Leisure-time physical inactivity is a global public health concern affecting all people in different walks of life, including employees. This inactivity is associated with chronic diseases of lifestyle as well as low work capacity. The purpose of this study was two-fold: to determine leisure-time physical activity (LTPAI), coronary risk- (CRI), health status (HSI) and lifestyle (LSI) indexes of some executive employees in selected African countries; and to determine the effect of leisure-time physical activity (LTPA) on the coronary risk-, health status- and lifestyle- indexes of some executive employees in selected African countries.A cross-sectional study design was followed on a group of 156 (mean age 41.22±10.17) executive employees. Participants were grouped according to age (<35 years; 36–46 years and > 46 years). Standardized questionnaires were used to collect data. Out of 156 participants in the study, 43% occupied top level management and 57% middle level management positions. When data were analyzed according to age groups, 31% and 69% in the less than 35 years age group were in the top and the middle level management, respectively. In the age group 36 to 46 years of age, 47% were in the top level of management and 52.8% middle level management. With regard to LTPA, top level managers (71.6%) scored low LTPA as compared to middle level managers (62.9%). Top level managers scored higher percentages (14.9%) for developing the risk of coronary heart disease. The results show a negative effect of physical activity on selected health parameters, with significant negative relationships between low LTPA and daily lifestyle index (r= -0.52; p=0.01), and moderate LTPA and daily lifestyle index (r= -0.71; p<0.001) for middle managers. It can be concluded that both top and middle level managers exhibited low LTPA and high risk for developing coronary heart disease. It was apparent that the managers in low LTPA are prone to bad stages of life style, health status and coronary risk- indexes compared to the ones with moderate and high LTPA. Additionally, low and moderate LTPA inversely affected selected health parameters of executive employees. No significant association was found for high LTPA with selected health parameters. The study therefore recommends a strategic intervention programme geared towards improving the present state of affairs among the managers in the corporate environment. / Thesis (MA (Biokinetics))--North-West University, Potchefstroom Campus, 2013.

Physical activity has several advantages for health. The first objective of this research was to determine the relationship between physical activity and selected physical and psychological health components. The physical components include: diabetes risk, obesity, cholesterol and cardiovascular disease. The psychological health components include stress and depression. Secondly, this research aimed to determine the relationship between physical activity and medical costs. Medical costs were divided into pharmaceutical, general practitioners and hospital claims. A total of 9 860 employees of the same financial institution in South Africa, between the ages 18 and 64 (x̄ = 35.3 ± 18.6 years), participated in the study and participation was voluntary. No differentiation was made between race groups. The assessment of selected health risk factors and physical activity was done by using the Health Risk Assessment (HRA) methodology developed by the company, Monitored Health Risk (MHM). Assessment included a physical activity, diabetes risk and cardiovascular risk questionnaire, BMI and random blood glucose measurements, as well as stress and depression scores. The amount of days absent from work in the past six months was also determined by the questionnaire. Participants was categorised in three groups – low, moderate and high physical activity participation. Medical expenditure data was obtained from Monitored Health Risk Management Pty (Ltd). Hospital, pharmaceutical and general practitioners (GP) claims included all costs occurring during a six month period. The majority of the study group showed low physical activity participation (78.27%). The results also showed that both men and women showed an increased risk for diabetes, and high physical activity levels have a practically and statistically significant effect on the reduction of diabetes risk. In this study all the physical activity groups of both males and females showed an increased average body mass index (BMI) and therefore are considered to be an increased risk according to the classification as stipulated by the study perimeters. The average means for cholesterol in all groups are categorised as low risk. No significant differences are seen between the female groups as well as between the different male groups. The men in the study group showed higher cardiovascular risk than women. There are no statistically significant differences between the women’s groups. However, regarding the male groups, the low physically active male group showed significant differences to the high physical active male group. Thus, in this study it appears that the men participating in high levels of physical activity show the lowest risk for cardiovascular disease and therefore appear to be influenced by physical activity. The majority of the study group is shown to be in the high stress category (55.48%). It seems that work issues (82%), financial problems (74%) and family problems (69%) contribute most to the population’s high stress levels and depression experience. The Physical activity index (PAI) in relation to stress only shows practical significance in moderate and high physical women. The PAI and stress-related index reports statistically (p≤0.05; 0.001) significant and practice significant difference within the population. There was also a statistically significant (p≤0.05) relation between stress and physical activity in relation to days absent. Although high levels of stress and low levels of physical activity are present in the population, the relation become statistically significant in relation with depression. The study group was divided into two groups when the medical cost was examined. One group consisted of those individuals who do not use chronic medication and the other group, those individuals that use chronic medication. The majority of the study group (chronic and nonchronic medication use), show low physical activity participation (average of 78.80%). The results show statistically and practically significant differences between the groups that do not use chronic medication and the groups that use chronic medication. The women that use chronic medication show an increase in pharmaceutical costs with an increase in physical activity. However, when investigating the GP cost of women who use chronic medication, there is only a small difference in GP cost in the different physical activity participation categories. The data shows that men have higher pharmaceutical costs than women in all the physical activity categories. The results also indicate that men who use chronic medication, participating in low levels of physical activity do show higher pharmacy and GP costs. Medical cost associated with hospitalisation of those men whose chronic medications show an average higher medical cost (R231.72 versus R672.71). The women who are on chronic medication show about two and a half times higher hospitalisation cost (R253.97 versus R650.82) and the men an almost four times higher cost (R189.34 versus R721.71). No practically significant difference was found between the groups. The women show an increased incidence of low physical activity participation (82.38%), whereas 68.80% of the men show low physical activity participation. Women who use chronic medication and participate in moderate physical activity show lower hospital costs. The women in this study group that use chronic medication and participate in high levels of physical activity show the highest hospital cost. The men’s profile indicates that medical cost due to hospital claims rise with the higher levels of physical activity. / Thesis (PhD (Human Movement Sciences))--North-West University, Potchefstroom Campus, 2013.

Background: South Africa is a multicultural, multi-ethnic developing country currently experiencing a unique quadruple burden of disease, of which malnutrition (both over- and under nutrition) is one of them. The increase in childhood obesity within the current South-African health setting is of serious concern, approximately 14% boys and 18% girls currently are overweight and it is estimated that this number will increase to 25% within the next decade. Healthy eating habits and increased physical activity are important components of a healthy lifestyle, and decrease the risk of overweight and obesity. It is also often the corner stone of many lifestyle modification intervention programmes aimed at preventing or decreasing overweight/obesity. Aim: This sub-study was part of a larger intervention study where a nutrition education intervention programme (NEIP) for children in the form of a musical play (based on the South African Food Based Dietary Guidelines [SAFBDG]) was developed to increase nutrition knowledge and thereby also contribute towards healthy lifestyle behaviour. The aim of this sub-study was therefore to explore and describe the attitude of a specific group of primary school children (aged 6-12 years) towards healthy eating, unhealthy eating, and physical activity before and after a NEIP as well as the standard school curriculum. Secondly, it was aimed to identify possible barriers to and motivators for healthy eating, unhealthy eating and physical activity. Methods: Children were randomly selected from the experimental group (n=143) of the main study. Children were selected into one of four focus groups per school (6 children per focus group) from which qualitative data were gathered on children’s attitude and perception towards healthy eating, unhealthy eating, and physical activity. Focus groups were defined by age and gender (boys and girls seperately, grades I-III and grades IVVI seperately), totalling a number of 96 children. A total of 75 children completed this sub-study, 21 children dropped out due to school-related problems or after school activities that clashed with the time slots during which the NEIP was implimented. Quantitative data was gathered with a socio-demographic and physical activity questionnaire, as well as a 3-point hedonic facial expression scale which was used to quantify attitude towards healthy eating, unhealhty eating and physical activity. All data (quantitative and qualitative) were collected at both baseline and end measurements. Results: The main findings of this sub-study were that the attitude of most primary school children towards healthy eating, unhealthy eating or physical activity remained unchanged after a unique NEIP. Five major themes were identified out of focus group discussions namely health awareness, healthy eating, unhealthy eating, physical activity, and consequences of unhealthy eating and sedentary behaviour. Mothers were identified as the main motivator for eating healthy and avoiding unhealthy eating. The taste and smell of food were both either identified as motivators or barriers for healthy eating and unhealthy eating. Older girls associate unhealthy eating with becoming fat while many children associate the combination of unhealthy eating and being sedentary with becoming fat. Most children have a positive attitude towards physical activity and enjoy doing it although the biggest motivator for partaking in physical activity is their parents and not themselves. Conclusion: Even though some children’s attitude did change in the desired direction after the implementation of a unique and fun NEIP, most children’s attitude towards healthy eating, unhealthy eating and physical activity remained unchanged. This might have been due to the measurement tool that was not sensitive enough to detect subtle changes. Various factors that can influence children’s attitude and perceptions towards healthy eating, unhealthy eating and physical activity both positively or negatively were identified. This study is one of only a few that explored and described the ‘true’ motivators of and barriers for children’s attitude towards healthy eating, unhealthy eating and physical activity. Results generated from this sub-study can thus make a valuable contribution to the existing literature available in this specific study field. / Thesis (MSc (Dietetics))--North-West University, Potchefstroom Campus, 2012

The increasing prevalence of childhood obesity worldwide is viewed as a global epidemic (World Health Organization, 2010). It is associated with a variety of health problems as well as physical– (cardio–respiratory endurance, flexibility, muscular strength, muscular endurance, and body composition), and motor proficiency (fine manual control, manual coordination, body coordination, and strength–and–agility) (Asayama et al., 2003:644; Okely et al., 2004:242; Tokmakidis et al., 2006:870). As far as the South African context is concerned, there is little research examining these relationships and the effect of physical intervention there upon, in nine– to 12–year old children. The first and second objectives of this study were to determine whether obesity would influence the physical– and/or the motor proficiency of nine– to 12–year–old South African children. The third and fourth objectives of this study were to determine the effect of a multidisciplinary intervention on the physical– and the motor proficiency of nine– to 12–year–old obese children. For objectives one and two, a cross–sectional study was performed on 280 children (128 boys and 152 girls), with an average age of 10.6 years (±1.05). Anthropometric–, physical– and motor measurements were obtained by the 'Fitnessgram' (Meredith & Welk, 1999) and the 'Bruininks–Oseretsky Test of Motor Proficiency–II' (Bruininks & Bruininks, 2005). Body mass index (BMI) cut–off points were used to classify the children as normal, overweight, or obese (Cole et al., 2000). The data was analysed with regard to the above–mentioned objectives with the Statistica computer program, by means of descriptive statistics, Spearman rank correlations, and variance analyses. The results show that the physical fitness variables, cardio–respiratory endurance and muscular strength, particularly leg muscular strength, showed significant decreases with an increase in BMI. A progressive, but insignificant, decrease was found in muscular endurance with an increase in BMI, while flexibility showed the weakest relationship to BMI. The motor variables strength–and–agility weakened significantly with an increase in BMI, while fine manual control, manual coordination, and body coordination showed the weakest relationships to BMI. Variance analysis showed further significant relationships among BMI, cardio–respiratory endurance, muscular strength, and running speed–and–agility (p<0.05). It can be concluded that health–promoting physical fitness and the motor proficiency of young South African children are negatively influenced by obesity and intervention strategies are recommended to promote the quality of life of such children. For objectives three and four, an availability random sample of 37 experimental subjects, with an average age of 11 years (±0.99) was taken, where 20 subjects (seven boys and 13 girls) took part in a multidisciplinary intervention programme, and 17 subjects (six boys and 11 girls) formed part of a control group. Body composition, physical–, and motor proficiency were analysed by the 'Fitnessgram' (Meredith & Welk, 1999) and the 'Bruininks–Oseretsky Test of Motor Proficiency–II' (Bruininks & Bruininks, 2005) during baseline measurements, on completion of the intervention programme, and after a follow–up period of three months. The results, which were analysed with a repeated–measures analysis, Bonferroni–post–hoc analysis, and dependent and independent t–tests, show that the intervention programme brought about a significant change in all the body composition variables, excluding body height. Flexibility, muscular strength, and abdominal muscular endurance, as well as one of the four fine manual control test items (folding paper), two of the 12 body coordination test items (tapping feet and fingers - opposite sides synchronised, and standing on one leg on a line - eyes closed), and six of the seven strength and agility test items (shuttle run, stepping sideways over a balance beam, one–legged stationary hops, one–legged side hops, two–legged side hops, and sit–ups), showed significant differences from the control group on completion of the intervention programme. The results indicate that the intervention brought about differences in body composition and physical– and motor proficiency and also showed a sustainable effect over a period of three months on body fat percentage, subscapular skinfold and leg muscular strength. From this, it can be deduced that young obese children need sustained guidance to be able to maintain the lifestyle adaptations that are required by obesity interventions. It can be concluded that the physical– and motor proficiency of children is negatively influenced by obesity, that a multidisciplinary intervention programme improves the body composition profile of obese children and has a positive effect on the physical– and the motor proficiency of obese nine– to 12–year old South African children, although the effect is not sustainable without ongoing, controlled intervention. / Thesis (Ph.D. (Kinderkinetics))--North-West University, Potchefstroom Campus, 2012.

The increasing prevalence of childhood obesity worldwide is viewed as a global epidemic (World Health Organization, 2010). It is associated with a variety of health problems as well as physical– (cardio–respiratory endurance, flexibility, muscular strength, muscular endurance, and body composition), and motor proficiency (fine manual control, manual coordination, body coordination, and strength–and–agility) (Asayama et al., 2003:644; Okely et al., 2004:242; Tokmakidis et al., 2006:870). As far as the South African context is concerned, there is little research examining these relationships and the effect of physical intervention there upon, in nine– to 12–year old children. The first and second objectives of this study were to determine whether obesity would influence the physical– and/or the motor proficiency of nine– to 12–year–old South African children. The third and fourth objectives of this study were to determine the effect of a multidisciplinary intervention on the physical– and the motor proficiency of nine– to 12–year–old obese children. For objectives one and two, a cross–sectional study was performed on 280 children (128 boys and 152 girls), with an average age of 10.6 years (±1.05). Anthropometric–, physical– and motor measurements were obtained by the 'Fitnessgram' (Meredith & Welk, 1999) and the 'Bruininks–Oseretsky Test of Motor Proficiency–II' (Bruininks & Bruininks, 2005). Body mass index (BMI) cut–off points were used to classify the children as normal, overweight, or obese (Cole et al., 2000). The data was analysed with regard to the above–mentioned objectives with the Statistica computer program, by means of descriptive statistics, Spearman rank correlations, and variance analyses. The results show that the physical fitness variables, cardio–respiratory endurance and muscular strength, particularly leg muscular strength, showed significant decreases with an increase in BMI. A progressive, but insignificant, decrease was found in muscular endurance with an increase in BMI, while flexibility showed the weakest relationship to BMI. The motor variables strength–and–agility weakened significantly with an increase in BMI, while fine manual control, manual coordination, and body coordination showed the weakest relationships to BMI. Variance analysis showed further significant relationships among BMI, cardio–respiratory endurance, muscular strength, and running speed–and–agility (p<0.05). It can be concluded that health–promoting physical fitness and the motor proficiency of young South African children are negatively influenced by obesity and intervention strategies are recommended to promote the quality of life of such children. For objectives three and four, an availability random sample of 37 experimental subjects, with an average age of 11 years (±0.99) was taken, where 20 subjects (seven boys and 13 girls) took part in a multidisciplinary intervention programme, and 17 subjects (six boys and 11 girls) formed part of a control group. Body composition, physical–, and motor proficiency were analysed by the 'Fitnessgram' (Meredith & Welk, 1999) and the 'Bruininks–Oseretsky Test of Motor Proficiency–II' (Bruininks & Bruininks, 2005) during baseline measurements, on completion of the intervention programme, and after a follow–up period of three months. The results, which were analysed with a repeated–measures analysis, Bonferroni–post–hoc analysis, and dependent and independent t–tests, show that the intervention programme brought about a significant change in all the body composition variables, excluding body height. Flexibility, muscular strength, and abdominal muscular endurance, as well as one of the four fine manual control test items (folding paper), two of the 12 body coordination test items (tapping feet and fingers - opposite sides synchronised, and standing on one leg on a line - eyes closed), and six of the seven strength and agility test items (shuttle run, stepping sideways over a balance beam, one–legged stationary hops, one–legged side hops, two–legged side hops, and sit–ups), showed significant differences from the control group on completion of the intervention programme. The results indicate that the intervention brought about differences in body composition and physical– and motor proficiency and also showed a sustainable effect over a period of three months on body fat percentage, subscapular skinfold and leg muscular strength. From this, it can be deduced that young obese children need sustained guidance to be able to maintain the lifestyle adaptations that are required by obesity interventions. It can be concluded that the physical– and motor proficiency of children is negatively influenced by obesity, that a multidisciplinary intervention programme improves the body composition profile of obese children and has a positive effect on the physical– and the motor proficiency of obese nine– to 12–year old South African children, although the effect is not sustainable without ongoing, controlled intervention. / Thesis (Ph.D. (Kinderkinetics))--North-West University, Potchefstroom Campus, 2012.

The evolution of aerobic metabolic processes unavoidably led to the production of reactive oxygen species (ROS). ROS have the ability to cause harmful oxidative damage to biomolecules. Increased ROS generation and subsequent oxidative stress have been associated with aging and neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases as a result of the extreme sensitivity of the central nervous system to damage from ROS. Antioxidant defence systems have co–evolved with aerobic metabolic processes to counteract oxidative damage inflicted by ROS. The impact of neurodegenerative disorders on society is increasing rapidly as the life expectancy of the global population increases. In this day and age, a much younger group of the population is also experiencing neurodegenerative symptoms as a result of the harmful effect of the human immunodeficiency virus (HIV) on the central nervous system. Plants are an invaluable source of medicinal compounds. The use of plants for their healing properties is rooted in ancient times. The aim of this study was to select from twenty one plants, the plant with the most promising antioxidant activity and to determine whether extracts of this plant could act as free radical scavengers, comparing the results to Trolox, a known free radical scavenger. The next step was to isolate and characterize a compound from an extract exhibiting promising antioxidant activity. Bioassay–guided fractionation was followed to achieve this. During screening trials, twenty one plants, namely Berula erecta, Heteromorpha arborescens, Tarchonanthus camphoratus, Vernonia oligocephala, Gymnosporia buxifolia, Acacia karroo, Elephantorrhiza elephantina, Erythrina zeyheri, Leonotis leonurus, Plectranthus ecklonii, P. rehmanii, P. venteri, Salvia auretia, S. runcinata, Solenostemon latifolius, S. rotundifolius, Plumbago auriculata, Clematis brachiata, Vangueria infausta, Physalis peruviana and Lippia javanica were selected from literature, based on reported antioxidant activity within the plant families, for screening of their antioxidant activity. One hundred and ten extracts were prepared from the leaves, using Soxhlet extraction and the solvents petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc) and ethanol (EtOH), consecutively. The focus during initial screening trials was on chemistry–based assays. The oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays were employed for the primary screening of the one hundred and ten leaf extracts. The ORAC assay was used to determine whether the plant extracts were able to scavenge peroxyl radicals and the FRAP assay was used to determine the reducing abilities of the extracts. Quantification of the peroxyl radical scavenging activity by the ORAC assay revealed that activity was observed for most of the extracts, with the ethyl acetate and ethanol extracts of L. javanica exhibiting the most promising activity. This pattern of activity was also found with the reducing capacity evaluated by the FRAP assay in which the EtOAc and EtOH extracts of L. javanica also exhibited the most promising activity. L. javanica was selected for further study by screening for biological activity, employing the nitro–blue tetrazolium (NBT) assay and thiobarbituric acid reactive substances (TBARS) assay. Using a cyanide model to induce neurotoxic effects in rat brain homogenate, the neuroprotective properties of the extracts of L. javanica leaves were examined using the NBT assay and compared to that of Trolox. The NBT assay determines the level of superoxide anions. All the extracts of L. javanica significantly reduced superoxide anion generation at all concentrations used. The petroleum ether and ethyl acetate extracts, at all concentrations, reduced superoxide anion generation to values lower than that of the control, suggesting that these extracts may be able to attenuate normal free radical processes in the brain. The petroleum ether extract exhibited the most promising activity at a concentration of 1.25 and 2.5 mg/ml and also exhibited similar results as the ethyl acetate extract at a lower concentration than the ethyl acetate extract (2.5 mg/ml compared to 5 mg/ml). A toxin–solution consisting of hydrogen peroxide (H2O2), iron(III)chloride (FeCl3) and ascorbic acid was used to induce lipid peroxidation and the ability of the extracts of the leaves of L. javanica to attenuate lipid peroxidation was investigated in rat brain homogenate and compared to that of Trolox. All of the extracts of L. javanica significantly attenuated toxininduced lipid peroxidation at all concentrations used. All of the extracts were also able to significantly attenuate toxin–induced lipid peroxidation to values lower than that of the control. These results suggest that all of the extracts of L. javanica possess the ability to attenuate not only toxin–induced lipid peroxidation, but also lipid peroxidation that occurs during normal processes in the brain. The petroleum ether extract was subjected to bioassay–guided fractionation using column and thin–layer chromatography and the NBT and TBARS assays. Fraction DD1 was investigated by means of nuclear magnetic resonance, infrared and mass spectrometry. The exact structure of fraction DD1 was not elucidated. Considering all the results, it is clear that L. javanica shows great potential as a medicinal plant with antioxidant activity and may therefore be beneficial in diminishing the destructive oxidative effects inflicted by free radicals. There are however still many compounds to be isolated from L. javanica. Key words: Verbenaceae, Lippia javanica, antioxidant, neurodegeneration, oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), nitro–blue tetrazolium assay (NBT), thiobarbituric acid reactive substances assay (TBARS). / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2011.

The evolution of aerobic metabolic processes unavoidably led to the production of reactive oxygen species (ROS). ROS have the ability to cause harmful oxidative damage to biomolecules. Increased ROS generation and subsequent oxidative stress have been associated with aging and neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases as a result of the extreme sensitivity of the central nervous system to damage from ROS. Antioxidant defence systems have co–evolved with aerobic metabolic processes to counteract oxidative damage inflicted by ROS. The impact of neurodegenerative disorders on society is increasing rapidly as the life expectancy of the global population increases. In this day and age, a much younger group of the population is also experiencing neurodegenerative symptoms as a result of the harmful effect of the human immunodeficiency virus (HIV) on the central nervous system. Plants are an invaluable source of medicinal compounds. The use of plants for their healing properties is rooted in ancient times. The aim of this study was to select from twenty one plants, the plant with the most promising antioxidant activity and to determine whether extracts of this plant could act as free radical scavengers, comparing the results to Trolox, a known free radical scavenger. The next step was to isolate and characterize a compound from an extract exhibiting promising antioxidant activity. Bioassay–guided fractionation was followed to achieve this. During screening trials, twenty one plants, namely Berula erecta, Heteromorpha arborescens, Tarchonanthus camphoratus, Vernonia oligocephala, Gymnosporia buxifolia, Acacia karroo, Elephantorrhiza elephantina, Erythrina zeyheri, Leonotis leonurus, Plectranthus ecklonii, P. rehmanii, P. venteri, Salvia auretia, S. runcinata, Solenostemon latifolius, S. rotundifolius, Plumbago auriculata, Clematis brachiata, Vangueria infausta, Physalis peruviana and Lippia javanica were selected from literature, based on reported antioxidant activity within the plant families, for screening of their antioxidant activity. One hundred and ten extracts were prepared from the leaves, using Soxhlet extraction and the solvents petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc) and ethanol (EtOH), consecutively. The focus during initial screening trials was on chemistry–based assays. The oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays were employed for the primary screening of the one hundred and ten leaf extracts. The ORAC assay was used to determine whether the plant extracts were able to scavenge peroxyl radicals and the FRAP assay was used to determine the reducing abilities of the extracts. Quantification of the peroxyl radical scavenging activity by the ORAC assay revealed that activity was observed for most of the extracts, with the ethyl acetate and ethanol extracts of L. javanica exhibiting the most promising activity. This pattern of activity was also found with the reducing capacity evaluated by the FRAP assay in which the EtOAc and EtOH extracts of L. javanica also exhibited the most promising activity. L. javanica was selected for further study by screening for biological activity, employing the nitro–blue tetrazolium (NBT) assay and thiobarbituric acid reactive substances (TBARS) assay. Using a cyanide model to induce neurotoxic effects in rat brain homogenate, the neuroprotective properties of the extracts of L. javanica leaves were examined using the NBT assay and compared to that of Trolox. The NBT assay determines the level of superoxide anions. All the extracts of L. javanica significantly reduced superoxide anion generation at all concentrations used. The petroleum ether and ethyl acetate extracts, at all concentrations, reduced superoxide anion generation to values lower than that of the control, suggesting that these extracts may be able to attenuate normal free radical processes in the brain. The petroleum ether extract exhibited the most promising activity at a concentration of 1.25 and 2.5 mg/ml and also exhibited similar results as the ethyl acetate extract at a lower concentration than the ethyl acetate extract (2.5 mg/ml compared to 5 mg/ml). A toxin–solution consisting of hydrogen peroxide (H2O2), iron(III)chloride (FeCl3) and ascorbic acid was used to induce lipid peroxidation and the ability of the extracts of the leaves of L. javanica to attenuate lipid peroxidation was investigated in rat brain homogenate and compared to that of Trolox. All of the extracts of L. javanica significantly attenuated toxininduced lipid peroxidation at all concentrations used. All of the extracts were also able to significantly attenuate toxin–induced lipid peroxidation to values lower than that of the control. These results suggest that all of the extracts of L. javanica possess the ability to attenuate not only toxin–induced lipid peroxidation, but also lipid peroxidation that occurs during normal processes in the brain. The petroleum ether extract was subjected to bioassay–guided fractionation using column and thin–layer chromatography and the NBT and TBARS assays. Fraction DD1 was investigated by means of nuclear magnetic resonance, infrared and mass spectrometry. The exact structure of fraction DD1 was not elucidated. Considering all the results, it is clear that L. javanica shows great potential as a medicinal plant with antioxidant activity and may therefore be beneficial in diminishing the destructive oxidative effects inflicted by free radicals. There are however still many compounds to be isolated from L. javanica. Key words: Verbenaceae, Lippia javanica, antioxidant, neurodegeneration, oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), nitro–blue tetrazolium assay (NBT), thiobarbituric acid reactive substances assay (TBARS). / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2011.

Fluoxetine and escitalopram are the only antidepressants approved by the Food and Drug Administration of the United States of America (FDA) for treatment of major depression in children and adolescents. Both drugs are selective serotonin reuptake inhibitors (SSRIs). In recent years there has been a growing concern over the long-term developmental effects of early-life exposure to SSRIs. The current study employed male Flinders Sensitive Line (FSL) rats, a well described and validated translational model of depression, to investigate the long term effects of pre-pubertal fluoxetine exposure. First we examined the effect of such early-life exposure on the development of depressive-like behaviour, locomotor activity and anxiety-like behaviour as manifested in early adulthood. Next, the current study investigated the effect of pre-pubertal fluoxetine exposure on the acute monoaminergic stress response, as displayed later in life. Animals received either saline (vehicle control), or 10 mg/kg/day fluoxetine from postnatal day (ND+) 21 to ND+34 (pre-puberty). The treatment period was chosen to coincide with a developmental phase where the serotonergic system’s neurodevelopment had been completed, yet the noradrenergic and dopaminergic systems had not, a scenario comparable to neurodevelopment in human adolescents. Both behavioural and in vivo intra-cerebral microdialysis experiments were conducted after ND+60 (early adulthood). On ND+60 rats allocated to behavioural experiments were evaluated for depressive-like behaviour in the forced swim test (FST), locomotor activity in the open field test (OFT), and anxiety-like behaviour in the OFT. Corticosterone concentrations were shown to be significantly higher in male FSL rats exposed to a 10 minute forced swim stress when compared to male FSL rats not exposed to a forced swim stress on ND+60. In the microdialysis experiments the rats were exposed to an acute 10 minute forced swim stress and the concentrations of the monoamines and their metabolites were measured before, during, and after the acute stressor. Relative to saline-treated (control) rats, fluoxetine-treated FSL rats did not show long-term changes in immobility in the FST (i.e. no anti-depressant-like activity) on ND+60. Like-wise anxiety-like behaviour in the OFT did not change. However, a significant decrease in locomotor activity was observed in fluoxetine-treated FSL rats compared to saline-treated (control) rats. These data suggest that a long-lasting anti-depressant-like effect of fluoxetine may be masked by the effect on locomotor activity. With measurements from the microdialysis experiments a significant attenuation of the noradrenergic stress response was observed in fluoxetine-treated rats compared to saline controls. A similar picture was observed for 5-hydroxyindole-3-acetic acid (5-HIAA), a metabolite of serotonin (5-HT), although the latter was not statistically significant. At baseline, before the stressor, significant increase in dopamine (DA) levels were observed in fluoxetine treated rats when compared to saline controls, suggesting that enhanced dopamine neurotransmission may comprise a long-term effect of pre-pubertal fluoxetine treatment. There were no discernible differences in homovanilllic acid (HVA) concentrations between fluoxetine-treated rats and saline controls. In conclusion significant developmental effects of pre-pubertal fluoxetine exposure were observed later in life and these findings warrant further investigation. / MPharm (Pharmacology), North-West University, Potchefstroom Campus, 2015

Fluoxetine and escitalopram are the only antidepressants approved by the Food and Drug Administration of the United States of America (FDA) for treatment of major depression in children and adolescents. Both drugs are selective serotonin reuptake inhibitors (SSRIs). In recent years there has been a growing concern over the long-term developmental effects of early-life exposure to SSRIs. The current study employed male Flinders Sensitive Line (FSL) rats, a well described and validated translational model of depression, to investigate the long term effects of pre-pubertal fluoxetine exposure. First we examined the effect of such early-life exposure on the development of depressive-like behaviour, locomotor activity and anxiety-like behaviour as manifested in early adulthood. Next, the current study investigated the effect of pre-pubertal fluoxetine exposure on the acute monoaminergic stress response, as displayed later in life. Animals received either saline (vehicle control), or 10 mg/kg/day fluoxetine from postnatal day (ND+) 21 to ND+34 (pre-puberty). The treatment period was chosen to coincide with a developmental phase where the serotonergic system’s neurodevelopment had been completed, yet the noradrenergic and dopaminergic systems had not, a scenario comparable to neurodevelopment in human adolescents. Both behavioural and in vivo intra-cerebral microdialysis experiments were conducted after ND+60 (early adulthood). On ND+60 rats allocated to behavioural experiments were evaluated for depressive-like behaviour in the forced swim test (FST), locomotor activity in the open field test (OFT), and anxiety-like behaviour in the OFT. Corticosterone concentrations were shown to be significantly higher in male FSL rats exposed to a 10 minute forced swim stress when compared to male FSL rats not exposed to a forced swim stress on ND+60. In the microdialysis experiments the rats were exposed to an acute 10 minute forced swim stress and the concentrations of the monoamines and their metabolites were measured before, during, and after the acute stressor. Relative to saline-treated (control) rats, fluoxetine-treated FSL rats did not show long-term changes in immobility in the FST (i.e. no anti-depressant-like activity) on ND+60. Like-wise anxiety-like behaviour in the OFT did not change. However, a significant decrease in locomotor activity was observed in fluoxetine-treated FSL rats compared to saline-treated (control) rats. These data suggest that a long-lasting anti-depressant-like effect of fluoxetine may be masked by the effect on locomotor activity. With measurements from the microdialysis experiments a significant attenuation of the noradrenergic stress response was observed in fluoxetine-treated rats compared to saline controls. A similar picture was observed for 5-hydroxyindole-3-acetic acid (5-HIAA), a metabolite of serotonin (5-HT), although the latter was not statistically significant. At baseline, before the stressor, significant increase in dopamine (DA) levels were observed in fluoxetine treated rats when compared to saline controls, suggesting that enhanced dopamine neurotransmission may comprise a long-term effect of pre-pubertal fluoxetine treatment. There were no discernible differences in homovanilllic acid (HVA) concentrations between fluoxetine-treated rats and saline controls. In conclusion significant developmental effects of pre-pubertal fluoxetine exposure were observed later in life and these findings warrant further investigation. / MPharm (Pharmacology), North-West University, Potchefstroom Campus, 2015

The rising number of the population that present with major depressive disorder has intensified the need to identify and elucidate new biological markers for the diagnosis and treatment of depression. Depression presents with evidence of changes in the nitric oxide (NO) pathway. In this study, levels of various endogenous markers of the NO cascade, viz. nitrite (NO2–), asymmetrical dimethylarginine (ADMA) and arginase II activity, were investigated in the Flinders Sensitive Line (FSL) rat, a genetic animal model of depression. The aim of the current study was to determine if there are differences between these markers in the plasma of the FSL rat compared to its healthy control, the (Flinders Resistant Line) FRL rat, with the possibility of considering their use as biomarkers of depression. Nitrite was chosen as metabolite over nitrate (NO3–) because the dietary intake of nitrite and/or nitrate does not significantly affect nitrite (NO2–) levels in plasma. Although this is of no significance if applied to rats, it is an important factor to be considered when doing clinical studies. For neurochemical determination of nitrite a sensitive fluorometric reversed phase high–performance liquid chromatographic (HPLC) assay was developed to analyze nitrite in human and rat plasma. Derivatization of sample nitrite was performed with 2,3–diaminonaphthalene (DAN) followed by the quantification of the stable and highly fluorescent product, 2,3–naphthotriazole (NAT). Determination of arginase II activity was performed by measuring L–arginine and L–ornithine concentrations in the plasma, while ADMA was measured simultaneously with L–arginine and L–ornithine using liquid chromatography/tandem mass spectrometry, or LC/MS/MS. Plasma nitrite levels of FSL rats were significantly decreased compared to plasma nitrite levels in the FRL rat, but neither the levels of ADMA nor arginase II activity showed a significant difference between the FSL and FRL rat groups. From these results it is concluded that in accordance with previous studies, the NO pathway plays an important role in the pathophysiology of depression, as depicted in the differences found between plasma nitrite levels in the FSL rat compared to its healthy control. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2011.