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Winget, C. M.

Publications and source records attributed to Winget, C. M..

At least 19 records

Use of Novel Light Sources and Melatonin Delivery Systems in the Maintenance of Temporal Organization of Physiological and Behavioral Circadian Rhythms

The synchronization of physiological and behavioral rhythms are controlled by an endogenous biological clock. It is generally accepted that environmental lighting is the strongest entrainer of this clock. The pineal gland is an important physiological transducer of environmental lighting via systemic melatonin secretion. We have used a novel light source using light emitting diode (LED) technology to entrain circadian rhythms in rats, and propose a novel percutaneous exogenous melatonin delivery system to entrain rat rhythms. We used 5 groups of Sprague-Dawley rats (175-350 g; N = 8/group) and showed normal entrainment of gross locomotor activity, feeding, and drinking circadian rhythms at light intensities varying from 80 lux to 0.1 lux (22.4 to 0.03 sq cm). To improve the delivery of melatonin across the skin stratum corneum it was formulated in a suitable vehicle in a transdermal drug delivery system. Various saturated and unsaturated fatty acids were used E, akin penetration enhancers. Our best vehicle formulation was achieved with a combination-of ethano1:water (60:40) along with 5% oleic acid as the enhancer. This formulation mixture was studied using Franz diffusion cell (0.636 sq cm diffusional area) and 1 cu cm dorsal skin isolated from Sprague Dawley rats. Our results showed that oleic acid in combination with the water ethanol mixture improved the flux of melatonin by more than 18 fold. The lag time for melatonin permeation was 2-3 hrs and the peak concentrations were achieved in 8-10 hrs. Our approaches in the future will involve the use of our transdermal melatonin delivery system and under the influence of LED light and microgravity.

Winget, C. M.

Light-Emitting Diodes (LED) for Primary Animal Habitat Lighting in Highly Controlled Environments

Significant alterations in Biological Clock responses have been reported following sidereal time changes (e.g., Jet-lag), and exposure to microgravity (e.g., daytime sleepiness). Additionally, light reduces circulating melatonin (spectral specificity greatest between 450-500 nm). It was hypothesized that LEDs can replace the current light sources used in zero gravity and terrestrial research laboratories because of their small size, low mass, low energy consumption and long functional life. This report evaluates the capacity of LEDs to entrain the circadian system of rats as judged by measurement of overt behavioral circadian rhythms (activity, feeding, drinking). These data were collected in highly controlled environments similar to the shuttle Animal Enclosure Modules. Two groups were compared: control - animals exposed to standard cool-white fluorescent lights, and test - animals exposed to LEDs with a spectral power distribution matching the fluorescent lights. Gross locomotor activity, feeding and drinking frequencies were continuously monitored and stored at 10 minute intervals. Animals were exposed to the following photoperiods: 28 days of 12L:12D, 19 days of 24L:0D and 16 days of 12L:12D. Light intensities tested varied between 0.1 to 100 lux. Rats received food and water ad libitum, and temperature and humidity were controlled throughout the study. The general health status of all rats was acceptable for each day of this study. No incidents of aggressive behavior were observed. Growth, locomotor activity, food and water consumption were comparable for all groups of animals, i.e, the circadian characteristics of the animals under these conditions were comparable. These results indicate that LED arrays are as effective in maintaining circadian rhythm stability as the commonly used cool-white fluorescent light sources. LEDs with their flexible spectrum, low energy requirements and minimal heat production have advantages for some chronopharmacology studies and for microgravity animal habitats.

Winget, C. M.

Technologies for Maintaining Animals in Space: Lighting, Air Quality, Noise, Food and Water

In the terrestrial environment multiple time cues exist. Zeitgebers have been identified and studied for their ability to convey temporal information to various physiological systems, In the microgravity experiment it is necessary to define time cues within the flight hardware prior to flight. During flight if changes in the Circadian System (e.g., mean, phase angle, period) occur this would indicate that the gravity vector is important relative to biological timing. This presentation is concerned with the environmental parameters to support rodent experiments in microgravity. The Animal Enclosure Module (AEM) provides solid food bars and water via lixits ad libitum. Flight animals (Sprague-Dawley rats, 60 - 300g) when compared to ground controls show similar growth (mean growth per day, g +/- SD; flight 5.4 +/- 2.0, ground 5.9 +/- 2.1). Current AEMs use incandescent lighting (approx. 5 Lux). Light emitting diode (LED) arrays are being developed that provide a similar light environment as cool-white fluorescent sources (40 Lux). In ground based tests (12L:12D), these arrays show normal circadian entrainment (Tau = 24.0) with respect to the behavioral responses. measured (drinking, eating, gross locomotor activity). A newly developed ultra high efficiency filter system can entrap all feces, urine and odors from 6 rats for 24 days. Maximum sound level exposure limits (per octave band 22 Hz - 179 kHz) have been established. The AEM will effectively support animal experiments in microgravity.

Winget, C. M.

Technologies For Maintaining Animals In Space: Lighting, Air Quality, Noise, Food And Water

In the terrestrial environment multiple time cues exist. Zeitgebers have been identified and studied for their ability to convey temporal information to various physiological systems. In the microgravity experiment it is necessary to define time cues within the flight hardware prior to flight. During flight if changes in the Circadian System (e.g., mean, phase angle, period) occur this would indicate that the gravity vector is important relative to biological timing. This presentation is concerned with the environmental parameter: to support rodent experiments in microgravity. The Animal Enclosure Module (AEM) provides solid food bars and water via lixits and ad libitum. Flight animals (Sprague-Dawley rats, 60 - 300g) when compared to ground controls show similar growth (mean growth per day g, plus or minus SD; flight 5.4 plus or minus 2.0, ground 5.9 plus or minus 2.1). Current AEMs use incandescent lighting (approx. 5 Lux). Light emitting diode (LED) arrays are being developed that provide a similar light environment as cool-white fluorescent sources (40 Lux). In ground based tests (12L:12D), these arrays show normal circadian entrainment (Tau = 24.0) with respect to the behavioral responses, measured (drinking, eating, gross locomotor activity). A newly developed ultra high efficiency filter system can entrap all feces, urine and odors from 6 rats for 24 days. Maximum sound level exposure limits (per octave band 22 Hz - 179 kHz) have been established. The AEM will effectively support animal experiments in microgravity.

Winget, C. M.

The Influence of Sound Cues on the Maintenance of Temporal Organization in the Sprague-Dawley Rat

Temporal organization is a fundamental property of living matter. From single cells to complex animals including man, most physiological systems undergo daily periodic changes in concert with environmental cues (e.g., light, temperature etc.). It is known that pulsed Environmental synchronizers, zeitgebers, (e.g. light) can modify rhythm parameters. Rhythm stability is a necessary requirement for most animal experiments. The extent to which sound can influence the circadian system of laboratory rats is poorly understood. This has implications to animal habitats in the novel environments of the Space-Laboratory or Space Station. A series of three white noise (88+/-0.82 db) zeitgeber experiments were conducted (n=6/experiment).The sound cue was introduced in the circadian free-running phase (DD-NQ) and in one additional case sound was added to the usual photoperiod (12L:12D) to determine masking effects. Circadian rhythm parameters of drinking frequency, feeding frequency, and gross locomotor activity were continuously monitored. Data analysis for these studies included macroscopic and microscopic methods. Raster plots to visually detect entrainment versus free-running period, were plotted for each animal, for all three parameters, during all sound perturbation tested. These data were processed through a series of detrending (robust locally weighted regression analyses) and complex demodulation analyses. In summary, these findings show that periodic "white" noise "influences" the rats circadian system but does not "entrain" the feeding, drinking or locomotor activity rhythms.

Winget, C. M.

Five biomedical experiments flown in an Earth orbiting laboratory: Lessons learned from developing these experiments on the first international microgravity mission from concept to landing

There are numerous problems associated with accommodating complex biological systems in microgravity in the flexible laboratory systems installed in the Orbiter cargo bay. This presentation will focus upon some of the lessons learned along the way from the University laboratory to the IML-1 Microgravity Laboratory. The First International Microgravity Laboratory (IML-1) mission contained a large number of specimens, including: 72 million nematodes, US-1; 3 billion yeast cells, US-2; 32 million mouse limb-bud cells, US-3; and 540 oat seeds (96 planted), FOTRAN. All five of the experiments had to undergo significant redevelopment effort in order to allow the investigator's ideas and objectives to be accommodated within the constraints of the IML-1 mission. Each of these experiments were proposed as unique entities rather than part of the mission, and many procedures had to be modified from the laboratory practice to meet IML-1 constraints. After a proposal is accepted by NASA for definition, an interactive process is begun between the Principal Investigator and the developer to ensure a maximum science return. The success of the five SLSPO-managed experiments was the result of successful completion of all preflight biological testing and hardware verification finalized at the KSC Life Sciences Support Facility housed in Hangar L. The ESTEC Biorack facility housed three U.S. experiments (US-1, US-2, and US-3). The U.S. Gravitational Plant Physiology Facility housed GTHRES and FOTRAN. The IML-1 mission (launched from KSC on 22 Jan. 1992, and landed at Dryden Flight Research Facility on 30 Jan. 1992) was an outstanding success--close to 100 percent of the prelaunch anticipated science return was achieved and, in some cases, greater than 100 percent was achieved (because of an extra mission day).

Winget, C. M.

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

In most mammals, the suprachiasmatic nucleus of the anterior hypothalamus has been implicated as the central driving 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.

Tischler, A. C.

Cells In Space

Report of "Cells in Space - II" conference held from 31 October through 4 November 1988 in San Juan Bautista, CA, contains abstracts of 32 oral presentations discussing 3 aspects of cell research in space: suitability of cell as subject in microgravity experiments; requirements of generic flight equipment to support microgravity cell research; and potential for collaboration between academia, industry, and government to develop these studies in space.

Callahan, P. X.

Experiments to be flown in an Earth orbiting laboratory: The US experiments on the first international microgravity laboratory, from concept to flight

The current life cycle of NASA ARC-managed flight experiments is presented. The two main purposes are: (1) to bring to the attention of biologists, and in particular cell and plant biologists, some of the requirements for flying a life science experiment in space; and (2) to introduce the subject to biologists embarking on studies in the field and to delineate some of the specific requirements that will be encountered by an ARC-managed microgravity experiment. This is not intended to be an exhaustive encyclopedia of all techniques used to prepare an experiment to evaluate the effect of microgravity on plant and animal cells. However, many of the requirements are the same for all biological systems and for other NASA centers. Emphasis is on the principle investigator's (PI's) involvement in the activities required for successful completion of major reviews. The PI support required for activities other than these reviews is also discussed, as are the interactions between ARC and the PI that will be required as problems or questions arise throughout experiment and payload development. It is impossible to predict the extent of this activity because it varies according to the complexity of the experiment and the flight experience of the PI.

Winget, C. M.

Significance of light and social cues in the maintenance of temporal organization in man

The effects of light:darkness (LD) cycles and social interaction on the response to long-term confinement (105 days) were investigated experimentally in three groups of three male subjects aged 20-24 years. Data from measurements of physiological parameters indicating changes in circadian rhythms are presented in graphs and analyzed; it is found that the LD-induced rhythm changes observed in previous studies of subjects isolated singly do not appear when subjects are confined in groups of three, suggesting a positive adaptive effect of social contact. In one subject who was transferred to a different group at day 84, hostile social interactions and poor circadian-rhythm entrainment were observed; the possible reasons for this response are considered.

Winget, C. M.

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.

Winget, C. M.

Influences of horizontal hypokinesia on performance and circadian physiological rhythms in female humans

Eight females from 35-45 yr of age were subjected to seven days of ambulatory control, seven days of bed rest, and a five day recovery period, with 30 min of centrifugation on day seven of bedrest to determine the effects of weightlessness on the circadian rhythms of females in that age group. Heart rate and rectal temperature (RT) were monitored and each subject was tested in a flight simulator twice a day in conditions of varying levels of turbulence. The flight simulations were run during the morning and acrophase of the circadian RT and performance errors wery monitored for 6 min. No significant differences were detected in the group performance data pre-, during, and post-bedrest, although better performance in the simulator was observed after the centrifuge exposure. An RT phase shift was statistically significant between pre- and during bedrest stages.

Winget, C. M.

Bioinstrumentation for evaluation of workload in payload specialists - Results of ASSESS II

Results of the medical experiment on payload specialist workloads conducted as part of the ASSESS II airborne simulation of Spacelab conditions are reported. Subjects were fitted with temperature probes and ECG, EEG and EOG electrodes, and hormone and electrolyte excretion was monitored in order to evaluate the changes in circadian rhythms, sleep patterns and stress responses brought about by mission schedules over the ten days of the experiment. Internal dissociations of circadian rhythms, sleep disturbances and increased stress levels were observed, especially during the first three days of the experiment, indicating a considerable workload to be imposed upon the payload specialists. An intensive premission simulation is suggested as a means of estimating overall workloads and allowing payload specialist adaptation to mission conditions. The bioinstrumentation which was developed and applied to the airborne laboratory is concluded to be a practical and reliable tool in the assessment of payload specialist workloads.

Wegmann, H. M.

The importance of light, postural and social cues in the regulation of the plasma cortisol rhythm in man

A series of experiments was conducted to assess the role of photoperiodic postural and social cues in the regulation of the plasma cortisol rhythm in normal human subjects. Young healthy adult male volunteers, aged 20-25, were used as the test subjects and were selected following extensive physical and psychological examinations. The time at which peak plasma cortisol concentration occurred was calculated from harmonic curves fitted to each set of 24-hr data from each subject. The findings suggest that the plasma cortisol rhythm is not affected appreciably by the absence of postural change, whereas light and social interaction affect this rhythm profoundly.

Vernikos-Danellis, J.

Biorhythms and space experiments with nonhuman primates

Man's response to exposure to spaceflight and weightlessness is expressed in physiological adjustments which involve his health and ability to function. The amplitude and periodicity of fluctuations in biological processes affect various functions and responses to provocative stimuli. Primates and other species are subjected to tests to determine the consequences of an altered biorhythm on work and performance, emotional stability, biomedical evaluation in space, the ability to cope with the unexpected, and susceptibility to infection, toxicity, radiation, drugs, and stress. Factors in the environment or operational setup which can change the physiological baseline must be determined and controlled.

Winget, C. M.

The capuchin monkey as a flight candidate

The highly evolved nervous system and associated complex behavioral capabilities of the nonhuman primates make them good candidates for certain studies in the space environment since deleterious changes in these more complex aspects of a biological status can only be demonstrated by species which share such highly evolved features with man. Important assets which urge the selection of the capuchin monkey for space experiments include his small size, high intelligence, relative disease resistance, nutritional requirements, and lower volume life support systems. The species is particularly suited for experiments on the nervous system or on process under neural control because of the similarity of capuchin and human blood chemistry profiles and endocrine systems involved in the maintenance of homeostasis and vasomotor tone.

Winget, C. M.

Loss of circadian rhythmicity in body temperature and locomotor activity following suprachiasmatic lesions in the rat

In experiments on male and female ambulatory rats, the effect of bilateral suprachiasmatic lesions on deep body temperature and locomotor activity circadian rhythms was investigated. A L/D:12/12 cycle and 23 C ambient temperature were maintained. One-half of the rats received radiofrequency lesions in the suprachiasmic nucleus (SCN) while the second group were sham operated by lowering the radiofrequency electrode to the SCN without producing electrolytic lesions. Four weeks were allowed for recuperation. Autopsies were conducted to make sure that the lesions were restricted to SCN. The results show the complete disappearance of circadian rhythm in the SCN lesioned rats and only a slight diminution for the sham operated rats.

Saleh, M. A.

Effect of suprachiasmatic lesions on diurnal heart rate rhythm in the rat

Heart rate and locomotor activity of rats kept under 12L/12D illumination regimen were recorded every six minutes for ten days using implantable radio transmitters. Some of the rats then received bilateral RF lesions into the suprachiasmatic nucleus (SCN). Control sham operations were performed on the rest of the animals. After recovery from surgery, recording of heart rate and locomotor activity was continued for ten days. SCN-lesioned rats showed no significant diurnal fluctuation in heart rate, while normal and sham-operated rats showed the normal diurnal rhythm in that function. The arrhythmic diurnal heart-rate pattern of SCN rats appeared to be correlated with their sporadic activity pattern. The integrity of the suprachiasmatic nucleus is therefore necessary for the generation and/or expression of diurnal rhythmicity in heart rate in the rat.

Saleh, M. A.