1 Lux will maintain entrained circadian rhythms of feeding, drinking, and locomotor activity.

Circadian rhythms and athletic performance.

Daily or circadian rhythmical oscillations occur in several physiological and behavioral functions that contribute to athletic performance. These functions include resting levels of sensory motor, perceptual, and cognitive performance and several neuromuscular, behavioral, cardiovascular, and metabolic variables. In addition, circadian rhythms have been reported in many indices of aerobic capacity, in certain physiological variables at different exercise levels, and, in a few studies, in actual athletic performance proficiency. Circadian rhythmicity in components of athletic performance can be modulated by workload, psychological stressors, motivation, "morningness/eveningness" differences, social interaction, lighting, sleep disturbances, the "postlunch dip" phenomenon, altitude, dietary constituents, gender, and age. These rhythms can significantly influence performance depending upon the time of day at which the athletic endeavor takes place. Disturbance of circadian rhythmicity resulting from transmeridian flight across several time zones can result in fatigue, malaise, sleep disturbance, gastrointestinal problems, and performance deterioration in susceptible individuals (circadian dysrhythmia or "jet-lag"). Factors influencing the degree of impairment and duration of readaptation include direction of flight, rhythm synchronizer intensity, dietary constituents and timing of meals, and individual factors such as morningness/eveningness, personality traits, and motivation. It is the intent of the authors to increase awareness of circadian rhythmic influences upon physiology and performance and to provide a scientific data base for the human circadian system so that coaches and athletes can make reasonable decisions to reduce the negative impact of jet-lag and facilitate readaptation following transmeridian travel.

A review of human physiological and performance changes associated with desynchronosis of biological rhythms.

This review discusses the effects, in the aerospace environment, of alterations in approximately 24-h periodicities (circadian rhythms) upon physiological and psychological functions and possible therapies for desynchronosis induced by such alterations. The consequences of circadian rhythm alteration resulting from shift work, transmeridian flight, or altered day lengths are known as desynchronosis, dysrhythmia, dyschrony, jet lag, or jet syndrome. Considerable attention is focused on the ability to operate jet aircraft and manned space vehicles. The importance of environmental cues, such as light-dark cycles, which influence physiological and psychological rhythms is discussed. A section on mathematical models is presented to enable selection and verification of appropriate preventive and corrective measures and to better understand the problem of dysrhythmia.

Bioinstrumentation for evaluation of workload in payload specialists: results of ASSESS II.

ASSESS II (Airborne Science/Spacelab Experiments System Simulation) was a cooperative NASA-ESA project which consisted of a detailed simulation of Spacelab operations using the NASA Ames Research Center CV-990 aircraft laboratory. The Medical Experiment reported on in this paper was part of the complex payload consisting of 11 different experiments. Its general purpose was to develop a technology, possibly flown on board of Spacelab, and enabling the assessment of workload through evaluating changes of circadian rhythmicity, sleep disturbances and episodical or cumulative stress. As parameters the following variables were measured: Rectal temperature, ECG, sleep-EEG and -EOG, the urinary excretion of hormones and electrolytes. The results revealed evidence that a Spacelab environment, as simulated in ASSESS II, will lead to internal dissociation of circadian rhythms, to sleep disturbances and to highly stressful working conditions. Altogether these effects will impose considerable workload upon Payload Specialists. It is suggested that an intensive pre-mission system simulation will reduce these impairments to a reasonable degree. The bioinstrumentation applied in this experiment proved to be a practical and reliable tool in assessing the objectives of the study.

Biological aspects of suicide: circadian disorganization.

Disturbances in the circadian rhythmicity of biological functions have been reported in various mental disorders. Four lines of research--hormonal, electroencephalographic, cerebral spinal fluid, and circadian rhythmicity--suggest possible changes in suicidal individuals. During a study investigating the effect of a photoperiod shift on circadian rhythms, 15 male, healthy, normal subjects were used. Following a 5-day baseline period a 12-hour photoperiod shift took place and was followed by 10 days of recovery period. Multiple parameters were monitored. Two weeks following completion of the study one subject suicided. The data were examined to determine whether the suicided subject differed, rhythmically, from other subjects. Summation dials describing phase changes and vector difference dials describing dynamic phase relationships of rhythm pairs showed that the rhythms of this subject were poorly synchronized internally during baseline. Total urinary output of all parameters was lower than all other subjects during baseline and more of his urinary parameters rephased incompletely during recovery. The results suggest that circadian asynchrony and an inability to respond effectively to a phase shift may characterize a presuicidal state. These results are discussed in terms of the four lines of research involving biological aspects of suicide and suggest some intriguing interactions.

Physiological effects of rotational work shifting: a review.

The high cost of capital equipment, demands of the world markets, and continuity requirements of many technological processes have forced industry to operate three-shift, 24-hour days. Workers on fixed schedules experience no particular problems from shift work, but those who are shifted periodically can undergo physiological and emotional disturbances. These disturbances occur because most human systems function according to circadian rhythms that can be easily disoriented. The primary cause is the periodic shifting of the light-dark, wake-sleep cycles. Extensive literature exists on the cause and symptoms of disturbances in the human physiological rhythms. The information contained in this literature can be applied to protecting the health and well-being of the worker.

Circadian patterns of stress-induced ACTH secretion are modified by corticosterone responses.

To test whether there is a circadian rhythm in the ACTH response to stress, young female rats were exposed to a variety of ACTH-releasing stimuli at 0600 and 1800 h and changes in circulating ACTH and corticosterone were measured. The results of these experiments suggested that after the high intensity stimuli of laparotomy with intestinal traction or 250 mug histamine ip/100 g BW, the morning ACTH response was greater than the evening response. However, the ACTH response to ip saline was greater in the evening in one experiment and greater in the morning in a second experiment. Plasma corticosterone responses were faster and greater in the morning in the first experiment and in the evening in the second experiment. The ACTH response to 125 mug histamine ip/100 g BW was greater in the evening and the change in corticosterone was greater in the morning. Thus, after low intensity stimuli, the ACTH responses appeared to depend on both the lag time prior to the corticosterone response, and its magnitude. To test this possibility, rats were adrenalectomized and the ACTH response was measured 7.5 and 15 min after the start of surgery and after injection with either 2% EtOH-saline, or 50 mug corticosterone at operation, or with 30 mug corticosterone at 5 min. Compared with ACTH levels in rats treated with vehicle, ACTH levels were decreased 7.5 min after 50 mug corticosterone at operation (P less than 0.01), but not after 30 mug corticosterone at 5 min. ACTH levels were slightly reduced 10 min after 30 mug corticosterone at 5 min compared with those of rats injected with vehicle at operation (P less than 0.05). These results are consistent with the interpretation that corticosterone secretion modifies stress-induced ACTH secretion via the fast-feedback effect. Comparison of the ACTH responses to acute adrenalectomy plus injection with EtOH-saline at 0600 and 1800 h demonstrated that, in the absence of a corticosterone response to the stress, the ACTH response is greater in the morning that in the evening (P less than 0.01). Finally, this group of experiments suggests strongly that the responsivenss of rat adrenal glands to ACTH increases markedly between 0600 and 1800 h.

The effect of low light intensity on the maintenance of circadian synchrony in human subjects.

The light-intensity threshold for humans is not known. In past space flights owing to power restrictions, light intensities have been minimal and reported to be as low as 15 ft. c. This study was conducted to determine whether the light (L)/dark (D) environment of 16L : 8D at the relatively low light intensity of 15 ft. c. was adequate for the maintenance of circadian synchrony in human subjects. Six healthy male subjects aged 20-23 years were exposed for 21 days to a 16L : 8D photoperiod. During the first 7 days the light intensity was 100 ft. c.; it was reduced to 15 ft. c. during the next 7 days and increased again to 100 ft. c. during the last 7 days of the study. Rectal temperature (RT) and heart rate (HR) were recorded continuously throughout the 21 days of the study. In the 100 ft. c. 16L : 8D the RT and HR rhythms remained stable and circadian throughout. When the light intensity was decreased to 15 ft. c. the periodicity of the HR rhythm was significantly decreased and this rhythm showed marked instability. In contrast the period of the RT rhythm did not change but a consistent phase delay occurred due to a delay in the lights-on associated rise in RT. These divergent effects on these two rhythms in internal desynchronization and performance decrement during the 15 ft. c. exposure. The data emphasize the need for establishing accurately the minimal lighting requirements for the maintenance of circadian rhythms of humans in confined environments.

Space motion sickness medications: interference with biomedical parameters.

The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen for space motion sickness may have interfered with their biomedical evaluation in space was investigated. Healthy volunteers received combinations of Scopolamine/Dexedrine for four days in regimens similar to those used in these missions. Urine samples, heart rate, body temperature, mood and performance were analyzed for drug-related changes. Twenty-four hour urine samples were analyzed by the same procedures as those used to analyze the flight samples. Hormone concentrations determined included cortisol, epinephrine, norepinephrine, aldosterone and antidiuretic hormone (ADH). In addition, volume, specific gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), inorganic phosphate, uric acid and creatinine were measured. Performance was not affected by the Scopolamine/Dexedrine. The drug combination increased daily mean heart rate (HR) significantly in all the subjects and daily mean rectal temperature (RT) in some of the subjects. A 2-4 hr phase shift in the HR circadian rhythm was also observed which indicates that internal circadian synchrony was disturbed by the drugs. Psychological and subjective evaluation indicated that the subjects could usually identify which days they were given the drugs by an increase in tension and anxiety, decreased patience, restlessness, decreased appetite, difficulty in sleeping and feelings of increased heart rate and body temperature. Urinary electrolytes were not changed significantly by the drug, but marked and significant changes occurred in urine volume and hormone excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary cortisol and epinephrine and a transient elevation in ADH. Norepinephrine excretion was decreased, but there was no significant change in aldosterone excretion or in 24 hr urine volume. A comparison of these findings with the first four days of inflight data from the SL-3 and SL-4 missions leads to the conclusion that the dramatic increases in aldosterone excretion during the first three days of spaceflight probably can be directly attributed to weightlessness, whereas the antimotion sickness medication could have substantially contributed to the early increased excretion of epinephrine and cortisol during these missions.

Psychologic and psychophysiologic response to 105 days of social isolation.

The responses of nine subjects to 105 d of social isolation are reported. The study reveals that crew selection plus ongoing support by psychiatric staff permits continued function in an exotic milieu. Prediction of psychophysiologic symptoms was possible using paper and pencil tests. Trait anxiety was altered by the isolation in a psychologically healthy direction. Sudden time shifts of 8 h led to an immediate significant increase in depression, aggression, and hostility, and are accompanied by marked increases in physical symptoms. During the first free-running phase of the experiment, significant shifts were found on four psychological measures. The shifts indicate that subjects became less trusting, more orderly, more routinized, less energetic, and more depressed. A reducer-augmenter scale predicted the number of psychophysiologic complaints reported by individual subjects while isolated. A group interaction effect on circadian rhythms was isolated but needs further examination.

Changes in glucose, insulin, and growth hormone levels associated with bedrest.

Changes in plasma glucose, insulin, and growth hormone (HGH) resulting from exposure to 56 d of bedrest were determined in five healthy young male subjects. Blood samples were collected by repeated venous puncture at 4-h intervals for 48-h periods before bedrest, at 10, 20, 30, 42 and 54 d after confinement to bed and at 10 and 20 d after bedrest. Changes in the daily levels of these factors for each subject were expressed as the mean of the six samples per 24-h period. The level of HGH dropped after 10 d of bedrest, then showed a 1.5-fold increase at 20 d (p less than 0.05) and subsequently decreased gradually reaching levels of 2.5 mg/ml/24 h, well below pre-bedrest controls of 4.2 mg/ml/24 h, by the 54th d. In spite of a marked increase in the daily plasma insulin levels during the first 30 d of bedrest, glucose levels remained unchanged. Beyond 30 d of bedrest, insulin began decreasing toward pre-bedrest levels and glucose followed with a similar reduction to below the control levels of 75 mg/100 ml/24 h on day 54. The daily mean changes reflect a change in the amplitude of the diurnal variation. The daily peak in plasma insulin shifted progressively to the late evening during the bedrest period.

Response of mice to repeated photoperiod shifts: susceptibility to stress and barbiturates.

Three inbred strains of mice selected for their spontaneous aggressive behavior and differential susceptibility to stress were exposed to a controlled environment where on an average of once every 4 days for 76 days and subsequently on an average of once every 2 days for an additional 55 days a 12L:12D photoperiod was reversed by 180 degrees. This procedure did not affect the growth of the mice and appeared to reduce fighting. However, plasma corticosterone concentrations in all three strains of mice were high, and their response to a 24-hr cold stress was no longer evident. The most pronounced effect of the altered photoperiod was on the barbiturate-induced sleeping time which showed a 40% reduction in all strains in spite of differential suceptibility to the drug among strains. It is concluded that repeated random phase shifting by varying the photoperiod is a stressful experience to which animals do not adapt and that the ability to respond to an additional stimulus or drugs may be greatly altered.