THE TRANSPORT AND MODULATION OF HIV PROTEASE INHIBITORS INTO THE RAT CENTRAL NERVOUS SYSTEM AND MILK

The objective of this dissertation is to study the mechanism by which HIV protease inhibitors enter into the central nervous system (CNS) and breast milk of rats, and what effects MDR modulators have on the distribution and metabolism of HIV protease inhibitors. The transporter P-glycoprotein (P-gp) has been shown to limit the distribution of HIV protease inhibitors into the CNS of rodents. This thesis examined the effects of GF120918, an MDR modulator, on the CNS distribution of amprenavir, an HIV protease inhibitor, in rats. GF120918 significantly increased the unbound CNS concentrations of amprenavir without altering the unbound blood concentrations of amprenavir. The results of these studies show that GF120918 can inhibit P-gp at the blood brain barrier (BBB) to increase the unbound CNS concentration of amprenavir and potentially other HIV protease inhibitors. Many first generation MDR modulators inhibited both P-gp transport and CYP3A metabolism. Therefore, a principal goal of this thesis was to determine if GF120918 could selectively inhibit P-gp transport without inhibiting CYP3A metabolism. Using in vitro (human) and in vivo (rat) studies, GF120918 selectively inhibited P-gp at the BBB without inhibiting CYP3A metabolism. The transporter MRP1 has been shown to both transport HIV protease inhibitors and expressed in the CNS. Studies contained in the thesis have shown that mrp1 is not localized to the BBB of rats, therefore, mrp1 is unlikely to play a significant role in the distribution of HIV protease inhibitors into the CNS of rats. The distribution of nelfinavir, an HIV protease inhibitor, into rat breast milk was studied in the thesis as a first approach in understanding the extent to which HIV protease inhibitors can accumulate into milk. The concentration of nelfinavir in rat milk was approximately half that of plasma. P-gp protein expression was detected in lactating rat mammary tissue. However, GF120918 showed no effect on the distribution of nelfinavir into rat milk suggesting that P-gp does not play a significant role in the distribution of HIV protease inhibitors into milk

Isle D\u27Amour : Hesitation Waltz

https://digitalcommons.library.umaine.edu/mmb-ps/2519/thumbnail.jp

Isle D\u27Amour : Isle of Love

https://digitalcommons.library.umaine.edu/mmb-vp/1905/thumbnail.jp

Isle D\u27 Amour / music by Leo. Edwards; words by Earl Carroll

Cover: Photo of Jose Collins; Publisher: Leo Feist Inc. (New York)https://egrove.olemiss.edu/sharris_c/1059/thumbnail.jp

Sediment transport and channel morphology in a small mountain stream in Western Oregon

Sediment transport measurements on Flynn Creek, a headwater stream in the Oregon Coast Range, have illustrated the magnitude of fluvial transfer processes, primarily of the bedload component, during a moderate storm runoff season (1979 water year). The total dissolved solids concentration of storm runoff averaged 40 mg/L, and was independent of water discharge. Most particulate export from the 202 ha forested watershed occurred during the annual peak flow of 0.75 m³/sec-km² (2-year return interval). Suspended load was the most important transport mode, with a total yield of 5.7 x l0⁴ kg during the 24 h peak flow period. The export of coarse particulate organic matter during the same period was 1.5 x 10³ kg. Bedload discharge, as measured with vortex tube and Helley-Smith samplers, occurred in pulses of short duration that did not necessarily coincide with peak streamflow. For the same 24 h storm runoff period, the total bedload yield at the mouth of the watershed was only 2.6 x 10³ kg (particles > 0.25 mm), and consisted primarily of sand-size material. Bedload discharge at an upstream site (1.3 x 10⁴ kg) was dominated by gravel-size particles. Channel morphology and in-stream obstructions (organic debris, fish trap) appear to cause significant spatial and temporal variations in sediment transport and streambed composition. Although streamflow was the principal variable controlling sediment transport, results suggest that supply limitations exist. The supply of transportable materials is dependent on the retention characteristics of the stream channel and on local hydraulic conditions. The discharge of both suspended solids and coarse particulate organic matter peaked early in the storm; however, pulses of the latter component on the recession limb appeared to be related to streambed disturbances. Bedload movement is an important process regulating both bed composition and particulate yields in this Coast Range stream. The Helley-smith sampler was the preferable method for use in streams having a large fraction of bedload in the sand-size range. The vortex tube trapped from 60-70% of the bedload sediment measured by an upstream Helley-smith sampler, with trapping efficiency of the former increasing as transport increased. The variability in bedload movement suggests that monitoring designs must address: (1) rapid temporal fluctuations in bedload discharge, (2) variations in bedload transport along a stream, (3) lateral variations in bedload discharge at a cross section, and (4) the type of sampler used.Keywords: bed material load, sedimentation, bedload transport, coarse particulate organic matter, mountain streams, vortex tube sampler, suspended load, Helley-Smith sampler, channel morpholog

Digital Surface Modelling in Developing Countries Using Spaceborne SAR Techniques

Topographic databases at the national level, in the form of Digital Surface Models (DSMs), are required for a large number of applications which have been spurred on by the increased use of Geographic Information Systems (GIS). Ground-Based (surveying, GPS, etc.) and traditional airborne approaches to generating topographic information are proving to be time consuming and costly for applications in developing countries. Where these countries are located in the tropical zone, they are affected by the additional problem of cloud cover which could cause delays for almost 75% of the year in obtaining optical imagery. The Caribbean happens to be one such affected territory that is in need of national digital topographic information for its GIS database developments, 3D visualization of landscapes and for use in the digital ortho-rectification of satellite imagery. The use of Synthetic Aperture Radar (SAR), with its cloud penetrating and day/night imaging capabilities, is emerging as a possible remote sensing tool for use in cloud affected territories. There has been success with airborne single-pass dual antennae systems (e.g. STAR 3i) and the Shuttle Radar Topographic Mapping (SRTM) mission. However, the use of these systems in the Caribbean are restrictive and datasets will not be generally available. The launching of imaging radar satellites such as ERS-1, ERS-2, Radarsat-1 and more recently Envisat have provided additional opportunities for augmenting the technologies available for generating medium accuracy, low cost, topographic information for developing countries by using the techniques of Radargrammetry (StereoSAR) and Interferometric SAR (InSAR). The primary aim of this research was to develop, from scratch, a prototype StereoSAR system based on automatic stereo matching and space intersection algorithms to generate medium accuracy, low cost DSMs, using various influencing parameters without any recourse to ground control points. The result was to be a software package to undertake this process for implementation on a personal computer. The DSMs generated from Radarsat-1 and Envisat SAR imagery were compared with a reference surface from airborne InSAR and conclusions with respect to the quality of the StereoSAR DSMs are presented. Work required to further improve the StereoSAR system is also suggested

Diagnosis of lipomatous hypertrophy of the atrial septum by two-dimensional echocardiography

Originally described in 1964, lipomatous hypertrophy of the atrial septum currently remains a diagnosis established primarily at autopsy. Clinical interest in this disorder has centered on the reported association with supraventricular arrhythmias and sudden death. Because two-dimensional echocardiography allows detailed assessment of atrial septal configuration, we reviewed two-dimensional echocardiographic reports obtained over a 1 year period and identified 17 patients who had features consistent with lipomatous hypertrophy of the atrial septum. Nine were men and the average age was 70 years. Autopsy confirmation of the echographic findings was possible in one patient. In nine patients, ideal body weight was exceeded by 10% or more. The atrial septum viewed from the subcostal transducer position showed a distinctive echo-dense globular thickening sparing the valve of the fossa ovalis. The resultant tomographic image of the atrial septum had a characteristic dumbbell appearance. The mean thickness of the atrial septum was 21 mm (range 15 to 29). Seven patients had supraventricular arrhythmias, and eight had P wave abnormalities.The two-dimensional echocardiographic features described are distinctive and suggest that this technique is the procedure of choice not only for establishing the diagnosis of lipomatous hypertrophy of the atrial septum but also for providing a means for prospective follow-up of patients with this little known entity

Digital Surface Modelling in Developing Countries Using Spaceborne SAR Techniques

Topographic databases at the national level, in the form of Digital Surface Models (DSMs), are required for a large number of applications which have been spurred on by the increased use of Geographic Information Systems (GIS). Ground-Based (surveying, GPS, etc.) and traditional airborne approaches to generating topographic information are proving to be time consuming and costly for applications in developing countries. Where these countries are located in the tropical zone, they are affected by the additional problem of cloud cover which could cause delays for almost 75% of the year in obtaining optical imagery. The Caribbean happens to be one such affected territory that is in need of national digital topographic information for its GIS database developments, 3D visualization of landscapes and for use in the digital ortho-rectification of satellite imagery. The use of Synthetic Aperture Radar (SAR), with its cloud penetrating and day/night imaging capabilities, is emerging as a possible remote sensing tool for use in cloud affected territories. There has been success with airborne single-pass dual antennae systems (e.g. STAR 3i) and the Shuttle Radar Topographic Mapping (SRTM) mission. However, the use of these systems in the Caribbean are restrictive and datasets will not be generally available. The launching of imaging radar satellites such as ERS-1, ERS-2, Radarsat-1 and more recently Envisat have provided additional opportunities for augmenting the technologies available for generating medium accuracy, low cost, topographic information for developing countries by using the techniques of Radargrammetry (StereoSAR) and Interferometric SAR (InSAR). The primary aim of this research was to develop, from scratch, a prototype StereoSAR system based on automatic stereo matching and space intersection algorithms to generate medium accuracy, low cost DSMs, using various influencing parameters without any recourse to ground control points. The result was to be a software package to undertake this process for implementation on a personal computer. The DSMs generated from Radarsat-1 and Envisat SAR imagery were compared with a reference surface from airborne InSAR and conclusions with respect to the quality of the StereoSAR DSMs are presented. Work required to further improve the StereoSAR system is also suggested