Magister Scientiae (Physiotherapy) - MSc(Physio) / Rheumatic disease is estimated to be one of the most disabling diseases in South Africa and the world. The most common rheumatic diseases are osteoarthritis, fibromyalgia, rheumatoid arthritis, gout and systemic lupus erythematosus. The symptoms of the disease include pain, stiffness, swelling, decreased function. The patient’s functional abilities are severely affected by the pain which in turn, leads to poor quality of life and adverse stress. As a result patients who suffer with one or with a combination of rheumatic disease will experience pain, stress, decreased functional abilities and poor quality of life. The physical properties of water and the therapeutic effects of hydrotherapy, make hydrotherapy an effective form of exercise available to physiotherapists in the treatment of rheumatic disease. The aim of the current study was to determine the effects of a hydrotherapy intervention on the pain, stress, quality of life and functional abilities in patients with rheumatic disease. A quantitative and qualitative research design was employed to meet the objectives. The quantitative aspect involved an A-B-A design and the qualitative part of the study compromised indepth interviews which took place after the intervention. The instruments used were the WHOQOL-BREF instrument, the Visual Analogue Scale (VAS), the Weekly Stress Inventory-Short Form (WSI-SF) and the Health Assessment Questionnaire. (HAQ). The sample consisted of 19 patients who were diagnosed with one or a combination of rheumatic disease. The study was conducted at the hydrotherapy pool at Groote Schuur Hospital in Cape Town. Within the study sample, the majority of the participants were female (84%) with osteoarthritis being common among the participants (53%). The mean age was 60 years. The intervention had a significant impact on pain reduction (p = 0.0001), quality of life (p<0.05). However, the impact of hydrotherapy on stress and the social relationship domain in quality of life was inconclusive. It is thus evident from this study that hydrotherapy as a treatment modality for physiotherapists can be used to impact on the pain, quality of life and functional abilities in patients with rheumatic disease. iv Keywords

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There is an unmet medical need in the treatment of gout. This type of inflammatory arthritis can be efficiently alleviated by the enzyme uricase. This enzyme breaks down uric acid, the causative agent of gout, so it can be flushed from the body. In humans and the other great apes, uricase is a pseudogene and as such is inactive. Research on therapeutic uricases has focused on using enzymes from naturally occurring sources; however, these foreign proteins can be very antigenic and present a potentially life-threatening safety risk to patients. We address the challenges of developing a safer uricase therapeutic by exploiting evidence that, while inactive, the human pseudogene is expressed in the human body and may be recognized as self by the immune system. To develop a ﾓhuman-likeﾔ? uricase we apply the hybrid computational and experimental approach of Ancestral Sequence Reconstruction to search functional sequence space of uricase proteins to engineer an enzyme with high sequence identity to the human pseudogene, and possessing therapeutic levels of activity for the breakdown of uric acid. This dissertation describes the development and characterization of several uricase leads. The most active ancestral uricase possesses both enhanced in vitro and in vivo stability (in healthy rats) when assayed head-to-head Pegloticase, the only FDA approved uricase for the treatment of gout.

La thèse se propose de faire une incursion dans la pensée esthétique du fin XVIIe siècle-début XVIIIe, c'est-à-dire dans les débuts de cette nouvelle discipline en tant que science à part. Les contributions de Jean-Baptiste Dubos à la naissance de cette discipline sont massives, donc ce philosophe de l'art retient et mérite toute notre attention. D'abord, grâce à la Querelle des Anciens et des Modernes, son esprit s'enrichit et se forme, ses connaissances se multiplient de façon à lui permettre de réaliser une synthèse, dans son système d'esthétique, de la riche palette eidétique déployée jusqu'à lui. Ayant comme point de départ le cartésianisme, dont il se distingue entièrement, et dont il hérite uniquement le dogmatisme (l'universalité), cette fois-ci appliqué au sixième sens, celui qui juge de la valeur d'une œuvre artistique, il aboutit à s'ériger en auteur d'un courant opposé, apparenté au sensualisme. L'éloge des sens, au détriment de la raison, qui sont impliqués dans le jugement de goût du public invité à la diffusion de l'art, témoigne d'une coupure entre les époques ; la nouvelle ère appartient à Dubos et à ses disciples, qui répondent même des territoires étrangers, de l'Angleterre et même d'Allemagne. Les cinq parties de la thèse contiennent la description de la marche en avant, des pas de géant effectués dans le domaine des idées esthétiques par l'abbé Dubos. Si, dans la première partie, à l'occasion de la Querelle des Anciens et des Modernes, on découvre une rupture au sein des notions ; la notion de climat étant le noyau d'une théorie esthétique formulée avec le plus grand soin de détail par Dubos ; on découvre donc aussi une focalisation sur le sujet, créateur ou récepteur, siège du sentiment, la deuxième partie vient pour continuer à relever les mérites de Dubos, qui rend possible une attitude différente du public, public qui ne cherche plus l'instruction dans l'art, mais le plaisir, né de la satisfaction du besoin d'être occupé. Les trois autres parties explorent d'une façon plus profonde l'apport esthétique de Dubos : la critique psychologique, la critique scientifique et la critique comparée poésie/peinture. Les qualités de bon psychologue de Dubos, qui plonge dans l'âme du public au moment où il est attendri, rendent possible une meilleure création du génie, qui sait désormais s'adresser au public, de façon émouvante. À cet usage, Dubos formule une théorie du plaisir de l'art, du beau artistique et de l'émotion, qu'il incorpore de façon soudée à son système. Dans la quatrième partie, la critique scientifique, Dubos sonde l'âme du génie, le créateur surpris dans l'enthousiasme nécessaire à la naissance de l'œuvre d'art véritable, créée en vue de plaire. Lors du devenir du génie, les causes formatrices comme les causes morales ou les causes physiques se veulent responsables de ses productions artistiques, poésies ou peintures. De ces dernières nous nous sommes occupés dans la cinquième partie, en réalisant un parallèle, non seulement chez Dubos, mais aussi chez ses successeurs, comme Lessing, prioritairement. Une conclusion nous rappelle les mérites de l'abbé Dubos dans la fondation de l'esthétique moderne.

La thèse se propose de faire une incursion dans la pensée esthétique du fin XVIIe siècle-début XVIIIe, c’est-à-dire dans les débuts de cette nouvelle discipline en tant que science à part. Les contributions de Jean-Baptiste Dubos à la naissance de cette discipline sont massives, donc ce philosophe de l’art retient et mérite toute notre attention. D’abord, grâce à la Querelle des Anciens et des Modernes, son esprit s’enrichit et se forme, ses connaissances se multiplient de façon à lui permettre de réaliser une synthèse, dans son système d’esthétique, de la riche palette eidétique déployée jusqu’à lui. Ayant comme point de départ le cartésianisme, dont il se distingue entièrement, et dont il hérite uniquement le dogmatisme (l’universalité), cette fois-ci appliqué au sixième sens, celui qui juge de la valeur d’une œuvre artistique, il aboutit à s’ériger en auteur d’un courant opposé, apparenté au sensualisme. L’éloge des sens, au détriment de la raison, qui sont impliqués dans le jugement de goût du public invité à la diffusion de l’art, témoigne d’une coupure entre les époques ; la nouvelle ère appartient à Dubos et à ses disciples, qui répondent même des territoires étrangers, de l’Angleterre et même d’Allemagne. Les cinq parties de la thèse contiennent la description de la marche en avant, des pas de géant effectués dans le domaine des idées esthétiques par l’abbé Dubos. Si, dans la première partie, à l’occasion de la Querelle des Anciens et des Modernes, on découvre une rupture au sein des notions ; la notion de climat étant le noyau d’une théorie esthétique formulée avec le plus grand soin de détail par Dubos ; on découvre donc aussi une focalisation sur le sujet, créateur ou récepteur, siège du sentiment, la deuxième partie vient pour continuer à relever les mérites de Dubos, qui rend possible une attitude différente du public, public qui ne cherche plus l’instruction dans l’art, mais le plaisir, né de la satisfaction du besoin d’être occupé. Les trois autres parties explorent d’une façon plus profonde l’apport esthétique de Dubos : la critique psychologique, la critique scientifique et la critique comparée poésie/peinture. Les qualités de bon psychologue de Dubos, qui plonge dans l’âme du public au moment où il est attendri, rendent possible une meilleure création du génie, qui sait désormais s’adresser au public, de façon émouvante. À cet usage, Dubos formule une théorie du plaisir de l’art, du beau artistique et de l’émotion, qu’il incorpore de façon soudée à son système. Dans la quatrième partie, la critique scientifique, Dubos sonde l’âme du génie, le créateur surpris dans l’enthousiasme nécessaire à la naissance de l’œuvre d’art véritable, créée en vue de plaire. Lors du devenir du génie, les causes formatrices comme les causes morales ou les causes physiques se veulent responsables de ses productions artistiques, poésies ou peintures. De ces dernières nous nous sommes occupés dans la cinquième partie, en réalisant un parallèle, non seulement chez Dubos, mais aussi chez ses successeurs, comme Lessing, prioritairement. Une conclusion nous rappelle les mérites de l’abbé Dubos dans la fondation de l’esthétique moderne. / The thesis proposes to make a foray into the aesthetic thinking of late seventeenth century and early eighteenth century, that is to say into the beginnings of this new discipline as a science apart. Contributions from Jean-Baptiste Dubos to the birth of this discipline are massive, so the philosopher of art retains and is worthing all our attention. First, thanks to the Quarrel of the Ancients and the Moderns, his mind is enriched and formed, his knowledge grows in order to enable him to achieve a synthesis, in his aesthetic system, of the rich eidetic pallet deployed up to him. Having as a starting point the Cartesianism, from whom he differs entirely and from whom he inherits only dogmatism (universality), this time applied to the sixth sense, one who judges about the value of a work of art, Dubos arrives at setting himself up as a writer of an opposite current, akin to sensationalism. The praise of the senses, to the detriment of reason, senses involved in the judgment of taste of the public, invited to the dissemination of art, shows a break between periods ; the new era belongs to Dubos and his disciples, who answer, even from foreign territories, as England and even Germany. The five parts of the thesis contain the description of the evolution, of the gigantic steps forward made in the field of aesthetic ideas by Abbe Dubos. If, in the first part, thanks to the Quarrel of the Ancients and the Moderns, we find a break into the notions; the concept of climate being the nucleus of an aesthetic theory formulated with the utmost care of detail Dubos ; so also we find a focus on the subject, creator or receiver, subject who feels, the second part comes to continue to reveal the merits of Dubos, who makes possible a different attitude of public , public that no longer seeks for instruction in art, but for pleasure, born of a satisfied need, the one to be busy. The other three parts are exploring in a deeper way the aesthetic contribution of Dubos : psychological criticism, scientific criticism and comparative poetry / painting criticism. The qualities of Dubos as a good psychologist, who dips into the soul of the public when it is moved, make possible a better creation of genius, who now knows to speak to public, so moving. In this purpose, Dubos formulates a theory of the pleasure of art, artistic beauty and emotion, that he incorporates so welded to his system. In the fourth part, the scientific criticism, Dubos probes the soul of genius, the creator caught in the enthusiasm necessary for the birth of the true work of art, created to please. When the built of genius, formative causes as moral causes or physical causes are responsible for his artistic productions, poems or paintings. Both we have dealt with in the fifth part, by carrying out a parallel, not only in Dubos , but also among his successors, as Lessing priority . A conclusion reminds us of the merits of the Abbe Dubos in the foundation of modern aesthetics.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Hyptis pectinata L. Poit. (Lamiaceae), widely known as Sambacaitá, is an example of a plant commonly used in folk Medicine; various biological effects are associated with its extracts, such as: analgesic, anti-inflammatory, and anti-microbial. Many studies in vivo and in vitro has assessed the effects promoted by the aqueous extract and essential oil of the leaves of the plant, whose chemical composition constitute their water soluble compounds and their volatile compounds, respectively. This study aimed at keeping on these studies, determining the chemical constituents and the acute toxicity of the sample of the aqueous extract and essential oil used to study the analgesic effect of these extracts in an acute articular inflammatory condition, similar to an episode of acute arthritis as in Gout. The phyto-chemical studies of aqueous extract identified the presence of alkaloid, tannin and flavonoid. The analysis of the constituents of the essential oil was made by gas chromatography and mass spectrometer, showing as main constituents: β- cariofilene and Germacrene-D. The evaluation of acute toxicity was represented by the establishment of DL50 in Swiss mice, obtained by the probits method, it was not possible to measure the DL50 of the aqueous extract due to its low toxicity, as for the essential oil, it was obtained a 1.1 g/kg DL50. The analgesic effect was studied using the sodium urate crystals induced arthritis model, in Wistar mice, as proposed by Coderre and Wall; the aqueous extract presented expressive analgesic effect with the 50 mg/kg doses, which was reverted by the opioid antagonist, naloxone (5 mg/kg). The essential oil did not present analgesic effect with the tested doses. The results showed that the aqueous extract has low toxicity and it presents analgesic effect in a rheumatic condition, similar to Gout arthritis, while the essential oil presents medium toxicity and it does not show analgesic effect in the proposed rheumatic condition. / A Hyptis pectinata L. Poit. (Lamiaceae), vulgarmente conhecida como sambacaitá, é um exemplo de planta comumente utilizada na medicina popular; diversos efeitos biológicos estão associados aos seus extratos, tais como analgésico, antiinflamatório e antimicrobiano. Vários estudos in vivo e in vitro têm avaliado estes efeitos promovidos pelo extrato aquoso e óleo essencial das folhas da planta, cujas composições químicas, constituem os seus compostos solúveis em água e os seus compostos voláteis respectivamente. Este trabalho objetivou dar continuidade a esses estudos, determinando os constituintes químicos e a toxicidade aguda da amostra de extrato aquoso e óleo essencial utilizados, para estudar o efeito antinociceptivo (analgésico) dos extratos citados, em uma condição inflamatória articular aguda, similar a um ataque de artrite aguda como o ocorrido na gota. Os estudos fitoquímicos do extrato aquoso identificaram a presença de alcalóides, taninos e flavonóides. A análise dos constituintes do óleo essencial se deu por cromatografia gasosa e espectrômetro de massa, revelando como principais constituintes: β-cariofileno e germacreno-D. A avaliação da toxicidade aguda foi representada pela determinação da DL50, em camundongos swiss, obtida pelo método dos probitos; não foi possível mensurar a DL50 do extrato aquoso, devido a sua baixa toxicidade, já o óleo essencial, obteve uma DL50 de 1,1 g/kg. O efeito antinociceptivo foi estudado usando o modelo de artrite induzida por cristais de urato de sódio, em ratos wistar, proposto por Coderre e Wall. O extrato aquoso apresentou efeito antinociceptivo significativo na dose de 50 mg/Kg, o qual foi revertido pelo antagonista opióide, naloxona (5mg/kg). O óleo essencial não apresentou efeito antinociceptivo nas doses testadas. Os resultados mostraram que o extrato aquoso possui baixa toxicidade e apresenta atividade antinociceptiva numa condição reumática, semelhante à artrite gotosa; enquanto o óleo essencial apresenta toxicidade média e não apresenta atividade antinociceptiva na condição reumática proposta.

v anglickém jazyce Introduction: No information was known about frequency of common inflammatory disorders in rheumatology in the Czech Republic. Aims of the study: To estimate the standardized annual incidence (INC) and point prevalence (PREV) of six diseases (rheumatoid arthritis-RA, juvenile idiopathic arthritis-JIA, gout, psoriatic arthritis-PsA, ankylosing spondylitis-AS, reactive arthritis-ReA) in a population-based study in two regions of the Czech Republic (CR). Methods: INC: Incident cases were registered on condition that the definite diagnosis was confirmed according to existing classification criteria during the study period. PREV was studied on the basis of identification of established diagnoses at a time point. Crude rates were standardized for age and sex. Results: Both INC and PREV are shown per 100.000 inhabitants. RA INC:31 (95%CI 20-42), PREV:610 (95%CI 561-658). Gout-INC:41 (95%CI 28-53), PREV:300 (95% CI 266-334). JIA-INC: 13 (95% CI 1-20), PREV:140 (95%CI 117-280). PsA-INC:3,6 (95% CI 1-8), PREV:49 (95%CI 40-60). AS-INC:6 (95% CI 3-11), PREV:94 (95% CI 94-109). ReA-INC:9 (95% CI 6-15), PREV:91 (95% CI 78-106). Conclusion: This is the first population-based study estimating annual incidence and prevalence rates of the most common rheumatological disorders in the Czech...