Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart

Background: Carbonic anhydrase enzymes (CA) catalyze the reversible hydration of carbon dioxide to bicarbonate in mammalian cells. Trans-membrane transport of CA-produced bicarbonate contributes significantly to cellular pH regulation. A body of evidence implicates pH-regulatory processes in the hypertrophic growth pathway characteristic of hearts as they fail. In particular, Na+ /H+ exchange (NHE) activation is pro-hypertrophic and CA activity activates NHE. Recently Cardrase (6-ethoxyzolamide), a CA inhibitor, was found to prevent and revert agonist-stimulated cardiac hypertrophy (CH) in cultured cardiomyocytes. Our goal thus was to determine whether hypertrophied human hearts have altered expression of CA isoforms. Methods: We measured CA expression in hypertrophied human hearts to begin to examine the role of carbonic anhydrase in progression of human heart failure. Ventricular biopsies were obtained from patients undergoing cardiac surgery (CS, n = 14), or heart transplantation (HT, n = 13). CS patients presented mild/moderate concentric left ventricular hypertrophy and normal right ventricles, with preserved ventricular function; ejection fractions were ~60%. Conversely, HT patients with failing hearts presented CH or ventricular dilation accompanied by ventricular dysfunction and EF values of 20%. Non-hypertrophic, non-dilated ventricular samples served as controls. Results: Expression of atrial and brain natriuretic peptide (ANP and BNP) were markers of CH. Hypertrophic ventricles presented increased expression of CAII, CAIV, ANP, and BNP, mRNA levels, which increased in failing hearts, measured by quantitative real-time PCR. CAII, CAIV, and ANP protein expression also increased approximately two-fold in hypertrophic/dilated ventricles. Conclusions: These results, combined with in vitro data that CA inhibition prevents and reverts CH, suggest that increased carbonic anhydrase expression is a prognostic molecular marker of cardiac hypertrophy.Fil: Alvarez, Bernardo. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Quon, Anita L.. University Of Alberta. Faculty Of Medicine And Oral Health Sciences; CanadáFil: Mullen, John. University of Alberta; CanadáFil: Casey, Joseph R.. University Of Alberta. Faculty Of Medicine And Oral Health Sciences; Canad

Initial Integration of Noise Prediction Tools for Acoustic Scattering Effects

This effort provides an initial glimpse at NASA capabilities available in predicting the scattering of fan noise from a non-conventional aircraft configuration. The Aircraft NOise Prediction Program, Fast Scattering Code, and the Rotorcraft Noise Model were coupled to provide increased fidelity models of scattering effects on engine fan noise sources. The integration of these codes led to the identification of several keys issues entailed in applying such multi-fidelity approaches. In particular, for prediction at noise certification points, the inclusion of distributed sources leads to complications with the source semi-sphere approach. Computational resource requirements limit the use of the higher fidelity scattering code to predict radiated sound pressure levels for full scale configurations at relevant frequencies. And, the ability to more accurately represent complex shielding surfaces in current lower fidelity models is necessary for general application to scattering predictions. This initial step in determining the potential benefits/costs of these new methods over the existing capabilities illustrates a number of the issues that must be addressed in the development of next generation aircraft system noise prediction tools

Quantification of carbonic anhydrase gene expression in ventricle of hypertrophic and failing human heart

Background: Carbonic anhydrase enzymes (CA) catalyze the reversible hydration of carbon dioxide to bicarbonate in mammalian cells. Trans-membrane transport of CA-produced bicarbonate contributes significantly to cellular pH regulation. A body of evidence implicates pH-regulatory processes in the hypertrophic growth pathway characteristic of hearts as they fail. In particular, Na+/H+ exchange (NHE) activation is pro-hypertrophic and CA activity activates NHE. Recently Cardrase (6-ethoxyzolamide), a CA inhibitor, was found to prevent and revert agonist-stimulated cardiac hypertrophy (CH) in cultured cardiomyocytes. Our goal thus was to determine whether hypertrophied human hearts have altered expression of CA isoforms.Methods: We measured CA expression in hypertrophied human hearts to begin to examine the role of carbonic anhydrase in progression of human heart failure. Ventricular biopsies were obtained from patients undergoing cardiac surgery (CS, n = 14), or heart transplantation (HT, n = 13). CS patients presented mild/moderate concentric left ventricular hypertrophy and normal right ventricles, with preserved ventricular function; ejection fractions were ~60%. Conversely, HT patients with failing hearts presented CH or ventricular dilation accompanied by ventricular dysfunction and EF values of 20%. Non-hypertrophic, non-dilated ventricular samples served as controls.Results: Expression of atrial and brain natriuretic peptide (ANP and BNP) were markers of CH. Hypertrophic ventricles presented increased expression of CAII, CAIV, ANP, and BNP, mRNA levels, which increased in failing hearts, measured by quantitative real-time PCR. CAII, CAIV, and ANP protein expression also increased approximately two-fold in hypertrophic/dilated ventricles.Conclusions: These results, combined with in vitro data that CA inhibition prevents and reverts CH, suggest that increased carbonic anhydrase expression is a prognostic molecular marker of cardiac hypertrophy.Centro de Investigaciones Cardiovasculare

Exposure to Household Air Pollution from Biomass Cookstoves and Levels of Fractional Exhaled Nitric Oxide (FeNO) among Honduran Women

Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justastoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO)

ANOPP Landing Gear Noise Prediction Comparisons to Model-scale Data

The NASA Aircraft NOise Prediction Program (ANOPP) includes two methods for computing the noise from landing gear: the "Fink" method and the "Guo" method. Both methods have been predominately validated and used to predict full-scale landing gear noise. The two methods are compared, and their ability to predict the noise for model-scale landing gear is investigated. Predictions are made using both the Fink and Guo methods and compared to measured acoustic data obtained for a high-fidelity, 6.3%-scale, Boeing 777 main landing gear. A process is developed by which full-scale predictions can be scaled to compare with model-scale data. The measurements were obtained in the NASA Langley Quiet Flow Facility for a range of Mach numbers at a large number of observer polar (flyover) and azimuthal (sideline) observer angles. Spectra and contours of the measured sound pressure levels as a function of polar and azimuthal angle characterize the directivity of landing gear noise. Comparisons of predicted noise spectra and contours from each ANOPP method are made. Both methods predict comparable amplitudes and trends for the flyover locations, but deviate at the sideline locations. Neither method fully captures the measured noise directivity. The availability of these measured data provides the opportunity to further understand and advance noise prediction capabilities, particularly for noise directivity

Study Protocol for a Stepped-Wedge Randomized Cookstove Intervention in Rural Honduras: Household Air Pollution and Cardiometabolic Health

Growing evidence links household air pollution exposure from biomass-burning cookstoves to cardiometabolic disease risk. Few randomized controlled interventions of cookstoves (biomass or otherwise) have quantitatively characterized changes in exposure and indicators of cardiometabolic health, a growing and understudied burden in low- and middle-income countries (LMICs). Ideally, the solution is to transition households to clean cooking, such as with electric or liquefied petroleum gas stoves; however, those unable to afford or to access these options will continue to burn biomass for the foreseeable future. Wood-burning cookstove designs such as the Justa (incorporating an engineered combustion zone and chimney) have the potential to substantially reduce air pollution exposures. Previous cookstove intervention studies have been limited by stove types that did not substantially reduce exposures and/or by low cookstove adoption and sustained use, and few studies have incorporated community-engaged approaches to enhance the intervention

Growth of Captive Juvenile Tripletail Lobotes surinamensis

Early-juvenile tripletail Lobotes surinamensis (n = 27; range 45–115 mm TL, 0 = 73.0 mm; range 3.2–34.7 g TW, 0 = 12.9 g) captured in pelagic Sargassum algae off coastal Mississippi in mid-July 1999 were reared in a recirculating seawater system for 210 days. Fish were maintained on a natural light-dark cycle and fed to satiation 3 times per day. Water temperature ranged from 25.2° to 29.0° C and salinity was 28.0‰. All fish were measured for length and weight on days 1, 60, 135 and 210 of the study. Between these dates, mean daily TL growth rates were 2.2 mm/day, 1.2 mm/day, and 1.0 mm/day, respectively, where as 0 daily TW growth rates were 2.9 g/day, 4.3 g/day, and 7.1 g/day. Over the entire study, 0 TL and TW growth rates were 1.4 mm/day and 4.9 g/day, respectively. There was a significant correlation between length and weight vs. date of measurement. At the end of the study, specimens ranged from 272–431 mm TL (0 = 359 mm) and from 443.9–2,380.0 g TW (0 = 1,012.5 g)