CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A HansenÃase à uma doenÃa infecciosa, de evoluÃÃo lenta, transmitida pelo Mycobacterium leprae que acomete nervos e pele. O tratamento especÃfico das pessoas portadoras de hansenÃase foi enfatizado no inÃcio dos anos 80 pela OrganizaÃÃo Mundial de SaÃde (OMS) com o objetivo de curar o indivÃduo da infecÃÃo pelo Mycobacterium leprae e evitar o desenvolvimento de incapacidades. A OMS implementou a poliquimioterapia (PQT) composta pelas drogas dapsona, clofazimina e rifampicina, cuja associaÃÃo evita a resistÃncia medicamentosa do bacilo. A PQT mata o bacilo, evita a evoluÃÃo da doenÃa, e sendo realizada de forma completa e correta, garante a cura da doenÃa. O objetivo geral deste estudo foi avaliar parÃmetros laboratoriais antes e durante a PQT, em uma populaÃÃo de 102 pacientes hansÃnicos, com idade entre 5 e 78 anos, diagnosticados e assistidos no Centro de Dermatologia Dona LibÃnia (CDERM) no perÃodo de Janeiro de 2005 a Janeiro de 2006. Propomos um estudo para avaliaÃÃo da funÃÃo hepÃtica (TGO, TGP, Bilirrubinas Totais e fraÃÃes e Fosfatase Alcalina), renal (UrÃia e Creatinina) e parÃmetros hematolÃgicos (Leucograma, HematÃcrito e Hemoglobina). O estudo foi feito atravÃs da anÃlise laboratorial no soro do paciente para avaliaÃÃo da funÃÃo hepÃtica, renal e sangue total para parÃmetros hematolÃgicos. Destes, 50 (49%) pacientes foram classificados como paucibacilares (PB) e 52 (51%) multibacilares (MB). Teve como metodologia: ficha de investigaÃÃo, revisÃo de prontuÃrio e coleta de sangue antes de iniciar o tratamento e durante o tratamento, com 6 e 12 meses. Dentre os 102 pacientes estudados 48(47%) eram do sexo feminino e 54(53%) do sexo masculino, 12(11,7%) tinham 1 grau incompleto ou eram analfabetos e 6(5,8%) eram de nÃvel superior. Quanto à situaÃÃo financeira, 40(39,2%) nÃo possuÃam renda e 34(33,3%) ganhavam atà um salÃrio mÃnimo. A mÃdia da idade populacional foi de 40,8 anos (DP=19,3), entretanto a incidÃncia de pacientes com idade inferior a 10 anos foi maior no PB. Com relaÃÃo à forma clÃnica, 2(1,9%) eram da forma Indeterminada, 32(31,3%) TuberculÃide, 31(30,3%) Dimorfa, 15(14,7%) Dimorfa/TuberculÃide, 3(2,9%) Dimorfa/Virchowiana e 8(7,8%) da forma Virchowiana. Com relaÃÃo à anÃlise hematolÃgica, a anemia foi a alteraÃÃo mais freqÃente estando presente antes e durante o tratamento, tendo sido mais significativa no grupo MB no sexto mÃs de tratamento. No leucograma, linfocitose e eosinofilia foram as alteraÃÃes mais freqÃentes antes e durante a PQT nos dois grupos PB e MB. Em relaÃÃo aos parÃmetros bioquÃmicos, foram observadas alteraÃÃes nos nÃveis de TGO 6(5,8%) e TGP 5(4,9%) sem significÃncia estatÃstica. Considerando a inexistÃncia de um perfil laboratorial caracterÃstico para a hansenÃase, as alteraÃÃes encontradas em alguns parÃmetros durante a poliquimioterapia, nÃo podem ser atribuÃdas somente aos efeitos adversos deste esquema, e sim tambÃm aos efeitos inerentes à hansenÃase e/ou ao uso da PQT. Para a realizaÃÃo de um tratamento poliquimioterÃpico seguro à necessÃria a realizaÃÃo de exames laboratoriais antes e durante a poliquimioterapia / Leprosy or Hansenâs disease is an infectious disease with slow flow velocity, transmitted by Mycobacterium leprae that attacks nerves and skin. The specific treatment for people who suffer of leprosy was emphasized in the beginning of the 80âs by the World Health Organization (WHO) in order to cure the infection with Mycobacterium leprae and prevent disability. The WHO has implemented a multidrug therapy (MDT) composed of dapsone, rifampicin and clofazimine, an association that prevents bacillus resistance. The MDT kills the bacillus, prevents the aggravation of the disease, and if followed precisely, guarantees the cure of the disease. The objective of this study was to evaluate laboratory parameters, before and during the MDT, in a population of 102 hansenian patients, aged 5 to 78 years, diagnosed and assisted at the Center of Dermatology Dona LibÃnia (CDERM) between January 2005 and January 2006. Evaluation of liver function (GOT, GPT, total bilirubin and fractions and alkaline phosphatase), renal function (urea and creatinine) and haematological parameters (leukogram, hematocrit and hemoglobin) was done through blood serum analysis or patientâs clinical history. A review of patientâs medical records as well as blood tests was done before treatment, after 6 months and after one year. A total of 102 patients participated on the study. Fifty patients (49%) were classified as paucibacillary (PB) and 52 (51%) multibacillary (MB). Social-demographic characteristics showed that 48 (47%) were female and 54 (53%) were male; 12 (11.7%) were either illiterate or have not finished the first grade; 6 (5,8%) were graduating; 40 (39.2%) did not have income and 34 (33.3%) earned no more than the minimum wage. Mean age was 40,8 years (SD = 19,3) and the number of patients younger than 10 years was higher in PB. As to the clinical form, 32 patients (31.3%) presented the tuberculoid form, followed by dimorph (30.3%); dimorph / tuberculoid (14.7%); Virchowian (7.8%); dimorph / Virchowian (2.9%); and undetermined (1.9%). Hematological analysis showed that anemia was the most frequent alteration, being present before and during treatment, and was most significant in the group MB in the sixth month of treatment. The most frequent alterations showed in the leukogram before and during the MDT in both PB and MB groups were lymphocytosis and eosinophilia. Regarding to biochemical parameters, that changes in the levels of GOT (5.8%) and GPT (4.9%) without statistical significance. Considering the lack of a typical laboratory profile for leprosy, the changes found in some parameters during polychemotherapy can not be attributed only to adverse effects of this therapy but to other effects that are inherent to leprosy and the use of MDT. Therefore, a safe polychemotherapy requires the realization of laboratory tests before and during treatment

by Mei Choi Tang. / Thesis submitted in 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references. / Abstract also in Chinese. / Chapter Chapter 1. --- Introduction --- p.1-22 / Chapter Chapter 2. --- PAE studies for antimicrobial combinations using the Fractional Maximal Effect method (FME method) --- p.23-64 / Chapter Chapter 3. --- Effect of sequential antibiotic administration on the postantibiotic effect exhibited by an antimicrobial combination: A case for the combination of rifampin and tobramycin against E.coli ATCC 25922 --- p.65-84 / Chapter Chapter 4. --- Effect of antimicrobial resistance to the components of an antimicrobial combination: A pilot study with piperacillin and gentamicin against Ps. aeruginosa --- p.85-100 / Chapter Chapter 5. --- Conclusions --- p.101-106 / Appendix I --- p.107-113 / Appendix II --- p.114-116 / Appendix III --- p.117-120 / Appendix IV --- p.121-138 / Appendix V --- p.139-153

by Lee Hon Kit. / Thesis (M.Sc.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 80-89). / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Lipids and Lipoproteins --- p.1 / Chapter 1.1.1 --- Chemistry and Classification of Lipids --- p.1 / Chapter 1.1.2 --- Lipoprotein and Apolipoprotein --- p.3 / Chapter 1.1.2.1 --- Lipoprotein: Structure and Classification --- p.3 / Chapter 1.1.2.2 --- Apolipoprotein: Structure and Function --- p.5 / Chapter 1.1.2.3 --- Lipoprotein (a) and Apolipoprotein (a) --- p.8 / Chapter 1.1.3 --- Outline of Lipid and Lipoprotein Metabolism --- p.10 / Chapter 1.1.3.1 --- Exogenous Lipid Metabolism --- p.10 / Chapter 1.1.3.2 --- Endogenous Lipid Pathway --- p.13 / Chapter 1.2 --- "Dyslipidaemia: Definition, Classification and Coronary Heart Disease" --- p.20 / Chapter 1.2.1 --- Definition --- p.20 / Chapter 1.2.2 --- Classification of Dyslipidaemia --- p.21 / Chapter 1.2.3 --- Dyslipidaemia and CHD --- p.24 / Chapter 1.3 --- Dyslipoproteinaemia and Atherogenesis --- p.25 / Chapter 1.3.1 --- Pathology and Pathogenesis --- p.25 / Chapter 1.3.2 --- Central Role of Oxidised LDL in Atherogenesis --- p.29 / Chapter 1.3.3 --- LDL Heterogeneity and Atherogenesis --- p.37 / Chapter 1.4 --- Management of Dyslipidaemia --- p.41 / Chapter 1.4.1 --- Drug therapy --- p.43 / Chapter 1.4.1.1 --- Triglyceride Lowering Drugs --- p.43 / Chapter 1.4.1.2 --- Cholesterol Lowering Drugs --- p.45 / Chapter 1.4.1.3 --- Combination Drug Therapy --- p.46 / Chapter 1.5 --- Aims of this study --- p.49 / Chapter 2. --- Materials and Methods --- p.50 / Chapter 2.1 --- Materials --- p.50 / Chapter 2.1.1 --- Patients and Controls --- p.50 / Chapter 2.1.2 --- Drug Administration Trials --- p.51 / Chapter 2.1.3 --- Blood Samples --- p.52 / Chapter 2.1.4 --- Chemicals and Solutions --- p.52 / Chapter 2.1.5 --- Apparatus and Equipments --- p.52 / Chapter 2.2 --- Methods --- p.54 / Chapter 2.2.1 --- "Serum Cholesterol, Triglyceride and High Density Lipoprotein cholesterol" --- p.54 / Chapter 2.2.2 --- "Apolipoprotein AI, B-100 and Lipoprotein (a) Assays" --- p.54 / Chapter 2.2.3 --- Ultracentrifugation of LDL Fraction --- p.55 / Chapter 2.2.4 --- In Vitro Assessment of LDL Oxidisability --- p.55 / Chapter 2.2.4.1 --- De-Salting of LDL Fraction --- p.55 / Chapter 2.2.4.2 --- Continuously Diene Formation Monitoring --- p.56 / Chapter 2.2.5 --- LDL Particle Size --- p.56 / Chapter 2.2.6 --- Statistical Analysis --- p.57 / Chapter 3. --- Results --- p.59 / Chapter 3.1 --- Quantitative Measurement of apo B-100 --- p.59 / Chapter 3.2 --- "Associations between Serum Triglyceride, LDL Particle Size and LDL Oxidisability" --- p.60 / Chapter 3.3 --- "Effect of single drug and combination drug therapy on lipids, lipoproteins and apolipoproteins" --- p.64 / Chapter 3.3.1 --- Quantitative Changes of Lipids and Lipoproteins --- p.64 / Chapter 3.3.2 --- Qualitative changes of LDL particles --- p.65 / Chapter 4. --- Discussion --- p.74 / Chapter 4.1 --- "Associations between Triglyceride concentration, HDL Cholesterol concentration, LDL oxidisability and Particle Size" --- p.74 / Chapter 4.2 --- Effects of Fluvastatin and Gemfibrozil on Combined Hyperlipidaemic Patients --- p.76

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Vita. Bibliography: p.97-109

Objetivos: O objetivo deste estudo foi o de identificar compostos seletivamente tóxicos ao carcinoma espinocelular de boca in vitro por meio do reposicionamento de fármacos. Material e Métodos: Por meio de um escaneamento baseado na viabilidade celular de 1.280 fármacos, nós selecionamos três princípios ativos (luteolin, metixene hydrochloride e nitazoxanide) letais às células de câncer de boca SCC-25 e pouco tóxicos às células de queratinócitos cutâneos imortalizados HaCaT. Os fármacos candidatos foram investigados quanto à sua dose- e tempo-resposta bem como comparados e combinados à agentes quimioterápicos padrão por meio do ensaio por colorimetria com brometo de tiazolil azul de tetrazolio (MTT). O impacto dos fármacos na motilidade do SCC-25 e do HaCaT foi verificado pelo ensaio de migração celular e seus mecanismos de ação também foram explorados por meio da verificação dos níveis das proteínas fosforiladas pelo western blotting. Todos os experimentos foram realizados em triplicata e, pelo menos, três vezes independentes. O teste t de student foi utilizado para confrontar as variáveis e nível de significância de 5% foi estabelecido para todos os testes. Resultados: O flavonoide natural luteolin exerceu citotoxicidade potente contra as células de câncer de boca in vitro, apresentando baixa toxicidade ao HaCaT e alta eficiência quando comparado a quimioterápicos como a cisplatina e o AG1478. Do ponto de vista molecular, a luteolin ativou a via de sinalização do dano do DNA e, combinada com um inibidor do Chk, apresentou efeitos potencializados. Além disso, nós demonstramos que a nitazoxanide e o metixene hydrochloride são capazes de destruir células SCC-25 porém não as HaCaT de maneira proporcional à dose e ao tempo de tratamento. As combinações entre os três fármacos hit e com a cisplatina ou o AG1478 potencializaram seus efeitos contra as células malignas. Conclusões: O presente estudo traz a luteolin, o metixene hydrochloride e a nitazoxanide como fortes candidatos a agentes terapêuticos contra o câncer de boca uma vez que estes compostos apresentam maior eficácia contra células de câncer de boca e menor toxicidade contra células não tumorais in vitro do que agentes quimioterápicos convencionais. / Objectives: Here we aimed at identifying and reposition approved drugs that could be selectively toxic towards oral squamous cell carcinoma cells. Materials and Methods: Through a cell-based drug screening of 1,280 chemical molecules, we selected 3 compounds (luteolin, metixene hydrochloride, and nitazoxanide) lethal to oral cancer SCC-25 cells, while sparing immortalized keratinocyte HaCaT cells. The drugs were then further challenged for their time- and dose-responses, as well as their comparison and combination to standard chemotherapeutic agents by colorimetric assay 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan, Thiazolyl blue formazan (MTT). The impact on SCC-25 and HaCaT motility as well as the mode of action of the drugs was then further explored by scratching assay and western blotting, respectively. All the experiments were performed in triplicated and, at least, three independent times. Students t test was performed to verify the differences among the variables and the level of significance was set at 5%. Results: The natural flavonoid luteolin was a potent cytotoxic agent against oral cancer cells in vitro, presenting low toxicity against HaCaT cells and high efficiency as compared to standard-of-care, such as cisplatin and AG1478. From a molecular standpoint, luteolin coopted the DNA-damage pathway and could be efficiently combined with Chk pharmacological inhibitor. Moreover, we demonstrated that nitazoxanide and metixene hydrochloride kill the SCC-25 but not the HaCaT cells in a dose- and time-dependent. The combinations among the three drugs hit and with cisplatin and AG1478 improved their effect against the malignant cells. Conclusions: Luteolin, metixene hydrochloride, and nitazoxanide emerge as strong cytotoxic and/or adjuvant therapy in oral cancer, as these compounds present higher efficiency and lower toxicity against oral cancer cells in vitro than conventional chemotherapeutic agents.

Objetivos: O objetivo deste estudo foi o de identificar compostos seletivamente tóxicos ao carcinoma espinocelular de boca in vitro por meio do reposicionamento de fármacos. Material e Métodos: Por meio de um escaneamento baseado na viabilidade celular de 1.280 fármacos, nós selecionamos três princípios ativos (luteolin, metixene hydrochloride e nitazoxanide) letais às células de câncer de boca SCC-25 e pouco tóxicos às células de queratinócitos cutâneos imortalizados HaCaT. Os fármacos candidatos foram investigados quanto à sua dose- e tempo-resposta bem como comparados e combinados à agentes quimioterápicos padrão por meio do ensaio por colorimetria com brometo de tiazolil azul de tetrazolio (MTT). O impacto dos fármacos na motilidade do SCC-25 e do HaCaT foi verificado pelo ensaio de migração celular e seus mecanismos de ação também foram explorados por meio da verificação dos níveis das proteínas fosforiladas pelo western blotting. Todos os experimentos foram realizados em triplicata e, pelo menos, três vezes independentes. O teste t de student foi utilizado para confrontar as variáveis e nível de significância de 5% foi estabelecido para todos os testes. Resultados: O flavonoide natural luteolin exerceu citotoxicidade potente contra as células de câncer de boca in vitro, apresentando baixa toxicidade ao HaCaT e alta eficiência quando comparado a quimioterápicos como a cisplatina e o AG1478. Do ponto de vista molecular, a luteolin ativou a via de sinalização do dano do DNA e, combinada com um inibidor do Chk, apresentou efeitos potencializados. Além disso, nós demonstramos que a nitazoxanide e o metixene hydrochloride são capazes de destruir células SCC-25 porém não as HaCaT de maneira proporcional à dose e ao tempo de tratamento. As combinações entre os três fármacos hit e com a cisplatina ou o AG1478 potencializaram seus efeitos contra as células malignas. Conclusões: O presente estudo traz a luteolin, o metixene hydrochloride e a nitazoxanide como fortes candidatos a agentes terapêuticos contra o câncer de boca uma vez que estes compostos apresentam maior eficácia contra células de câncer de boca e menor toxicidade contra células não tumorais in vitro do que agentes quimioterápicos convencionais. / Objectives: Here we aimed at identifying and reposition approved drugs that could be selectively toxic towards oral squamous cell carcinoma cells. Materials and Methods: Through a cell-based drug screening of 1,280 chemical molecules, we selected 3 compounds (luteolin, metixene hydrochloride, and nitazoxanide) lethal to oral cancer SCC-25 cells, while sparing immortalized keratinocyte HaCaT cells. The drugs were then further challenged for their time- and dose-responses, as well as their comparison and combination to standard chemotherapeutic agents by colorimetric assay 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan, Thiazolyl blue formazan (MTT). The impact on SCC-25 and HaCaT motility as well as the mode of action of the drugs was then further explored by scratching assay and western blotting, respectively. All the experiments were performed in triplicated and, at least, three independent times. Students t test was performed to verify the differences among the variables and the level of significance was set at 5%. Results: The natural flavonoid luteolin was a potent cytotoxic agent against oral cancer cells in vitro, presenting low toxicity against HaCaT cells and high efficiency as compared to standard-of-care, such as cisplatin and AG1478. From a molecular standpoint, luteolin coopted the DNA-damage pathway and could be efficiently combined with Chk pharmacological inhibitor. Moreover, we demonstrated that nitazoxanide and metixene hydrochloride kill the SCC-25 but not the HaCaT cells in a dose- and time-dependent. The combinations among the three drugs hit and with cisplatin and AG1478 improved their effect against the malignant cells. Conclusions: Luteolin, metixene hydrochloride, and nitazoxanide emerge as strong cytotoxic and/or adjuvant therapy in oral cancer, as these compounds present higher efficiency and lower toxicity against oral cancer cells in vitro than conventional chemotherapeutic agents.

Thesis (M.S.P.H.)--University of South Florida, 2009. / Title from PDF of title page. Document formatted into pages; contains 57 pages. Includes bibliographical references.

Made available in DSpace on 2014-07-29T15:04:27Z (GMT). No. of bitstreams: 1 dissertacao-dalva-aparecida.pdf: 328745 bytes, checksum: 4af67ad606d4d4ef8515b6d4cc3d79eb (MD5) Previous issue date: 2008-03-24 / The high effectiveness of the combined antiretroviral therapy for HIV/AIDS is wellknown, but it depends on the efficient adhesion of the patient to the treatment. The efficient adhesion to the treatment guarantees its effectiveness because increasing the patient s adherence to the antiretroviral treatment constitutes a global goal to stop the HIV/AIDS epidemic. This study aimed to understand the adhesion to the treatment the HIV/AIDS in the experience of the woman. Ethnographic study based on Geertz theoretical presuppositions. The data collection occurred by semistructuralized interviews and participant observation ith eight women of a Public Hospital Group of Adhesion in Goiás, Brazil, from 2007 January to December. The first moment of data analysis started as soon as it was initiate the interviews and where we sought to find the units of meanings. The second moment occurred in an inference process and findings theorization and its interrelation with our subject, but always searching answers to the study objectives and the theoretical concepts. From data analysis process emerged four meaning units, as known, confrontation of the cultural values in the experience of the adhesion; the rite of the experience in the adhesion to the treatment; practical customs and in the experience of the adhesion and taking care of in the interpersonal relations. Results allow an understanding that adhesion to the treatment for HIV/AIDS is ruled in the aspects of the local culture, in spite of the biomedical deductions and reducing imposed by professionals with a large scientific and technological knowledge. Also allow to understand that the experience of the adhesion to the treatment for the HIV/AIDS in the woman perceptions consists in a wire of meanings built inside a popular culture. And the culture where these women are inserted, keeps its controlling mechanisms for the person living with the HIV/AIDS survival. / A alta eficácia da terapia antiretroviral combinada para HIV/AIDS é notória, mas depende da adesão eficiente do paciente ao tratamento. A adesão eficiente ao tratamento garante sua efetividade porque aumentando a adesão do paciente ao tratamento antiretroviral constitui uma meta global para frear a epidemia HIV/AIDS. Este estudo teve como objetivo compreender a adesão ao tratamento pra o HIV/AIDS na experiência da mulher. Estudo etnográfico baseado nos pressupostos de Geertz como aporte teórico. A coleta de dados ocorreu através de entrevistas semi-estruturadas e observação participante com oito informantes do Grupo de Adesão de um Hospital Público de Goiás, no período de janeiro a dezembro de 2007. O primeiro momento da analise dos dados começou com a realização das primeiras entrevistas, quando buscamos identificar as unidades de significados. O segundo momento ocorreu em um processo de inferência e teorização dos achados e a sua relação com o nosso tema, mas sempre buscando o enlace aos nossos objetivos e pressupostos teóricos. Do processo de análise dos dados emergiram quatro unidades de significados tais como, enfrentamento dos valores culturais na experiência da adesão; o rito da experiência na adesão ao tratamento; costumes e práticas na experiência da adesão e o cuidar nas relações interpessoais. A análise nos permite compreender que a adesão ao tratamento para o HIV/AIDS está pautada nos aspectos da cultura local, apesar das deduções biomédicas e reducionistas impostas por profissionais com um vasto conhecimento científico tecnológico. Também nos permite compreender que a experiência da adesão ao tratamento para o HIV/AIDS na visão da mulher consiste em uma teia de significados construídos dentro da cultura popular. E a cultura onde estas mulheres estão inseridas, mantém seus mecanismos de controle para a sobrevivência da pessoa vivendo com o HIV/AIDS.