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Search Results: 1 - 10 of 144805 matches for " Reginald F. Frye "
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Current clinical evidence on pioglitazone pharmacogenomics
Marina Kawaguchi-Suzuki,Reginald F. Frye
Frontiers in Pharmacology , 2013, DOI: 10.3389/fphar.2013.00147
Abstract: Pioglitazone is the most widely used thiazolidinedione and acts as an insulin-sensitizer through activation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ). Pioglitazone is approved for use in the management of type 2 diabetes mellitus (T2DM), but its use in other therapeutic areas is increasing due to pleiotropic effects. In this hypothesis article, the current clinical evidence on pioglitazone pharmacogenomics is summarized and related to variability in pioglitazone response. How genetic variation in the human genome affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined. For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks of fracture or edema, and the increase in body mass index in response to pioglitazone based on genotype were examined. The genes CYP2C8 and PPARG are the most extensively studied to date and selected polymorphisms contribute to respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We hypothesized that genetic variation in pioglitazone pathway genes contributes meaningfully to the clinically observed variability in drug response. To test the hypothesis that genetic variation in PPARG associates with variability in pioglitazone response, we conducted a meta-analysis to synthesize the currently available data on the PPARG p.Pro12Ala polymorphism. The results showed that PPARG 12Ala carriers had a more favorable change in fasting blood glucose from baseline as compared to patients with the wild-type Pro12Pro genotype (p = 0.018). Unfortunately, findings for many other genes lack replication in independent cohorts to confirm association; further studies are needed. Also, the biological functionality of these polymorphisms is unknown. Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy and better optimize therapy in patients with T2DM or other conditions for which pioglitazone is being used.
Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment
William R. Wikoff, Reginald F. Frye, Hongjie Zhu, Yan Gong, Stephen Boyle, Erik Churchill, Rhonda M. Cooper-Dehoff, Amber L. Beitelshees, Arlene B. Chapman, Oliver Fiehn, Julie A. Johnson, Rima Kaddurah-Daouk, Pharmacometabolomics Research Network
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057639
Abstract: Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are poorly understood. In this study we use metabolomics, a global biochemical approach to investigate biochemical changes induced by the beta-adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma from individuals treated with atenolol was collected at baseline (untreated) and after a 9 week treatment period and analyzed using a GC-TOF metabolomics platform. The metabolomic signature of atenolol exposure included saturated (palmitic), monounsaturated (oleic, palmitoleic) and polyunsaturated (arachidonic, linoleic) free fatty acids, which decreased in Caucasians after treatment but were not different in African Americans (p<0.0005, q<0.03). Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in Caucasians by 33% (p<0.0001, q<0.0001) but was unchanged in African Americans. The contribution of genetic variation in genes that encode lipases to the racial differences in atenolol-induced changes in fatty acids was examined. SNP rs9652472 in LIPC was found to be associated with the change in oleic acid in Caucasians (p<0.0005) but not African Americans, whereas the PLA2G4C SNP rs7250148 associated with oleic acid change in African Americans (p<0.0001) but not Caucasians. Together, these data indicate that atenolol-induced changes in the metabolome are dependent on race and genotype. This study represents a first step of a pharmacometabolomic approach to phenotype patients with hypertension and gain mechanistic insights into racial variability in changes that occur with atenolol treatment, which may influence response to the drug.
Remote Sensing of Selected Winter and Spring Host Plants of Tarnished Plant Bug (Heteroptera: Miridae) and Herbicide Use Strategies as a Management Tactic  [PDF]
Donald L. Sudbrink, Steven J. Thomson, Reginald S. Fletcher, F. Aubrey Harris, Patrick J. English, James T. Robbins
American Journal of Plant Sciences (AJPS) , 2015, DOI: 10.4236/ajps.2015.68131
Abstract: Remote sensing was used in a series of experiments over a three-year period to obtain spectral reflectance data for studying differences in vegetation indices between grasses, broadleaf plants, and grass/broadleaf plant mixtures. Selected non-crop winter and spring host plants of tarnished plant bug, Lygus lineolaris, were planted in field-plot experiments. Multispectral reflectance data were aerially acquired with both a Real-Time Digital Airborne Camera System (RDACS) sensor and Geospatial Systems (Duncan Tech) MS-2100 multispectral camera. The following six vegetation indices of spectral reflectance were evaluated in this study: normalized difference vegetation index, ratio vegetation index, green normalized difference vegetation index, green vegetation index, green ratio vegetation index, and Ashburn vegetation index. Vegetation indices calculated with imagery data for the grasses and broadleaves differed significantly; there appeared to be more discriminating differences between vegetation indices for grasses and broadleaf plants when the indices were based on a combination of green and near infrared or green and red spectral bands than when the indices were based on red and near infrared spectral bands. Insect data from these studies confirm that tarnished plant bug prefers broadleaf host plants, but can use Italian ryegrass for food and reproduction. The narrow temporal window of host suitability for Italian ryegrass may limit its significance. Herbicide destruction of broadleaf host plants in early spring prevented the tarnished plant bug population increases that occurred in untreated plots. Findings of this study would be useful in site-specific vegetation management decisions in programs such as the prototypical area-wide tarnished plant bug management experiment conducted in the Delta region of Mississippi.
Photochemical Rearrangement of a 6-Azasteroid Oxaziridine to a Novel 17β-Carbomethoxy-A-homo-B-seco-6-aza-3, 5-androstanedione
Frye, Stephen;
Journal of the Mexican Chemical Society , 2009,
Abstract: 4- and 6-azasteroids have been shown to be potent inhibitors of human 5α,-reductase and certain azasteroids have shown significant clinical benefit in the treatment of androgen-related disorders. in an effort to expand the diversity of steroidal heterocycles synthetically accessible for structure-activity relationship exploration, a novel reaction sequence was applied to the preparation of the 6-aza-steroid framework. to this end, photolysis of the oxaziridine derived from 17β-carbomethoxy-3β-triisopropylsilyloxy-6-azaandrost-5-ene (1) yielded a novel 7, 5-steroidal ring system that was evaluated for inhibition of human type 1 and 2 5α-reductase.
Photochemical Rearrangement of a 6-Azasteroid Oxaziridine to a Novel 17B-Carbomethoxy-A-homo-B-seco-6-aza-3, 5-androstanedione
Stephen Frye
Revista de la Sociedad Química de México , 2009,
Abstract: Los 4- y 6-azaesteroides mostraron ser potentes inhibidores de la 5a-reductasa humana, y otros azaesteroides fueron eficientes en el tratamiento clínico de desórdenes relacionados a los andrógenos. En un esfuerzo para ampliar la diversidad de heterociclos esteroidales que se obtengan sintéticamente, con el fin de explorar sus relaciones de estructura-actividad, se empleó una novedosa secuencia de reacciones para la preparación de 6-azaesteroides. De esta forma, la fotólisis de la oxaziridina derivada del 17B-carbometoxi-3B-triisopropilsililoxi- 6-azaandrost-5-eno (1) proporcionó un nuevo sistema esteroidal de anillos fusionados de 5 y 7 miembros, el cual se evaluó en la inhibición de la 5 -reductasa humana de tipos 1 y 2.
Non-stationary drivers of polar sea ice area  [PDF]
Reginald R. Muskett
Natural Science (NS) , 2011, DOI: 10.4236/ns.2011.35047
Abstract: From 2002 through 2008 the secular rate of de-creasing sea ice area in the northern hemisphere accelerated by a factor of 18, whereas the secular rate of increasing sea ice area in the southern hemisphere accelerated by a factor of 16, relative to the rates from 1978 through 2007. These were derived from the daily sea ice area retrieved from the Scanning Multi-channel Microwave Radiometer – Special Sensor Microwave/Imager and the Advanced Microwave Scan- ning Radiometer for the Earth Observation Sys- tem. The “annual” cycle of northern and southern sea ice areas, the number of days between maxima and minima is 372.4, on average, a frequency modulation, with a recurrence interval of 61.7 years. Significant spectral power occurs at the quasi-4-day through 120-day frequencies. The frequency content and modulation of the daily time series’ are consistent inter-monthly to inter-seasonal frequencies of solar irradiance, atmospheric-oceanic Rossby waves, length-of- day, and polar motion. This suggests conserva-tion of angular momentum of the atmosphere – sea-ice – ocean system. The near 60-year modu- lation and analysis of the detrended daily time series of the Arctic and Antarctic sea ice areas suggest the accelerations shown by the secular trends are relatively short-lived and reversible within an interval of one-quarter (15-years) to one-half (30-years) of the modulation period.
Multi-Satellite and Sensor Derived Trends and Variation of Snow Water Equivalent on the High-Latitudes of the Northern Hemisphere  [PDF]
Reginald R. Muskett
International Journal of Geosciences (IJG) , 2012, DOI: 10.4236/ijg.2012.31001
Abstract: Utilizing more than 30 years of satellite-microwave sensor derived snow water equivalent data on the high-latitudes of the northern hemisphere we investigate regional trends and variations relative to elevation. On the low-elevation tundra regions encircling the Arctic we find high statistically significant trends of snow water equivalent. Across the high Arctic Siberia and Far East Russia through North America and northern Greenland we find increasing trends of snow water equivalent with local region variations in strength. Yet across the high Arctic of western Russia through Norway we find decreasing trends of snow water equivalent of varying strength. Power density spectra identify significant power at quasi-biennial and associated lunar nodal cycles. These cycles of the upper atmosphere circulation, ENSO and ocean circulation perturbations from tides forms the causative linkage between increasing snow water equivalent on low-elevation tundra landscapes and decreasing coastal sea ice cover as part of the Arctic system energy and mass cycles.
Remote Sensing, Model-Derived and Ground Measurements of Snow Water Equivalent and Snow Density in Alaska  [PDF]
Reginald R. Muskett
International Journal of Geosciences (IJG) , 2012, DOI: 10.4236/ijg.2012.35114
Abstract: Snow water equivalent (SWE) is important for investigations of annual to decadal-scale changes in Arctic environment and energy-water cycles. Passive microwave satellite-based retrieval algorithm estimates of SWE now span more than three decades. SWE retrievals by the Advanced Microwave Scanning Radiometer for the Earth Observation System (AMSR-E) onboard the NASA-Aqua satellite ended at October 2011. A critical parameter in the AMSR-E retrieval algorithm is snow density assumed from surveys in Canada and Russia from 1940s-1990s. We compare ground SWE measurements in Alaska to those of AMSR-E, European Space Agency GlobSnow, and GIPL model. AMSR-E SWE underperforms (is less than on average) ground SWE measurements in Alaska through 2011. Snow density measurements along the Alaska permafrost transect in April 2009 and 2010 show a significant latitude-gradient in snow density increasing to the Arctic coast at Prudhoe Bay. Large differences are apparent in comparisons of our measured mean snow densities on a same snow cover class basis March-April 2009-2011 Alaska to those measured in Alaska winter 1989-1992 and Canadian March-April 1961-1990. Snow density like other properties of snow is an indicator of climate and a non-stationary variable of SWE.
MODIS-Derived Arctic Land-Surface Temperature Trends  [PDF]
Reginald R. Muskett
Atmospheric and Climate Sciences (ACS) , 2013, DOI: 10.4236/acs.2013.31008

Across the Arctic changes in active layer, melting of glaciers and ground ice, thawing of permafrost and sequestration changes of carbon storage are driven in part by variations of land surface heat absorption, conduction and re-radiation relative to solar irradiance. We investigate Arctic land-surface temperature changes and regional variations derived by the MODIS sensors on NASA Aqua and Terra from March 2000 through July 2012. Over this decadal period we detect increase in the number of days with daytime land-surface temperature above 0. There are indications of increasing trends of land-surface temperature change. Regional variations of the changes in land-surface temperature likely arise due to surface material types and topography relative to the daytime variation of solar irradiance.

GOSAT CH4 and CO2, MODIS Evapotranspiration on the Northern Hemisphere June and July 2009, 2010 and 2011  [PDF]
Reginald R. Muskett
Atmospheric and Climate Sciences (ACS) , 2013, DOI: 10.4236/acs.2013.32019

The Greenhouse gases Observing Satellite (GOSAT) affords an ability to assess and monitor CH4 and CO2 near-surface atmospheric concentrations globally on monthly scales pertaining to biogeochemical cycles and anthropogenic emissions. In addition to GOSAT our investigation incorporates global-monthly estimates of evapotranspiration (ET) from the Moderate Resolution Spectroradiometer (MODIS) and fire/wildfire locations for correspondence and comparison. We restrict the investigation to the months of June and July in years 2009, 2010 and 2011. After processing and assessment on the northern hemisphere we focus on two regions in Eurasia for interrogation: 40? to 80?E by 50? to 58?N and 100? to 140?E by 50? to 58?N. The regions allow for contrasting regional settings, an agricultural-industrial-urban west-region to a boreal-steppe discontinuous permafrost zone palsa and thaw lake east-region. Joint probability density functions allow us to identify significant modes, the highest probable values of background levels of CH4 and CO2 to ET and develop regressions for correlated relationships. We found that background levels of CH4, CO2 and ET were not affected by the wildfires of 2010. Regressions indicate significant inverse relationships of CH4 and CO2 to ET in the west-region and no significant relationships in the east-region. The east-region shows significantly higher background levels of CH4, CO2 and ET owing to the heterogeneity of ecosystems, hydrology, physical processes and terrain in the discontinuous permafrost zone of the central Siberian Plateau.

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