Observations of production and transport of NOx formed by energetic particle precipitation in the polar night atmosphere

This work is focused on the effects of energetic particle precipitation of solar or magnetospheric origin on the polar middle atmosphere. The energetic charged particles have access to the atmosphere in the polar areas, where they are guided by the Earth's magnetic field. The particles penetrate down to 20-100 km altitudes (stratosphere and mesosphere) ionising the ambient air. This ionisation leads to production of odd nitrogen (NOx) and odd hydrogen species, which take part in catalytic ozone destruction. NOx has a very long chemical lifetime during polar night conditions. Therefore NOx produced at high altitudes during polar night can be transported to lower stratospheric altitudes. Particular emphasis in this work is in the use of both space and ground based observations: ozone and NO2 measurements from the GOMOS instrument on board the European Space Agency's Envisat-satellite are used together with subionospheric VLF radio wave observations from ground stations. Combining the two observation techniques enabled detection of NOx enhancements throughout the middle atmosphere, including tracking the descent of NOx enhancements of high altitude origin down to the stratosphere. GOMOS observations of the large Solar Proton Events of October-November 2003 showed the progression of the SPE initiated NOx enhancements through the polar winter. In the upper stratosphere, nighttime NO2 increased by an order of magnitude, and the effect was observed to last for several weeks after the SPEs. Ozone decreases up to 60 % from the pre-SPE values were observed in the upper stratosphere nearly a month after the events. Over several weeks the GOMOS observations showed the gradual descent of the NOx enhancements to lower altitudes. Measurements from years 2002-2006 were used to study polar winter NOx increases and their connection to energetic particle precipitation. NOx enhancements were found to occur in a good correlation with both increased high-energy particle precipitation and increased geomagnetic activity. The average wintertime polar NOx was found to have a nearly linear relationship with the average wintertime geomagnetic activity. The results from this thesis work show how important energetic particle precipitation from outside the atmosphere is as a source of NOx in the middle atmosphere, and thus its importance to the chemical balance of the atmosphere.

Medicines information sources and services for consumers : A special focus on the Internet and people with depression

The range of consumer health and medicines information sources has diversified along with the increased use of the Internet. This has led to a drive to develop medicines information services and to better incorporate the Internet and e-mail into routine practice in health care and in community pharmacies. To support the development of such services more information is needed about the use of online information by consumers, particularly of those who may be the most likely to use and to benefit from the new sources and modes of medicines communication. This study explored the role and utilization of the Internet-based medicines information and information services in the context of a wider network of information sources accessible to the public in Finland. The overall aim was to gather information to develop better and more accessible sources of information for consumers and services to better meet the needs of consumers. Special focus was on the needs and information behavior among people with depression and using antidepressant medicines. This study applied both qualitative and quantitative methods. Consumer medicines information needs and sources were identified by analyzing the utilization of the University Pharmacy operated national drug information call center (Study I) and surveying Finnish adults (n=2348) use of the different medicines information sources (Study II). The utilization of the Internet as a source of antidepressant information among people with depression was explored by focus group discussions among people with depression and with current or past use of the antidepressant(s) (n=29, Studies III & IV). Pharmacy response to the needs of consumers in term of providing e-mail counseling was assessed by conducting a virtual pseudo customer study among the Finnish community pharmacies (n=161, Study V). Physicians and pharmacists were the primary sources of medicines information. People with mental disorders were more frequent users of telephone- and Internet-based medicines information sources and patient information leaflets than people without mental disorders. These sources were used to complement rather than replace information provided face-to-face by health professionals. People with depression used the Internet to seek facts about antidepressants, to share experiences with peers, and for the curiosity. They described that the access to online drug information was empowering. Some people reported lacking the skills necessary to assess the quality of online information. E-mail medication counseling services provided by community pharmacies were rare and varied in quality. Study results suggest that rather than discouraging the use of the Internet, health professionals should direct patients to use accurate and reliable sources of online medicines information. Health care providers, including community pharmacies should also seek to develop new ways of communicating information about medicines with consumers. This study determined that people with depression and using antidepressants need services enabling interactive communication not only with health care professionals, but also with peers. Further research should be focused on developing medicines information service facilitating communication among different patient and consumer groups.

The role of phospholipid transfer protein and cholesteryl ester transfer protein in reverse cholesterol transport

In atherosclerosis, cholesterol accumulates in the vessel wall, mainly in the form of modified low-density lipoprotein (LDL). Macrophages of the vessel wall scavenge cholesterol, which leads to formation of lipid-laden foam cells. High plasma levels of high-density lipoprotein (HDL) protect against atherosclerosis, as HDL particles can remove peripheral cholesterol and transport it to the liver for excretion in a process called reverse cholesterol transport (RCT). Phospholipid transfer protein (PLTP) remodels HDL particles in the circulation, generating prebeta-HDL and large fused HDL particles. In addition, PLTP maintains plasma HDL levels by facilitating the transfer of post-lipolytic surface remnants of triglyceride-rich lipoproteins to HDL. Most of the cholesteryl ester transfer protein (CETP) in plasma is bound to HDL particles and CETP is also involved in the remodeling of HDL particles. CETP enhances the heteroexchange of cholesteryl esters in HDL particles for triglycerides in LDL and very low-density lipoprotein (VLDL). The aim of this thesis project was to study the importance of endogenous PLTP in the removal of cholesterol from macrophage foam cells by using macrophages derived from PLTP-deficient mice, determine the effect of macrophage-derived PLTP on the development of atherosclerosis by using bone marrow transplantation, and clarify the role of the two forms of PLTP, active and inactive, in the removal of cholesterol from the foam cells. In addition, the ability of CETP to protect HDL against the action of chymase was studied. Finally, cholesterol efflux potential of sera obtained from the study subjects was compared. The absence of PLTP in macrophages derived from PLTP-deficient mice decreased cholesterol efflux mediated by ATP-binding cassette transporter A1. The bone marrow transplantation studies showed that selective deficiency of PLTP in macrophages decreased the size of atherosclerotic lesions and caused major changes in serum lipoprotein levels. It was further demonstrated that the active form of PLTP can enhance cholesterol efflux from macrophage foam cells through generation of prebeta-HDL and large fused HDL particles enriched with apoE and phospholipids. Also CETP may enhance the RCT process, as association of CETP with reconstituted HDL particles prevented chymase-dependent proteolysis of these particles and preserved their cholesterol efflux potential. Finally, serum from high-HDL subjects promoted more efficient cholesterol efflux than did serum derived from low-HDL subjects which was most probably due to differences in the distribution of HDL subpopulations in low-HDL and high-HDL subjects. These studies described in this thesis contribute to the understanding of the PLTP/CETP-associated mechanisms underlying RCT.