No description available.

The romance of leadership is over. So is the romance of followership. Indeed, followers are notpassive as they used to be considered. The majority of the scholars underline their active rolein the creation of the relationship with the leader. This is why when it comes to toxic leadership;the leader is not the only one to blame. Actually, followers are equally responsible for themaintenance and even the creation of toxicity in an organization context. Padilla et al. (2007)argue that toxic leadership comes from the interaction of a toxic leader, susceptible followersand a conducive environment.This research paper focuses on the interaction of two of these components: susceptiblefollowers and the conducive environment. The aim is to understand the role of the influence ofthe environment on decision making in a first time. Then, how individuals, under pressure whenit comes to decision making are more likely to maintain or foster toxicity.After a deep digging into the psychological and sociological mechanisms which are at the basisof the following process, this paper ends by a reflection on human being’s relation withfreedom.

No description available.

As algae-derived biofuel is a promising renewable energy source, it is well-established that micro-algae have the potential to make a significant contribution to transportation fuel demand. Although it has many advantages including high areal productivity, there are many negative factors. One of these factors is the predation of algae by amoebas, protozoans, ciliates and rotifers, particularly in open pond systems. For example, the rotifer Brachionus plicatilis, is able to eat as much as 12,000 algae cells per hour and can be responsible for an entire pond crash within days. Thus, these higher organisms need to be controlled in order to satisfy large-scale algae crop and biofuel production demand. One method of predation control involves the introduction of a toxic chemical to an algal culture that the predator has a higher sensitivity to with respect to algae. Ideally, predation could be minimized or eliminated without a substantial effect on the algal culture growth. Chlorella kessleri was used as the algal culture and Brachionus calyciflorus as the source of predation. Research was conducted in five stages. First, chlorine dissipation tests were carried out using spring water, distilled water, Bolds Basal Medium (BBM), and three different dry weights of algal suspension in order to analyze the dissipation rate of the residual chlorine. The results showed that chlorine in distilled water and spring water rarely dissipated while chlorine concentration in algal suspension rapidly decreased by a maximum of 90% within the second hour. Second, acute chlorine toxicity tests were conducted in order to find the 24-hr LC50 of B. calyciflorus. The 24-hr LC50 of the test animal was 0.198 mg Cl/L. Third, chlorine toxicity tests were conducted in order to find the LC50 of Chlorella kessleri. The 24-hr LC50 of C. kessleri was 0.321 mg Cl/L. Based on these results, the test animal was more sensitive to chlorine than the test algae; therefore chlorine may be used to avoid algae pond crashes by B. calyciflorus. Fourth, C. kessleri and B. calyciflorus were combined into one test to determine how long it would take to observe an algal culture crash. The result demonstrated that the higher the population of predators in algal suspension, the faster it crashed. Finally, chlorine, C. kessleri, and B. calyciflorus were combined into one test to determine what chlorine concentration and dosing interval was needed to significantly reduce predation without significantly reducing algae growth. The results of the fifth experiment showed that the effective intermittent chlorine concentration was between 0.45 and 0.60 mg Cl/L, and a short interval of chlorine dosing was effective in inhibiting rotifers in algal suspension. Even though the rotifers in algal suspension were inhibited by 0.45 to 0.60 mg Cl/L, algae growth was greatly inhibited by chlorine. In this respect, future work is needed to reduce the effect on algae by chlorine or alternative chemicals.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

The use of traditional and natural medicines in primary healthcare or alternative therapy is on the increase. However, the safety and efficacy of these medicines have not yet been confirmed. Pharmacognosy, the study of the properties of drugs, potential drugs or drug substances of natural origin and the search for new drugs from natural resources, is therefore of extreme importance in today’s healthcare environment. Cotyledon orbiculata L. var. orbiculata (Haw.) DC., a succulent shrub that is widely distributed over the whole of southern Africa, is an example of a plant used in traditional medicine for its antiepileptic effects. Oxidative stress can either be the cause of, or be secondary to epilepsy pathogenesis. Lipid peroxidation causes the disruption of cell membranes which leads to cell destruction and, in the case of neurological disorders, neurodegeneration. Reactive species have also been found to influence neurotransmission by affecting neurotransmitter metabolism and functions. Reactive species can therefore be responsible for the development of convulsions. Conventional anti-epileptics have shown to exert neuroprotective effects but information or research regarding their ability to prevent epilepsy from becoming chronic does either not exist or is not promising. Antioxidants have potential in the treatment of epileptic seizures as well as the prevention of chronic epilepsy by preventing the effects that oxidative stress has on neurotransmitter metabolism and functions that cause alterations in neuronal excitability and seizure threshold, ultimately leading to epileptic foci. The aim of this study was to evaluate the potential of the bufadienolide orbicusides of C. orbiculata and analogues as anti-epileptic treatment through antioxidant activity. Initially the isolation of novel antioxidants from C. orbiculata leaf juice was attempted. The antioxidant activity of the concentrated juice and fractions resulting thereof were evaluated with two assays. The thiobarbituric acid (TBA) assay was used to measure the extent of lipid peroxidation and nitroblue tetrazolium (NBT) assay was used to measure superoxide scavenging activity in rat brain homogenate. The low concentrations of orbicusides prompted the determination of the activity of two commercial bufadienolides (bufalin and cinobufotalin) and two bufadienolide analogues, synthesised by the esterification of trans-androsterone and androstanolone, respectively, using coumalic acid, producing Compound 1 and Compound 2. The toxicity of the commercial bufadienolides and synthesised analogues were evaluated by using the MTT assay (a cell viability assay). C. orbiculata juice showed significant pro-oxidant activity in both assays. Bufalin showed significant pro-oxidant activity in the TBA assay. Cinobufotalin showed no significant activity. Compound 1 showed pro-oxidant activity in the TBA assay and Compound 2 showed slight antioxidant activity in the NBT assay. The commercial bufadienolides showed low cell viability, indicating significant toxicity. The synthesised analogues showed a significant reduction in toxicity (despite Compound 2 being moderately toxic) when compared to the toxicity of the commercial bufadienolides. The low concentrations of orbicusides in the plant material and the antioxidant assay results of the two commercial bufadienolides suggested that the orbicusides may not be involved in the antioxidant properties of C. orbiculata. However, the antioxidant activity of Compound 2 showed that altering the pyrone moiety of bufadienolides could possibly improve antioxidant activity. The reduced toxicity and slight antioxidant activity of the synthesised bufadienolide analogues motivates further investigation. / MSc (Pharmaceutical Chemistry), North-West University, Potchefstroom Campus, 2014

The use of traditional and natural medicines in primary healthcare or alternative therapy is on the increase. However, the safety and efficacy of these medicines have not yet been confirmed. Pharmacognosy, the study of the properties of drugs, potential drugs or drug substances of natural origin and the search for new drugs from natural resources, is therefore of extreme importance in today’s healthcare environment. Cotyledon orbiculata L. var. orbiculata (Haw.) DC., a succulent shrub that is widely distributed over the whole of southern Africa, is an example of a plant used in traditional medicine for its antiepileptic effects. Oxidative stress can either be the cause of, or be secondary to epilepsy pathogenesis. Lipid peroxidation causes the disruption of cell membranes which leads to cell destruction and, in the case of neurological disorders, neurodegeneration. Reactive species have also been found to influence neurotransmission by affecting neurotransmitter metabolism and functions. Reactive species can therefore be responsible for the development of convulsions. Conventional anti-epileptics have shown to exert neuroprotective effects but information or research regarding their ability to prevent epilepsy from becoming chronic does either not exist or is not promising. Antioxidants have potential in the treatment of epileptic seizures as well as the prevention of chronic epilepsy by preventing the effects that oxidative stress has on neurotransmitter metabolism and functions that cause alterations in neuronal excitability and seizure threshold, ultimately leading to epileptic foci. The aim of this study was to evaluate the potential of the bufadienolide orbicusides of C. orbiculata and analogues as anti-epileptic treatment through antioxidant activity. Initially the isolation of novel antioxidants from C. orbiculata leaf juice was attempted. The antioxidant activity of the concentrated juice and fractions resulting thereof were evaluated with two assays. The thiobarbituric acid (TBA) assay was used to measure the extent of lipid peroxidation and nitroblue tetrazolium (NBT) assay was used to measure superoxide scavenging activity in rat brain homogenate. The low concentrations of orbicusides prompted the determination of the activity of two commercial bufadienolides (bufalin and cinobufotalin) and two bufadienolide analogues, synthesised by the esterification of trans-androsterone and androstanolone, respectively, using coumalic acid, producing Compound 1 and Compound 2. The toxicity of the commercial bufadienolides and synthesised analogues were evaluated by using the MTT assay (a cell viability assay). C. orbiculata juice showed significant pro-oxidant activity in both assays. Bufalin showed significant pro-oxidant activity in the TBA assay. Cinobufotalin showed no significant activity. Compound 1 showed pro-oxidant activity in the TBA assay and Compound 2 showed slight antioxidant activity in the NBT assay. The commercial bufadienolides showed low cell viability, indicating significant toxicity. The synthesised analogues showed a significant reduction in toxicity (despite Compound 2 being moderately toxic) when compared to the toxicity of the commercial bufadienolides. The low concentrations of orbicusides in the plant material and the antioxidant assay results of the two commercial bufadienolides suggested that the orbicusides may not be involved in the antioxidant properties of C. orbiculata. However, the antioxidant activity of Compound 2 showed that altering the pyrone moiety of bufadienolides could possibly improve antioxidant activity. The reduced toxicity and slight antioxidant activity of the synthesised bufadienolide analogues motivates further investigation. / MSc (Pharmaceutical Chemistry), North-West University, Potchefstroom Campus, 2014

South Africa is a country of great diversity. Different climate zones and a host of different habitats make South Africa the perfect platform for rich floral diversity. This floral diversity lends itself to the study of natural products by discovering new natural drugs that can be used in the treatment of many illnesses. Studies into the antioxidant properties of plants that are used in traditional medicine are an important aspect of research to determine the rationale of the use of plants by traditional healers. Many neurodegenerative diseases, like epilepsy, Parkinson s and Alzheimer s diseases, are linked to oxidative stress. Antioxidants could play a major role as neuroprotective agents and could alter the progression of these diseases. Epilepsy is one of the world s most prevalent central nervous system disorders and affects more than seventy per one thousand children in South Africa. Most of these cases are people in rural areas of South Africa where communities rely on the use of traditional medicine. Cotyledon orbiculata L. var orbiculata (Haw.) DC. is widely used in traditional medicine to treat epilepsy and other central nervous system disorders. The need to screen these plants for activity and toxicity is very important to understand the complex mechanism of action in the treatment of patients. In this study the methanol extract and three different fractions of the methanol extract of Cotyledon orbiculata were used to test for antioxidant activity and toxicity towards neuroblastoma cells. The freeze dried leaves of Cotyledon orbiculata were extracted with methanol using a Soxhlet apparatus. The concentrated extracts were analysed using HPLC (high pressure liquid chromatography) and three major peaks were selected for isolation. Three assays were performed to assess the antioxidant activity and toxicity of the isolated compounds. The thiobarbituric acid assay (TBA) quantifies the extent of the inhibition of lipid peroxidation in rat brain homogenates by the isolated fractions. All of the samples were able to attenuate lipid peroxidation as seen from the results obtained from the TBA assay. The methanol extract showed the best attenuation of lipid peroxidation in the rat brain homogenate with fraction 1 and 2 showing greater attenuation of lipid peroxidation than fraction 3. The nitroblue tetrazolium assay (NBT) quantifies the ability of the fractions to scavenge superoxide radicals in a rat brain homogenate. All samples were able to scavenge superoxide radicals as indicated by the NBT assay. The methanol extract showed the best superoxide scavenging abilities in the assay whereas fraction 1 showed better scavenging abilities than fraction 2 and 3. The 3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyltetrazolium bromide assay (MTT) indicates the toxicity of the fractions towards neuroblastoma cells. The methanol extract and fraction 2 in the highest concentration of 10 mg/ml were the only samples that showed toxicity towards neuroblastoma cells. The molecular structure of a compound from fraction 2 was determined by using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), and mass spectroscopy (MS). This compound was identified as diethyl malate. Diethyl malate is an artefact that is generated in HPLC procedures in the presence of malic acid (which naturally occurs in the leaves of Cotyledon orbiculata) and ethanol. The methanol extract of Cotyledon orbiculata has high antioxidant activity and could be due to the presence of malic acid in the leaves of the plant. The rationale in the use of Cotyledon orbiculata in the treatment of epilepsy could not be determined due to the isolation of an artefact, diethyl malate, obtained from the fraction. Further research should include methods to prevent artefact formation and purification of the samples that are obtained. / Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2012.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

South Africa is a country of great diversity. Different climate zones and a host of different habitats make South Africa the perfect platform for rich floral diversity. This floral diversity lends itself to the study of natural products by discovering new natural drugs that can be used in the treatment of many illnesses. Studies into the antioxidant properties of plants that are used in traditional medicine are an important aspect of research to determine the rationale of the use of plants by traditional healers. Many neurodegenerative diseases, like epilepsy, Parkinson s and Alzheimer s diseases, are linked to oxidative stress. Antioxidants could play a major role as neuroprotective agents and could alter the progression of these diseases. Epilepsy is one of the world s most prevalent central nervous system disorders and affects more than seventy per one thousand children in South Africa. Most of these cases are people in rural areas of South Africa where communities rely on the use of traditional medicine. Cotyledon orbiculata L. var orbiculata (Haw.) DC. is widely used in traditional medicine to treat epilepsy and other central nervous system disorders. The need to screen these plants for activity and toxicity is very important to understand the complex mechanism of action in the treatment of patients. In this study the methanol extract and three different fractions of the methanol extract of Cotyledon orbiculata were used to test for antioxidant activity and toxicity towards neuroblastoma cells. The freeze dried leaves of Cotyledon orbiculata were extracted with methanol using a Soxhlet apparatus. The concentrated extracts were analysed using HPLC (high pressure liquid chromatography) and three major peaks were selected for isolation. Three assays were performed to assess the antioxidant activity and toxicity of the isolated compounds. The thiobarbituric acid assay (TBA) quantifies the extent of the inhibition of lipid peroxidation in rat brain homogenates by the isolated fractions. All of the samples were able to attenuate lipid peroxidation as seen from the results obtained from the TBA assay. The methanol extract showed the best attenuation of lipid peroxidation in the rat brain homogenate with fraction 1 and 2 showing greater attenuation of lipid peroxidation than fraction 3. The nitroblue tetrazolium assay (NBT) quantifies the ability of the fractions to scavenge superoxide radicals in a rat brain homogenate. All samples were able to scavenge superoxide radicals as indicated by the NBT assay. The methanol extract showed the best superoxide scavenging abilities in the assay whereas fraction 1 showed better scavenging abilities than fraction 2 and 3. The 3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyltetrazolium bromide assay (MTT) indicates the toxicity of the fractions towards neuroblastoma cells. The methanol extract and fraction 2 in the highest concentration of 10 mg/ml were the only samples that showed toxicity towards neuroblastoma cells. The molecular structure of a compound from fraction 2 was determined by using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), and mass spectroscopy (MS). This compound was identified as diethyl malate. Diethyl malate is an artefact that is generated in HPLC procedures in the presence of malic acid (which naturally occurs in the leaves of Cotyledon orbiculata) and ethanol. The methanol extract of Cotyledon orbiculata has high antioxidant activity and could be due to the presence of malic acid in the leaves of the plant. The rationale in the use of Cotyledon orbiculata in the treatment of epilepsy could not be determined due to the isolation of an artefact, diethyl malate, obtained from the fraction. Further research should include methods to prevent artefact formation and purification of the samples that are obtained. / Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2012.