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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
71

Characterisation, toxicology and clinical effects of crocodile oil in skin products / by Telanie Venter.

Venter, Telanie January 2012 (has links)
Natural oils are regularly used in cosmetics and as treatment for numeral skin conditions (Nielsen, 2006:575). The natural products industry is a multibillion dollar industry and has grown tremendously over the past few years. Natural oils used in cosmetics contain a range of fatty acids which contribute to several valuable properties in cosmetic- and personal care products. Fatty acids are divided into saturated acids and unsaturated acids (Vermaak et al., 2011:920,922). Because of the popularity and wide diversity of skin care products, it is necessary to create products that will distinguish themselves from the rest of the commercial products. To include natural oils in skin care products is a new way to prevent skin ageing, as well as other dermatological conditions. In this study, a natural oil, namely crocodile oil was used. Crocodile oil is obtained from the fat of the Nile crocodile (Crocodylus niloticus). Crocodile oil has the same composition as human skin oil. It only differs with regard to the percentages of the ingredients present. Crocodile oil contains saturated and unsaturated fatty acids. Because of the similar composition as human skin oil, crocodile oil will rarely be allergenic when applied to human skin and therefore will be a very accepted and harmless product to use (Croc city, 2012). There are many claims of positive results when crocodile oil containing products have been used. It includes fading of freckles, treatment of acne and pimple marks, dark lines, wrinkles and laugh lines. It also includes vanishing of dark shadows, sun spots and other discolorations. It helps prevent discolorations from forming and makes the skin softer, brighter and more attractive. It also controls rashness and dryness (Croc city, 2012). Because of crocodile oil’s anti-ageing, anti-fungal and anti-bacterial effects claimed by crocodile oil suppliers, and due to the fact that little scientific data is available on crocodile oil, it was decided to investigate the claims. In this study, the aims and objectives were to use natural oil, namely crocodile oil, and investigate the fatty acid profile, anti-microbial and anti-fungal activity, anti-oxidant activity, toxicity studies, stability determination of crocodile oil lotion and clinical efficacy testing of the anti-ageing effects. To determine the fatty acid profile of crocodile oil, fatty acid methyl ester (FAME) analysis with gas chromatography were used. Identification of FAME peaks in the samples was made by comparing the relative retention times of FAME peaks from samples to those of reference standards. The composition of fatty acids in crocodile oil compared well to fatty acids found in human skin oil. Anti-microbial and anti-fungal tests were done by Envirocare Laboratories, North-West University, Potchefstroom. Staphylococcus aureus, Esterichia coli, Pseudomanas aeruginosa, Candida albicans, Brasiliensis, Propionibacterium acnes and Trichophyton rubrum cultures were used to determine the anti-microbial and anti-fungal activity of crocodile oil. Unfortunately no activity was observed. The anti-oxidant properties of crocodile oil and crocodile oil lotion were determined by using the most commonly used method for measuring Malondialdehyde (MDA) in biological samples, namely the thiobarbituric acid (TBA) test. This method is based on spectrophotometric quantification of the pink complex formed after reaction of MDA with two molecules of TBA. No anti-oxidant activity was observed in the oil or the lotion. Toxicity studies were performed by Dr. D. Goosen (BVSc Hons. Pret.) from Tswane University of Technology (Pretoria, South Africa). The studies showed that the lotion had no toxicity in the skin sensitisation, acute dermal toxicity and acute dermal irritation studies. To determine the stability of the crocodile oil lotion, the formulated products were store at 25 °C / 60% RH (relative humidity), 30 °C / 60% RH and 40 °C / 75% RH for 6 months in the original packaging as well as a glass container. The stability tests included pH, viscosity, visual appearance assessment, zeta-potential, droplet size and mass loss. The crocodile cream lotion was stable over the 6 months period in both containers. Clinical efficacy testing was performed at the CEL (Clinical Efficacy Laboratory) of the North-West University, Potchefstroom, South Africa. A short-term study over a period of 3 h was performed to investigate the hydrating effects of crocodile oil lotion. A long-term study over a period of 12 weeks was performed to examine the anti-ageing effects of crocodile oil lotion. An erythema study was also conducted to test the anti-erythema properties of crocodile oil lotion. Although the crocodile oil lotion as well as the placebo lotion showed an increase in skin hydration, there was no significant difference between the two treatments. Crocodile oil lotion also showed no anti-erythema properties. / Thesis (PhD (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.
72

Investigation of radiation sensitive normoxic polymer gels for radiotherapy dosimetry

Venning, Anthony James January 2006 (has links)
The overall objective of this study was to develop and characterise new normoxic polymer gel formulations for evaluation of complex 3-D treatment volumes for application in radiotherapy dosimetry. Throughout this thesis, the essential characteristics of normoxic polymer gels have been extensively investigated. Studies were performed on the chemical components of the MAGIC gel and an improved formulation was proposed. Various anti-oxidants were studied and different versions of the MAGIC gel with fewer chemicals were developed and named MAGAS and MAGAT gel dosimeters. The ascorbic acid anti-oxidant was found to have a slow oxygen scavenging rate and therefore a delay period between manufacture and irradiation of the MAGAS gel was necessary before the gel became radiation sensitive. Vacuum pumping on the MAGAS gel solution to remove dissolved oxygen was shown to initially increase the R2-dose response and sensitivity of the dosimeter, reducing the time between manufacture and irradiation. Studies of the MAGAS gel for measurement of depth dose showed that MAGAS gel has potential as a clinical radiotherapy dosimetry tool. The radiological properties of MAGIC, MAGAS and MAGAT gels were investigated. Due to their high gelatine and monomer concentration, differences with water were observed for the cross-section ratios for attenuation, energy absorption and collision stopping power coefficient ratios through the therapeutic energy range. It was determined that when using and developing normoxic polymer gels the most important consideration for radiological water equivalence are the mass and relative electron densities. A preliminary study was performed with the hypoxic PAG gel dosimeter combined with tetrakis (hydroxymethyl) phosphonium chloride anti-oxidant to form a normoxic PAG gel dosimeter named PAGAT gel. It was found PAGAT gel compared favourably with previous studies of the hypoxic PAG gel. An extensive study was subsequently undertaken in which PAGAT gel was investigated for a number of essential characteristics. The PAGAT gel formulation showed potential as a normoxic polymer gel for clinical radiotherapy dosimetry, which has a significantly reduced manufacturing time and procedure compared with the hypoxic PAG gel dosimeter. The radiological attenuation properties of the PAGAT and MAGAT gels were investigated as a feasibility study for using x-ray computerised tomography (CT) as an evaluation technique of normoxic polymer gels. CT was shown to have potential as an evaluation tool for measuring the dose response of normoxic polymer gel dosimeters. An investigation was performed on the CT diagnostic dose response of normoxic polymer gels. Normoxic polymer gels were found to have potential for use as a specialised tool in measuring computerised tomography dose index (CTDI) for acceptance testing and quality assurance of CT scanners in diagnostic radiology. These findings provide a significant contribution toward the development and successful implementation of normoxic polymer gel dosimetry to clinical radiotherapy.
73

Caracteriza??o f?sico-qu?mica e a??es farmacol?gicas hepatoprotetora, antiinflamat?ria, pr?-angiog?nica, antioxidante e anticoagulante da fra??o rica em fucana 0,8FRF 0,8 da alga marrom Lobophora variegata

Will, Luiza Sheyla Evenni Porf?rio 21 December 2012 (has links)
Made available in DSpace on 2014-12-17T14:03:40Z (GMT). No. of bitstreams: 1 LuizaSEPW_DISSERT.pdf: 2731256 bytes, checksum: a154afda557a95d39d943b76672810db (MD5) Previous issue date: 2012-12-21 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / This study examines the physical and chemical composition and the pharmacological effects of brown seaweed FRF 0.8 Lobophora variegata. Fractionation of the crude extract was done with the concentration of 0.8 volumes of acetone, obtaining the FRF 0.8. The physicochemical characterization showed that it was a fucana sulfated. Anti-inflammatory activity was assessed by paw edema model by the high rates of inhibition of the edema and the best results were in the fourth hour after induction (100 ? 1.4% at the dose of 75 mg / kg) and by the strong inhibitory activity of the enzyme myeloperoxidase (91.45% at the dose of 25 mg / kg). The hepataprote??o was demonstrated by measurements of enzymatic and metabolic parameters indicative of liver damage, such as bilirubin (reduction in 68.81%, 70.68% and 68.21% for bilirubin total, direct and indirect, respectively at a dose of 75 mg / kg), ALT, AST and γ-GT (decrease of 76.93%, 44.58% and 50% respectively at a dose of 75 mg / kg) by analysis of histological slides of liver tissue, confirming that hepatoprotective effect the polymers of carbohydrates, showing a reduction in tissue damage caused by CCl4 and the inhibition of the enzyme complex of cytochrome P 450 (increasing sleep time in 54.6% and reducing the latency time in 71.43%). The effectiveness of the FRF 0.8 angiogenesis was examined in chorioallantoic membrane (CAM) of fertilized eggs, with the density of capillaries evaluated and scored, showing an effect proangig?nico at all concentrations tested FRF (10 mg- 1000 mg). The FRF showed antioxidant activity on free radicals (by inhibiting Superoxide Radical in 55.62 ? 2.10%, Lipid Peroxidation in 100.15 ? 0.01%, Hydroxyl Radical in 41.84 ? 0.001% and 71.47 Peroxide in ? 2.69% at concentration of 0.62 mg / mL). The anticoagulant activity was observed with prolongation of activated partial thromboplastin time (aPTT) at 50 mg (> 240 s), showing that its action occurs in the intrinsic pathway of the coagulation cascade. Thus, our results indicate that these sulfated polysaccharides are an important pharmacological target / Este estudo analisa a composi??o f?sico-qu?mica e os efeitos farmacol?gicos da FRF 0,8 da alga marrom Lobophora variegata. O fracionamento do extrato bruto foi feito com a concentra??o de 0,8 volumes de acetona, obtendo a FRF 0,8. A caracteriza??o f?sico-qu?mica mostrou que se tratava de uma fucana sulfatada. Foi verificada a atividade antinflamat?ria pelo modelo de edema de pata, atrav?s das altas taxas de inibi??o do edema e os melhores resultados foram na quarta hora ap?s a indu??o (100 ? 1,4% com a dose de 75 mg/kg) e pela forte atividade inibidora da enzima mieloperoxidase (91,45% com a dose de 25 mg/kg). A hepataprote??o foi demonstrada pelas dosagens de par?metros metab?licos e enzim?ticos indicativos de dano hep?tico, como bilirrubina (redu??o em 68,81%, 70,68% e 68,21% para bilirrubinas total, direta e indireta, respectivamente na dose de 75 mg/kg), ALT , AST e γ-GT (diminui??o em 76,93%, 44,58% e 50%, respectivamente na dose de 75 mg/kg), pela an?lise das l?minas histol?gicas do tecido hep?tico, que confirmam esse efeito hepatoprotetor dos pol?meros de carboidrato, mostrando uma redu??o no dano tecidual causado por CCl4, e pela inibi??o do complexo enzim?tico do citocromo P 450 (aumentando o tempo de sono em 54,6% e reduzindo o tempo de lat?ncia em 71,43%). A efic?cia sobre a angiogenese da FRF 0,8 foi examinada na membrana corioalant?ica (CAM) de ovos fertilizados, com a densidade dos capilares avaliadas e pontuadas, mostrando um efeito proangig?nico em todas as concentra??es de FRF testadas (10 μg-1000 μg). A FRF apresentou a??o antioxidante sobre radicais livres (inibindo o Radical Super?xido em 55,62?2,10%, Peroxida??o Lip?dica em 100,15?0,01%, Radical Hidroxila em 41,84?0,001% e Per?xido em 71,47?2,69%, todos na concentra??o de 0,62 mg/mL). A atividade anticoagulante foi verificada com o prolongamento do tempo de tromboplastina parcial ativada (aPTT) a 50 μg (>240 s), mostrando que sua a??o ocorre na via intr?nseca da cascata de coagula??o. Sendo assim, nossos resultados indicam que estes polissacar?deos sulfatados constituem um importante alvo farmacol?gico
74

AVALIAÇÃO DOS MARCADORES DO ESTRESSE OXIDATIVO EM INDIVÍDUOS SUPLEMENTADOS COM FERRO E ÁCIDO ASCÓRBICO / EVALUATION OF OXIDATIVE STRESS MARKERS IN VOLLUNTERS SUPPLEMENTED WITH IRON IS ASCORBIC ACID

Colpo, Elisângela 13 February 2007 (has links)
Iron is an essential nutrient for cellular activities including oxygen transport, electron transfer, and gene regulation. However, iron is potentially toxic via its redox reactions which generate reactive oxygen species (ROS). Oxidative damage to biomolecules can be modulated by antioxidants such as ascorbic acid (AA). However, it is well known that in the presence of redox-active iron, AA can act as a pro-oxidant in vitro and contribute to the formation of hydroxyl radicals. Based on the possible pro-oxidant interaction of iron and AA, we evaluated the manifestations of supplementation of iron associated with the ascorbic acid. The study was delineated by nine non-smoking male healthy volunteers, aged between 20 and 31 years. The volunteers were supplemented with a single dose containing 2g of AA (first group), 150mg of iron (second group) and 2g of AA plus 150mg of iron (third group). The 9 volunteers were submitted the all the treatments, which were alternate every 15 days. The volunteers were submitted to blood collections before the supplementation and 2, 5 and 24 hours after the supplementation. They were evaluated the levels of iron and ferritin, the activity of the antioxidants enzymes catalase (CAT), gluthatione peroxidase (GPx), superoxide dismutase (SOD), the level non-enzymatic antioxidants: AA, non-protein-SH, as well as markers of the oxidative stress Thiobarbituric acid reactive substances (TBARS), diclorofluorescein oxidation and delta-amino levulinate dehydratase (ALA-D) activity. The results showed that plasma AA levels were increased at 2, 5 and 24 hours after AA or AA plus iron ingestion. Plasmatic iron level was increased at 2 hours after iron ingestion and 2, 5 hours in the group AA plus iron. The erythrocytes TBARS levels decreased at 5 hours after AA and 5, 24 hours after AA plus iron ingestion. The erythrocytes CAT levels caused a significant increase 5 hours after supplementation with AA plus iron. The other results showed no significant different in the determinations. Thus, the present study does not support the hypothesis that the combination of high plasma oncentrations of AA and iron, or iron alone, causes oxidative damage in vivo. However, further studies are required to determine if iron and AA interactions could have a pro-oxidant effect in vivo. / O ferro é um nutriente essencial para atividades das células incluindo transporte de oxigênio, transferência de elétrons e regulação genética. Entretanto, esse mineral é potencialmente tóxico por participar de reações de óxido-redução, que favorecem a formação de espécies reativas ao oxigênio (ERO). O dano oxidativo nas biomoléculas pode ser modulado por antioxidantes como o ácido ascórbico (AA). Entretanto, sabe-se que na presença de ferro, o ácido ascórbico pode atuar como um pró-oxidante in vitro e contribuir para formação de radicais hidroxila. Baseado na possibilidade pró-oxidante da interação entre o ferro e o ácido ascórbico, for avaliados as manifestações da suplementação do ferro associado com o ácido ascórbico. O estudo foi delineado por 9 voluntários saudáveis, não tabagistas, entre 20 e 31 anos. Os voluntários foram suplementados com uma dose única contendo 2g de ácido ascórbico (primeiro grupo), 150mg de ferro (segundo grupo) e 2g de ácido ascórbico mais 150mg de ferro (terceiro grupo). Os 9 indivíduos foram submetidos a todos os tratamentos, os quais foram alternados a cada 15 dias. Os voluntários foram submetidos a coletas sanguíneas antes da suplementação e 2, 5 e 24 horas após a suplementação. Foram avaliados os níveis de ferro e ferritina, a atividade das enzimas antioxidantes catalase (CAT), glutationa peroxidase (GPx), superóxido dismutase (SOD), os níveis dos antioxidantes não-enzimáticos: ácido ascórbico, tiois não proteicos (NPSH), bem como os marcadores do estresse oxidativo: espécies reativas ao ácido tiobarbitúrico (TBARS), oxidação da diclorifluoresceína e a atividade da delta aminolevulinato desidratase (ALA-D) . Os resultados encontrados mostraram que os níveis plasmáticos de ácido ascórbico aumentaram significativamente em 2, 5 e 24 horas após a ingestão de ácido ascórbico mais ferro ou somente ácido ascórbico. Os níveis plasmáticos de ferro aumentaram significativamente 2 horas após a ingestão de ferro e 2 e 5 horas no grupo ferro mais ácido ascórbico. Os níveis de TBARS eritrocitário diminuíram significativamente em 5 e 24 horas após a ingestão de ferro, bem como, em 5 horas após a ingestão de ferro mais ácido ascórbico. A atividade da CAT eritrocitária aumentou significativamente em 5 horas após a ingestão de ácido ascórbico mais ferro. Os demais parâmetros avaliados não mostraram diferenças significativas. Com isso, o presente estudo não confirma a hipótese que a combinação de altas doses de ácido ascórbico e ferro, ou apenas ferro causam dano oxidativo in vivo. Entretanto, mais estudos são necessários para determinar se a interação entre o ferro e o ácido ascórbico pode causar efeito pró-oxidante in vivo.
75

Lipid associated biomarkers in patients with systemic lupus erythematosus and rheumatoid arthritis

Almohmedhusain, Awal January 2013 (has links)
Patients with chronic inflammatory conditions such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) experience premature cardiovascular mortality and morbidity compared with the general population. The increased risk of cardiovascular disease (CVD) may in part, result from an interaction between traditional and non-traditional risk factors, modulated by chronic inflammation. The aim of this project was to look at lipid associated biomarkers in patients with SLE/RA and the association between these markers and cardiovascular disease outcomes. We also aimed to study the effect of inflammation reduction on vascular biomarkers. In the first study we examined 168 SLE patients median (IQR) age was 53 (46-61) years and median disease duration 13 (7, 23) years and 56 healthy controls median age 50 (39-60) years. We demonstrated elevated level of oxidised-LDLin SLE patients compared with healthy controls (76 (57, 99) U/l vs 56 (42, 88)U/l P= 0.02). We further explored the association between oxidant stress and premature atherosclerosis as measured by carotid intima media thickness (cIMT) and plaque. In addition to age and systolic blood pressure, oxidised-LDL and urinary 8-isoprostane were significantly and independently associated with cIMTin SLE patients _ coefficient 95%CI [0.00007 (5.29−6, 0.0001) and 0.003 (0.0008,0.004)], respectively. In healthy controls, age was the only independent variable. In the Norfolk Arthritis Register, 1266 patients with early inflammatory polyarthritis (IP) were studied. A linear regression analysis revealed a significant negative association between CRP and lipid profile namely TC, LDL, TG and ApoA-1. During a median (IQR) follow up = 5.5 (3.7-7.7) years 100 (7%) patients died (all causes) of which 33% (33) deaths were attributed to CVD. Forward stepwise regression analysis demonstrated that a low total cholesterol was independently associated with all cause mortality HR (95%CI) 0.75 (0.61, 0.91) and CVD mortality HR (95%CI) 0.49 (0.29, 0.85). In a small cohort 27 SLE patients and 15 healthy controls. We measured endothelial function using flow mediated dilatation of the brachial artery. At baseline we found a significant increase in TG level [1.36 (0.9, 1.87) mmol/l vs0.88 (0.64, 1) mmol/l P= 0.009] and a significant impaired endothelial function in SLE patients compared to the healthy controls [2.86 (0.6, 5.3) vs 6.81 (3.46,8.57), P= 0.03]. After treatment, there was a trend towards reduced TG level and improved endothelial function. Oxidised-LDL did not change significantly. In conclusion, oxidant stress is increased in SLE patients and relates to some measures of subclinical atherosclerosis. Control of inflammation may not be sufficient to completely control this in routine practice. In early RA, active inflammationmay mask any tendency to hyperlipidemia in this population. Low total cholesterol may be the best biomarker of the overall metabolic and inflammatory status of the patients as well as indicating a group with increased risk of future mortality.
76

Efficacité de l'acide alpha-lipoïque (traitement anti-oxydant) dans la prévention des escarres au cours du vieillissement / Effects of Alpha-lipoic acid (anti-oxidant treatment) in the prevention of pressure ulcers during aging

Décorps, Johanna 24 February 2015 (has links)
Le vieillissement diminue les propriétés mécaniques protectrices de la peau qui prédispose le sujet âgé aux ulcères de pression, les escarres. Ce travail a pour objectif de (1) tester les capacités de défense de la peau face aux contraintes mécaniques au cours du vieillissement, (2) identifier les facteurs responsables de la dégénérescence des capacités de protection de la peau avec l'âge et (3) évaluer les effets d'un traitement chronique anti-oxydant. Les capacités de résistance de la peau aux pressions ainsi que l'incidence d'escarres suite à une ischémie prolongée ont été étudiées chez des rats jeunes (6 mois), matures (12 mois) et âgés (24 mois) de deux souches : Brown Norway (longévité accrue), et Wistar. Des études complémentaires ont permis d'identifier les facteurs responsables de cette dégénérescence, en particulier le versant vasculaire, l'atteinte nerveuse sensorielle et les modifications de la structure et des propriétés visco-élastiques de la peau. L'efficacité du traitement anti-oxydant sur les capacités mécaniques protectrices de la peau a été estimée. Les résultats montrent une altération des propriétés mécaniques protectrices de la peau avec l'âge, plus ou moins précoce selon la souche de rats, associée à une atteinte fonctionnelle vasculaire (chez les rats Wistar), l'installation progressive d'une neuropathie périphérique sensorielle et d'un défaut visco-élastique cutané dans les deux souches de rats. Ces atteintes ne reflètent pas systématiquement la fragilité de la peau âgée face aux escarres, modulée par l'état du tissu adipeux. Le traitement antioxydant permet de réduire plusieurs atteintes mais a induit des effets contradictoires entre les deux souches de rats étudiées vis-à-vis de l'incidence d'escarres / The aging decreases the protective properties of the skin, which predisposes the aging subject to pressure ulcers. This thesis had for objective (1) to test the defence capacities of the skin to resist mechanical stress during aging, (2) identify the factors responsible for the degeneration of the protection capacity of the aging skin and (3) evaluate the effects of a chronic antioxidant treatment. To meet this three objectives, the cutaneous responses to pressures of different intensities together with the pressure ulcer incidence following a prolonged ischemia were studied on 3 different ages of rats: young (6 months), mature (12 months) and aged (24 months). Those 3 stages of aging were studied on 2 different rat strains: “Brown Normay”, healthy aging model with an accrued longevity and “Wistar”, control rats. Complementary studies allowed identifying the mechanism who leads to a diminution of the protective capacities of the skin. In particular, the vascular dysfunctions (endothelial and smooth muscular cells), the sensory nervous dysfunctions, the modifications of the skin structure and the viscoelastic properties were evaluated. The efficiency of the anti-oxidant treatment was estimated focusing principally on the effects on the nervous and vascular capacities, the structure of the skin and the impact of the pressure ulcer. The results show that the aging induces a more or less early alteration of the protective properties of the skin in response to pressures, more or less precocious depending on the strain of the rat. The decrease of the natural defences is associated to a vascular dysfunction (endothelium with the Wistar rats), the progressive installation of a sensory peripheral neuropathy and a deterioration of cutaneous viscoelastic properties with the two strains of rats. These deteriorations do not reflect systematically the fragility of the aged skin towards pressure ulcers, modulated by the state of the subcutaneous adipose tissue. The chronic anti-oxidant treatment allows to reduce several dysfunctions but has induced contradictory effects between the two studied strains of rats towards the incidence of pressure ulcers
77

The antidiabetic and antioxidant properties of Athrixia phylicoides aqueous extract : an in vitro and ex vivo assessment

Chellan, Nireshni 03 1900 (has links)
Thesis (MScMedSc)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Introduction: Athrixia phylicoides is an aromatic, indigenous shrub with high antioxidant content and numerous indigenous medicinal properties inferred by ingestion of an herbal brew of the plant. Commercialization of “bush tea” (derived from A. phylicoides) holds economic and developmental potential for indigenous communities provided the safety and efficacy of the herbal tea is established. Recently A. phylicoides has been shown by McGaw et al. (2007) to have similar antioxidant activity to Rooibos tea, and a unique, new flavonol (i.e. a polyphenolic antioxidant plant metabolite) 5-hydroxy-6,7,8,3′,4′,5′-hexamethoxyflavon-3-ol, unique to A. phylicoides, was isolated by Mashimbye et al. in 2006. With changes in the socio-economic climate and a new trend in merging Western lifestyle with traditional practices, new interest has been shown in herbal/natural remedies. Study Aim: The aim of this study was to firstly, determine the in vitro effect of A. phylicoides aqueous extract on glucose metabolism in cell lines that mimic the three key organs implicated in glucose homeostasis. Secondly, the study aimed to determine the potential ex vivo antioxidant and anti-inflammatory effect of the extract in pancreatic β-cells and peripheral mononuclear cells respectively. Methods: Leaves and fine twigs of A. phylicoides were processed into an aqueous extract. C2C12, Chang and 3T3-L1 cells were cultured under standard conditions and acutely exposed to increasing concentrations of extract and water vehicle, as well as 1 μM insulin and metformin as positive controls. Glucose uptake from 8 mM glucose culture media was determined using a fluorimetric oxidase method. Radioactive 14C-glucose oxidation to 14CO2 and determination of glycogen content of cells were used to assess the fate of intracellular glucose. RT-PCR was used to assess the extract effect on insulin-signalling gene expression. The antioxidative effect of A. phylicoides extract in pancreatic β-cells isolated from Wistar rats was determined by measuring nitric oxide (NO) production in response to hyperglycemic conditions. NO was labelled with diaminofluorocein diacetate and fluorescence was measured using flow cytometry. Insulin secretion of pancreatic β- cells was measured using radio-immuno assay. The anti-oxidative effect of the extract in lipopolysaccharide-stimulated peripheral mononuclear cells isolated from Wistar rats was determined by measuring the production of TNF-α using an ELISA kit. Results: C2C12 myocytes showed maximal increased glucose uptake at the 0.05 μg/μl extract concentration (228.3% ± 66.2, p<0.001). In Chang cells, A. phylicoides extract maximally increased the amount of glucose taken up at the 0.05 μg/μl concentration (134.5% ± 2.5, p<0.05). In 3T3-L1 cells, the extract maximally increased the amount of glucose taken up at the 0.025 μg/μl concentration (143.5% ± 10.3, p<0.001). An extract-induced increase in insulin receptor and glucose transporter four expression was seen in C2C12 myocytes. The oxidation of 14C-glucose to 14CO2 by C2C12 myocytes was maximally increased following acute exposure to the extract at 0.1 μg/μl (2919.3 fmol/1x10^6 cells ± 428, p<0.01). The oxidation of 14C-glucose to 14CO2 by Chang cells was maximally increased following acute exposure to extract at 0.1 μg/μl (4476.7 fmol/1x10^6 cells ± 1620, p<0.05); as seen in the C2C12 cells. A. phylicoides extract increased glycogen storage at all three concentrations tested in Chang cells, but maximally at the 0.025 μg/μl concentration (13.6 μg/1x10^6 cells ± 0.7, p<0.05). A. phylicoides extract did not have any measurable effect on the oxidative status of β-cells or the anti-inflammatory status of peripheral mononuclear cells. The extract did show an increase in first phase insulin secretion of β-cells in hyperglycemic conditions, although it was not significant. Conclusion: Athrixia phylicoides aqueous extract stimulates in vitro glucose uptake and metabolism in an insulin-mimetic manner, suggesting that this extract could potentially be beneficial to type two diabetics as an adjunct therapy. / AFRIKAANSE OPSOMMING: Inleiding: Athrixia phylicoides is 'n aromatiese, inheemse struik met 'n hoë antioksidant inhoud. Vele tradisionele medisinale eienskappe is gekoppel aan die ingestie van 'n kruie brousel van die plant, wat ook bekend as “bostee” is. Kommersialisering van “bostee” hou ekonomiese en ontwikkelings potensiaal in vir inheemse gemeenskappe mits die veiligheid en effektiwiteit van die kruietee bevestig kan word. McGaw et al. (2007) het onlangs bevind dat A. phylicoides se antioksidant aktiwiteit vergelykbaar is met die van rooibostee. 'n Unieke nuwe flavonol ('n polifenoliese antioksidant plant metaboliet) 5-hydroksie-6,7,8,3′,4′,5′-hexamethoksieflavon-3-ol, eie aan A. phylicoides, is deur Mashimbye et al. in 2006 geïsoleer. Met veranderings in die sosio-ekonomiese klimaat en 'n nuwe tendens om die westerse lewenstyl met tradisionele gebruike aan te vul word nuwe belangstelling in kruie/natuurlike rate ondervind. Studie Doelwitte: Die doelwitte van hierdie studie was eerstens om die in vitro effek van A. phylicoides waterekstrak op die glukosemetabolisme van drie sellyne wat die sleutel organe naboots wat glukosehomeostase beheer, te bepaal. Tweedens, is die potensiële ex vivo antioksidant en anti-inflammatoriese effek van die ekstrak op pankreatiese β-selle en perifere mononuklêere-selle onderskeidelik ondersoek. Metodes: n Waterige ekstrak is van die blare en fyn takkies van A. phylicoides berei. C2C12, Chang and 3T3-L1 selle is gekultuur onder standaard kondisies en akuut blootgestel aan stygende ekstrakkonsentrasies. Water het as kontrole gedien, met 1 μM insulien en metformien as positiewe kontroles. Glukose opname vanuit 8 mM glukose kultuurmedia is bepaal deur 'n fluorimetriese oksidase metode. Radioaktiewe 14C-glukose-oksidasie na 14CO2 en die bepaling van die glukogeen inhoud van selle is gebruik om die lot van intrasellulêre glukose te bepaal. RT-PKR is gebruik om die effek van die ekstrak op die insulien-seinpad geen-uitdrukking te ondersoek. Die antioksidant effek van A. phylicoides ekstrak in pankreatiese β-selle geïsoleer van Wistar rotte, is bepaal deur stikstofoksied (NO) produksie na aanleiding van hiperglukemiese kondisies. NO is met diaminofluorosien diasetaat gemerk en die fluoresensie gemeet deur vloeisitometrie. Insulien afskeiding deur die pankreatiese β-selle is deur radio-immuno metode bepaal. Die anti-oksidatiewe effek van die ekstrak op lipopolisakkaried-gestimuleerde perifere mononuklêere-selle afkomstig van Wistar rotte is bepaal deur die meting van TNF-α produksie met 'n ELISA kit. Resultate: C2C12 miosiete het 'n maksimale toename in glukoseopname by 'n 0.05 μg/μl ekstrakkonsentrasie (228.3% ± 66.2, p<0.001) gehad. Dieselfde ekstrakkonsentrasie het maksimale toename in glukoseopname in Chang selle (134.5% ± 2.5, p<0.05 getoon. In 3T3-L1 selle is maksimale toename in die glukoseopname by 'n konsentrasie van 0.025 μg/μl (143.5% ± 10.3, p<0.001) bereik. 'n Ekstrak-geinduseerde verhoging in die insulienreseptor en glukosetransporter vier ekspressie is in C2C12 miosiete waargeneem. Die oksidasie van 14C-glukose na 14CO2 deur C2C12 miosiete is maksimaal verhoog deur akute blootstelling aan die ekstrak by 'n konsentrasie van 0.1 μg/μl (2919.3 fmol/1x10^6 cells ± 428, p<0.01). Die oksidasie van 14C-glukose na 14CO2 deur Chang selle was maksimaal verhoog deur akute blootstelling aan die ekstrak by 'n konsentrasie van 0.1 μg/μl (4476.7 fmol/1x10^6 cells ± 1620, p<0.05) soos gevind in die C2C12 selle. Die ekstrak het glukogeenstoring verhoog teen al drie die konsentrasies waarteen getoets is in Chang selle, maar 'n maksimale effek is gevind by 'n konsentrasie van 0.025 (13.6 μg/1x10^6 cells ± 0.7, p<0.05). A. phylicoides ekstrak het nie 'n meetbare effek op die oksidatiewe status van β-selle of die anti-inflammatoriese status van perifere mononuklêere-selle gehad nie. Die ekstrak het wel 'n verhoging in die eerstefase insuliensekresie van β-selle in hyperglukemiese kondisies gehad, alhoewel die verhoging nie statisties betekenisvol was nie. Afleiding: Athrixia phylicoides waterekstrak stimuleer in vitro glukoseopname en metabolisme in 'n insulin-mimetiese manier, wat beteken dat die ekstrak potensiëel voordele vir tipe twee diabete kan inhou as aanvullingsterapie.
78

Propriedades antioxidantes e pró-oxidantes de compostos de cobre com ligantes diimínicos: estudos cinéticos e intermediários de reação / Antioxidant and prooxidant properties of copper compounds with Diimine binders: Kinetic studies and reaction intermediates

Santos, Maria Lucia Pires dos 27 February 2002 (has links)
Complexos diimínicos de cobre(II) têm despertado grande interesse como modelos estruturais e funcionais do sítio ativo de diversas proteínas e enzimas dependentes deste metal, particularmente aquelas relacionadas ao oxigênio molecular e seus derivados reduzidos. Embora sejam bons miméticos da SOD, uma enzima antioxidante, estes compostos também podem apresentar atividade peroxidásica considerável, causando danos oxidativos a diversos substratos. Neste trabalho, 3 novos complexos diimínicos de cobre(II), derivados de 2,3-butanodiona e 2-(2-aminofenil)benzimidazol, 2-(aminometil)benzimidazol ou 2-(2-aminoetil)piridina, foram sintetizados e posteriormente caracterizados através de análise elementar, medidas magnéticas e espectroscopia UV/Vis, IR e EPR, com a finalidade de verificar como modificações no ligante podem modular suas propriedades, especialmente frente a oxidantes biológicos, como peróxido de hidrogênio e peroxinitrito. Estes novos complexos preparados tiveram ainda suas propriedades comparadas às de espécies semelhantes, derivadas de piridinaldeído e etilenodiamina ou acetilpirazina e propilenodiamina, estudadas anteriormente. As propriedades antioxidantes dos complexos foram estimadas através da atividade catalítica acentuada na dismutação de radicais superóxidos, em comparação a complexos similares descritos na literatura, indicando que estas espécies são bons miméticos da SOD. Evidências da distorção tetraédrica ao redor do íon cobre, similar à observada na enzima nativa, foram obtidas através de parâmetros espectroscópicos característicos. Os novos complexos também mostraram atividade pró-oxidante, gerando radicais hidroxil em quantidades apreciáveis, em presença de peróxido de hidrogênio, detectados e identificados por EPR com a adição de captador de spin. Danos oxidativos promovidos por estas espécies complexas foram observados através da peroxidação lipídica de lipossomos de fosfatidilcolina de lecitina. Estes danos foram expressivamente aumentados em presença de íons nitrito e/ou bicarbonato. Sua atividade catalítica na decomposição do peroxinitrito, em presença e ausência de dióxido de carbono, bem como na nitração do 4-hidroxifenilacetato, mediada por peroxinitrito, foi também estudada através de medidas de cinética rápida (stopped-flow). Evidências de intermediários de reação foram obtidas através de mudanças significativas no espectro EPR. As propriedades eletroquímicas e a estabilidade termodinâmica relativa dessas espécies, estimada pela técnica de dicroismo circular, usando a albumina bovina como quelante fisiológico, foram também verificadas. Todos os estudos relatados foram desenvolvidos para melhor correlacionar a reatividade observada com determinadas características estruturais dos complexos de cobre preparados. / Many investigations on diimine copper(II) complexes have been carried out in order to mimic functional and structural properties of the active sites in proteins and enzymes dependent on this metal. Special interest has been focused on their reactivity toward molecular oxygen and its reduced derivatives, and more recently toward peroxynitrite. These diimine copper(II) complexes exhibited SOD-like activities, but have also shown considerable peroxidase activity, causing oxidative damage to different targets. In this work, some new diimine copper(II) complexes were prepared, derived from 2,3-butanedione and 2-(2-aminophenyl)benzimidazole, 2-(aminomethyl) benzimidazole or 2-(2-aminoethyl)pyridine, and characterized using UV/Vis, IR and EPR spectroscopy, elemental analysis and determination of the effective magnetic moment. Those complexes have also been compared to similar species, derived from pyridinaldehyde and ethylenediamine, or acetylpyrazine and propylenediamine, previously prepared. The studied complexes showed significant SOD activity, indicative of antioxidant properties, and a pronounced tetrahedral distortion around the copper ion, estimated by characteristic spectroscopic parameters. On the other hand, the new compounds also exhibited pro-oxidant activities, by generating hydroxyl radicals in the presence of hydrogen peroxide, detected by the spin-trapping EPR method. The extension of lipid peroxidation promoted by these diimine copper(II) complexes was also investigated, using liposomes of lecithin L-&#945;-phosphatidylcholine as membrane mimics. An enhancement of their peroxidase activity in the presence of bicarbonate and/or nitrite anion was also observed. Further, the decomposition of peroxynitrite, in the presence and absence of carbon dioxide, and the peroxynitrite-mediated nitration of 4-hydroxyphenylacetate, catalyzed by these copper compounds, was measured by stopped-flow kinetic runs. Evidence of intermediary species was provided by significant changes in the EPR spectra. Finally, their electrochemical properties were estimated by cyclic voltammetry and their relative thermodynamic stability was verified through the technique of circular dicroism, using a competitive reaction with albumin, a physiological Cu(II) chelator. All those studies were performed at the aim of correlating some structural characteristics to the observed reactivity of the diimine copper(II) complexes.
79

Propriedades antioxidantes e pró-oxidantes de compostos de cobre com ligantes diimínicos: estudos cinéticos e intermediários de reação / Antioxidant and prooxidant properties of copper compounds with Diimine binders: Kinetic studies and reaction intermediates

Maria Lucia Pires dos Santos 27 February 2002 (has links)
Complexos diimínicos de cobre(II) têm despertado grande interesse como modelos estruturais e funcionais do sítio ativo de diversas proteínas e enzimas dependentes deste metal, particularmente aquelas relacionadas ao oxigênio molecular e seus derivados reduzidos. Embora sejam bons miméticos da SOD, uma enzima antioxidante, estes compostos também podem apresentar atividade peroxidásica considerável, causando danos oxidativos a diversos substratos. Neste trabalho, 3 novos complexos diimínicos de cobre(II), derivados de 2,3-butanodiona e 2-(2-aminofenil)benzimidazol, 2-(aminometil)benzimidazol ou 2-(2-aminoetil)piridina, foram sintetizados e posteriormente caracterizados através de análise elementar, medidas magnéticas e espectroscopia UV/Vis, IR e EPR, com a finalidade de verificar como modificações no ligante podem modular suas propriedades, especialmente frente a oxidantes biológicos, como peróxido de hidrogênio e peroxinitrito. Estes novos complexos preparados tiveram ainda suas propriedades comparadas às de espécies semelhantes, derivadas de piridinaldeído e etilenodiamina ou acetilpirazina e propilenodiamina, estudadas anteriormente. As propriedades antioxidantes dos complexos foram estimadas através da atividade catalítica acentuada na dismutação de radicais superóxidos, em comparação a complexos similares descritos na literatura, indicando que estas espécies são bons miméticos da SOD. Evidências da distorção tetraédrica ao redor do íon cobre, similar à observada na enzima nativa, foram obtidas através de parâmetros espectroscópicos característicos. Os novos complexos também mostraram atividade pró-oxidante, gerando radicais hidroxil em quantidades apreciáveis, em presença de peróxido de hidrogênio, detectados e identificados por EPR com a adição de captador de spin. Danos oxidativos promovidos por estas espécies complexas foram observados através da peroxidação lipídica de lipossomos de fosfatidilcolina de lecitina. Estes danos foram expressivamente aumentados em presença de íons nitrito e/ou bicarbonato. Sua atividade catalítica na decomposição do peroxinitrito, em presença e ausência de dióxido de carbono, bem como na nitração do 4-hidroxifenilacetato, mediada por peroxinitrito, foi também estudada através de medidas de cinética rápida (stopped-flow). Evidências de intermediários de reação foram obtidas através de mudanças significativas no espectro EPR. As propriedades eletroquímicas e a estabilidade termodinâmica relativa dessas espécies, estimada pela técnica de dicroismo circular, usando a albumina bovina como quelante fisiológico, foram também verificadas. Todos os estudos relatados foram desenvolvidos para melhor correlacionar a reatividade observada com determinadas características estruturais dos complexos de cobre preparados. / Many investigations on diimine copper(II) complexes have been carried out in order to mimic functional and structural properties of the active sites in proteins and enzymes dependent on this metal. Special interest has been focused on their reactivity toward molecular oxygen and its reduced derivatives, and more recently toward peroxynitrite. These diimine copper(II) complexes exhibited SOD-like activities, but have also shown considerable peroxidase activity, causing oxidative damage to different targets. In this work, some new diimine copper(II) complexes were prepared, derived from 2,3-butanedione and 2-(2-aminophenyl)benzimidazole, 2-(aminomethyl) benzimidazole or 2-(2-aminoethyl)pyridine, and characterized using UV/Vis, IR and EPR spectroscopy, elemental analysis and determination of the effective magnetic moment. Those complexes have also been compared to similar species, derived from pyridinaldehyde and ethylenediamine, or acetylpyrazine and propylenediamine, previously prepared. The studied complexes showed significant SOD activity, indicative of antioxidant properties, and a pronounced tetrahedral distortion around the copper ion, estimated by characteristic spectroscopic parameters. On the other hand, the new compounds also exhibited pro-oxidant activities, by generating hydroxyl radicals in the presence of hydrogen peroxide, detected by the spin-trapping EPR method. The extension of lipid peroxidation promoted by these diimine copper(II) complexes was also investigated, using liposomes of lecithin L-&#945;-phosphatidylcholine as membrane mimics. An enhancement of their peroxidase activity in the presence of bicarbonate and/or nitrite anion was also observed. Further, the decomposition of peroxynitrite, in the presence and absence of carbon dioxide, and the peroxynitrite-mediated nitration of 4-hydroxyphenylacetate, catalyzed by these copper compounds, was measured by stopped-flow kinetic runs. Evidence of intermediary species was provided by significant changes in the EPR spectra. Finally, their electrochemical properties were estimated by cyclic voltammetry and their relative thermodynamic stability was verified through the technique of circular dicroism, using a competitive reaction with albumin, a physiological Cu(II) chelator. All those studies were performed at the aim of correlating some structural characteristics to the observed reactivity of the diimine copper(II) complexes.
80

Avalia??o do car?ter oxidante da violace?na / Avalia??o do car?ter oxidante da violace?na

Leal, Ang?lica Maria de Sousa 28 September 2011 (has links)
Made available in DSpace on 2015-03-03T13:58:19Z (GMT). No. of bitstreams: 1 AngelicaMSL_DISSERT.pdf: 779404 bytes, checksum: 28160c948fb7d8a8df206e8b5a2b131e (MD5) Previous issue date: 2011-09-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Violacein is a violet pigment isolated from many gram-negative bacteria, especially from Chromobacterium violaceum, a betaproteobacterium found in the Amazon River in Brazil. It has potential medical applications as an antibacterial, fungicide, anti-tryptanocidal, anti-ulcerogenic and anti-cancer drug, among others. Furthermore, its pro-oxidant activity has been suggested, but only in two specific tumor lineages. Thus, in the present study, the prooxidant effects of violacein were investigated in both normal and tumor cells, seeking to evaluate the cell responses. The evaluation of violacein cytotoxicity using the Trypan blue dye exclusion method indicated that CHO-K1 cells were more resistant than tumor HeLa cells. The oxidative stress induced by violacein was manifested as an increase in intracellular SOD activity in CHO-K1 and MRC-5 cells at a specific concentration range. Nevertheless, a decrease was detected specifically at 6-12 ?M in HeLa and MRC-5 cells. Interestingly, the increase in SOD activity was not followed by a concomitant increase in catalase activity. Regarding to oxidative stress biomarkers, increased protein carbonylation and lipid hydroperoxides levels were detected respectively in CHO-K1 and MRC-5 cells treated with violacein at 1.5-3 ?M and 3 ?M, which may be an evidence that this compound causes oxidative stress specifically in these conditions. Additionally, it is believed that the decline in cell viability observed in MRC-5 cells and HeLa treated with violacein at 6-12 M is due to mechanisms not related to oxidative stress. Moreover, the results suggested that violacein might cause oxidative stress by increasing endogenous levels of O2 -, since the occurrence of an expressive change in SOD activity. In addition, in order to evaluate the antioxidant activity of violacein in the absence of a biological system, the total antioxidant and iron chelating activity were evaluated, so that antioxidant activities were detected at 30 and 60 ?M of violacein. Altogether, the results indicate that although oxidative stress is triggered by incubation with violacein, it did not seem to be high enough to cause serious damage to cell biomolecules in HeLa cells and only at specific concentrations in CHOK-1 and MRC-5 cells. Comparing the results obtained in cell culture and the in vitro antioxidant activity evaluation, the results confirmed that violacein presents opposing oxidant features when in presence or absence of a biological system and the antioxidant character only occurs at high concentrations of the pigment. / A violace?na ? um pigmento violeta isolado de v?rias esp?cies de bact?rias gram-negativas, especialmente da Chromobacterium violaceum, uma betaproteobact?ria encontrada no rio Amazonas, no Brasil. Diversas atividades biol?gicas j? foram descritas para este pigmento e dentre elas destacam-se a antibacteriana, antif?ngica, tripanocida, antileishmaniose, anti-?lcerog?nica, antiviral e antitumoral. Apesar de uma atividade antioxidante in vitro ter sido sugerida, a atividade pr?-oxidante tamb?m j? foi observada especificamente em duas linhagens tumorais e parece ser dependente de mecanismos espec?ficos para cada linhagem. Nesse sentido, os efeitos citot?xicos e pr?oxidantes da violace?na foram investigados em c?lulas normais e tumorais buscando-se avaliar a ocorr?ncia de diferentes respostas celulares. A an?lise da citotoxicidade da violace?na indicou que c?lulas CHO-K1 foram mais resistentes ao composto em rela??o ?s tumorais HeLa. Quanto ?s enzimas do aparato antioxidante, observou-se um aumento significativo na atividade da SOD intracelular nas linhagens CHO-K1 e MRC-5. Por?m, houve uma diminui??o na atividade enzim?tica especificamente nos tratamentos com 6 e 12 M nas linhagens MRC-5 e HeLa. Interessantemente, o aumento na atividade da SOD n?o foi acompanhado pelo aumento concomitante na atividade da catalase. Em rela??o aos biomarcadores de estresse oxidativo, n?veis elevados de prote?nas carboniladas e hidroper?xidos de lip?dio foram observados em c?lulas CHO-K1 e MRC-5 quando tratadas respectivamente com 1,5-3 ?M e 3 ?M de violace?na, indicando que o pigmento apresenta efeitos pr?-oxidantes especificamente nessas concentra??es. Adicionalmente, acredita-se que a acentuada queda na viabilidade celular observada em c?lulas MRC-5 e HeLa tratadas com 6-12 ?M de violace?na se deve a outros mecanismos n?o relacionados ? gera??o de estresse oxidativo propriamente dita. Os resultados obtidos em cultura de c?lulas sugerem tamb?m que a violace?na induz estresse oxidativo por eleva??o dos n?veis end?genos de O2 ??, visto a ocorr?ncia de uma significativa altera??o nos n?veis de atividade de SOD. Em adi??o, com o objetivo de avaliar o car?ter antioxidante in vitro da violace?na na aus?ncia de um sistema biol?gico celular, a capacidade antioxidante total e a atividade de quela??o f?rrica do pigmento foram avaliadas, de forma que atividades antioxidantes foram detectadas a 30 e 60 ?M de violace?na. Frente aos resultados obtidos, apesar do desencadeamento do estresse oxidativo ap?s a incuba??o com violace?na, este parece n?o ser suficiente para causar danos significativos aos componentes e estruturas celulares em c?lulas HeLa e apenas em concentra??es espec?ficas de pigmento para CHO-K1 e MRC-5, dentro das condi??es avaliadas. Por fim, os resultados confirmam que violace?na apresenta car?teres oxidantes opostos quando na presen?a ou aus?ncia de um sistema biol?gico, al?m de que o car?ter antioxidante s? se d? em concentra??es elevadas do pigmento

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