Solubility and physical stability improvement of natiral xanthine derivatives

Use of natural xanthine derivates in medicine is complicated with their physical properties. Theobromine is poorly soluble while theophylline is highly sensitive to hydration. The aim of this study was to improve bioavailability of xanthines by co-crystallization, theophylline was also cocrystallized with carboxylic acids (capric, citric, glutaric, malenic, malonic, oxalic, stearic, succinic) and HPMC. Co-crystallization was performed by slow evaporation and ball milling. Physical stability was checked by wet granulation and water sorption methods, solubility was measured by intrinsic tablet dissolution. Theobromine formed co-crystal with other xanthines and theophylline interacted with all acids except stearic and HPMC, the latter showed alternative interactions based on hydrogen bonding. Hydration resistance was good in theophylline:succinic acid co-crystal and excellent in complexes containing capric, stearic acids and HPMC. Theophylline:HPMC showed improved solubility. The reported approach can promote use of xanthines and can be recommended for other compounds with similar problems.

Leisure-time physical activity, health related functioning and retirement : a prospective cohort study among middle-aged employees

Physical inactivity has become a major threat to public health worldwide. The Finnish health and welfare policies emphasize that the working population should maintain good health and functioning until their normal retirement age and remain in good health and independence later in life. Health behaviours like physical activity potentially play an important role in reaching this target as physical activity contributes to better physical fitness and to reduced risk of major chronic diseases. The aim of this study was to examine first whether the volume and intensity of leisure-time physical activity impacts on subsequent physical health functioning, sickness absence and disability retirement. The second aim was to examine changes in leisure-time physical activity of moderate and vigorous intensity after transition to retirement. This study is part of the ongoing Helsinki Health Study. The baseline data were collected by questionnaires in 2000 - 02 among the employees of the City of Helsinki aged 40 to 60. The follow-up survey data were collected in 2007. Data on sickness absence were obtained from the employer s (City of Helsinki) sickness absence registers and pension data were obtained from the Finnish Centre for Pensions. Leisure-time physical activity was measured in four grades of intensity and classified according to physical activity recommendations considering both the volume and intensity of physical activity. Statistical techniques including analysis of covariance, logistic regression, Cox proportional hazards models and Poisson regression were used. Employees who were vigorously active during leisure time especially had better physical health functioning than those physically inactive. High physical activity in particular contributed to the maintenance of good physical health functioning. High physical activity also reduced the risk of subsequent sickness absences as well as the risk of all-cause disability retirement and retirement due to musculoskeletal and mental causes. Among those transferred to old-age retirement moderate-intensity leisure-time physical activity increased on average by more than half an hour per week and in addition the occurrence of physical inactivity reduced. Such changes were not observed among those remained employed and those transferred to disability retirement. This prospective cohort study provided novel results on the effects of leisure-time physical activity on health related functioning and changes in leisure-time physical activity after retirement. Although the benefits of moderate-intensity physical activity for health are well known these results suggest the importance of vigorous physical activity for subsequent health related functioning. Thus vigorous physical activity to enhance fitness should be given more emphasis from a public health perspective. In addition, physical activity should be encouraged among those who are about to retire.

Physical properties of a boreal clay soil under differently managed perennial vegetation

The physical properties of surface soil horizons, essentially pore size, shape, continuity and affinity for water, regulate water entry into the soil. These properties are prone to changes caused by natural forces and human activity. The hydraulic properties of the surface soil greatly impact the generation of surface runoff and accompanied erosion, the major concern of agricultural water protection. The general target of this thesis was to improve our understanding of the structural and hydraulic properties of boreal clay soils. Physical properties of a clayey surface soil (0 - 10 cm, clay content 51%), with a micaceous/illitic mineralogy subjected to three different management practices of perennial vegetation, were studied. The study sites were vegetated buffer zones located side by side in SW Finland: 1) natural vegetation with no management, 2) harvested once a year, and 3) grazed by cattle. The soil structure, hydraulic properties, shrinkage properties and soil water repellency were determined at all sites. Two distinct flow domains were evident. The surface soil was characterized by subangular blocky, angular blocky and platy aggregates. Hence, large, partially accommodated, irregular elongated pores dominated the macropore domain at all sites. The intra-aggregate pore system was mostly comprised of pores smaller than 30 μm, which are responsible for water storage. Macropores at the grazed site, compacted by hoof pressure, were horizontally oriented and pore connectivity was poorest, which decreased water and air flux compared with other sites. Drying of the soil greatly altered its structure. The decrease in soil volume between wet and dry soil was 7 - 10%, most of which occurred in the moisture range of field conditions. Structural changes, including irreversible collapse of interaggregate pores, began at matric potentials around -6 kPa indicating, instability of soil structure against increasing hydraulic stress. Water saturation and several freezethaw cycles between autumn and spring likely weakened the soil structure. Soil water repellency was observed at all sites at the time of sampling and when soil was dryer than about 40 vol.%. (matric potential < -6 kPa). Therefore, water repellency contributes to water flow over a wide moisture range. Water repellency was also observed in soils with low organic carbon content (< 2%), which suggests that this phenomenon is common in agricultural soils of Finland due to their relatively high organic carbon content. Aggregate-related pedofeatures of dense infillings described as clay intrusions were found at all sites. The formation of these intrusions was attributed to clay dispersion and/or translocation during spring thaw and drying of the suspension in situ. These processes generate very new aggregates whose physical properties are most probably different from those of the bulk soil aggregates. Formation of the clay infillings suggested that prolonged wetness in autumn and spring impairs soil structure due to clay dispersion, while on the other hand it contributes to the pedogenesis of the soil. The results emphasize the dynamic nature of the physical properties of clay soils, essentially driven by their moisture state. In a dry soil, fast preferential flow is favoured by abundant macropores including shrinkage cracks and is further enhanced by water repellency. Increase in soil moisture reduces water repellency, and swelling of accommodated pores lowers the saturated hydraulic conductivity. Moisture- and temperature-related processes significantly alter soil structure over a time span of 1 yr. Thus, the pore characteristics as well as the hydraulic properties of soil are time-dependent.

"Oma entinen on palannut takaisin elämään" : Kuntoutuksen vaikuttavuus aikuisena kuuroutuneiden henkilöiden elämänhallintaan ja psykososiaaliseen hyvinvointiin

Objective The objective of this study was to learn about the psychosocial well-being and life management of Finnish adults with late deafness or hearing loss and to observe the effectiveness of the rehabilitation courses they participated in. Methods For my study I used indicators which were suitable for the evaluation of life management and psychosocial well-being of late-deafened adults. The first part of the study was conducted during 2009 as a questionnaire on three rehabilitation courses in Kopola, a course center of the Finnish Federation of Hard of Hearing. The follow-up study was done at the third period of the courses during 2009 2010. The questionnaire contained both open and structured questions. The questionnaire consisted of five areas concerning life management and psychosocial well-being: sense of coherence (life management), human relations and social support, mood, self-esteem and satisfaction with life. I also asked the participants to reflect on their experiences of group rehabilitation. Results and conclusions The participants consisted of seven women and three men. They were approximately 63 years old and were all retired. Loss of hearing was described to have affected their social life, free time, and in general made their lives more difficult. From the course the participants hoped to gain new skills such as signed speech and lip-reading, uplift their mood, accept their loss of hearing and experience peer support. After the courses they replied that they had more close relations with whom they also were a little more in contact with. More participants were satisfied with e.g. their ability to take care of themselves, their free time, financial situation, family life, mental resources and physical shape. Majority of the participants showed symptoms of depression when the courses started, but at the end of the courses these signs had moderated or disappeared for most of them. The participants felt that during the rehabilitation they had been heard, respected, accepted and been taken care of. The course provided the possibility for confiding, and the discussions gave the participants support and consolidation. In conclusion, the course affected positively on the acclimatization to the hearing loss and the empowerment of the participants. The results of this study can be utilized in disability services, the development of rehabilitation and in the social- and health services of senior citizens.

Functional outcome and health-related quality of life after traumatic brain injury in the framework of the International Classification of Functioning, Disability and Health (ICF)

Traumatic brain injury (TBI) affects people of all ages and is a cause of long-term disability. In recent years, the epidemiological patterns of TBI have been changing. TBI is a heterogeneous disorder with different forms of presentation and highly individual outcome regarding functioning and health-related quality of life (HRQoL). The meaning of disability differs from person to person based on the individual s personality, value system, past experience, and the purpose he or she sees in life. Understanding of all these viewpoints is needed in comprehensive rehabilitation. This study examines the epidemiology of TBI in Finland as well as functioning and HRQoL after TBI, and compares the subjective and objective assessments of outcome. The frame of reference is the International Classification of Functioning, Disability and Health (ICF). The subjects of Study I represent the population of Finnish TBI patients who experienced their first TBI between 1991 and 2005. The 55 Finnish subjects of Studies II and IV participated in the first wave of the international Quality of life after brain injury (QOLIBRI) validation study. The 795 subjects from six language areas of Study III formed the second wave of the QOLIBRI validation study. The average annual incidence of Finnish hospitalised TBI patients during the years 1991-2005 was 101:100 000 in patients who had TBI as the primary diagnosis and did not have a previous TBI in their medical history. Males (59.2%) were at considerably higher risk of getting a TBI than females. The most common external cause of the injury was falls in all age groups. The number of TBI patients ≥ 70 years of age increased by 59.4% while the number of inhabitants older than 70 years increased by 30.3% in the population of Finland during the same time period. The functioning of a sample of 55 persons with TBI was assessed by extracting information from the patients medical documents using the ICF checklist. The most common problems were found in the ICF components of Body Functions (b) and Activities and Participation (d). HRQoL was assessed with the QOLIBRI which showed the highest level of satisfaction on the Emotions, Physical Problems and Daily Life and Autonomy scales. The highest scores were obtained by the youngest participants and participants living independently without the help of other people, and by people who were working. The relationship between the functional outcome and HRQoL was not straightforward. The procedure of linking the QOLIBRI and the GOSE to the ICF showed that these two outcome measures cover the relevant domains of TBI patients functioning. The QOLIBRI provides the patients subjective view, while the GOSE summarises the objective elements of functioning. Our study indicates that there are certain domains of functioning that are not traditionally sufficiently documented but are important for the HRQoL of persons with TBI. This was the finding especially in the domains of interpersonal relationships, social and leisure activities, self, and the environment. Rehabilitation aims to optimize functioning and to minimize the experience of disability among people with health conditions, and it needs to be based on a comprehensive understanding of human functioning. As an integrative model, the ICF may serve as a frame of reference in achieving such an understanding.

Early Growth and Later Health, Focus on Metabolic Syndrome, Obesity and Physical Activity

The Developmental Origins of Health and Disease Hypothesis proposes that adverse health outcomes in adult life are in part programmed during fetal life and infancy. This means that e.g. restricted nutrition during pregnancy programmes the offspring to store fat more effectively, to develop faster and to reach puberty earlier. These adaptations are beneficial in terms of short term survival. However, in developed countries these adaptations often lead to an increased risk of obesity and metabolic disturbances in later life, due to a mismatch between the prenatal and postnatal environment. This thesis aimed to study the role of early growth in people who are obese as adults, but metabolically healthy as well as in those who are normal in weight but metabolically obese. Other study aims were to assess whether physical activity and cardiorespiratory fitness are programmed early in life. The role of socioeconomic status in the development of obesity from a life course setting was also studied. These studies included 2003 men and women born in Helsinki between 1934 and 1944 with detailed information of their prenatal and childhood growth as well as living conditions. They participated in the detailed clinical examination during the years 2001-2004. A sub-group of the subjects participated in the UKK Institute 2-kilometre walk test. Metabolic syndrome was defined according to the 2005 criteria of the International Diabetes Federation. Among the obese men and women 20 % were metabolically healthy. Those with metabolic syndrome did not differ in birth size compared to the healthy ones, but by two years of age, they were lighter and thinner, and remained so up to 11 years. The period when changes in BMIs were predictive of the metabolic syndrome was from birth to 7 years. Of the normal weight individuals 17 % were metabolically obese. Again, there were no differences in birth size. However, by the age 7 years, those men who later developed metabolic syndrome were thinner. Gains in BMI during the first two years of life were protective of the syndrome. Children who were heavier, and especially taller, were more physically active, exercised with higher intensity and had higher cardiorespiratory fitness in their adult life than those who were shorter and thinner as children. Lower educational attainment and lower adult social class were associated with obesity in both men and women. Childhood social class was inversely associated with body mass index only in men while lower household income was associated with higher BMI in women. These results support the role of early life factors in the development of metabolic syndrome and adult life style. Early detection of risk factors predisposing to these conditions is highly relevant from a public health point of view.