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  • Life Sciences (General); Aerospace Medicine  (3)
  • INSTRUMENTATION AND PHOTOGRAPHY  (2)
  • Key words Troglitazone  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 54 (1998), S. 567-571 
    ISSN: 1432-1041
    Keywords: Key words Troglitazone ; Hepatic insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Troglitazone is an agonist of the peroxisome proliferator-activated receptor-γ (PPAR-γ), which has been shown to improve the metabolic control of type 2 diabetes. Troglitazone undergoes hepatic metabolism to an inactive sulphate conjugate and an oxidative quinone metabolite with minor activity. The objective of this study was to compare the pharmacokinetics of troglitazone in patients with hepatic insufficiency and normal subjects. Methods: Three groups of eight subjects with normal liver function and moderate or severe hepatic impairment (Pugh-Child classification) completed this open study. Subjects received a single 400-mg dose of troglitazone 30 min after breakfast. Plasma concentrations of troglitazone and its metabolites were measured and standard pharmacokinetic parameters derived. Results: A 46% increase in area under the plasma concentration-time curve (AUClast) was observed for troglitazone, together with a 154% increase for the quinone metabolite in the patients with moderate hepatic impairment compared with normal subjects, but these did not reach statistical significance. Corresponding increases of 18% and 53% in the severe group also failed to reach statistical significance. For the sulphate conjugate, the AUClast values for both moderate and severe hepatic impairment were in the order of fourfold higher than those in the normal group. There were reductions in the maximum observed plasma concentration (Cmax) of troglitazone to 61% of the normal group in the severe group for troglitazone, and twofold increases in sulphate metabolite Cmax in the moderate and severe groups. There was an approximately threefold increase in the half-life of the sulphate conjugate in subjects with both moderate and severe impairment of liver function compared with normal individuals. First times to maximum concentrations of troglitazone, its sulphate conjugate and the quinone metabolite were significantly longer in all severely impaired subjects compared with those with normal hepatic function, although the range was wide in all cases. Plasma protein binding was high in all subjects measured (mean unbound fraction range 0.7–5.1%), but there were insufficient samples to compare across groups. Conclusion: The formation of metabolites of troglitazone following a single dose is not impaired in the presence of reduced liver function although the capacity to eliminate the metabolites is altered. The clinical significance of the effect of liver disease on the conjugates is not clear.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 55 (1999), S. 101-104 
    ISSN: 1432-1041
    Keywords: Key words Troglitazone ; Erythropoietic ; parameters ; Plasma volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Troglitazone is a new anti-diabetic agent for the treatment of type 2 diabetes. In placebo-controlled trials troglitazone improves glycaemic control, reduces hyperinsulinaemia and has beneficial effects on blood lipids. However, minor, reversible reductions in erythrocyte count, haemoglobin and haematocrit with no associated clinical symptoms have been observed in some troglitazone-treated patients. The primary objective of the present study was to determine if these changes could be explained by a decrease in red cell mass or change in plasma volume. Methods: Twenty-four healthy males were randomized in a double-blind manner to troglitazone (200 or 600 mg per day) or placebo for 6 weeks. Blood samples for the measurement of red cell mass and plasma volume were obtained in the 2 weeks prior to treatment and after 6 weeks of treatment. Reticulocyte and erythrocyte counts, haemoglobin and haematocrit were also measured. Results: At the end of the treatment period there were no statistically significant changes in red cell mass. Similarly there were no changes in reticulocyte count, erythropoietin or soluble transferrin receptors. These data indicate that troglitazone does not affect erythropoiesis. In addition, troglitazone was not associated with increased red blood cell destruction or haemolysis. There was a trend towards increased plasma volume in the troglitazone groups: increases of 2.5 ml · kg−1 (5.7% increase) in the troglitazone 200 mg group and 3.4 ml · kg−1 (7.8% increase) in the troglitazone 600 mg group were observed compared with placebo. Conclusion: These data suggest that dilutional effects related to a modest increase in plasma volume may explain the haematological changes seen in other clinical trials with high doses of troglitazone, although this study has shown that the changes in plasma volume are not statistically significant.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2011-08-16
    Description: We describe a simple and inexpensive means of enhancing repetitive signals obscured by noise with roughly equal amplitude. The signal and noise are displayed on an oscilloscope, and we perform a time average over many traces by time exposure photography. If the oscilloscope triggering is synchronous with the signal, the result is a significant suppression of the offending noise.
    Keywords: INSTRUMENTATION AND PHOTOGRAPHY
    Type: Review of Scientific Instruments; 43; May 1972
    Format: text
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  • 4
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    In:  Other Sources
    Publication Date: 2019-07-13
    Description: Gamma radiation spectrometer using standard scintillation detector and outputs gamma spectrum with spurious peaks and tails corrected
    Keywords: INSTRUMENTATION AND PHOTOGRAPHY
    Type: NUCLEAR SCIENCE SYMPOSIUM; Oct 31, 1967 - Nov 02, 1967; LOS ANGELES, CA|; INESE JOURNAL OF PHY
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  • 5
    Publication Date: 2019-07-19
    Description: Enhanced screening for the Visual Impairment/Intracranial Pressure (VIIP) syndrome has been implemented to better characterize the ocular and vision changes observed in some long-duration crewmembers. This includes implementation of in-flight ultrasound in 2010 and optical coherence tomography (OCT) in 2013. Potential risk factors for VIIP include cardiovascular health, diet, anatomical and genetic factors, and environmental conditions. Carbon dioxide (CO2), a potent vasodilator, is chronically elevated on the International Space Station (ISS) relative to ambient levels on Earth, and is a plausible risk factor for VIIP. In an effort to understand the possible associations between CO2 and VIIP, this study explores the relationship of ambient CO2 levels on ISS compared to inflight ultrasound and OCT measures of the eye obtained from ISS crewmembers. CO2 measurements were aggregated from Operational Data Reduction Complex and Node 3 major constituent analyzers (MCAs) on ISS or from sensors located in the European Columbus module, as available. CO2 levels in the periods between each ultrasound and OCT session are summarized using timeseries metrics, including time-weighted means and variances. Partial least squares regression analyses are used to quantify the complex relationship between specific ultrasound and OCT measures and the CO2 metrics simulataneously. These analyses will enhance our understanding of the possible associations between CO2 levels and structural changes to the eye which will in turn inform future analysis of inflight VIIP data.
    Keywords: Life Sciences (General); Aerospace Medicine
    Type: JSC-CN-37739 , Human Research Program Investigators'' Workshop (2017 HRP IWS); Jan 23, 2017 - Jan 27, 2017; Galveston, TX; United States
    Format: application/pdf
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  • 6
    Publication Date: 2019-08-13
    Description: Research by NASA [1] established that significant risks for visual and ocular impairments associated with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. It is well established in physiology and pathology that a fundamental role of the microvasculature is to mediate fluid transfers and remodel actively in response to environmental, immune and other stresses. We therefore hypothesize that remodeling of retinal blood vessels necessarily occurs during accommodation of microgravity-induced fluid shifts prior to subsequent development of visual and ocular impairments. Potential contributions of retinal vascular remodeling to VIIP etiology are therefore being investigated by NASA's innovative VESsel GENeration Analysis (VESGEN) software for two studies: (1) U.S. crew members before and after ISS missions, and (2) head-down tilt in human subjects before and after 70 days of bed rest. We anticipate that results of the two studies will be complete by the Investigators Workshop (January 22, 2017). METHODS: For the 2013 NASA NRA award, we are concluding the analysis of 30 degree infrared (IR) Heidelberg Spectralis images of retinal blood vessels by VESGEN (patents pending), a mature, automated software developed as a translational and basic vascular research discovery tool, particularly for retinal vascular disease. Subjects of our retrospective study include eight ISS crew members monitored for routine occupational surveillance pre- and post-flight, who provided their study consents to NASAs Lifetime Surveillance of Astronaut Health (LSAH) in coordination with approval of the VESGEN retrospective study protocol by NASAs Institutional Review Board (IRB). The ophthalmic retinal images (average image resolution, approximately 5.6 microns per pixel) are blinded as to pre and post ISS status until the second portion of our study, when VESGEN results will be correlated with other ophthalmic and medical findings for the crew members. Due to image resolution challenges, a novel Matlab tool was developed for aligning pre and post images, and comparing (querying) the two images for differences in the morphology of small vessels. RESULTS: During the past year, LSAH approved the release of all astronaut retinal images to our study for VESGEN analysis. Substantial progress on the initial blinded portion of the study is in place. We anticipate that VESGEN analysis of the 32 Spectralis IR retinal images will be complete for presentation at the 2017 IWS meeting. CONCLUSIONS: Modified retinal vascular patterning may offer early-stage predictions of ocular changes resulting in decreased visual acuity for the VIIP syndrome. Novel insights provided by VESGEN into progressively pathological and blinding vascular remodeling in the human retina currently help to guide other NIH- and NASA-supported therapeutic studies of retinal disease and modeling of the VIIP risk. Results of our vascular investigation of the retinas of astronauts pre- and post-flight may help advance the understanding of both healthy and pathological adaptations to fluid shifts in microgravity associated with the VIIP syndrome. Preliminary results indicate that imaging of higher resolution, such as the new OCT angiography (OCT-A) technology, will be required to determine conclusively the role of the smaller retinal and choroidal vessels in VIIP etiology.
    Keywords: Life Sciences (General); Aerospace Medicine
    Type: ARC-E-DAA-TN38902 , 2017 Human Research Program Investigator''s Workshop; Jan 23, 2017 - Jan 26, 2017; Galveston, TX; United States
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  • 7
    Publication Date: 2019-08-13
    Description: Carbon dioxide (CO2) levels on ISS have typically averaged 2.3 to 5.3mm Hg, with large fluctuations occurring over periods of hours and days. CO2 has effects on cerebral vascular tone, resulting in vasodilation and alteration of cerebral blood flow(CBF). Increased CBF leads to elevated intracranial pressure(ICP), which is a factor leading to visual disturbance, headaches, and other central nervous system symptoms. Ultrasound of the optic nerve provides a surrogate measurement of ICP. Inflight ultrasounds were implemented as an enhanced screening tool for the Visual Impairment/Intracranial Pressure (VIIP) Syndrome. This analysis examines the relationships between ambient CO2 levels on ISS and ultrasound measures of the eye in an effort to understand how CO2 may be associated with VIIP and to inform future analysis of inflight VIIP data. Results as shown in Figure2, there was a large timeframe where CO2 readings were removed due to sensor fault errors(see Limitations), from June 2011 to January 2012. After extensive cleaning of the CO2 data, metrics for all of the data were calculated (Table2). Preliminary analyses showed possible associations between variability measures of CO2 and AP diameter (Figure3),and average CO2 exposure and ONSD(Figure4). Adjustments for multiple comparisons were not made due to the exploratory nature of the analysis.
    Keywords: Life Sciences (General); Aerospace Medicine
    Type: JSC-CN-35418 , 2016 Human Research Program Investigators'' Workshop; Aug 08, 2016 - Aug 11, 2016; Galveston, TX; United States
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