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NASA NTRS2014

Environmental and Socio-Demographic Determinants of Dengue Fever in Colombo City, Sri Lanka

Dengue fever has increased exponentially in Sri Lanka, from 24.4 cases per 100,000 in 2003 to 165.3 per 100,000 population in 2013. Although early warning systems using predictor models have been previously developed in other settings, it is important to develop such models in each local setting. Further, the ability of these models to be applicable at smaller geographic units will enhance current vector control and disease surveillance measures. The aim of this paper was to identify environmental and socio-economic status (SES) risk factors that may predict dengue fever at the Gram Niladhari Divisions (GND) level (smallest administrative unit) in Colombo city, Sri Lanka. These factors included landcover classes, amount of vegetation, population density, water access and neighborhood SES as determined by roof type. A geographically weighted regression (GWR) was used to develop the prediction model. A total 55 GND units covering an area of 37 sq km were investigated. We found that GND units with decreased vegetation, higher built-up area, higher population density and poor access to tap-water supply were associated with high risk of dengue; the pertinent GND units were concentrated in the center of the city. This is the first study in Sri Lanka to include both environmental and socio-demographic factors in prediction models for dengue fever. The methodology may be useful in enhancing ongoing dengue fever control measures in the country, and to be extended to other countries in the region that have an increasing incidence of dengue fever.

Tipre, Meghan↗
NASA NTRS1983

Use of remote sensing for land use policy formulation

Multispectral scanning, infrared imagery, thematic mapping, and spectroradiometry from LANDSAT, GOES, and ground based instruments are being used to determine conifer distribution, maximum and minimum temperatures, topography, and crop diseases in Michigan's lower Peninsula. Image interpretation and automatic digital processing information from LANDSAT data are employed to classify and map the coniferous forests. Radiant temperature data from GOES were compared to temperature readings from the climatological station network. Digital data from LANDSAT is being used to develop techniques for detecting, monitoring, and modeling land surface change. Improved reflectance signatures through spectroradiometry aided in the detection of viral diseases in blueberry fields and vineyards. Soil survey maps from aerial reconnaissance are included as well as information on education, conferences, and awards.

Source record↗
NASA NTRSDate not supplied

Effects of Low Dose Radiation and Radiation Countermeasures on Infection By Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1.Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. We have completed infection studies of the 3-D biomimetic intestinal tissue models and are currently analyzing the data.

Jennifer Barrila↗
NASA NTRSDate not supplied

Effects of Low Dose Radiation and Radiation Countermeasures on Infection by Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1.Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. We have completed infection studies of the 3-D biomimetic intestinal tissue models and are currently analyzing the data.

Jennifer Barrila↗
NASA NTRS2012

Use of MODIS Satellite Data to Evaluate Juniperus spp. Pollen Phenology to Support a Pollen Dispersal Model, PREAM, to Support Public Health Allergy Alerts

Pollen can be transported great distances. Van de Water et. al., 2003 reported Juniperus spp. pollen was transported 200-600 km. Hence local observations of plant phenology may not be consistent with the timing and source of pollen collected by pollen sampling instruments. The DREAM (Dust REgional Atmospheric Model, Nickovic et al. 2001) is a verified model for atmospheric dust transport modeling using MODIS data products to identify source regions and concentrations of dust. We are modifying the DREAM model to incorporate pollen transport. Pollen emission is based on MODIS-derived phenology of Juniperus spp. communities. Ground-based observational records of pollen release timing and quantities will be used as model verification. This information will be used to support the Centers for Disease Control and Prevention's National Environmental Public Health Tracking Program and the State of New Mexico environmental public health decision support for asthma and allergies alerts.

Luvall, J. C.↗
NASA NTRS2013

Use of MODIS Satellite Data to Evaluate Juniperus spp. Pollen Phenology to Support a Pollen Dispersal Model, PREAM, to Support Public Health Allergy Alerts

Pollen can be transported great distances. Van de Water et. al., 2003 reported Juniperus spp. pollen was transported 200-600 km. Hence local observations of plant phenology may not be consistent with the timing and source of pollen collected by pollen sampling instruments. The DREAM (Dust REgional Atmospheric Model) is a verified model for atmospheric dust transport modeling using MODIS data products to identify source regions and concentrations of dust. We are modifying the DREAM model to incorporate pollen transport. Pollen emission is based on MODIS-derived phenology of Juniperus spp. communities. Ground-based observational records of pollen release timing and quantities will be used as model verification. This information will be used to support the Centers for Disease Control and Prevention s National Environmental Public Health Tracking Program and the State of New Mexico environmental public health decision support for asthma and allergies alerts

Luvall, J. C.↗
NASA NTRS2014

Oculometric Assessment of Dynamic Visual Processing

Eye movements are the most frequent (~3 per second), shortest-latency (~150-250 ms), and biomechanically simplest (1 joint, no inertial complexities) voluntary motor behavior in primates, providing a model system to assess sensorimotor disturbances arising from trauma, fatigue, aging, or disease states (e.g., Diefendorf and Dodge, 1908). We developed a 15-minute behavioral tracking protocol consisting of randomized stepramp radial target motion to assess several aspects of the behavioral response to dynamic visual motion, including pursuit initiation, steadystate tracking, direction-tuning, and speed-tuning thresholds. This set of oculomotor metrics provide valid and reliable measures of dynamic visual performance (Stone and Krauzlis, 2003; Krukowski and Stone, 2005; Stone et al, 2009; Liston and Stone, 2014), and may prove to be a useful assessment tool for functional impairments of dynamic visual processing.

smooth pursuit↗
NASA NTRS2015

Experimental Design for Pre-Clinical Animal Model Study in Microgravity

The Rodent Research program at NASAs Ames Research Center (ARC) has pioneered a new research capability on the International Space Station in less than four years and has progressed toward translating research to the ISS utilizing commercial rockets, collaborating with academia and science industry, and training crew for research purposes on-orbit. Animal models are the foundation of pre-clinical research to understand human diseases and evaluate new therapeutics. Advancement in alleviating ground diseases such as muscle atrophy and osteoporosis can come from the study of similar conditions that are known to occur as a result of exposure to the spaceflight environment. During the completion of the flight phase of two missions, our practices, hardware and operations evolved from tested to developed standards, which successfully translated the studies from ground to space. Results from these studies contribute to the science community via both the primary investigation and banked samples that are shared in publicly available data repository such as GeneLab. Every completed mission sets a foundation to build and design greater complexity into future research and answer questions about common human diseases on ground and in space. Here, we present methods developed for the translation of a rodent experiment to the ISS including a description of hardware and kits available for investigators and a discussion of operational constraints.

Rodent Research↗
NASA NTRS1992

SAR backscatter from coniferous forest gaps

A study is in progress comparing Airborne Synthetic Aperture Radar (AIRSAR) backscatter from coniferous forest plots containing gaps to backscatter from adjacent gap-free plots. Issues discussed are how do gaps in the range of 400 to 1600 sq m (approximately 4-14 pixels at intermediate incidence angles) affect forest backscatter statistics and what incidence angles, wavelengths, and polarizations are most sensitive to forest gaps. In order to visualize the slant-range imaging of forest and gaps, a simple conceptual model is used. This strictly qualitative model has led us to hypothesize that forest radar returns at short wavelengths (eg., C-band) and large incidence angles (e.g., 50 deg) should be most affected by the presence of gaps, whereas returns at long wavelengths and small angles should be least affected. Preliminary analysis of 1989 AIRSAR data from forest near Mt. Shasta supports the hypothesis. Current forest backscatter models such as MIMICS and Santa Barbara Discontinuous Canopy Backscatter Model have in several cases correctly predicted backscatter from forest stands based on inputs of measured or estimated forest parameters. These models do not, however, predict within-stand SAR scene texture, or 'intrinsic scene variability' as Ulaby et al. has referred to it. For instance, the Santa Barbara model, which may be the most spatially coupled of the existing models, is not truly spatial. Tree locations within a simulated pixel are distributed according to a Poisson process, as they are in many natural forests, but tree size is unrelated to location, which is not the case in nature. Furthermore, since pixels of a simulated stand are generated independently in the Santa Barbara model, spatial processes larger than one pixel are not modeled. Using a different approach, Oliver modeled scene texture based on an hypothetical forest geometry. His simulated scenes do not agree well with SAR data, perhaps due to the simple geometric model used. Insofar as texture is the expression of biological forest processes, such as succession and disease, and physical ones, such as fire and wind-throw, it contains useful information about the forest, and has value in image interpretation and classification. Forest gaps are undoubtedly important contributors to scene variance. By studying the localized effects of gaps on forest backscatter, guided by our qualitative model, we hope to understand more clearly the manner in which spatial heterogeneities in forests produce variations in backscatter, which collectively give rise to scene texture.

Day, John L.↗
NASA NTRS2014

The AgMIP Coordinated Climate-Crop Modeling Project (C3MP): Methods and Protocols

Climate change is expected to alter a multitude of factors important to agricultural systems, including pests, diseases, weeds, extreme climate events, water resources, soil degradation, and socio-economic pressures. Changes to carbon dioxide concentration ([CO2]), temperature, and water (CTW) will be the primary drivers of change in crop growth and agricultural systems. Therefore, establishing the CTW-change sensitivity of crop yields is an urgent research need and warrants diverse methods of investigation. Crop models provide a biophysical, process-based tool to investigate crop responses across varying environmental conditions and farm management techniques, and have been applied in climate impact assessment by using a variety of methods (White et al., 2011, and references therein). However, there is a significant amount of divergence between various crop models' responses to CTW changes (Rotter et al., 2011). While the application of a site-based crop model is relatively simple, the coordination of such agricultural impact assessments on larger scales requires consistent and timely contributions from a large number of crop modelers, each time a new global climate model (GCM) scenario or downscaling technique is created. A coordinated, global effort to rapidly examine CTW sensitivity across multiple crops, crop models, and sites is needed to aid model development and enhance the assessment of climate impacts (Deser et al., 2012). To fulfill this need, the Coordinated Climate-Crop Modeling Project (C3MP) (Ruane et al., 2014) was initiated within the Agricultural Model Intercomparison and Improvement Project (AgMIP; Rosenzweig et al., 2013). The submitted results from C3MP Phase 1 (February 15, 2013-December 31, 2013) are currently being analyzed. This chapter serves to present and update the C3MP protocols, discuss the initial participation and general findings, comment on needed adjustments, and describe continued and future development. AgMIP aims to improve substantially the climate, crop, and economic simulation tools that are used to characterize the agricultural sector, to assess future world food security under changing climate conditions, and to enhance adaptation capacity both globally and regionally. To understand better and improve the modeled crop responses, AgMIP has conducted detailed crop model intercomparisons at closely observed field sites for wheat (Asseng et al., 2013), rice (Li et al., in review), maize (Bassu et al., 2014), and sugarcane (Singels et al., 2013). A coordinated modeling exercise was one of the original motivations for AgMIP, and C3MP provides rapid estimation of crop responses to CO2, water, and temperature (CTW) changes, adding dimension and insight into the crop model intercomparisons, while facilitating interactions within the global community of modelers. C3MP also contributes a fast-track, multi-model climate sensitivity assessment for the AgMIP climate and crop modeling teams on Research Track 2 (Fig. 1), which seeks to understand the impact of projected climatic changes on crop production and food security (Rosenzweig et al., 2013; Ruane et al., 2014).

agriculture↗
NASA NTRS2012

NASA Earth Observation Systems and Applications for Public Health and Air Quality Models and Decisions Support

Health and Air Quality providers and researchers need environmental data to study and understand the geographic, environmental, and meteorological differences in disease. Satellite remote sensing of the environment offers a unique vantage point that can fill in the gaps of environmental, spatial, and temporal data for tracking disease. This presentation will demonstrate the need for collaborations between multi-disciplinary research groups to develop the full potential of utilizing Earth Observations in studying health. Satellite earth observations present a unique vantage point of the earth's environment from space, which offers a wealth of health applications for the imaginative investigator. The presentation is directly related to Earth Observing systems and Global Health Surveillance and will present research results of the remote sensing environmental observations of earth and health applications, which can contribute to the public health and air quality research. As part of NASA approach and methodology they have used Earth Observation Systems and Applications for Public Health and Air Quality Models to provide a method for bridging gaps of environmental, spatial, and temporal data for tracking disease. This presentation will provide an overview of projects dealing with infectious diseases, water borne diseases and air quality and how many environmental variables effect human health. This presentation will provide a venue where the results of both research and practice using satellite earth observations to study weather and it's role in public health research.

Estes, Sue↗
NASA NTRS2013

NASA Earth Observation Systems and Applications for Public Health and Air Quality Models and Decisions Support

Health and Air Quality providers and researchers need environmental data to study and understand the geographic, environmental, and meteorological differences in disease. Satellite remote sensing of the environment offers a unique vantage point that can fill in the gaps of environmental, spatial, and temporal data for tracking disease. This presentation will demonstrate the need for collaborations between multi-disciplinary research groups to develop the full potential of utilizing Earth Observations in studying health. Satellite earth observations present a unique vantage point of the earth's environment from space, which offers a wealth of health applications for the imaginative investigator. The presentation is directly related to Earth Observing systems and Global Health Surveillance and will present research results of the remote sensing environmental observations of earth and health applications, which can contribute to the public health and air quality research. As part of NASA approach and methodology they have used Earth Observation Systems and Applications for Public Health and Air Quality Models to provide a method for bridging gaps of environmental, spatial, and temporal data for tracking disease. This presentation will provide an overview of projects dealing with infectious diseases, water borne diseases and air quality and how many environmental variables effect human health. This presentation will provide a venue where the results of both research and practice using satellite earth observations to study weather and it's role in public health research.

Estes, Sue↗
NASA NTRS2002

HI-STAR. Health Improvements through Space Technologies and Resources: Executive Summary

Our mission is to develop and promote a global strategy to help combat malaria using space technology. Like the tiny yet powerful mosquito, HI-STAR (Health Improvements Through Space Technologies and Resources) is a small program that aspires to make a difference. Timely detection of malaria danger zones is essential to help health authorities and policy makers make decisions about how to manage limited resources for combating malaria. In 2001, the technical support network for prevention and control of malaria epidemics published a study. HI-STAR focuses on malaria because it is the most common and deadly of the vector-borne diseases. Malaria also shares many commonalities with other diseases, which means the global strategy developed here may also be applicable to other parasitic diseases. HI-STAR would like to contribute to the many malaria groups already making great strides in the fight against malaria. Some examples include: Roll Back Malaria, The Special Program for Research and Training in Tropical Diseases (TDR) and the Multilateral Initiative on Malaria (MIM). Other important groups that are among the first to include space technologies in their model include: The Center for Health Application of Aerospace Related Technologies (CHAART) and Mapping Malaria Risk in Africa (MARA). Malaria is a complex and multi-faceted disease. Combating it must therefore be equally versatile. HI-STAR incorporates an interdisciplinary, international, intercultural approach.called 'Malaria Early Warning Systems; Concepts, Indicators and Partners.' This study, funded by Roll Back Malaria, a World Health Organization initiative, offers a framework for a monitoring and early warning system. HI-STAR seeks to build on this proposal and enhance the space elements of the suggested framework. It is the work of fifty-three professionals and students from the International Space University's 2002 Summer Session Program held in California, USA.

Finarelli, Margaret G.↗
NASA NTRS2024

Effects of Low Dose Radiation and Radiation Countermeasures on Infection By Spaceflight Analogue Cultured Salmonella Using 3-D Biometric Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1. Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. This study has been initiated and data collection is beginning.

Jennifer Barrila↗
NASA NTRSDate not supplied

Effects of Low Dose Radiation and Radiation Countermeasures on Infection by Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1. Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. This study has been initiated and data collection is beginning.

Jennifer Barrila↗
NASA NTRS2003

Dust Emissions, Transport, and Deposition Simulated with the NASA Finite-Volume General Circulation Model

Mineral dust aerosols have radiative impacts on Earth's atmosphere, have been implicated in local and regional air quality issues, and have been identified as vectors for transporting disease pathogens and bringing mineral nutrients to terrestrial and oceanic ecosystems. We present for the first time dust simulations using online transport and meteorological analysis in the NASA Finite-Volume General Circulation Model (FVGCM). Our dust formulation follows the formulation in the offline Georgia Institute of Technology-Goddard Global Ozone Chemistry Aerosol Radiation and Transport Model (GOCART) using a topographical source for dust emissions. We compare results of the FVGCM simulations with GOCART, as well as with in situ and remotely sensed observations. Additionally, we estimate budgets of dust emission and transport into various regions.

Colarco, Peter↗
NASA NTRS2003

Time course of epiphyseal growth plate fusion in rat tibiae

Although the rat is the most common animal model used in studying osteoporosis, it is often used inappropriately. Osteoporosis is a disease that most commonly occurs in humans long after growth plate fusion with the associated cessation of longitudinal bone growth, but there has been a question as to when or to what extent the rat growth plate fuses. To investigate this question, we used microcomputed X-ray tomography, at voxel resolutions ranging from (5.7 micro m)(3) to (11 micro m)(3), to image the proximal epiphyseal growth plates of both male (n = 19) and female (n = 15) rat tibiae, ranging in age from 2 to 25 months. The three-dimensional images were used to evaluate fusion of the epiphyseal growth plate by quantitating the amount of cancellous bone that has bridged across the growth plate. The results suggest that the time course of fusion of the epiphyseal growth plate follows a sigmoidal pattern, with 10% of the maximum number of bridges having formed by 3.9 months in the male tibiae and 5.8 months in the female tibiae, 50% of the maximum number of bridges having formed by 5.6 months in the male tibiae and 5.9 months in the female tibiae, and 90% of the total maximum of bridges have formed by 7.4 months for the males and 6.5 months for the females. The total volume of bridges per tibia at the age at which the maximum number of bridges per tibia has first formed is 0.99 mm(3)/tibia for the males and 0.40 mm(3)/tibia for the females. After the maximum number of bridges (-290 for females, -360 for males) have formed the total volume of bridges per tibia continues to increase for an additional 7.0 months in the males and 17.0 months for the females until they reach maximum values (-1.5 mm(3)/tibia for the males and -2.2 mm(3)/tibia for the females).

NASA Discipline Cell Biology↗
NASA NTRS2002

Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expression

A mechanism explaining the differential skeletal effects of intermittent and continuous elevation of serum parathyroid hormone (PTH) remains elusive. Intermittent PTH increases bone formation and bone mass and is being investigated as a therapy for osteoporosis. By contrast, chronic hyperparathyroidism results in the metabolic bone disease osteitis fibrosa characterized by osteomalacia, focal bone resorption, and peritrabecular bone marrow fibrosis. Intermittent and continuous PTH have similar effects on the number of osteoblasts and bone-forming activity. Many of the beneficial as well as detrimental effects of the hormone appear to be mediated by osteoblast-derived growth factors. This hypothesis was tested using cDNA microgene arrays to compare gene expression in tibia of rats treated with continuous and pulsatile administration of PTH. These treatments result in differential expression of many genes, including growth factors. One of the genes whose steady-state mRNA levels was increased by continuous but not pulsatile administration was platelet-derived growth factor-A (PDGF-A). Administration of a PDGF-A antagonist greatly reduced bone resorption, osteomalacia, and bone marrow fibrosis in a rat model for hyperparathyroidism, suggesting that PDGF-A is a causative agent for this disease. These findings suggest that profiling changes in gene expression can help identify the metabolic pathways responsible for the skeletal responses to the hormone.

Review↗