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At least 199 records · Page 11

Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

Space Motion Sickness (SMS) is often treated in space with promethazine (PMZ). Anecdotal reports indicate that the common side effects of drowsiness and decrements in cognitive performance that are associated with PMZ administration (50 mg IM on the ground, are absent or less pronounced in space suggesting I that-the bioavailability and/or pharmacodynamic behavior of PMZ may be altered during space flight. There are limited flight opportunities available for clinical research in space, the NRA-99, therefore, solicits research required to improve, or answer specific questions about in-flight diagnosis, therapy, and post-flight rehabilitation. We propose here, to establish a noninvasive method for pharmacodynamic and therapeutic assessment of PMZ. The specific objectives of the proposed research are to, 1. Establish a saliva to plasma ratio of PMZ after administration, 2. Estimate the relative bioavailability of the three flight-specific dosage forms of PMZ, and 3. Establish the dose-response relationship of PMZ. We will estimate the bioavailability of intramuscular injection (IM), oral tablets and rectal suppositories in normal subjects during ambulatory and antiorthostatic; bed rest (ABR) conditions using novel stable isotope techniques. Drowsiness, cognitive performance and salivary flow rate will be measured as a function of circulating drug concentrations after administration of three IM doses of PMZ. We will compare and contrast the bioavailability of PMZ during normal and ABR conditions to examine whether or not ABR can simulate changes in drug, absorption and availability similar to those anticipated in a microgravity environment. Results of this study will validate methods for an approved study with this medication awaiting a flight opportunity for manifestation. These data will also provide the much needed information on the dynamics and therapeutic index. of this medication and their implications on crew fatigue and performance in space. Key words: Promethazine, stable isotopes, bioavailability, pharmacodynamics, cognitive performance, antiorthostatic bed rest.

Putcha, Lakshmi↗

T Cell Activation Thresholds are Affected by Gravitational

T cells stimulated in space flight by various mitogenic signals show a dramatic reduction in proliferation and expression of early activation markers. Similar results are also obtained in a ground based model of microgravity, clinorotation, which provides a vector-averaged reduction of the apparent gravity on cells without significant shear force. Here we demonstrate that T cell inhibition is due to an increase in the required threshold for activation. Dose response curves indicate that cells activated during clinorotation require higher stimulation to achieve the same level of activation, as measured by CD69 expression. Interleukin 2 receptor expression, and DNA synthesis. The amount of stimulation necessary for 50% activation is 5 fold in the clinostat relative to static. Correlation of TCR internalization with activation also exhibit a dramatic right shift in clinorotation, demonstrating unequivocally that signal transduction mechanism independent of TCR triggering account for the increased activation threshold. Previous results from space flight experiments are consistent with the dose response curves obtained for clinorotation. Activation thresholds are important aspects of T cell memory, autoimmunity and tolerance Clinorotation is a useful, noninvasive tool for the study of cellular and biochemical event regulating T cell activation threshold and the effects of gravitation forces on these systems.

Adams, Charley↗

Bioimpedance Measurement of Segmental Fluid Volumes and Hemodynamics

Bioimpedance has become a useful tool to measure changes in body fluid compartment volumes. An Electrical Impedance Spectroscopic (EIS) system is described that extends the capabilities of conventional fixed frequency impedance plethysmographic (IPG) methods to allow examination of the redistribution of fluids between the intracellular and extracellular compartments of body segments. The combination of EIS and IPG techniques was evaluated in the human calf, thigh, and torso segments of eight healthy men during 90 minutes of six degree head-down tilt (HDT). After 90 minutes HDT the calf and thigh segments significantly (P < 0.05) lost conductive volume (eight and four percent, respectively) while the torso significantly (P < 0.05) gained volume (approximately three percent). Hemodynamic responses calculated from pulsatile IPG data also showed a segmental pattern consistent with vascular fluid loss from the lower extremities and vascular engorgement in the torso. Lumped-parameter equivalent circuit analyses of EIS data for the calf and thigh indicated that the overall volume decreases in these segments arose from reduced extracellular volume that was not completely balanced by increased intracellular volume. The combined use of IPG and EIS techniques enables noninvasive tracking of multi-segment volumetric and hemodynamic responses to environmental and physiological stresses.

Montgomery, Leslie D.↗

Dynamic Light Scattering of Diabetic Vitreopathy

Diabetes induces pathology throughout the body via nonenzymatic glycation of proteins. Vitreous, which is replete with type 11 collagen, undergoes significant changes in diabetes. The resultant diabetic vitreopathy plays an important role in diabetic retinopathy. Detecting these molecular changes could provide insight into diabetic eye disease as well as molecular effects elsewhere in the body. Human eyes were obtained at autopsy and studied in the fresh, unfixed state. Sclera, choroid, and retina were dissected off the vitreous for dark-field slit microscopy and dynamic light scattering (DLS). For the former, the entire vitreous was exposed. For the latter, only a window at the equator was dissected in some specimens, and the anterior segment was removed leaving the posterior lens capsule intact in others. DLS was performed to determine particle sizes at multiple sites 0.5 mm apart, spanning the globe at the equator (window dissections) and along the antero-posterior axis. Dark-field slit microscopy in diabetic subjects detected findings typical of age-related vitreous degeneration, but at much younger ages than nondiabetic controls. Noninvasive DLS measurements found a greater heterogeneity and larger particle sizes in vitreous of subjects with diabetes as compared to age-matched controls. DLS can detect and quantify the early molecular effects that cause vitreous collagen fibrils to cross-link and aggregate. This could provide valuable insight into ocular and systemic effects of hyperglycemia, because the molecular changes in diabetic vitreopathy could serve as an index of such effects throughout the body. In addition to the diagnostic implications, this methodology could provide a rapid, reproducible way to monitor the response to therapy with novel agents intended to prevent the complications of diabetes on a molecular level.

Sebag, J.↗

Distribution and Spectroscopy of Green Fluorescent Protein and Acyl-CoA: Cholesterol Acytransferase in Sf21 Insect Cells

Acyl-CoA: cholesterol acyltransferase (ACAT) is thought to significantly participate in the pathway of cholesterol esterification that underlies the pathology of artherosclerosis. This enzyme is a membrane protein known to be preferentially bound within the endoplasmic reticulum of mammalian cells, from which location it esterifies cholesterol derived from low density lipoprotein. Cultures of insect cells were separately infected with baculovirus containing the gene for green fluroescent protein (GFP) and with baculovirus containing tandem genes for GFP and ACAT. These infected cultures expressed GFP and the fusion protein GCAT, respectively, with maximum expression occurring on the fourth day after infection. Extraction of GFP- and of GCAT-expressing cells with urea and detergent resulted in recovery of fluorescent protein in aqueous solution. Fluorescence spectra at neutral pH were identical for both GFP and GCAT extracts in aqueous solution, indicating unperturbed tertiary structure for the GFP moiety within GCAT. In a cholesterol esterification assay, GCAT demonstrated ACAT activity, but with less efficiency compared to native ACAT. It was hypothesized that the membrane protein ACAT would lead to differences in localization of GCAT compared to GFP within the respective expressing insect cells. The GFP marker directly and also within the fusion protein GCAT was accordingly used as the intracellular probe that was fluorescently analyzed by the new biophotonics technique of hyperspectral imaging. In that technique, fluorescence imaging was obtained from two dimensional arrays of cells, and regions of interest from within those images were then retrospectively analyzed for the emission spectra that comprises the image. Results of hyperspectral imaging of insect cells on day 4 postinfection showed that GCAT was preferentially localized to the cytoplasm of these cells compared to GFP. Furthermore, the emission spectra obtained for the localized GCAT displayed a peak blue shift from 518nm obtained in neutral aqueous solution to 505nm obtained in localized regions within the cells. This blue shift indicates change in the fluorescence coupling of the GFP moiety of GCAT. It is hypothesized that change in tertiary environment of GCAT, coincident with intracellular deposition of GCAT, follows from intracellular trafficking of GCAT leading to membrane interactions with the ACAT moiety, and/or self-assembly of GCAT, that alters the chromophore environment of the GFP moiety of GCAT. These findings introduce a new technique of biophotonic imaging to studies of intracellular protein trafficking and interactions. This technique of hyperspectral imaging could contribute to advancing the emergent field of proteomics. Because of the noninvasive nature of this technique, kinetic processes associated with intracellular protein trafficking, and interactions of proteins within cellular domains, can be considered for investigation within a single cell as well as a cell population.

Richmond, R. C.↗

Eye-Movement Tracking Using Compressed Video Images

Infrared video cameras offer a simple noninvasive way to measure the position of the eyes using relatively inexpensive equipment. Several commercial systems are available which use special hardware to localize features in the image in real time, but the constraint of realtime performance limits the complexity of the applicable algorithms. In order to get better resolution and accuracy, we have used off-line processing to apply more sophisticated algorithms to the images. In this case, a major technical challenge is the real-time acquisition and storage of the video images. This has been solved using a strictly digital approach, exploiting the burgeoning field of hardware video compression. In this paper we describe the algorithms we have developed for tracking the movements of the eyes in video images, and present experimental results showing how the accuracy is affected by the degree of video compression.

Mulligan, Jeffrey B.↗

Measurement of Transcranial Distance During Head-Down Tilt Using Ultrasound

Exposure to microgravity probably elevates blood pressure and flow in the head which may increase intracranial volume (ICV) and pressure (ICP). Due to the slightly compliant nature of the cranium, any increase of ICP will increase ICV and transcranial distance. We used a noninvasive ultrasound technique to measure transcranial distance (frontal to occipital) during head-down tilt. Seven subjects (ages 26-53) underwent the following tilt angles: 90 deg. upright, 30 deg., 0 deg., -6 deg., -10 deg., -6 deg., 0 deg., 30 deg., and 90 deg. Each angle was maintained for 1 min. Ultrasound wave frequency was collected continuously and transcranial distance was calculated (Delta(x) = x(Delta)f/f, where x is path length and f is frequency of the wave) for each tilt angle. Frequency decreased from 503.687 kHz (90 deg. upright) to 502.619 kHz (-10 deg.). These frequencies translated to an increased transcranial distance of 0.403 mm. Although our data suggest a significant increase in transcranial distance during head-down tilt, this apparent increase may result, in part, from head-down tilt-induced subcutaneous edema or cutaneous blood volume elevation. In three subjects, when the above protocol was repeated with an ace bandage wrapped around the head to minimize such edema, the increased transcranial distance from 90 deg. to -10 deg. was reduced by 0.174 mm. Further development of the technique to quantify bone-to-bone expansion unconfounded by cutaneous fluid is necessary. Therefore, this ultrasound technique may provide measurements of changes in cranial dimensions during microgravity.

Torikoshi, Shigeyo↗

Near-Infrared Monitoring of Model Chronic Compartment Syndrome In Exercising Skeletal Muscle

Chronic compartment syndrome (CCS) is characterized by muscle ischemia, usually in the anterior oompartment of the leg, caused by high intramuscular pressure during exercise. Dual-wave near-infrared (NIR) spectroscopy is an optical technique that allows noninvasive tracking of variations in muscle tissue oxygenation (Chance et al., 1988). We hypothesized that with a model CCS, muscle tissue oxygenation will show a greater decline during exercise and a slower recovery post-exercise than under normal conditions.

Hargens, Alan R.↗

Monitoring Object Library Usage and Changes

The NASA Ames Numerical Aerodynamic Simulation program Aeronautics Consolidated Supercomputing Facility (NAS/ACSF) supercomputing center services over 1600 users, and has numerous analysts with root access. Several tools have been developed to monitor object library usage and changes. Some of the tools do "noninvasive" monitoring and other tools implement run-time logging even for object-only libraries. The run-time logging identifies who, when, and what is being used. The benefits are that real usage can be measured, unused libraries can be discontinued, training and optimization efforts can be focused at those numerical methods that are actually used. An overview of the tools will be given and the results will be discussed.

Owen, R. K.↗

A Robust Magnetic Resonance Imager For Ground and Flight Based Measurements of Fluid Physics Phenomena

Nuclear magnetic resonance (NMR) is a powerful and versatile, noninvasive method for studying fluid transport problems, However, its applications to these types of investigations have been limited. A primary factor that limits the application of NMR has been the lack of a user-friendly, versatile, and inexpensive NMR imaging apparatus that can be used by scientists who are not familiar with sophisticated NMR. To rectify this situation, we developed a user-friendly, NMR imager for projects of relevance to the MRD science community. To that end, we performed preliminary collaborative experiments between NASA, NCMR, and New Mexico Resonance in the high field NMR set up at New Mexico Resonance to track wetting front dynamics in foams under gravity. The experiments were done in a 30 cm, 1.9T Oxford magnet with a TECMAG Libra spectrometer (Tecmag, Inc., Houston, TX). We used two different imaging strategies depending on whether the water in the foam sample was static or moving. Stationary water distributions were imaged with the standard Fourier imaging method, as used in medical MRI, in which data are acquired from all parts of the region of interest at all times and Fourier transformed into a static spatial image.

Source record↗

Polarimetric Glucose Sensing Using Brewster Reflection off of Eye Lens: Theoretical Analysis

An important task of in vivo polarimetric glucose sensing is to find an appropriate way to optically access the aqueous humor of the human eye. In this paper two different approaches are analyzed theoretically and applied to the eye model of Le Grand. First approach is the tangential path of Cote, et al. (G.L. Cot6, M.D. Fox, and R.B. Northrop: Noninvasive Optical Polarimetric Glucose Sensing Using a True Phase Measurement Technique. IEEE Transactions on Biomedical Engineering, vol. 39, no. 7, pp. 752-756, 1992.) and the second is a new scheme of this paper of applying Brewster reflection off the eye lens.

Boeckle, Stefan↗

The Inside View

Bio-Imaging Research, Inc., has been included in Spinoff 1990 and 1993 with spinoffs from their ACTIS (Advanced Computed Tomography Inspection System) product developed under a Marshall Space Flight Center SBIR (Small Business Innovative Research) contract. The latest application is for noninvasive nuclear waste drum inspection. With the ACTIS CT (computed tomography, CATScan) scanner, radioactive waste is examined to prove that they do not contain one-half percent free liquid or that the drum wall has lost integrity before being moved across state lines or before being permanently disposed.

Source record↗

NASA EPSCoR Preparation Grant

The NASA EPSCoR project in Mississippi involved investigations into three areas of interest to NASA by researchers at the four comprehensive universities in the state. These areas involved: (1) Noninvasive Flow Measurement Techniques, (2) Spectroscopic Exhaust Plume Measurements of Hydrocarbon Fueled Rocket Engines and (3) Integration of Remote Sensing and GIS data for Flood Forecasting on the Mississippi Gulf Coast. Each study supported a need at the Stennis Space Center in Mississippi. The first two addressed needs in rocket testing, and the third, in commercial remote sensing. Students from three of the institutions worked with researchers at Stennis Space Center on the projects.

Sukanek, Peter C.↗

Programmable Pacemaker

Released in 1995, the Trilogy cardiac pacemaker is the fourth generation of a unit developed in the 1970s by NASA, Johns Hopkins Applied Physics Laboratory and St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.). The new system incorporates the company's PDx diagnostic and programming software and a powerful microprocessor that allows more functions to be fully automatic and gives more detailed information on the patient's health and the performance of the pacing systems. The pacemaker incorporates bidirectional telemetry used for space communications for noninvasive communication with the implanted pacemaker, smaller implantable pulse generators from space microminiaturization, and longer-life batteries from technology for spacecraft electrical power systems.

Source record↗

Development of a Multi-Channel, High Frequency QRS Electrocardiograph

With the advent of the ISS era and the potential requirement for increased cardiovascular monitoring of crewmembers during extended EVAs, NASA flight surgeons would stand to benefit from an evolving technology that allows for a more rapid diagnosis of myocardial ischemia compared to standard electrocardiography. Similarly, during the astronaut selection process, NASA flight surgeons and other physicians would also stand to benefit from a completely noninvasive technology that, either at rest or during maximal exercise tests, is more sensitive than standard ECG in identifying the presence of ischemia. Perhaps most importantly, practicing cardiologists and emergency medicine physicians could greatly benefit from such a device as it could augment (or even replace) standard electrocardiography in settings where the rapid diagnosis of myocardial ischemia (or the lack thereof) is required for proper clinical decision-making. A multi-channel, high-frequency QRS electrocardiograph is currently under development in the Life Sciences Research Laboratories at JSC. Specifically the project consisted of writing software code, some of which contained specially-designed digital filters, which will be incorporated into an existing commercial software program that is already designed to collect, plot and analyze conventional 12-lead ECG signals on a desktop, portable or palm PC. The software will derive the high-frequency QRS signals, which will be analyzed (in numerous ways) and plotted alongside of the conventional ECG signals, giving the PC-viewing clinician advanced diagnostic information that has never been available previously in all 12 ECG leads simultaneously. After the hardware and software for the advanced digital ECG monitor have been fully integrated, plans are to use the monitor to begin clinical studies both on healthy subjects and on patients with known coronary artery disease in both the outpatient and hospital settings. The ultimate goal is to get the technology out into the clinical world, where it has the potential to save lives.

DePalma, Jude L.↗

Physiological Feedback Method and System

A method and system provide physiological feedback for a patient and/or physician. At least one physiological effect experienced by a body part of a patient is measured noninvasively. A three-dimensional graphics model serving as an analogous representation of the body part is altered in accordance with the measurements. A binocular image signal representative of the three-dimensional graphics model so-altered is displayed for the patient and/or physician in a virtual reality environment.

Pope, Alan T.↗

Thermographic Inspections Save Skins and Prevent Blackouts

Scanning thermography involves heating a component s surface and subsequently measuring the surface temperature, using an infrared camera to identify structural defects such as corrosion and disbonding. It is a completely noninvasive and noncontacting process. Scans can detect defects in conventional metals and plastics, as well as in bonded aluminum composites, plastic- and resinbased composites, and laminated structures. The apparatus used for scanning is highly portable and can cover the surface of a test material up to six times faster than conventional thermography. NASA scientists affirm that the technology is an invaluable asset to the airlines, detecting potential defects that can cause structural failure.In 1996, ThermTech Services, Inc., of Stuart, Florida, approached NASA in an effort to evaluate the technology for application in the power and process industries, where corrosion is of serious concern. ThermTech Services proceeded to develop the application for inspecting boiler waterwall tubing at fossil-fueled electric-generating stations. In 1999, ThermTech purchased the rights to NASA s patented technology and developed the specialized equipment required to apply the inspecting method to power plant components. The ThermTech robotic system using NASA technology has proved to be extremely successful and cost effective in performing detailed inspections of large structures such as boiler waterwalls and aboveground chemical storage tanks. It is capable of inspecting a waterwall, tank-wall, or other large surfaces at a rate of approximately 10 square feet per minute or faster.

Source record↗

Detection and Prevention of Cardiac Arrhythmias During Space Flight

There have been reports suggesting that long-duration space flight might lead to an increased risk of potentially serious heart rhythm disturbances. If space flight does, in fact, significantly decrease cardiac electrical stability, the effects could be catastrophic, potentially leading to sudden cardiac death. It will be important to determine the mechanisms underlying this phenomenon in order to prepare for long-term manned lunar and interplanetary missions and to develop appropriate countermeasures. Our hypothesis is that prolonged exposure to microgravity will alter T wave alternans measurements, decrease heart rate variance, increase QT dispersion, decrease heart rate recovery and alter QT restitution curve. A recently published study has shown that long duration spaceflights prolong cardiac conduction and repolarization. They concluded that long duration flight is associated with QT interval prolongation and may increase arrhythmia susceptibility. We propose using computer technology as a noninvasive clinical tool to detect and study clinically significant TWA during standard exercise testing using electrode systems specifically adapted for the purpose of obtaining and measuring TWA. A population of approximately 15 healthy men and 5 healthy women subjects, representative of the astronaut cohort will be asked to voluntarily participate in this study. Their blood pressure and ECG/TWA will be measured pre-flight and in-flight. Prior to flight, subjects will be asked to participate in an orientation session. Still photos will be taken of the skin where the conductive gel is used for the multi-segment sensors. Photos will be recorded preflight, immediately postflight, and several times during the proceeding week until it has been determined that any skin reaction has disappeared or that no rash is present and will not appear.

Pillai, Dilip↗