The aim of this work is to study the kinetics of generation and inhibitory action of peroxy radicals by the potentiometric method on the 2,2'-azobis (2-methylpropionamidine) dihydrochloride (AAРH) model. The paper describes the causes and the effects of free radicals in the human body, the body's antioxidant system and methods for determining antioxidant / antiradical activity. In the course of the work, the kinetic parameters of the AAPH reaction with hexacyanoferrate (II) of potassium were studied by a potentiometric method. / Целью данной работы является исследование кинетики генерирования и ингибирующего действия пероксильных радикалов потенциометрическим методом на модели 2,2'-азобис(2-метилпропионамидин) дигидрохлорида (ААРН). В работе описаны причины возникновения и действия свободных радикалов в организме человека, антиоксидантная система организма и методы определения антиоксидантной/антирадикальной активности. В процессе работы исследованы кинетические параметры реакции ААРН с гексацианоферратом (II) калия потенциометрическим методом.

Целью выпускной квалификационной работы является комплексное исследование интегральных антиоксидантных параметров препаратов комбинированного действия для терапии вирусных и нейродегенеративных заболеваний. Были изучены пути образования свободных радикалов, рассмотрены антиоксидантные подходы в терапии различных заболеваний. С использованием предложенных потенциометрических методов была исследована антиоксидантная (АОЕ) и антирадикальная (АРЕ) емкость синтезированных триазолов и имидазолов, модифицированных полифенолами. АОЕ определяли потенциометрическим методом с использованием окислителя нерадикальной природы – K3[Fe(CN)6]/K4[Fe(CN)6], АРЕ оценивали потенциометрическим методом с использованием радикал-генерирующей системы 2,2´-азобис(2-метилпропионамидин) дигидрохлорида (ААРН). Стехиометрические коэффициенты ингибирования изученных триазолов принимают значения от 0 до 15, имидазолов от 0 до 5 в зависимости от количества активных групп в молекуле антиоксиданта, их расположением и с механизмом обрыва цепей на антиоксиданте. Были проведены корреляционные исследования с применением независимых спектрофотометрических методов. / Objective of the work: comprehensive study of integral antioxidant parameters of combined action drugs for the treatment of viral and neurodegenerative diseases. We have considered ways to form free radicals and antioxidant approaches in therapy of various diseases. In the process of work we investigated the antioxidant parameters adducts of triazole and imidazoles modified with polyphenols. Particularly, the determination of antioxidant capacity with oxidizing agents of a radical (2,2'-azobis (2-methylpropionamidine) dihydrochloride (AAPH)) and non-radical nature (K3[Fe(CN)6]/K4[Fe(CN)6) was performed by using the potentiometric method. Stoichiometric inhibition coefficients of the studied triazoles take values from 0 to 15, imidazoles – from 0 to 5, depending on the number of active groups in the antioxidant molecule, their location and the mechanism of chain termination on the antioxidant. Spectrophotometric studies were carried out using the reactions of the interaction of antioxidants with a stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and reagent Folin-Ciocalteu to confirm the correctness of the results.

<p>Aging erodes motivation, cognition, sensory modalities and physical capacities, effectively depleting quality of life. Declining sensory, cognitive and motor function are reliable biomarkers of aging and mortality risk. These declines are associated with dysregulation of systemic and cellular processes. We developed a complex dietary supplement (DSP) designed to ameliorate five mechanisms of aging (oxidative processes, inflammation, mitochondrial function, insulin resistance and membrane integrity). Remarkably, normal mice fed the DSP retained youthful functionality into old ages, reflecting slower aging rates. Marked improvements in motor function, memory capacity, spatial learning, muscle strength, visual acuity, olfaction, fecundity and important behavioral functions were observed in aging supplemented mice. Conversely, untreated control animals showed age-related declines in all of the above. Functional improvements were associated with reduced oxidative damage, elevated mitochondrial activity, positive cellular energy balance, improved glucose tolerance, boosted neurotransmitters, greater synaptic density and higher neuronal numbers throughout the brain. A 30% reduction in cancer rates was also documented for DSP treated p53+/- mice. The vast functional benefits greatly exceed the modest longevity extension (11%) in normal supplemented mice. For aging humans, maintaining functionality and performance into later years may provide greater socioeconomic and health benefits than simply prolonging lifespan. Implications of these findings extend to common age-related pathologies including dementia and neurodegenerative diseases, diabetes, cancer, sarcopenia and age-related macular degeneration. Although identifying the role of specific ingredients remains outstanding, results provide proof of principle that complex dietary cocktails can powerfully ameliorate biomarkers of aging and modulate mechanisms considered ultimate goals for aging interventions.</p> / Doctor of Philosophy (PhD)

Cette étude vise à mieux comprendre les réactions impliquées dans le craquage thermique des huiles en basins sédimentaires. Des pyrolyses d'octane, de toluène et de mélanges octane/toluène ont été effectuées entre 330°C et 450°C et des pressions allant de 1 bar à 700 bar. Le mécanisme radicalaire développé permet de rendre compte de l’influence de la température et de la pression sur la distribution des produits ainsi que sur la conversion jusqu'aux conditions de gisement (200°C, 150-1000 bar). Les pyrolyses du toluène pur et du mélange octane/toluène ont permis de modéliser le rôle inhibiteur des alkylaromatiques sur le craquage des hydrocarbures. Cette étude démontre l'importance des co réactions et donc de la composition des huiles sur la stabilité thermique des pétroles en gisements / This study aims at a better understanding of the reactions involved in the thermal cracking of oil within sedimentary basins. Pyrolysis of octane, toluene and mixtures of octane / toluene were performed between 330°C and 450°C and at pressures going from 1 bar to 700 bar. The constructed radical mechanism allows to report the influence of temperature and pressure on the distribution of products as well as the conversion from laboratory to reservoir conditions (200°C, 150-1000 bar). The pyrolysis of pure toluene and the octane / toluene mixture allowed to model the inhibition effect of alkylaromatics on the cracking of hydrocarbons. This study demonstrates the importance of co reactions and thus the composition of oil on the thermal stability of petroleums in reservoirs

&#946;2-glicoproteína I (&#946;2GPI) é encontrada (200&#181;g/mL) no plasma, 60% livre e 40% em lipoproteínas. Esta proteína de fase aguda, com afinidade por superfícies negativas pode ser clivada pela plasmina. Fragmentos são purificados como dímeros ou multímeros de &#946;2GPI. Formas monomérica e dimérica de &#946;2GPI foram purificadas de soro humano e identificadas por SDS-PAGE, imunoblot e ELISA Somente a forma monomérica foi detectada no teste ELISA Os efeitos de ambas as formas sobre o burst respiratório de polimorfonucleares humanos (PMN), estimulados in vitro com zymosan opsonizado, foram estudados por quimioluminescência amplificada por luminol ou lucigenina e citometria de fluxo, pela oxidação do OCFH. A forma monomérica inibiu a quimioluminescência amplificada por luminol (-43.6 x -7.33 AEU/s), mas não por lucigenina, e aumentou a oxidação de DCFH e a produção de Óxido Nítrico (&#8226;NO). É provável que o &#8226;No, via peroxinitrito, medeie os efeitos de &#946;2GPI sobre o burst respiratório de PMN. / Circulating blood contains approximately 200&#181;g/mL of &#946; 2-glycoprotein I (&#946;2GPI), either free (60%) or lipoprotein bound (40%). This acute phase protein, with affinity for negative surfaces, can be cleaved by plasmin. Fragments purify as dimeric or multimeric (&#946;2GPI. Both (&#946;2GPI forms were purified from human sera and identified by SDS-PAGE, immunoblotting and ELISA. ELISA reactivity was dependent on the monomeric status of (&#946;2GPI. The effects of dimeric and monomeric (&#946;2GPI upon respiratory burst of human polimorphonuclear neutrophils (PMN) stimulated in vitro with opsonized zymosan were studied. Respiratory burst was evaluated by luminol- or lucigenin-amplified chemiluminescence, or by DCFH oxidation (flow-cytometry assay). The monomeric, but not the dimeric form, inhibited the luminol chemiluminescence of zymosan-stimulated PMNs (-43.6 x -7.33 AEU/s). Lucigenin chemiluminescence was insensitive to (&#946;2-GPI. Monomeric (&#946;2GPI increases both DCFH oxidation and nitric oxide production. Nitric oxide, probably through peroxynitrite reactions, mediates (&#946;2GPI effects upon PMNs respiratory burst.

<p>Ispitivanja hemijskog sastava etarskih ulja i<br />ekstrakata izvedena su na vrsti Myrtus communis<br />L. sa pet lokaliteta iz Crne Gore. Pored toga,<br />ispitana je njihova antioksidantna aktivnost u<br />razlicitim in vitro sistemima kako bi se utvrdio<br />uticaj pomenutih ekstrakata i etarskih ulja na<br />neutralizaciju DPPH, NO, OH i 2- radikala, kao<br />i njihov uticaj na lipidnu peroksidaciju u<br />lipozomima i inhibiciju enzima ksantin-oksidaze.<br />Takode, ispitana je i antibakterijska aktivnost<br />etarskih ulja i ekstrakata ove vrste na 9<br />bakterijskih sojeva, kao i njihov antimutageni<br />potencijal na bakterijskom soju Escherichia coli<br />IC 202.</p> / <p> In this tessis the chemical analysis of the<br /> essential oils and methanolic extracts<br /> from five plant samples of Myrtus<br /> communis L., collected from different<br /> localities in Montenegro, have been<br /> investigate. Beside that, their antioxidant<br /> activity in differwnt in vitro systems has<br /> been study to establish their scavenging<br /> potential towards DPPH, NO, OH, and<br /> O2- free radicals, as wel as their effects<br /> on lipid peroxidation in liposoma and<br /> inhibition enzyme XOD. Also, the<br /> antibacterial activity of the essential oils<br /> and methanolic extract has been study on<br /> 9 bacterial strains, as wel as their<br /> antimutagenic effects on bacterial strain<br /> E. Colli IC202.</p>

An investigation into stress experience and the use of coping skills by departemental heads of schools: guidelines for support. Stress occurs when one's perception of demands exceeds his perception of his abilities to meet them. Except for work related demands, a variety of demands and threats in the environment have to be faced continuously. As a result stress is created that manifest in people's behavior, work efficiency and socialization. In general, the education profession is considered among the most stressful careers in the world. This also applies to the South African educational system. U'hm teachers experience stress, it has a negative effect on their beloved ones. colleagues and the learners. Therefore teacher stress has a negative effect on the teaching system in general. Thus teacher stress can be considered to be a national problem. The real situation of teachers in South Africa was determined by means of an empirical study that \\as complimented by a qualitative investigation. In this study. stress is dealt with from the educational psychology. However. stress is a holistic multi-dimensional concept that can only by understood at best when it is approached from a multi-professional point of view. Equally all the actions to cope with stress are rnultidimensional actions. This research aims to develop among teachers an awareness of stress manifestations. with the purpose to identi6 and control stressors. These actions are strengthened by appropriate adaptations in life style and the management of resources. A comprehensive support program is suggested to guide teachers towards an understanding and control of stress. and the establishment of a social support system. while serious manifestations of stress should be addressed by means of professional services. Key words: stress. cope. stress management. education. self control. stress control, environment. work stress: organization stress. community stress. health. wellness. neurological exercise. physical exercise. physiological exercise. religion. humor. feeding. free radicals. anti-osidants. and diet. / Thesis (Ph.D. (Education))--North-West University, Potchefstroom Campus, 2006.

An investigation into stress experience and the use of coping skills by departemental heads of schools: guidelines for support. Stress occurs when one's perception of demands exceeds his perception of his abilities to meet them. Except for work related demands, a variety of demands and threats in the environment have to be faced continuously. As a result stress is created that manifest in people's behavior, work efficiency and socialization. In general, the education profession is considered among the most stressful careers in the world. This also applies to the South African educational system. U'hm teachers experience stress, it has a negative effect on their beloved ones. colleagues and the learners. Therefore teacher stress has a negative effect on the teaching system in general. Thus teacher stress can be considered to be a national problem. The real situation of teachers in South Africa was determined by means of an empirical study that \\as complimented by a qualitative investigation. In this study. stress is dealt with from the educational psychology. However. stress is a holistic multi-dimensional concept that can only by understood at best when it is approached from a multi-professional point of view. Equally all the actions to cope with stress are rnultidimensional actions. This research aims to develop among teachers an awareness of stress manifestations. with the purpose to identi6 and control stressors. These actions are strengthened by appropriate adaptations in life style and the management of resources. A comprehensive support program is suggested to guide teachers towards an understanding and control of stress. and the establishment of a social support system. while serious manifestations of stress should be addressed by means of professional services. Key words: stress. cope. stress management. education. self control. stress control, environment. work stress: organization stress. community stress. health. wellness. neurological exercise. physical exercise. physiological exercise. religion. humor. feeding. free radicals. anti-osidants. and diet. / Thesis (Ph.D. (Education))--North-West University, Potchefstroom Campus, 2006.

Monosialoganglioside (GM1) is a component of most cell membranes and is thought to play a role in development, recognition and cellular differentiation. Furthermore, GM1 is a neuroprotective agent that has been reported to scavenge free radicals generated during reperfusion and to protect receptors and enzymes from oxidative damage. In the present study we investigate the effect of GM1 on the catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, on the spontaneous chemiluminescence and total radical-trapping potential (TRAP) in cortex of rats ex vivo and in vitro. Systemic GM1 administration (50 mg/kg, i.p.; twice) reduced spontaneous chemiluminescence and increased CAT activity ex vivo. On the other hand, GM1 (103-104 nM) reduced CAT activity in vitro. The other parameters were not affected by GM1 administration. These findings agree with the view that the antioxidant action of GM1 is not due to an intrinsic antioxidant activity of this glycolipid, but due to a secondary decrease of reactive species generation and/or increase of antioxidant defenses. Moreover, we evaluated whether GM1 could have a neuroprotective action on the experimental model of glutaric acidemia, an inherited metabolic disorder characterized by glutaric acid (GA) accumulation and neurological dysfunction, as striatal degeneration and convulsion. The systemic GM1 administration (50 mg/kg, i.p. twice) protected against the convulsions, oxidative damage markers increase (total protein carbonylation and thiobarbituric acid-reactive substances - TBARS) production and Na+,K+-ATPase activity inhibition induced by GA (4 mol/ 2 l) in striatum of rats. Furthermore, convulsive episodes induced by GA strongly correlated with Na+,K+-ATPase activity inhibition in the injected striatum, but not with oxidative stress marker measures. In addition, GM1 (50-200 M) protected against Na+,K+-ATPase inhibition induced by GA (6 mM), but not against oxidative damage in vitro. Intrastriatal administration of muscimol (46 pmol/striatum), a GABAA receptor agonist, but not glutamatergic receptor antagonists MK-801 (3 nmol/striatum) and DNQX (8 nmol/striatum), prevented GA-induced convulsions and inhibition of Na+,K+-ATPase activity. The protection of GM1 and muscimol against GA-induced seizures strongly correlated with Na+,K+-ATPase activity maintenance in the injected striatum with GA. Since GM1 and muscimol prevented neurotoxic effects induced by GA, we investigated the GM1 action after intrastriatal administration of pentylenetetrazole (PTZ), a GABAA receptor antagonist. GM1 treatment prevented seizures, Na+,K+-ATPase inhibition, and increase of TBARS and protein carbonyl induced by PTZ (1.8 mol/striatum) in the rats striatum. Furthermore, these data suggest that Na+,K+-ATPase and GABAA receptor-mediated mechanisms may play important roles in GA-induced seizures and in their prevention by GM1. / O monossialogangliosídeo (GM1) é um componente natural de membrana plasmática que está envolvido no crescimento, reconhecimento e diferenciação celular, além de proteger o SNC da ação dos radicais livres. No presente estudo investigou-se o efeito do GM1 sobre a atividade das enzimas antioxidantes catalase (CAT), superóxido dismutase (SOD) e glutationa peroxidase (GPx), assim como na quimiluminescência e capacidade antioxidante total (TRAP) em córtex cerebral de ratos machos adultos ex vivo e in vitro. A administração sistêmica de GM1 (50 mg/kg, i.p.; duas doses: 24 horas e 30 minutos antes do sacrifício) reduziu a quimiluminescência e aumentou significativamente a atividade da CAT ex vivo. A adição de GM1 (103-104 nM) ao meio de incubação diminuiu a atividade da CAT in vitro. Estes resultados sugerem que o efeito neuroprotetor do GM1 não é devido à ação antioxidante intrínseca deste glicoesfingolipídeo, mas devido ao aumento secundário das defesas antioxidantes e/ou uma redução da geração de radicais livres. Além disso, avaliamos se o GM1 tinha efeito neuroprotetor em um modelo experimental da acidemia glutárica, um erro inato do metabolismo caracterizado pelo acúmulo tecidual de ácido glutárico (GA) e alterações neurológicas, como degeneração estriatal e convulsões. A administração de GM1 preveniu as convulsões, o aumento da produção dos marcadores do dano oxidativo (carbonilação protéica total e substâncias reativas do ácido tiobarbitúrico - TBARS) e a inibição da atividade da Na+,K+-ATPase induzidas pelo GA (4 mol/2 µl) em estriado de ratos. Além disso, os episódios convulsivos induzidos por GA apresentaram uma correlação significativa com a inibição da atividade da Na+,K+-ATPase no estriado injetado, mas não com os níveis dos marcadores do estresse oxidativo. A adição de GM1 (50 200  ao meio de incubação preveniu a inibição da Na+,K+-ATPase, mas não reduziu o dano oxidativo induzido por GA (6 mM) in vitro. A administração intraestriatal de muscimol (46 pmol/0,5 l), um agonista de receptor GABAA, mas não dos antagonistas de receptores glutamatérgicos, MK-801 (3 nmol/0,5 l) e DNQX (8 nmol/0,5 l), preveniu as convulsões e a inibição da atividade da Na+,K+-ATPase induzidas por GA. A proteção do GM1 e muscimol contra as convulsões induzidas por GA apresentou uma correlação significativa com a manutenção da atividade da Na+,K+-ATPase no estriado injetado com GA. Desde que o GM1 e o muscimol preveniram os efeitos neurotóxicos induzidos pelo GA, investigou-se a ação do GM1 após a administração intraestriatal de pentilenotetrazol (PTZ), um antagonista de receptores GABAA. O tratamento com GM1 preveniu as convulsões, o dano oxidativo e a inibição da atividade da Na+,K+-ATPase induzidas por PTZ (1,8 µmol/2 µl). Esses dados sugerem que a atividade da Na+,K+-ATPase e mecanismos mediados pela ativação de receptores GABAérgicos podem ser de grande importância para a atividade convulsiva induzida por GA, bem como nos mecanismos de neuroproteção induzidos pelo GM1.

&#946;2-glicoproteína I (&#946;2GPI) é encontrada (200&#181;g/mL) no plasma, 60% livre e 40% em lipoproteínas. Esta proteína de fase aguda, com afinidade por superfícies negativas pode ser clivada pela plasmina. Fragmentos são purificados como dímeros ou multímeros de &#946;2GPI. Formas monomérica e dimérica de &#946;2GPI foram purificadas de soro humano e identificadas por SDS-PAGE, imunoblot e ELISA Somente a forma monomérica foi detectada no teste ELISA Os efeitos de ambas as formas sobre o burst respiratório de polimorfonucleares humanos (PMN), estimulados in vitro com zymosan opsonizado, foram estudados por quimioluminescência amplificada por luminol ou lucigenina e citometria de fluxo, pela oxidação do OCFH. A forma monomérica inibiu a quimioluminescência amplificada por luminol (-43.6 x -7.33 AEU/s), mas não por lucigenina, e aumentou a oxidação de DCFH e a produção de Óxido Nítrico (&#8226;NO). É provável que o &#8226;No, via peroxinitrito, medeie os efeitos de &#946;2GPI sobre o burst respiratório de PMN. / Circulating blood contains approximately 200&#181;g/mL of &#946; 2-glycoprotein I (&#946;2GPI), either free (60%) or lipoprotein bound (40%). This acute phase protein, with affinity for negative surfaces, can be cleaved by plasmin. Fragments purify as dimeric or multimeric (&#946;2GPI. Both (&#946;2GPI forms were purified from human sera and identified by SDS-PAGE, immunoblotting and ELISA. ELISA reactivity was dependent on the monomeric status of (&#946;2GPI. The effects of dimeric and monomeric (&#946;2GPI upon respiratory burst of human polimorphonuclear neutrophils (PMN) stimulated in vitro with opsonized zymosan were studied. Respiratory burst was evaluated by luminol- or lucigenin-amplified chemiluminescence, or by DCFH oxidation (flow-cytometry assay). The monomeric, but not the dimeric form, inhibited the luminol chemiluminescence of zymosan-stimulated PMNs (-43.6 x -7.33 AEU/s). Lucigenin chemiluminescence was insensitive to (&#946;2-GPI. Monomeric (&#946;2GPI increases both DCFH oxidation and nitric oxide production. Nitric oxide, probably through peroxynitrite reactions, mediates (&#946;2GPI effects upon PMNs respiratory burst.