Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [122]-147).

Diabetics often have elevated levels of serum lipids and cholesterol and increased risk of cardiovascular disease. Streptozotocin-induced diabetes was used to determine whether elevated serum cholesterol levels in diabetics are due to loss of control of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes the committed step in cholesterol synthesis. Strain A/ST female mice were fed 10% corn oil diets, half with 2% cholesterol. Experimental groups were injected with 9.0 mg streptozotocin / 100g body weight. Diabetes was confirmed by weight loss, elevated blood sugars, and enlarged spleens. Reductase activity was assayed spectrophotometrically. Serum cholesterol levels were determined by gas liquid chromatography. Both diabetic and control mice fed cholesterol had elevated serum cholesterol levels and decreased reductase activities. These observations suggest that HMG CoA reductase is not the primary control point in the control of serum cholesterol levels in diabetic mice. The increase in serum cholesterol in the SI mice was not more than in the control group, suggesting that increased serum cholesterol is not a key factor in the control of coronary heart disease and related diseases in diabetics. The HMG CoA reductase activity was reduced in both SI and control mice fed 2% cholesterol, but not significantly, possibly due to a small sample size. Other substances that control serum cholesterol are all density classes of lipoproteins (high, intermediate, low, and very low) as well as the chylomicrons. / Department of Biology

Thesis (Ph.D.)--The University of Texas Southwestern Medical Center at Dallas, 2006. / Embargoed. Vita. Bibliography.

Class of 2012 Abstract / Objectives: To evaluate the literature with respect to drug-drug interactions of the hydroxymethylglutaryl CoA reductase inhibitors atorvastatin, fluvastatin, lovastatin, pitavastitin, pravastatin, simvastatin, and rosuvastatin with warfarin. Methods: This descriptive retrospective study identified articles reporting on each drug-drug interaction from the online databases PubMed (1970 – February 2012) and the drug compendia Micromedex and Facts & Comparisons. The studies included in this investigation were primary literature reports, written in English with human subjects. All studies included were evaluated using the van Roon 5-point quality of evidence scale developed in the Netherlands to assess drug-drug interactions. This scale rates the study type from lowest to highest quality, from zero to four. Case-reports were evaluated using the Drug Interaction Probability Scale (DIPS). The DIPS tool uses 10 questions to evaluate the probability that an adverse event is caused by a drug-drug interaction. Results: Twenty studies met the inclusion criteria. One study involved atorvastatin, four for fluvastatin, three for lovastatin, 2 for pitavastatin, 1 for pravastatin, 5 for rosuvastatin, and 6 for simvastatin. The mean van Roon quality of evidence score was 2.1+/- 0.74, the mean score for atorvastatin, pitavastatin, and pravastatin was 3, with the mean score of fluvastatin, lovastatin, rosuvastatin, and simvastatin was 2. 70% of the literature reviewed were case-reports or letters. Conclusions: The studies and reports supporting HMG-CoA reductase inhibitors and warfarin drug-drug interactions are most commonly case-reports and are of low quality and quantity.

As revisões sistemáticas são consideradas os desenhos experimentais capazes de guiar os cuidados em saúde. Contudo, as revisões narrativas ainda são largamente publicadas até o presente momento. No âmbito do tratamento das doenças periodontais, diversos estudos têm reportado que o uso adjuvante de estatinas à terapia periodontal mecânica pode acarretar melhorias nos parâmetros clínicos periodontais, como adicionais reduções de profundidade de sondagem e ganhos de inserção clínica. O objetivo deste trabalho é contextualizar a informação advinda de uma revisão sistemática realizada sobre um tema clínico significativo e compreender qual o seu papel como suporte da atenção ao paciente periodontal, a partir da compreensão obtida no estudo bibliométrico de revisões de literatura. No estudo bibliométrico, uma amostra representativa das revisões de literatura, publicadas na base Scopus, foi selecionada. Tipo de revisão, número de citações, ano de publicação, temática do estudo e outras variáveis foram coletadas. Nesse estudo, observou-se que o número de revisões sistemática tem aumentado significativamente ao longo dos anos quando comparados com o número de revisões narrativas. Apesar disso, o número ajustado de citações das revisões sistemáticas não difere significativamente das recebidas nas revisões narrativas. Já na revisão sistemática de uso adjuvante de estatinas, uma estratégia de busca nas bases Pubmed, Scopus e Embase foi realizada para identificar todos os ensaios clínicos que tenham utilizado estatinas como adjuvantes ao tratamento periodontal mecânico em comparação à terapia periodontal mecânica isolada ou associada a placebo. Quinze estudos foram selecionados. Observou-se que, na maioria dos estudos, o uso adjuvante de estatina apresentou adicionais reduções de profundidade de sondagem e ganhos de inserção clínica quando comparado com seus respectivos grupos controles. Contudo, a alta heterogeneidade desse resultado e o grande número de estudos ser executado por um mesmo grupo de pesquisa são fatores limitadores dessa revisão sistemática. Dessa maneira, pode-se concluir que o número de revisões sistemáticas vem aumentando a longo do tempo, porém o seu número de citações parece não acompanhar as mesmas tendências. Além disso, o uso adjuvante de estatina na terapia periodontal ainda não deve ser recomendado até a execução de outros estudos com melhor qualidade. / Systematic review is considered the experimental design capable of guiding the health care. However, narrative reviews are broadly published nowadays. Regarding periodontal diseases treatment, several studies reported that the adjuvant use of statins to mechanical periodontal treatment may promote additional improvements in clinical periodontal parameters, such as additional reduction in probing depth and clinical attachment gain. This study aimed to contextualize the information obtained in a systematic review about a significant clinical thematic and comprehend is its role in the periodontal care, through information gathered in a bibliometric study of literature review studies in Dentistry. In the bibliometric study, a representative sample of literature reviews studies, published in Scopus database, was selected. Type of review, number of citations, year of publication, study thematic, and other variables were collected. It was showed that the number of systematic reviews increased throughout the years in comparison to narrative reviews. Additionally, the Dentistry clinical fields presented the highest number of published systematic reviews. Despite of that, the mean adjusted number of citations granted for systematic reviews did not differ from the narrative ones. Regarding the performed systematic review, a search strategy was conducted on Pubmed, Scopus, and Embase databases to identify all clinical trials that used statins as adjuvant to mechanical periodontal treatment in comparison to mechanical periodontal treatment alone or in association with placebo. Fifteen studies were included. It was showed that most of the included studies presented additional reduction in probing depth and clinical attachment gain in comparison to their control groups. However, the high heterogeneity among the studies and the high number of studies conducted by the same research group are limitations of the present systematic review. It was concluded that the number of systematic review are increasing dramatically throughout the years, but this trend is not followed by the number of citations granted to this type of study. Furthermore, the adjuvant use of statin in the mechanical periodontal therapy may not be recommended until further well-designed studies have been published.

nÃo hà / O aumento nos Ãltimos anos de indivÃduos imunocomprometidos, como portadores da SÃndrome da ImunodeficiÃncia Adquirida, de doenÃas malignas, transplantados e outros usuÃrios de terapias imunossupressoras, favorece o surgimento de infecÃÃes oportunistas, principalmente as de teor fÃngico, como a candidÃase e a criptococose. Apesar de a terapia antifÃngica atual ser eficiente na maioria dos casos, algumas vezes fazem-se necessÃrias novas drogas que atuem como alternativa ou como coadjuvantes no tratamento para potencializar o efeito dos antifÃngicos utilizados. As estatinas sÃo fÃrmacos hipolipemiantes mais prescritos mundialmente para doenÃas cardiovasculares. Entretanto, recentemente, tem sido descritos outros efeitos benÃficos destas drogas, como, por exemplo, o controle de infecÃÃes. Este trabalho teve como objetivo determinar a atividade antifÃngica in vitro das estatinas ante 51 cepas de Candida, sendo 16 de C. albicans, 11 de C. krusei, 12 de C. tropicalis e 12 de C. parapsilosis, e 25 cepas de Cryptococcus, sendo 12 de C. gattii e 13 de C. neoformans, por meio de testes de microdiluiÃÃo em caldo, segundo documento M27-A3 padronizado pelo CLSI. O intervalo de concentraÃÃo testado para pravastatina foi de 50 a 0,0977 mg/mL, para sinvastatina, 1 a 0,0020 mg/mL e para atorvastatina, 10 a 0,0200 mg/mL. Pravastatina inibiu 37 leveduras do gÃnero Candida apresentando concentraÃÃo inibitÃria mÃnima (CIM) na faixa de 1,56 a 6,25 mg /mL e as cepas restantes nÃo foram inibidas mesmo na maior concentraÃÃo testada (50 mg /mL), enquanto que sinvastatina e atorvastatina apresentaram atividade antifÃngica sobre todas as 51 cepas avaliadas, apresentando CIMs de 0,02 a 1 mg / mL e 0,04 a 5,00 mg / mL, respectivamente. Para o gÃnero Cryptococcus, apenas 4 cepas foram inibidas ante a pravastatina (CIM = 25 mg / mL), por outro lado, sinvastatina inibiu todas as 25 cepas (CIM = 0,06 a 1 mg / mL), e atorvastatina apenas 8 cepas (CIM = 0,62 a 2,5 mg / mL), sendo que as 17 restantes nÃo foram inibidas mesmo na maior concentraÃÃo testada ( ≥ 10 mg / mL). Foi determinada concentraÃÃo fungicida mÃnima (CFM) de pravastatina sobre 15 cepas do gÃnero Candida (CFM = 3,12 a 25 mg / mL), de sinvastatina sobre 34 cepas (CFM = 0,03 a 1 mg / mL), e de atorvastatina sobre 16 cepas (CFM = 0,04 a 0,31 mg / mL). Para o gÃnero Cryptococcus, das 25 cepas testadas, pravastatina exibiu CFM sobre apenas 3 cepas (CFM = 50 mg / mL), sinvastatina sobre 21 cepas (CFM = 0,12 a 1 mg / mL), e atorvastatina sobre 1 cepa (CFM = 1 mg / mL). Esta atividade inibitÃria in vitro de estatinas sobre espÃcies de Candida e Cryptococcus, abre uma perspectiva importante para a investigaÃÃo do possÃvel uso destas drogas com finalidade antifÃngica in vivo. / In the past years, fungal opportunistic infections, especially, candidiasis and cryptococcosis, have become more frequent because of the increase in the number of immunocompromised individuals, such as AIDS, transplant and cancer patients and those that are on immunosuppressive therapy. In spite of being effective, sometimes it is necessary to use new drugs as alternatives or as adjuvants in order to potentiate the effect of the classical antifungal therapy. Statins are the most prescribed hypolipemiant drugs worldwide for preventing cardiovascular diseases. However, other benefic effects for these drugs have been described, such as the control of infections. This work aimed at determining the antifungal activity of statins against Candida spp. and Cryptococcus spp. The minimum inhibitory concentrations (MICs) for three different statins (pravastatin, simvastatin and atorvastatin) were determined against 51 strains of Candida spp. (16 C. albicans, 11 C.krusei, 12 C. tropicalis and 12 C. parapsilosis) and 25 strains of Cryptococcus spp. (12 C. gattii and 13 C. neoformans), through broth microdilution assay, according to the Clinical Laboratory Standards Institute (CLSI - Document M27-A3). The concentration tested for pravastatin ranged from 50 to 0.0977 mg/mL, for simvastatin, it ranged from 1 to 0.0020 mg/mL and, for atorvastatin, it varied from 10 to 0.0200 mg/mL. Pravastatin inhibited 37 Candida strains, with MICs varying from 1.56 to 6.25 mg/mL and the remaining strains were not inhibited, even at the highest concentration tested (50 mg/mL). Simvastatin and atorvastatin, on the other hand, inhibited all 51 Candida strains evaluated, presenting MICs ranging from 0.02 to 1 mg/mL and from 0.04 to 5 mg/mL, respectively. Concerning Cryptococcus spp., only four strains were inhibited by pravastatin (MIC=25 mg/mL), while all 25 strains were inhibited by simvastatin (0.06≤MIC≤1 mg/mL) and eight were inhibited by atorvastatin (0.62≤MIC≤2.5 mg/mL) and the remaining 17 were not susceptible to the highest atorvastatin concentration tested (10 mg/mL). The minimum fungicidal concentrations (MFCs) for the tested statins were also determined. The MFC for pravastatin against Candida spp. was determined against 15 strains (3.12≤MIC≤25 mg/mL). The MFC values for simvastatin were determined for 34 strains of Candida spp. (0.03≤MFC≤1 mg/mL), while those for atorvastatin were determined against 16 strains (0.04≤MFC≤0,31 mg/mL). Concerning Cryptococcus spp., the 25 strains tested, MFC values for pravastatin were found against three strains (MFC=50 mg/mL), while those for simvastatin were determined against 21 strains (0.12≤MFC≤1 mg/mL) and those for atorvastatin were determined against one single strain (MFC=1 mg/mL). This in vitro inhibitory activity of statins against Candida spp. and Cryptococcus spp. creates an important perspective for the use of these drugs in vivo in order to control fungal infections.

Thesis (M.Sc.). / Written for the Dept. of Neurology and Neurosurgery. Title from title page of PDF (viewed 2008/05/14). Includes bibliographical references.

Dissertation (Ph.D.)--University of South Florida, 2006. / Includes vita. Includes bibliographical references. Also available online.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 82-90).

As revisões sistemáticas são consideradas os desenhos experimentais capazes de guiar os cuidados em saúde. Contudo, as revisões narrativas ainda são largamente publicadas até o presente momento. No âmbito do tratamento das doenças periodontais, diversos estudos têm reportado que o uso adjuvante de estatinas à terapia periodontal mecânica pode acarretar melhorias nos parâmetros clínicos periodontais, como adicionais reduções de profundidade de sondagem e ganhos de inserção clínica. O objetivo deste trabalho é contextualizar a informação advinda de uma revisão sistemática realizada sobre um tema clínico significativo e compreender qual o seu papel como suporte da atenção ao paciente periodontal, a partir da compreensão obtida no estudo bibliométrico de revisões de literatura. No estudo bibliométrico, uma amostra representativa das revisões de literatura, publicadas na base Scopus, foi selecionada. Tipo de revisão, número de citações, ano de publicação, temática do estudo e outras variáveis foram coletadas. Nesse estudo, observou-se que o número de revisões sistemática tem aumentado significativamente ao longo dos anos quando comparados com o número de revisões narrativas. Apesar disso, o número ajustado de citações das revisões sistemáticas não difere significativamente das recebidas nas revisões narrativas. Já na revisão sistemática de uso adjuvante de estatinas, uma estratégia de busca nas bases Pubmed, Scopus e Embase foi realizada para identificar todos os ensaios clínicos que tenham utilizado estatinas como adjuvantes ao tratamento periodontal mecânico em comparação à terapia periodontal mecânica isolada ou associada a placebo. Quinze estudos foram selecionados. Observou-se que, na maioria dos estudos, o uso adjuvante de estatina apresentou adicionais reduções de profundidade de sondagem e ganhos de inserção clínica quando comparado com seus respectivos grupos controles. Contudo, a alta heterogeneidade desse resultado e o grande número de estudos ser executado por um mesmo grupo de pesquisa são fatores limitadores dessa revisão sistemática. Dessa maneira, pode-se concluir que o número de revisões sistemáticas vem aumentando a longo do tempo, porém o seu número de citações parece não acompanhar as mesmas tendências. Além disso, o uso adjuvante de estatina na terapia periodontal ainda não deve ser recomendado até a execução de outros estudos com melhor qualidade. / Systematic review is considered the experimental design capable of guiding the health care. However, narrative reviews are broadly published nowadays. Regarding periodontal diseases treatment, several studies reported that the adjuvant use of statins to mechanical periodontal treatment may promote additional improvements in clinical periodontal parameters, such as additional reduction in probing depth and clinical attachment gain. This study aimed to contextualize the information obtained in a systematic review about a significant clinical thematic and comprehend is its role in the periodontal care, through information gathered in a bibliometric study of literature review studies in Dentistry. In the bibliometric study, a representative sample of literature reviews studies, published in Scopus database, was selected. Type of review, number of citations, year of publication, study thematic, and other variables were collected. It was showed that the number of systematic reviews increased throughout the years in comparison to narrative reviews. Additionally, the Dentistry clinical fields presented the highest number of published systematic reviews. Despite of that, the mean adjusted number of citations granted for systematic reviews did not differ from the narrative ones. Regarding the performed systematic review, a search strategy was conducted on Pubmed, Scopus, and Embase databases to identify all clinical trials that used statins as adjuvant to mechanical periodontal treatment in comparison to mechanical periodontal treatment alone or in association with placebo. Fifteen studies were included. It was showed that most of the included studies presented additional reduction in probing depth and clinical attachment gain in comparison to their control groups. However, the high heterogeneity among the studies and the high number of studies conducted by the same research group are limitations of the present systematic review. It was concluded that the number of systematic review are increasing dramatically throughout the years, but this trend is not followed by the number of citations granted to this type of study. Furthermore, the adjuvant use of statin in the mechanical periodontal therapy may not be recommended until further well-designed studies have been published.