ABSTRACT
Brain natriuretic peptide (BNP) and N-terminal proBNP (NTproBNP) are well established in the clinic as biomarkers of heart failure. BNP hormone and the inactive NTproBNP are predominantly secreted in the ventricles of the heart in response to pressure overload and, consequently, are being investigated as markers of drug-induced cardiac hypertrophy in rat to support drug development. In the work presented here, an immunoaffinity-based LC/MS/MS assay was developed and validated to measure a selective tryptic fragment of NTproBNP in rat serum. The assay covers the range of 13-329 pg/mL of the tryptic fragment LLELIR, corresponding to 0.1-2.5 ng/mL intact NTproBNP. A stable isotope-labeled version of NTproBNP containing the tryptic fragment LLELI[13C615N1]R was prepared by solid-phase peptide synthesis and was used as an internal standard to minimize assay variability. Due to endogenous NTproBNP present in rat serum, human serum was used as the control matrix, and parallelism between rat and human serum was established by standard addition. Assay accuracy (% RE) and precision (% CV) were measured at three concentrations on each of 4 days and did not exceed 4.2 and 14.5%, respectively. Additionally, study data are presented from the application of this assay in which rats demonstrated a significant increase in NTproBNP serum concentration following administration of an agent known to induce cardiac hypertrophy. In this study, the relationship between serum NTproBNP and cardiac hypertrophy was corroborated by increases in heart weight and magnetic resonance imaging of the test subjects' left ventricle. To our knowledge, this represents the first reported assay for NTproBNP in preclinical species for the assessment of cardiac hypertrophy.
Subject(s)
Cardiomyopathy, Hypertrophic/chemically induced , Chromatography, Liquid/methods , Immunoprecipitation/methods , Mass Spectrometry/methods , Natriuretic Peptide, Brain/blood , Amino Acid Sequence , Animals , Biomarkers/blood , Cardiomyopathy, Hypertrophic/metabolism , Cardiomyopathy, Hypertrophic/pathology , Disease Models, Animal , Humans , Molecular Sequence Data , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
Issues about commercialization of space have been a growing concern in the past decade for the space community. This paper focuses on the work from a team of 51 students attending the Summer Session Program of the International Space University in Bremen, Germany. CASH 2021 (Commercial Access and Space Habitation) documents a plan that identifies commercial opportunities for space utilization that will extend human presence in space, and will chart the way forward for the next 20 years. The group selected four commercial sectors that show the most promise for the future: tourism, entertainment, space system service, assembly and debris removal, and research and development/production. The content of this document presents the results of their research. Historical activities in each of the commercial sectors are reviewed along with the current market situation. To provide a coherent background for future commercialization possibilities a scenario has been developed. This scenario includes a postulated upon ideal future and includes social, political and economic factors that may affect the space industry over the timeline of the study. The study also presents a roadmap, within the limited optimistic scenario developed, for the successful commercialization of space leading to future human presence in space. A broad range of commercially viable opportunities, not only within the current limits of the International Space Station, but also among the many new developments that are expected by 2021 are discussed.
