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NASA NTRS1988

Management of hypophosphatemia

The etiology, clinical presentation, and management of hypophosphatemia are reviewed. Phosphorus is a major intracellular anion and plays an important role in many biochemical pathways relating to normal physiologic functions. Approximately 60 to 90% of the 1 to 1.5 g of daily dietary phosphorus intake is absorbed, and of that amount, about two thirds is excreted in the urine. The overall incidence of hypophosphatemia is about 2 to 3% of all hospitalized patients. Factors associated with hypophosphatemia include phosphate-binding antacid therapy, nasogastric suction, liver disease, sepsis, alcoholism, and acidosis associated with diabetic ketoacidosis. Patients receiving parenteral nutrient solutions were also at higher risk for hypophosphatemia before the routine supplementation of these formulations with phosphate. Patients with hypophosphatemia may be asymptomatic or may experience weakness, malaise, anorexia, bone pain, and respiratory arrest. The major systems involved include the neuromuscular, hematologic, and skeletal systems. Phosphorus-containing products used to treat hypophosphatemia are a combination of monobasic and dibasic phosphate salts. Therefore, it is essential to calculate doses in millimoles rather than milligrams or milliequivalents to more accurately reflect the phosphorus concentration and to avoid potentially serious dosage errors. Normal daily requirements are readily maintained by dietary sources of phosphorus such as milk products or may be supplemented by phosphate-containing products administered orally or intravenously. Since phosphorus is a key factor in many organ systems, it is essential to monitor serum phosphorus concentrations in patients at risk for hypophosphatemia.

Review, Tutorial↗
NASA NTRS2005

Ozone Exposure System Designed and Used to High-Altitude Airship Materials

High-altitude airships can receive high doses of ozone over short mission durations. For example, in 1 year at an altitude of 70,000 ft, the ozone fluence (number arriving per unit area) can be as high as 1.2 1024 molecules/sq cm. Ozone exposure at these levels can embrittle materials or change the performance of solar cells. It is important to expose components and materials to the expected ozone dosage to determine if the ozone exposure could cause any mission-critical failures.

Miller, Sharon K.↗
NASA NTRS2004

Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

The acute effects of exposure to microgravity include the development of space motion sickness, which usually requires therapeutic intervention. The current drug of choice, promethazine (PMZ), is available to astronauts in three different dosage forms during space flight; its side effects include nausea, dizziness, sedation and impaired psychomotor performance. This ground-based study is designed to validate flight-suitable methods for pharmacodynamic evaluation of PMZ and to estimate bioavailability and pharmacodynamics of PMZ. Experimental design consists of intramuscular administration of three doses of PMZ (12.5,25 and 50 mg) and placebo in a randomized double blind fashion to human subjects and collecting blood, urine and saliva samples for 72 h. Subjects also complete cognitive performance test batteries, WinSCAT (Windows based Space Cognitive Assessment Test) and ARES (ANAM Readiness Evaluation System). Preliminary results indicate a significant relationship (p=9.88e-05) between circulating PMZ levels and cognitive performance parameters. Time to accurately complete memory tasks increases significantly with concentrations; higher concentrations also increase response time and decrease accuracy of substitution and matching tasks. AUC and half-life estimates for PMZ ranged between 0.12 and 1.7 mg.h/L and 15 and 50 h, respectively. These preliminary results indicate that PMZ may exhibit dose-dependent pharmacokinetics in humans; also, WinSCAT and ARES are sensitive for pharmacodynamic assessment of PMZ, and may be applicable for assessing the pharmacodynamics of other neurocognitive drugs.

Boyd, J. L.↗
NASA NTRS2006

Europa Surface Radiation Environment for Lander Assessment

The Jovian magnetospheric particle environment at Europa's surface is critical to assessment of landed astrobiological experiments in three respects: (1) the landing site must be chosen for the best prospects for detectable organic or inorganic signs of Life, e.g. regions of freshly emergent flows from the subsurface; (2) lander systems must reach the surface through the Jovian magnetospheric environment and operate long enough on the surface to return useful data; (3) lander instrumentation must be capable of detecting signs of life in the context of the local environmental radiation and associated chemistry. The Galileo, Voyager, and Pioneer missions have provided a wealth of data on energetic particle intensities throughout the Jovian magnetosphere including from many flybys of Europa. cumulative radiation dosages for spacecraft enroute to Europa can be well characterized, but knowledge of the surface radiation environment is very limited. Energetic electrons should primarily impact the trailing hemisphere with decreasing intensity towards the center of the leading hemisphere and are the most significant radiation component down to meter depths in the surface regolith due to secondary interactions. Observed surface distribution for sulfates is suggestive of electron irradiation but may have alternative interpretations. Having much-larger magnetic gyroradii than electrons, energetic protons and heavier ions irradiate more of the global surface. The particular orientations of electron, proton, and ion gyromotion would project into corresponding directional (e.g., east-west) anisotropies of particle flu into the surface. Particular topographic features at the landing site may therefore offer shielding from part of the incident radiation.

Cooper, John F.↗
NASA NTRS2006

Irradiating of Bulk Soybeans: Influence on Their Functional and Sensory Properties for Soyfood Processing

Soybeans were chosen for lunar and planetary missions, where soybeans will be supplied in bulk or grown locally, due to their nutritive value and ability to produce oil and protein for further food applications. However, soybeans must be processed into foods prior to consumption. Radiation that soybeans would be exposed to during bulk storage prior to and during a Mars mission may influence their germination and functional properties. The influence of radiation includes the affect of surface pasteurization to ensure the astronauts safety from food-borne illnesses (HACCP, CCP), and the affect of the amount of radiation the soybeans receive during a Mars mission. Decreases in the amount of natural antioxidants free radical formation, and oxidation-induced changes in the soybean will influence the nutritional value, texture, color, and aroma of soyfoods. The objective of this study was to determine the influence of pasteurization and sterilization surface radiation on whole soybeans using gamma and electron beam radiation. The influence of 0, 1, 5, 10, and 30kGy on microbial load, germination rate, ease of processing, and quality of soymilk and tofu were determined. Surface radiation of whole dry soybeans using electron beam or gamma rays from 1-30kGy did provide microbial safety for the astronauts. However, the lower dose levels had surviving yeasts and molds. These doses caused oxidative changes that resulted in soymilk and tofu with rancid aromas. GC-MS of the aroma compounds using SPME Headspace confirmed the presence of lipid oxidation compounds. Soybean germination ability was reduced as radiation dosage increased. While lower doses may reduce these problems, the ability to insure microbial safety of bulk soybeans will be lost. Counter measures could include vacuum packaging, nitrogen flushing, added antioxidants, and radiating under freezing conditions. Doses below 1kGy need to be investigated further to determine the influence of the radiation encountered during Mars missions.

Chia, Chiew-Ling↗
NASA NTRS2004

Bioavailability and Pharmacodynamics of Promethazine on Long Duration Missions to the International Space Station

Space motion sickness (SMS) is often treated in space with promethazine (PMZ). Common side effects of PMZ administration (50 mg intramuscular) on the ground are drowsiness and impaired cognitive performance. Anecdotal reports indicate that these effects are absent or less pronounced in space. This suggests that the availability of PMZ to the body (bioavailability) and/or the response of the body to PMZ (pharmacodynamics) may change during space flight. Opportunities for clinical research in space are limited. The study described here is our response to a NASA Research Announcement for proposals for flight-based research needed to improve, or answer specific questions about, diagnosis and therapy during space flight, and post-flight rehabilitation. We propose here to evaluate noninvasive methods for determining the bioavailability and pharmacodynamics of PMZ. The specific objectives of the proposed research are to 1) compare pharmacokinetic and pharmacodynamic parameters of PMZ, estimated from saliva and plasma levels after administration of PMZ, 2) estimate the relative bioavailability of the three dosage forms of PMZ that are often administered to control motion sickness symptoms in space, and 3) establish the dose-response relationship of PMZ. We will estimate the bioavailability of an intramuscular injection (IM), oral tablet, and rectal suppository of PMZ in noma1 subjects during ambulatory and antiorthostatic bed rest (ABR) conditions using novel stable isotope techniques. We will compare and contrast the bioavailability of PMZ during normal and microgravity conditions to examine changes in drug absorption and bioavailability during microgravit. Results of this study will validate methods for an approved in-flight investigation with this medication awaiting an opportunity for manifestation..

Putcha, Lakshmi↗
NASA NTRS2006

Advances in Pharmacotherapeutics of Space Motion Sickness

Space Motion Sickness (SMS) is common occurrence in the U.S. manned space flight program and nearly 2/3 of Shuttle crewmembers experience SMS. Several drugs have been prescribed for therapeutic management of SMS. Typically, orally-administered SMS medications (scopolamine, promethazine) have poor bioavailability and often have detrimental neurocognitive side effects at recommended doses. Intramuscularly administered promethazine (PMZ) is perceived to have optimal efficacy with minimal side effects in space. However, intramuscular injections are painful and the sedating neurocognitive side effects of promethazine, significant in controlled ground testing, may be masked in orbit because injections are usually given prior to crew sleep. Currently, EVAs cannot be performed by symptomatic crew or prior to flight day three due to the lack of a consistently efficacious drug, concern about neurocognitive side effects, and because an in-suit vomiting episode is potentially fatal. NASA has long sought a fast acting, consistently effective anti-motion sickness medication which has only minor neurocognitive side effects. Development of intranasal formulations of scopolamine and promethazine, the two commonly used SMS drugs at NASA for both space and reduced gravity environment medical operations, appears to be a logical alternative to current treatment modalities for SMS. The advantages are expected to be fast absorption, reliable and high bioavailability, and probably reduced neurocognitive side effects owing to dose reduction. Results from clinical trials with intranasal scopolamine gel formulation and pre-clinical testing of a prototype microcapsule intranasal gel dosage form of PMZ (INPMZ) will be discussed. These formulations are expected to offer a dependable and effective noninvasive treatment option for SMS.

Putcha, Lakshmi↗
NASA NTRS2007

Pharmacotherapeutics of Intranasal Scopolamine: FDA Regulations and Procedures for Clinical Applications

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during the early flight days of a space mission. Bioavailability of oral (PO) SMS medications is often low and highly variable; additionally, physiological changes in a microgravity environment exacerbate variability and decrease bioavailability. These factors prompted NASA to develop an intranasal dosage form of scopolamine (INSCOP) suitable for the treatment of SMS. However, to assure safety and efficacy of treatment in space, NASA physicians prescribe commercially available pharmaceutical products only. Development of a pharmaceutical preparation for clinical use must follow distinct clinical phases of testing, phase I through IV to be exact, before it can be approved by the FDA for approval for clinical use. After a physician sponsored Investigative New Drug (IND) application was approved by the FDA, a phase I clinical trial of INSCOP formulation was completed in normal human subjects and results published. The current project includes three phase II clinical protocols for the assessment of pharmacokinetics and pharmacodynamics (PK/PD), efficacy, and safety of INSCOP. Three clinical protocols that were submitted to FDA to accomplish the project objectives: 1) 002-A, a FDA Phase II dose ranging study with four dose levels between 0.1 and 0.4 mg in 12 subjects to assess PK/PD, 2) 002-B, a phase II clinical efficacy study in eighteen healthy subjects to compare efficacy of 0.2 (low dose) and 0.4 mg (high dose) INSCOP for prophylactic treatment of motion-induces (off-axis vertical rotation) symptoms, and (3) 002-C, a phase II clinical study with twelve subjects to determine bioavailability and pharmacodynamics of two doses (0.2 and 0.4 mg) of INSCOP in simulated microgravity, antiorthostatic bedrest. All regulatory procedures were competed that include certification for Good laboratory Procedures by Theradex , clinical documentation, personnel training, selection of clinical research operations contractor, data capturing and management, and annual reporting of results to FDA were successfully completed. Protocol 002-A was completed and sample and data analysis is currently in progress. Protocol 002-B is currently in progress at Dartmouth Hitchcock Medical Center and Protocol 002-C has been submitted to the FDA and will be implemented at the same contractor site as 002-A. An annual report was filed as required by FDA on the results of Protocol 002-A. Once all the three Phase II protocols are completed, a New Drug Administration application will be filed with FDA for Phase III clinical assessment and approval for marketing of the formulation. A commercial vendor will be identified for this phase. This is critical for making this available for treatment of SMS in astronauts and military personnel on duty. Once approved by FDA, INSCOP can be also used by civilian population for motion sickness associated with recreational travel and other ailments that require treatment with anticholinergic drugs.

Das, H.↗
NASA NTRS2007

Effects of Hind Limb Unloading on Pharmacokinetics of Procainamide in Mice

The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in space. It is prudent to expect that low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration. Among the medications of special interest are the cardiovascular drugs, especially the antiarrhythmic agents. In this study we used hind limb unloaded (HLU) mice as a model to investigate possible changes in the PK of a common antiarrhythmic drug procainamide (PA). Prior to drug administration the experimental animals were tail suspended for 24 hours and the control animals were kept free. PA (150-250 mg per kg) was given orally by a gavage procedure. After that the experimental mice were kept suspended for additional 1, 2, 3 and 6 hours. At these time points the serum concentration of PA and N-acetyl-procainamide (NAPA), an active metabolite which is formed by N-acetyltransferase in the liver, were measured by the fluorescence polarization immunoassay (FPIA) on the AxSYM autoanalyzer (Abbott Laboratories, Abbott Park, IL). The serum level of PA in HLU mice at 1 hour after administration was almost 40% lower than in controls. At 2-3 hours the difference still maintained, however, it was not statistically significant; at 6 hours no difference was detected. The level of NAPA in HLU mice was slightly lower at 1 and 2 hours but the difference did not reach statistical significance. The estimated PA half-life time in HLU mice was almost 55% longer than in control animals. These results confirm that hind limb unloading and related hemodynamic changes significantly alter the PK of PA. The effects are most likely primarily associated with a decrease in the drug absorption, especially within the first two hours after administration. At the same time prolongation of the PA half-life time in the HLU mice points towards slower drug elimination from the circulation.

Risin, Semyon A.↗
NASA NTRS2007

Aerospace Toxicology and Microbiology

Toxicology dates to the very earliest history of humanity with various poisons and venom being recognized as a method of hunting or waging war with the earliest documentation in the Evers papyrus (circa 1500 BCE). The Greeks identified specific poisons such as hemlock, a method of state execution, and the Greek word toxos (arrow) became the root of our modern science. The first scientific approach to the understanding of poisons and toxicology was the work during the late middle ages of Paracelsus. He formulated what were then revolutionary views that a specific toxic agent or "toxicon" caused specific dose-related effects. His principles have established the basis of modern pharmacology and toxicology. In 1700, Bernardo Ramazzini published the book De Morbis Artificum Diatriba (The Diseases of Workers) describing specific illnesses associated with certain labor, particularly metal workers exposed to mercury, lead, arsenic, and rock dust. Modern toxicology dates from development of the modern industrial chemical processes, the earliest involving an analytical method for arsenic by Marsh in 1836. Industrial organic chemicals were synthesized in the late 1800 s along with anesthetics and disinfectants. In 1908, Hamilton began the long study of occupational toxicology issues, and by WW I the scientific use of toxicants saw Haber creating war gases and defining time-dosage relationships that are used even today.

James, John T.↗
NASA NTRS2006

Europa Missions: Generic Materials Test Methodology

This viewgraph presentation discusses: radiation fundamentals, radiation damage, how radiation dosage is determined, fluence testing approaches, ionization damage exposure, displacement damage exposure, Europa energy "bins", rationale for group flux (energy bins), electron/proton group fluences, electron beam exposure testing, proton sources, reactor exposures, gamma exposures, preliminary exposure findings, testing caveats, preliminary conclusions, internal discharge, and electron dose depth curves.

radiation↗
NASA NTRS2007

Hand-Held Instrument Fights Acne, Tops Over-the-Counter Market

Tyrell Inc., a Houston-based medical technologies company, was able to access engineering support in redesigning a heating element for a hand-held acne-fighting device through SATOP, NASA's Space Alliance Technology Outreach Program. SATOP put Tyrell in contact with The Boeing Company, which assessed the design and made several major contributions. The product, named Zeno, is now the highest selling over-the-counter medical device for the treatment of acne, and in 2006, Zeno was named the "SATOP Texas, Success Story of the Year." Zeno employs proprietary ClearPoint technology to provide relief of mild to moderate inflammatory acne by delivering a precisely controlled low-level dosage of heat to the blemish, causing the bacteria at the root of more than 90 percent of acne to self-destruct. Within its first year on the market, Zeno was cited by various publications for several awards, including Allure's 2005 "Best of Beauty," Marie Claire's "10 Best Gadgets for Girls," and Popular Science's 2005 "Best of What's New." A variation of the Zeno for use in treating herpetic lesions such as cold sores, by killing the virus that causes them, is currently undergoing FDA trials.

Source record↗
NASA NTRS1986

Apparatus for detecting at least one predetermined condition and providing an informational signal in response thereto in a medication infusion system

A medication infusion system provides redundant safety and includes condition detecting and informational alarm signal generating apparatus for indicating if (1) a fluid leak occurs in different portions of the system; (2) a programmable input from a patient or physician would result in exceeding a safe dosage limit; (3) the reservoir containing medication has been filled; (4) the intended medication pumping does not correlate with the pumping actually effected; (5) battery voltage is low; (6) the medication reserve is low; and (7) the system has been switched off. The apparatus may provide subcutaneous electrical, thermal, or audible stimulation to the patient and also provides a signal which a physician may monitor. The stimulation may be coded to separately identify each above-listed deviation in nominal system performance. In addition, the number of medication requests are correlated with actual medication dispensing to assure proper operation. An identification scheme is provided which matches the patient with his or her corresponding medication.

Fischell, Robert E.↗
NASA NTRS2008

Pharmacokinetics of Acetaminophen in Hind Limbs Unloaded Mice: A Model System Simulating the Effects of Low Gravity on Astronauts in Space

The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in Space. Low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration in astronauts. Acquiring of such knowledge has inherent difficulties due to limited opportunities for experimenting in Space. One of the approaches is to use model systems that simulate some of the Space conditions on Earth. In this study we used hind limbs unloaded mice (HLU) to investigate the possible changes in PK of acetaminophen, a widely used analgesic with high probability of use by astronauts. The HLU is recognized as an appropriate model for simulating the effects of low gravity on hemodynamic parameters. Mice were tail suspended (n = 24) for 24-96 hours prior to introduction of acetaminophen (150 - 300 mg/kg). The drug (in aqueous solution containing 10% ethyl alcohol by volume) was given orally by a gavage procedure and after the administration of acetaminophen mice were additionally suspended for 30 min, 1 and 2 hours. Control mice (n = 24) received the same dose of acetaminophen and were kept freely all the time. Blood specimens were obtained either from retroorbital venous sinuses or from heart. Acetaminophen concentration was measured in plasma by the fluorescent polarization immunoassay and the AxSYM analyzer (Abbott Laboratories). In control mice peak acetaminophen concentration was achieved at 30 min. By 1 hour the concentration decreased to less than 50% of the peak level and at 2 hours the drug was almost undetectable in the serum. HLU for 24 hours significantly altered the acetaminophen pharmacokinetic: at 30 min the acetaminophen concentrations were significantly (both statistically and medically significant) lower than in control mice. The concentrations also reduced less significantly after 1 and 2 hours. At 2 hours approximately 20% of the drug still remained in the circulation. After 96 hrs of HLU the changes in acetaminophen PK were less prominent. These data indicate that short term HLU causes significant changes in acetaminophen PK most likely associated with HUL-related hemodynamic changes. However, after 96 hour these changes diminished. This suggests hemodynamic adaptation to the HUL conditions that possibly occurs also in real space conditions.

Peterson, Amanda↗
NASA NTRS2008

Stability of Formulations Contained in the Pharmaceutical Payload Aboard Space Missions

Efficacious pharmaceuticals with adequate shelf life are essential for successful space medical operations in support of space exploration missions. Physical and environmental factors unique to space missions such as vibration, G forces and ionizing radiation may adversely affect stability of pharmaceuticals intended for standard care of astronauts aboard space missions. Stable pharmaceuticals, therefore, are of paramount importance for assuring health and wellness of astronauts in space. Preliminary examination of stability of formulations from Shuttle and International Space Station (ISS) medical kits revealed that some of these medications showed physical and chemical degradation after flight raising concern of reduced therapeutic effectiveness with these medications in space. A research payload experiment was conducted with a select set of formulations stowed aboard a shuttle flight and on ISS. The payload consisted of four identical pharmaceutical kits containing 31 medications in different dosage forms that were transported to the International Space Station (ISS) aboard the Space Shuttle, STS 121. One of the four kits was stored on the shuttle and the other three were stored on the ISS for return to Earth at six months intervals on a pre-designated Shuttle flight for each kit; the shuttle kit was returned to Earth on the same flight. Standard stability indicating physical and chemical parameters were measured for all pharmaceuticals returned from the shuttle and from the first ISS increment payload along with ground-based matching controls. Results were compared between shuttle, ISS and ground controls. Evaluation of data from the three paradigms indicates that some of the formulations exhibited significant degradation in space compared to respective ground controls; a few formulations were unstable both on the ground and in space. An increase in the number of pharmaceuticals from ISS failing USP standards was noticed compared to those from the shuttle flight. A comprehensive evaluation of results is in progress.

Putcha, Lakshmi↗
NASA NTRS2009

Stability of Pharmaceuticals in Space

Stability testing is a tool used to access shelf life and effects of storage conditions for pharmaceutical formulations. Early research from the International Space Station (ISS) revealed that some medications may have degraded while in space. This potential loss of medication efficacy would be very dangerous to Crew health. The aim of this research project, Stability of Pharmacotherapeutic Compounds, is to study how the stability of pharmaceutical compounds is affected by environmental conditions in space. Four identical pharmaceutical payload kits containing medications in different dosage forms (liquid for injection, tablet, capsule, ointment and suppository) were transported to the ISS aboard a Space Shuttle. One of the four kits was stored on that Shuttle and the other three were stored on the ISS for return to Earth at various time intervals aboard a pre-designated Shuttle flight. The Pharmacotherapeutics laboratory used stability test as defined by the United States Pharmacopeia (USP), to access the degree of degradation to the Payload kit medications that may have occurred during space flight. Once these medications returned, the results of stability test performed on them were compared to those from the matching ground controls stored on Earth. Analyses of the results obtained from physical and chemical stability assessments on these payload medications will provide researchers additional tools to promote safe and efficacious medications for space exploration.

Nguyen, Y-Uyen↗
NASA NTRS2011

Space Weathering Impact on Solar System Surfaces and Planetary Mission Science

We often look "through a glass, darkly" at solar system bodies with tenuous atmospheres and direct surface exposure to the local space environment. Space weathering exposure acts via universal space-surface interaction processes to produce a thin patina of outer material covering, potentially obscuring endogenic surface materials of greatest interest for understanding origins and interior evolution. Examples of obscuring exogenic layers are radiation crusts on cometary nuclei and iogenic components of sulfate hydrate deposits on the trailing hemisphere of Europa. Weathering processes include plasma ion implantation into surfaces, sputtering by charged particles and solar ultraviolet photons, photolytic chemistry driven by UV irradiation, and radiolytic chemistry evolving from products of charged particle irradiation. Regolith structure from impacts, and underlying deeper structures from internal evolution, affects efficacy of certain surface interactions, e.g. sputtering as affected by porosity and surface irradiation dosage as partly attenuated by local topographic shielding. These processes should be regarded for mission science planning as potentially enabling, e.g. since direct surface sputtering, and resultant surface-bound exospheres, can provide in-situ samples of surface composition to ion and neutral mass spectrometers on orbital spacecraft. Sample return for highest sensitivity compOSitional and structural analyses at Earth will usually be precluded by limited range of surface sampling, long times for return, and high cost. Targeted advancements in instrument technology would be more cost efficient for local remote and in-situ sample analysis. More realistic laboratory simulations, e.g. for bulk samples, are needed to interpret mission science observations of weathered surfaces. Space environment effects on mission spacecraft and science operations must also be specified and mitigated from the hourly to monthly changes in space weather and from longer term (e.g., solar cycle) evolution of space climate. Capable instrumentation on planetary missions can and should be planned to contribute to knowledge of interplanetary space environments. Evolving data system technologies such as virtual observatories should be explored for more interdisciplinary application to the science of planetary surface, atmospheric, magnetospheric, and interplanetary interactions.

Cooper, John F.↗
NASA NTRS2011

Summer Research Paper

Certain populations such as chemotherapy patients and atomic bomb survivors have been exposed to ionizing radiation and experience tissue damage and cancer initiation and progression. One cancer that can be initiated from radiation is esophageal squamous cell carcinoma (ESCC), an epithelial cancer that has a survival rate as low as 20%. Researchers have found that when protein tyrosine kinase receptors (RPTK) activate oncogenes, they can create epithelial tumors and cause deadly cancers like ESCC. The RPTK family has one group, MET, that has only two receptors, MET and RON, present in the human body. MET s ligand is the hepatocyte growth factor (HGF) and RON's ligand is the macrophage-stimulating protein (MSP-1). Both HGF and MSP-1 have been shown to activate their receptors and are implicated in certain processes. Since radiation damages cells throughout the biological system, researchers are investigating whether or not HGF and MSP-1 protects or kills certain normal and cancerous cells by being part of cell recovery processes. One research group recently reviewed that the HGF-MET pathway has an important role in the embryonic development in the liver, migration of myogenic precursor cells, regulation of epithelial morphogenesis and growth, and regeneration and protection in tissues. In addition, since the RON receptor is more commonly expressed in cells of epithelial origin, and when activated is part of epithelial cell matrix invasion, dissociation, and migration processes, scientists conclude that RON might be one of the factors causing epithelial cancer initiation in the biological system. In order to examine HGF and MSP-1 s effect on cancer initiation and progression we used two immortalized esophageal epithelial cell lines. One is a normal human cell line (EPC2-hTERT), while the other had a p53 mutation at the 175th amino acid position (EPC2-hTERT-p53(sup R175H)). For this investigation, we used 0(control), 2, and 4 Gray doses of gamma (Cs137) radiation and selected various concentrations from 0-100 ng/mL of HGF and MSP-1 in our assays. Since the HGF and MSP-1 pathways have proliferative roles in epithelial cells, we conducted the MTT proliferation assay to see if either drug enhances or inhibits cell proliferation over time. Also, a MTT cytotoxicity assay was necessary to observe whether the drugs are protecting the cells from radiation and if a trend is occurring depending upon the amount of dose added. In addition, a wound healing assay was done since both drugs have been to known to promote cell motility. Since cell damage occurs when radiation is added, apoptosis and micronuclei assays are vital to see if HGF and MSP-1 increase or decrease cell death and damage in normal and pre-cancerous cells and by how much based on the radiation dosage. Overall, we used the MTT, wound healing, apoptosis and micronuclei assays to investigate the effects ofHGF and MSP-1 on irradiated esophageal epithelial cells.

Patel, Zarana↗