Surfactant coated aerosol powders and their properties

The hygroscopic growth of aerosols is an important factor effecting particle size. The consequence of the hygroscopic growth of pharrnaceutical aerosols is a change in their deposition characteristics, such that there is an increase in the total amount deposited in the lung. In this study the hygroscopic growth of disodium fluorescein (DF) aerosol powders was investigated by coating the powders with lauric and capric acids. The coating procedure was carried out in dichloromethane and chloroform, which acted as cosolvents for the fatty acids. An assessment of the extent and the nature of the coating was carried out. The qualitative assessment of the coating was achieved by infra-red spectroscopy, electronscanning chemical analysis and scanning electron microscopy. The quantitative analysis was carried out by differential refractometry, ultra-violet spectroscopy and gas liquid chromatography. These powders were generated under conditions approaching those in the lung, of 97 % relative humidity and 37"C. Coated and uncoated DF aerosol powders were introduced into a controlled temperature and relative humidity apparatus, designed and constructed for the investigation of hygroscopic growth in these studies. A vertical spinning disc device was used to generate the powders. Under conditions of controlled temperature and relative humidity mentioned, the growth ratio of disodium fluorescein alone was 1.45 compared with 1.68, for a nominal coating of DF with lauric acid of 0.12 gg-1, 1.0 for a nominal lauric acid coating of 0.2 gg-1, and 1.02 for a nominal capric acid coating of 0.18 gg-1. The range of control of hygroscopic growth of these aerosols has implications for the deposition of these preparations in the respiratory tract. These implications are discussed in the light of the current knowledge of the effects of hygroscopic growth on the deposition of pharmaceutical and environmental aerosols. A series of experiments in which pulmonary ventilation using a simple radioaerosol generator and delivery system are reported showing that particle size determination may be used to aid the design of diagnostic aerosol generators

The 2009 Samoa and 2010 Chile Tsunamis as Observed in the Ionosphere using GPS Total Electron Content

Ground‐based Global Positioning System (GPS) measurements of ionospheric total electron content (TEC) show variations consistent with atmospheric internal gravity waves caused by ocean tsunamis following two recent seismic events: the Samoa earthquake of 29 September 2009 and the Chile earthquake of 27 February 2010. Both earthquakes produced ocean tsunamis that were destructive to coastal communities near the epicenters, and both were observed in tidal gauge and buoy measurements throughout the Pacific Ocean. We observe fluctuations in TEC correlated in time, space, and wave properties with these tsunamis using the Jet Propulsion Laboratory’s Global Ionospheric Mapping software. These TEC measurements were band‐pass filtered to remove ionospheric TEC variations with wavelengths and periods outside the typical range for tsunamis. Observable variations in TEC appear correlated with the tsunamis in some locations (Hawaii and Japan), but not in others (Southern California or near the epicenters). Where variations are observed, the typical amplitude tends to be ∼0.1–0.2 TEC units for these events, on the order of ∼1% of the background TEC value. These observations are compared to estimates of expected tsunami‐driven TEC variations produced by Embry Riddle Aeronautical University’s Spectral Full Wave Model, an atmosphere‐ionosphere coupled model, and are found to be in good agreement. Significant TEC variations are not always seen when a tsunami is present, but in these two events the regions where a strong ocean tsunami was observed coincided with clear TEC observations, while a lack of clear TEC observations coincided with smaller sea surface height amplitudes. There exists the potential to apply these detection techniques to real‐time GPS TEC data, providing estimates of tsunami speed and amplitude that may be useful for early warning systems

The Guinea Pig as a Model of Infectious Diseases

The words ‘guinea pig’ are synonymous with scientific experimentation, but much less is known about this species than many other laboratory animals. This animal model has been used for approximately 200 y and was the first to be used in the study of infectious diseases such as tuberculosis and diphtheria. Today the guinea pig is used as a model for a number of infectious bacterial diseases, including pulmonary, sexually transmitted, ocular and aural, gastrointestinal, and other infections that threaten the lives of humans. Most studies on the immune response to these diseases, with potential therapies and vaccines, have been conducted in animal models (for example, mouse) that may have less similarity to humans because of the large number of immunologic reagents available for these other species. This review presents some of the diseases for which the guinea pig is regarded as the premier model to study infections because of its similarity to humans with regard to symptoms and immune response. Furthermore, for diseases in which guinea pigs share parallel pathogenesis of disease with humans, they are potentially the best animal model for designing treatments and vaccines. Future studies of immune regulation of these diseases, novel therapies, and preventative measures require the development of new immunologic reagents designed specifically for the guinea pig

Ionospheric Signatures of Tohoku-Oki Tsunami of March 11, 2011: Model Comparisons Near the Epicenter

We observe ionospheric perturbations caused by the Tohoku earthquake and tsunami of March 11, 2011. Perturbations near the epicenter were found in measurements of ionospheric total electron content (TEC) from 1198 GPS receivers in the Japanese GEONET network. For the first time for this event, we compare these observations with the estimated magnitude and speed of a tsunami-driven atmospheric gravity wave, using an atmosphere-ionosphere-coupling model and a tsunami model of sea-surface height, respectively. Traveling ionospheric disturbances (TIDs) were observed moving away from the epicenter at approximate speeds of 3400 m/s, 1000 m/s and 200–300 m/s, consistent with Rayleigh waves, acoustic waves, and gravity waves, respectively. We focus our analysis on gravity waves moving south and east of the epicenter, since tsunamis propagating in the deep ocean have been shown to produce gravity waves detectable in ionospheric TEC in the past. Observed southeastward gravity wave perturbations, seen 60 min after the earthquake, are mostly between 0.5 to 1.5 TECU, representing up to 5% of the background vertical TEC (VTEC). Comparisons of observed TID gravity waves with the modeled tsunami speed in the ocean and the predicted VTEC perturbation amplitudes from an atmosphere-ionosphere-coupling model show the measurements and models to be in close agreement. Due to the dense GPS network and high earthquake magnitude, these are the clearest observations to date of the effect of a major earthquake and tsunami on the ionosphere near the epicenter. Such observations from a future real-time GPS receiver network could be used to validate tsunami models, confirm the existence of a tsunami, or track its motion where in situ buoy data is not available

Phase I, single-dose, dose-escalating study of inhaled dry powder capreomycin : a new approach to therapy of drug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) threatens global TB control. The lengthy treatment includes one of the injectable drugs kanamycin, amikacin, and capreomycin, usually for the first 6 months. These drugs have potentially serious toxicities, and when given as intramuscular injections, dosing can be painful. Advances in particulate drug delivery have led to the formulation of capreomycin as the first antituberculosis drug available as a microparticle dry powder for inhalation and clinical study. Delivery by aerosol may result in successful treatment with lower doses. Here we report a phase I, single-dose, dose-escalating study aimed at demonstrating safety and tolerability in healthy subjects and measuring pharmacokinetic (PK) parameters. Twenty healthy adults (n = 5 per group) were recruited to self-administer a single dose of inhaled dry powder capreomycin (25-mg, 75-mg, 150-mg, or 300-mg nominal dose) using a simple, handheld delivery device. Inhalations were well tolerated by all subjects. The most common adverse event was mild to moderate transient cough, in five subjects. There were no changes in lung function, audiometry, or laboratory parameters. Capreomycin was rapidly absorbed after inhalation. Systemic concentrations were detected in each dose group within 20 min. Peak and mean plasma concentrations of capreomycin were dose proportional. Serum concentrations exceeded 2 μg/ml (MIC for Mycobacterium tuberculosis) following the highest dose; the half-life (t1/2) was 4.8 ± 1.0 h. A novel inhaled microparticle dry powder formulation of capreomycin was well tolerated. A single 300-mg dose rapidly achieved serum drug concentrations above the MIC for Mycobacterium tuberculosis, suggesting the potential of inhaled therapy as part of an MDR-TB treatment regimen.Gates Foundation.http://aac.asm.orghb2013ay201

Initial Characterization of Micafungin Pulmonary Delivery via Two Different Nebulizers and Multivariate Data Analysis of Aerosol Mass Distribution Profiles

Pharmaceutical aerosols have been targeted to the lungs for the treatment of asthma and pulmonary infectious diseases successfully. Micafungin (Astellas Pharma US, Deerfield, IL, USA) has been shown to be an effective antifungal agent when administrated intravenously. Pulmonary delivery of micafungin has not previously been reported. In the present pilot study, we characterize the performance of two nebulizers and their potential for delivering micafungin to the lungs as well as the use of multivariate data analysis for mass distribution profile comparison. The concentration of micafungin sodium increased by 21% when delivered by the Acorn II nebulizer and by 20% when delivered by the LC Plus nebulizer, respectively, from the first to the second sampling period. The Acorn II nebulizer delivered a fine particle fraction FPF(5.8) (%<5.8 microm) of 92.5 +/- 0.8 and FPF(3.3) (%<3.3 microm) of 82.3 +/- 2.1 during the first sampling period. For the LC Plus nebulizer, FPF(5.8) was 92.3 +/- 0.1 and FPF(3.3) was 67.0 +/- 0.7 during the first sampling period. The mass median aerodynamic diameter (MMAD) increased from 1.67 +/- 0.05 to 1.77 +/- 0.04 mum (Acorn II nebulizer) and from 2.09 +/- 0.01 to 2.20 +/- 0.01 microm (Pari LC Plus nebulizer) from the first to the second sampling periods. These changes in MMAD were statistically significant by paired t test. Multivariate data analysis showed that this could be explained systematically by greater drug deposition on stages with larger cutoff sizes and reduced drug deposition on stages with smaller cutoff sizes rather than multimodal deposition or other anomalies in size distribution