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Quantitation of promethazine and metabolites in urine samples using on-line solid-phase extraction and column-switching.

A chromatographic method for the quantitation of promethazine (PMZ) and its three metabolites in urine employing on-line solid-phase extraction and column-switching has been developed. The column-switching system described here uses an extraction column for the purification of PMZ and its metabolites from a urine matrix. The extraneous matrix interference was removed by flushing the extraction column with a gradient elution. The analytes of interest were then eluted onto an analytical column for further chromatographic separation using a mobile phase of greater solvent strength. This method is specific and sensitive with a range of 3.75-1400 ng/ml for PMZ and 2.5-1400 ng/ml for the metabolites promethazine sulfoxide, monodesmethyl promethazine sulfoxide and monodesmethyl promethazine. The lower limits of quantitation (LLOQ) were 3.75 ng/ml with less than 6.2% C.V. for PMZ and 2.50 ng/ml with less than 11.5% C.V. for metabolites based on a signal-to-noise ratio of 10:1 or greater. The accuracy and precision were within +/- 11.8% in bias and not greater than 5.5% C.V. in intra- and inter-assay precision for PMZ and metabolites. Method robustness was investigated using a Plackett-Burman experimental design. The applicability of the analytical method for pharmacokinetic studies in humans is illustrated.

Humans↗

Distribution of Candida albicans genotypes among family members.

Thirty-three families (71 subjects) were screened for the presence of Candida albicans in mouthwash or stool specimens; 12 families (28 subjects) were culture-positive for this yeast. An enrichment procedure provided a twofold increase in the recovery of C. albicans from mouthwash specimens. Nine of the twelve culture-positive families had two positive members each, two families had three positive members each, and one family had four positive members. Genetic profiles were obtained by three methods: pulsed-field gel electrophoresis; restriction endonuclease analysis, and random amplification of polymorphic DNA analysis. DNA fingerprinting of C. albicans isolated from one body site three consecutive times revealed that each of the 12 families carried a distinct genotype. No two families shared the same strain, and two or more members of a family commonly shared the same strain. Intrafamily genotypic identity (i.e., each member within the family harbored the same strain) was demonstrated in six families. Genotypes of isolates from husband and wife differed from one another in five families. All three methods were satisfactory in determining genotypes; however, we concluded that restriction endonuclease analysis provided adequate resolving power.

Adult↗

Calcium and bone metabolism during space flight.

Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.

Biomarkers↗

NASA food systems: past, present, and future.

The development of space food has been evolving since the Soviet cosmonaut, German Titov, became the first human to eat in space in August 1961. John Glenn was the first American to consume food, applesauce, on the third manned Mercury mission in August 1962. Before these events, there was no knowledge that humans would be able to swallow and, hence, eat in weightlessness. Space food development began with highly engineered foods that met rigid requirements imposed by spacecraft design and short mission durations. Improvements in the habitability of the spacecraft have permitted improvements in the quality of space food. As the missions became longer, the need for better nutrition, more variety, and easily consumable foods also became more important. Currently, the International Space Station astronauts have a wide variety of foods. The goal is to provide acceptable foods that taste similar to foods we eat here on Earth. Extended planetary stays will require even more variety and more technologic advances. Plants will be grown to recycle the air and water and will provide food for the crew. These harvested crops will need to be processed into safe, healthy, and acceptable food ingredients that can then be prepared into menu items.

Eating↗

Red blood cell and iron metabolism during space flight.

Space flight anemia is a widely recognized phenomenon in astronauts. Reduction in circulating red blood cells and plasma volume results in a 10% to 15% decrement in circulatory volume. This effect appears to be a normal physiologic adaptation to weightlessness and results from the removal of newly released blood cells from the circulation. Iron availability increases, and (in the few subjects studied) iron stores increase during long-duration space flight. The consequences of these changes are not fully understood.

Adaptation, Physiological↗

Water and energy dietary requirements and endocrinology of human space flight.

Fluid and energy metabolism and related endocrine changes have been studied nearly from the beginning of human space flight in association with short- and long-duration flights. Fluid and electrolyte nutrition status is affected by many factors including the microgravity environment, stress, changes in body composition, diet, exercise habits, sleep cycles, and ambient temperature and humidity conditions. Space flight exposes astronauts to all these factors and consequently poses significant challenges to establishing dietary water, sodium, potassium, and energy recommendations. The purpose of this article is to review the results of ground-based and space flight research studies that have led to current water, electrolyte, and energy dietary requirements for humans during space flight and to give an overview of related endocrinologic changes that have been observed in humans during short- and long-duration space flight.

Body Temperature Regulation↗

History of nutrition in space flight: overview.

Major accomplishments in nutritional sciences for support of human space travel have occurred over the past 40 y. This article reviews these accomplishments, beginning with the early Gemini program and continuing through the impressive results from the first space station Skylab program that focused on life sciences research, the Russian contributions through the Mir space station, the US Shuttle life sciences research, and the emerging International Space Station missions. Nutrition is affected by environmental conditions such as radiation, temperature, and atmospheric pressures, and these are reviewed. Nutrition with respect to space flight is closely interconnected with other life sciences research disciplines including the study of hematology, immunology, as well as neurosensory, cardiovascular, gastrointestinal, circadian rhythms, and musculoskeletal physiology. These relationships are reviewed in reference to the overall history of nutritional science in human space flight. Cumulative nutritional research over the past four decades has resulted in the current nutritional requirements for astronauts. Space-flight nutritional recommendations are presented along with the critical path road map that outlines the research needed for future development of nutritional requirements.

Adaptation, Physiological↗

Variable practice with lenses improves visuo-motor plasticity.

Novel sensorimotor situations present a unique challenge to an individual's adaptive ability. Using the simple and easily measured paradigm of visual-motor rearrangement created by the use of visual displacement lenses, we sought to determine whether an individual's ability to adapt to visuo-motor discordance could be improved through training. Subjects threw small balls at a stationary target during a 3-week practice regimen involving repeated exposure to one set of lenses in block practice (x 2.0 magnifying lenses), multiple sets of lenses in variable practice (x 2.0 magnifying, x 0.5 minifying and up-down reversing lenses) or sham lenses. At the end of training, adaptation to a novel visuo-motor situation (20-degree right shift lenses) was tested. We found that (1) training with variable practice can increase adaptability to a novel visuo-motor situation, (2) increased adaptability is retained for at least 1 month and is transferable to further novel visuo-motor permutations and (3) variable practice improves performance of a simple motor task even in the undisturbed state. These results have implications for the design of clinical rehabilitation programs and countermeasures to enhance astronaut adaptability, facilitating adaptive transitions between gravitational environments.

Adaptation, Physiological↗

Modulation of head movement control in humans during treadmill walking.

The purpose of this study was to investigate the coordination of the head relative to the trunk within a gait cycle during gaze fixation. Nine normal subjects walked on a motorized treadmill driven at 1.79 m/s (20 s trials) while fixing their gaze on a centrally located earth-fixed target positioned at a distance of 2 m from their eyes. The net and relative angular motions of the head about the three axes of rotations, as well as the corresponding values for the moments acting on it relative to the trunk during the gait cycle were quantified and used as measures of coordination. The average net moment, as well as the average moments about the different axes were significantly different (P<0.01) between the high impact and low/no impact phases of the gait cycle. However, the average net angular displacement as well as the average angular displacement about the axial rotation axis of the head relative to the trunk was maintained uniform (P>0.01) throughout the gait cycle. The average angular displacement about the lateral bending axis was significantly increased (P<0.01) during the high impact phase while that about the flexion-extension axis was significantly decreased (P<0.01) throughout the gait cycle. Thus, the coordination of the motion of the head relative to the trunk during walking is dynamically modulated depending on the behavioral events occurring in the gait cycle. This modulation may serve to aid stabilization of the head by counteracting the force variations acting on the upper body that may aid in the visual fixation of targets during walking.

Adult↗

A quasi-static method for determining the characteristics of a motion capture camera system in a "split-volume" configuration.

The purpose of this study was to determine the accuracy, repeatability and resolution of a six-camera Motion Analysis system in a vertical split-volume configuration using a unique quasi-static methodology. The position of a reflective marker was recorded while it was moved quasi-statically over a range of 2.54 mm (0.100 inches) via a linearly-translating table. The table was placed at five different heights to cover both sub-volumes and the overlapping region. Data analysis showed that accuracy, repeatability and resolution values were consistent across all regions of the split-volume, including the overlapping section.

Analysis of Variance↗

Radiation dose from reentrant electrons.

In estimating the crew exposures during an extra vehicular activity (EVA), the contribution of reentrant electrons has always been neglected. Although the flux of these electrons is small compared to the flux of trapped electrons, their energy spectrum extends to several GeV compared to about 7 MeV for trapped electrons. This is also true of splash electrons. Using the measured reentrant electron energy spectra, it is shown that the dose contribution of these electrons to the blood forming organs (BFO) is more that 10 times greater than that from the trapped electrons. The calculations also show that the dose-depth response is a very slowly changing function of depth, and thus adding reasonable amounts of additional shielding would not significantly lower the dose to BFO.

Aerospace Medicine↗

Neutron measurements onboard the space shuttle.

The radiation environment inside a shielded volume is highly complex, consisting of both charged and neutral particles. Since the inception of human space flights, the charged particle component has received virtually all of the attention. There is however, a significant production of secondary neutrons, particularly from the aluminum structure in low earth orbiting spacecrafts. The interactions of galactic cosmic rays (GCR), and solar energetic particles with the earth's atmosphere produce a non-isotropic distribution of albedo neutrons. Inside any reasonable habitable module, the average radiation quality factor of neutrons is about 4-5 times larger than the corresponding average quality factor of charged particles. The measurement of neutrons and their energy spectra is a difficult problem due the intense sources of charged particles. This paper reviews the results of Shuttle flight experiments (made during both solar maximum and solar minimum) to measure the contribution of neutrons to the dose equivalent, as well as theoretical calculations to estimate the appropriate range of neutron energies that contribute most to the dose equivalent.

Cosmic Radiation↗

Proportional counter as neutron detector.

A technique to separate out the dose, and lineal energy spectra of neutrons and charged particles is described. It is based on using two proportional counters, one with a wall, and the other with similar characteristics but wall made from a non-hydrogen containing material. Results of a calibration in a neutron field are also shown.

Calibration↗

Validation of the galactic cosmic ray and geomagnetic transmission models.

A very high-momentum resolution particle spectrometer called the Alpha Magnetic Spectrometer (AMS) was flown in the payload bay of the Space Shuttle in a 51.65 degrees x 380-km orbit during the last solar minimum. This spectrometer has provided the first high statistics data set for galactic cosmic radiation protons, and helium, as well as limited spectral data on carbon and oxygen nuclei in the International Space Station orbit. First measurements of the albedo protons at this inclination were also made. Because of the high-momentum resolution and high statistics, the data can be separated as a function of magnetic latitude. A related investigation, the balloon borne experiment with a superconducting solenoid spectrometer (BESS), has been flown from Lynn Lake, Canada and has also provided excellent high-resolution data on protons and helium. These two data sets have been used here to study the validity of two galactic cosmic ray models and the geomagnetic transmission function developed from the 1990 geomagnetic reference field model. The predictions of both the CREME96 and NASA/JSC models are in good agreement with the AMS data. The shape of the AMS measured albedo proton spectrum, up to 2 GeV, is in excellent agreement with the previous balloon and satellite observations. A new LIS spectrum was developed that is consistent with both previous and new BESS 3He observations. Because the astronaut radiation exposures onboard ISS will be highest around the time of the solar minimum, these AMS measurements and these models provide important benchmarks for future radiation studies. AMS-02 slated for launch in September 2003, will provide even better momentum resolution and higher statistics data.

Cosmic Radiation↗

Comparison of graphite, aluminum, and TransHab shielding material characteristics in a high-energy neutron field.

Space radiation transport models clearly show that low atomic weight materials provide a better shielding protection for interplanetary human missions than high atomic weight materials. These model studies have concentrated on shielding properties against charged particles. A light-weight, inflatable habitat module called TransHab was built and shown to provide adequate protection against micrometeoroid impacts and good shielding properties against charged particle radiation in the International Space Station orbits. An experiment using a tissue equivalent proportional counter, to study the changes in dose and lineal energy spectra with graphite, aluminum, and a TransHab build-up as shielding, was carried out at the Los Alamos Nuclear Science Center neutron facility. It is a continuation of a previous study using regolith and doped polyethylene materials. This paper describes the results and their comparison with the previous study.

Aluminum↗

Response of a tissue equivalent proportional counter to neutrons.

The absorbed dose as a function of lineal energy was measured at the CERN-EC Reference-field Facility (CERF) using a 512-channel tissue equivalent proportional counter (TEPC), and neutron dose equivalent response evaluated. Although there are some differences, the measured dose equivalent is in agreement with that measured by the 16-channel HANDI tissue equivalent counter. Comparison of TEPC measurements with those made by a silicon solid-state detector for low linear energy transfer particles produced by the same beam, is presented. The measurements show that about 4% of dose equivalent is delivered by particles heavier than protons generated in the conducting tissue equivalent plastic.

Dose-Response Relationship, Radiation↗

Radiation measurements on the Mir Orbital Station.

Radiation measurements made onboard the MIR Orbital Station have spanned nearly a decade and covered two solar cycles, including one of the largest solar particle events, one of the largest magnetic storms, and a mean solar radio flux level reaching 250 x 10(4) Jansky that has been observed in the last 40 years. The cosmonaut absorbed dose rates varied from about 450 microGy day-1 during solar minimum to approximately half this value during the last solar maximum. There is a factor of about two in dose rate within a given module, and a similar variation from module to module. The average radiation quality factor during solar minimum, using the ICRP-26 definition, was about 2.4. The drift of the South Atlantic Anomaly was measured to be 6.0 +/- 0.5 degrees W, and 1.6 +/- 0.5 degrees N. These measurements are of direct applicability to the International Space Station. This paper represents a comprehensive review of Mir Space Station radiation data available from a variety of sources.

Astronauts↗