Inflight Pharmacokinetic and Pharmacodynamic Responses to Medications Commonly Used in Spaceflight

Researchers do not know if medications act the same in the spaceflight environment as they do on Earth. Aspects of the spaceflight environment (low gravity, radiation exposure, closed environment, stress) have been shown to alter human physiology. Some of these physiological changes could be expected to alter either pharmacokinetics (PK, how the body absorbs, distributes, metabolizes and excretes administered medications) or pharmacodynamics (PD, receptors or signaling systems that are the targets of medication action). Anecdotal data has suggested that, at least for certain medications or indications, inflight medication efficacy is poor. In order to prepare for exploration missions where speedy evacuation to Earth may not be a possibility, the likelihood of unexpected medication action must be determined

Why do young adults in the United States have such low rates of organ donation registration?

The demand for transplantable organs has outpaced the supply. Thus, 20 Americans die every day while waiting for an organ. Although most adults support organ donation, 42% are not registered. The rate is even lower among young adults who are not enrolled in/never graduated from college. The aim of this study was to use the Integrated Behavior Model (IBM) to identify factors that predicted organ donation registration among a racially diverse sample of non-student young adults. The study was observational and cross-sectional. Proportional allocation was used to identify a racially diverse sample of 550 non-student, young adults from ten states in the U.S. with the lowest registration rates. A valid and reliable survey was designed, pilot-tested, and administered. A total of 407 young adults completed the survey (74%). Only 19% were registered donors. Caucasians were more likely to be registered donors than racial minorities, χ 2 (3, N = 407) = 15.19, p = 0.002. Those with more positive direct attitudes toward registration were 1.5 times more likely to be registered than those who had negative direct attitudes. Among non-registrants, indirect descriptive norm and direct attitude were statistically significant predictors of behavioral intention. Moreover, those who knew someone who donated an organ and knew someone who needed a transplant were nearly three times more likely to intend to register in the next year. The IBM proved useful in elucidating factors that predicted intention to register among non-student young adults. The IBM should be used by those who desire to increase registration rates

Prediction of thioguanine-induced cytotoxicity by dual-parameter flow cytometric analysis

A method is presented for the quantitative analysis of delayed cytokinetic effects resulting from the treatment of L1210 cells with 6-thioguanine (TG). By using dual-parameter (DNA/protein) flow cytometry, we could observe the accumulation of late S/G2/M cells with abnormally high green fluorescence (i.e., protein content), indicative of unbalanced growth. The use of mitotic cells from a pseudotetraploid line (HT29) as external markers for both red and green fluorescence facilitated highly reproducible measurement of the mean green fluorescence (GFL mean ) of the arrested late S/G2/M population. We found that the dose dependence of the observed GFL mean values followed the same unusual biphasic pattern as did cytotoxicity in this cell line, indicating that this parameter might be a suitable means of predicting TG-induced toxicity in vivo. We propose that the low background expected for this kind of measurement would make it particularly appropriate for the analysis of clinical specimens (e.g., mononuclear bone marrow cells) from leukemic patients receiving thiopurines, to monitor (and, hopefully, predict) their response to treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46920/1/280_2004_Article_BF00304760.pd

The Future of Personalized Medicine in Space: From Observations to Countermeasures

The aim of personalized medicine is to detach from a “one-size fits all approach” and improve patient health by individualization to achieve the best outcomes in disease prevention, diagnosis and treatment. Technological advances in sequencing, improved knowledge of omics, integration with bioinformatics and new in vitro testing formats, have enabled personalized medicine to become a reality. Individual variation in response to environmental factors can affect susceptibility to disease and response to treatments. Space travel exposes humans to environmental stressors that lead to physiological adaptations, from altered cell behavior to abnormal tissue responses, including immune system impairment. In the context of human space flight research, human health studies have shown a significant inter-individual variability in response to space analogue conditions. A substantial degree of variability has been noticed in response to medications (from both an efficacy and toxicity perspective) as well as in susceptibility to damage from radiation exposure and in physiological changes such as loss of bone mineral density and muscle mass in response to deconditioning. At present, personalized medicine for astronauts is limited. With the advent of longer duration missions beyond low Earth orbit, it is imperative that space agencies adopt a personalized strategy for each astronaut, starting from pre-emptive personalized pre-clinical approaches through to individualized countermeasures to minimize harmful physiological changes and find targeted treatment for disease. Advances in space medicine can also be translated to terrestrial applications, and vice versa. This review places the astronaut at the center of personalized medicine, will appraise existing evidence and future preclinical tools as well as clinical, ethical and legal considerations for future space travel

The cys-loop ligand-gated ion channel gene superfamily of the nematode, Caenorhabditis elegans

The nematode, Caenorhabditis elegans, possesses the most extensive known superfamily of cys-loop ligand-gated ion channels (cys-loop LGICs) consisting of 102 subunit-encoding genes. Less than half of these genes have been functionally characterised which include cation-permeable channels gated by acetylcholine (ACh) and γ-aminobutyric acid (GABA) as well as anion-selective channels gated by ACh, GABA, glutamate and serotonin. Following the guidelines set for genetic nomenclature for C. elegans, we have designated unnamed subunits as lgc genes (ligand-gated ion channels of the cys-loop superfamily). Phylogenetic analysis shows that several of these lgc subunits form distinct groups which may represent novel cys-loop LGIC subtypes

Why Do Young Adults in the United States Have Such Low Rates of Organ Donation Registration?

The demand for transplantable organs has outpaced the supply. Thus, 20 Americans die every day while waiting for an organ. Although most adults support organ donation, 42% are not registered. The rate is even lower among young adults who are not enrolled in/never graduated from college. The aim of this study was to use the Integrated Behavior Model (IBM) to identify factors that predicted organ donation registration among a racially diverse sample of non-student young adults. The study was observational and cross-sectional. Proportional allocation was used to identify a racially diverse sample of 550 non-student, young adults from ten states in the U.S. with the lowest registration rates. A valid and reliable survey was designed, pilot-tested, and administered. A total of 407 young adults completed the survey (74%). Only 19% were registered donors. Caucasians were more likely to be registered donors than racial minorities, χ² (3, N = 407) = 15.19, p = 0.002. Those with more positive direct attitudes toward registration were 1.5 times more likely to be registered than those who had negative direct attitudes. Among non-registrants, indirect descriptive norm and direct attitude were statistically significant predictors of behavioral intention. Moreover, those who knew someone who donated an organ and knew someone who needed a transplant were nearly three times more likely to intend to register in the next year. The IBM proved useful in elucidating factors that predicted intention to register among non-student young adults. The IBM should be used by those who desire to increase registration rates