Effect of a nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, including inflammatory epithelial cells. NO has been detected in the exhaled air of normal human subjects, and its concentration is raised in asthmatic patients. To study whether exhaled NO arises from the respiratory tract, we administered a NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA), by inhalation (490 mg) in a double-blind randomized manner in nine normal and six asthmatic subjects. Because exhaled NO may arise from an inducible isoform of NO synthase that may be inhibited by glucocorticosteroids, we also studied the effects of oral prednisolone (30 mg orally for 3 d) in seven normal and six asthmatic subjects in a separate double-blind crossover study with matched placebo. After nebulized L-NMMA, there was a significant fall in peak exhaled NO compared with saline control values, with a mean fall of 43.6 +/- 5.6% in normal subjects (p < 0.01) and of 39.7 +/- 6.5% (p < 0.01) in asthmatic subjects, which persisted for 4 h. There were no effects of L-NMMA inhalation on heart rate, blood pressure, or FEV1 in either normal or asthmatic patients. Administration of oral prednisolone (30 mg) resulted in a fall in exhaled NO concentrations in asthmatic subjects by 21.6 +/- 5.0% at 48 h (p < 0.01) but no significant change in normal subjects. These data suggest that NOS inhibitors may be safely given in normal and asthmatic patients and that the increased exhaled NO seen in asthmatic patients is likely to be caused by induction of inducible NOS.     

Endometriosis in monozygotic twins

OBJECTIVE: To describe the occurrence of endometriosis in monozygotic twins. DESIGN: Postal questionnaire plus confirmation of disease status. SETTING: Twins were recruited via the American Endometriosis Association and the National Endometriosis Society of Great Britain and via British gynecologists. RESULT(S): Fourteen twin pairs were concordant for endometriosis, and two were discordant. Nine pairs of twins had moderate-severe endometriosis. CONCLUSION(S): These findings contribute to the growing body of literature that suggests endometriosis has a genetic basis.     

Transmission Electron Microscopy-Based Analysis of Electrically Conductive Surface Defects in Large Area GaSb Homoepitaxial Diodes Grown Using Molecular Beam Epitaxy

We investigate a mechanism causing shorting of large area GaSb diodes grown on GaSb substrates using molecular beam epitaxy (MBE). The source of these shorts is determined to be large crystallographic defects on the surface of the diodes that are formed around droplets of gallium ejected from the gallium Knudsen cells during MBE. The gallium droplets cause defects in the crystal structure, and, as the epitaxy continues, the gallium is incorporated into the surrounding material. The shape of the defects is pyramidal with a central void extending from the epi-surface to the gallium core. Processing a GaSb diode with these surface defects results in the top-side contact metal migrating into the defect and shorting the diode. This prevents realization of large area diodes that are critical to applications such as photovoltaics and detectors. The diodes in this study are electrically characterized and the defect formation mechanism is investigated using cross-section transmission electron microscopy and electron dispersive spectroscopy.     

A method for improving global pyranometer measurements by modeling responsivity functions

Accurate global solar radiation measurements are crucial to climate change research and the development of solar energy technologies. Pyranometers produce an electrical signal proportional to global irradiance. The signal-to-irradiance ratio is the responsivity (RS) of the instrument (RS = signal/irradiance = microvolts/(W/m²)). Most engineering measurements are made using a constant RS. It is known that RS varies with day of year, zenith angle, and net infrared radiation. This study proposes a method to find an RS function to model a pyranometer’s changing RS. Using a reference irradiance calculated from direct and diffuse instruments, we found instantaneous RS for two global pyranometers over 31 sunny days in a two-year period. We performed successive independent regressions of the error between the constant and instantaneous RS with respect to zenith angle, day of year, and net infrared to obtain an RS function. An alternative method replaced the infrared regression with an independently developed technique to account for thermal offset. Results show improved uncertainties with the function method than with the single-calibration value. Lower uncertainties also occur using a black-and-white (8-48), rather than all-black (PSP), shaded pyranometer as the diffuse reference instrument. We conclude that the function method is extremely effective in reducing uncertainty in the irradiance measurements for global PSP pyranometers if they are calibrated at the deployment site. Furthermore, it was found that the function method accounts for the pyranometer’s thermal offset, rendering further corrections unnecessary. The improvements in irradiance data achieved in this study will serve to increase the accuracy of solar energy assessments and atmospheric research.     

X-ray diffraction from intact tau aggregates in human brain tissue

We describe an instrument to record x-ray diffraction patterns from diseased regions of human brain tissue by combining an in-line visible light fluorescence microscope with an x-ray diffraction microprobe. We use thiazine red fluorescence to specifically label and detect the filamentous tau protein pathology associated with Pick's disease, as several labs have done previously. We demonstrate that thiazine red-enhanced regions within the tissue show periodic structure in x-ray diffraction that is not observed in healthy tissue. One observed periodicity (4.2 ?) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein.     

Order vs. Disorder: Cholesterol and Omega-3 Phospholipids Determine Biomembrane Organization

Lipid structural diversity strongly affects biomembrane chemico-physical and structural properties in addition to membrane-associated events. At high concentrations, cholesterol increases membrane order and rigidity, while polyunsaturated lipids are reported to increase disorder and flexibility. How these different tendencies balance in composite bilayers is still controversial. In this study, electron paramagnetic resonance spectroscopy, small angle neutron scattering, and neutron reflectivity were used to investigate the structural properties of cholesterol-containing lipid bilayers in the fluid state with increasing amounts of polyunsaturated omega-3 lipids. Either the hybrid 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine or the symmetric 1,2-docosahexaenoyl-sn-glycero-3-phosphocholine were added to the mixture of the naturally abundant 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine and cholesterol. Our results indicate that the hybrid and the symmetric omega-3 phospholipids affect the microscopic organization of lipid bilayers differently. Cholesterol does not segregate from polyunsaturated phospholipids and, through interactions with them, is able to suppress the formation of non-lamellar structures induced by the symmetric polyunsaturated lipid. However, this order/disorder balance leads to a bilayer whose structural organization cannot be ascribed to either a liquid ordered or to a canonical liquid disordered phase, in that it displays a very loose packing of the intermediate segments of lipid chains.