Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 4 uppsatser.

by Paul, Liu Po Lung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1994. / Includes bibliographical references (leaves 86-94). / ACKNOWLEDGMENT --- p.i / TABLE OF CONTENT --- p.ii / "LIST OF TABLE, FIGURE & PHOTO" --- p.viii / ABSTRACT --- p.x / Chapter CHAPTER ONE : --- INTRODUCTION --- p.1 / Chapter 1.1 --- ALKALINE PHOSPHATASE / Chapter 1.1.1 --- Alkaline Phosphatase Isoenzyme --- p.2 / Chapter 1.1.2 --- The Properties of Alkaline Phosphatases --- p.4 / Chapter 1.1.3 --- Serum Alkaline Phosphatases --- p.6 / Chapter 1.1.3.1 --- Placental Alkaline Phosphatase --- p.7 / Chapter 1.1.3.2 --- Intestinal Alkaline Phosphatase --- p.7 / Chapter 1.1.3.4 --- Skeletal Alkalne Phosphatase --- p.8 / Chapter 1.1.3.5 --- Hepatic Alkaline Phosphatase --- p.8 / Chapter 1.1.3.3 --- Renal Alkaline Phosphatase --- p.9 / Chapter 1.1.3.6 --- Miscellaneous Alkaline Phosphatase --- p.9 / Chapter 1.1.4 --- Problems in Discriminating the Skeletal and Hepatic Alkaline Phosphatase in Serum --- p.11 / Chapter 1.1.5 --- Quantitative measure of the Bone-Specific Alkaline Phosphatase --- p.12 / Chapter 1.1.6 --- Qualitative Detection of ALP isoenzymes --- p.14 / Chapter 1.2 --- OSTEOSARCOMA --- p.17 / Chapter 1.2.1 --- Definition --- p.17 / Chapter 1.2.2 --- Epidemiology and Statistics --- p.17 / Chapter 1.2.3 --- Clinical Presentation --- p.18 / Chapter 1.2.4 --- Radiographic finding --- p.19 / Chapter 1.2.5 --- Staging of Musculoskeletal Neoplasms --- p.20 / Chapter 1.2.6 --- Treatment of osteosarcoma --- p.21 / Chapter 1.2.6.1. --- Chemotherapy in Prince of Wales Hospital --- p.21 / Chapter 1.3 --- PLASMA AND TISSUE ALKALINE PHOSPHATASE IN NORMAL AND NEOPLASTIC CONDITION --- p.23 / Chapter 1.3.1 --- Normal values of plasma alkaline phosphatase --- p.23 / Chapter 1.3.2 --- Clinical use of elevated plasma & tissue alkaline phosphatase level in neoplastic conditions --- p.25 / Chapter 1.3.2.1 --- Helping the Diagnosis of the Osteosarcoma --- p.25 / Chapter 1.3.2.2 --- Monitoring the effect of chemotherapy --- p.26 / Chapter 1.3.2.3 --- Predicting the clinical course --- p.26 / Chapter 1.3.3 --- Qualitative measurement of ALP in plasma and tissue extract of osteosarcoma patient --- p.29 / Chapter 1.4 --- AIM AND SCOPE OF THE PRESENT DISSERATION --- p.30 / Chapter CHAPTER TWO : --- MATERIALS AND METHODS --- p.32 / Chapter 2.1 --- DIFERENT GROUPS OF PATIENTS --- p.33 / Chapter 2.1.1 --- Monitering the plasma bone specific ALP --- p.33 / Chapter 2.1.1.1 --- Osteosarcoma group --- p.33 / Chapter 2.1.1.2 --- Benign bone tumour group --- p.34 / Chapter 2.1.1.3 --- Metastasis group --- p.34 / Chapter 2.1.2 --- Collection of plasma samples preserve of tumor tissue --- p.34 / Chapter 2.2 --- QUANTITATIVE ANALYSIS OF THE PLASMA AND TISSUE BONE SPECIFIC ALKALINE PHOSPHATASE --- p.36 / Chapter 2.2.1 --- Extraction of tissue ALP --- p.36 / Chapter 2.2.1.1. --- Reagent --- p.36 / Chapter 2.2.1.2. --- Homogenization of the bone tissue --- p.36 / Chapter 2.2.1.3. --- Extraction of ALP --- p.37 / Chapter 2.2.2 --- Assay for Bone-specific ALP --- p.38 / Chapter 2.2.2.1. --- Reagents --- p.38 / Chapter 2.2.2.2. --- Procedures --- p.38 / Chapter 2.3 --- QUALITATIVE MEASUREMENT OF ALP ISOENZYME --- p.40 / Chapter 2.3.1 --- Equipment required --- p.40 / Chapter 2.2.2 --- Practical procedure --- p.40 / Chapter 2.3.3.1 --- Gel casting --- p.40 / Chapter 2.3.3.2 --- Sample preparation and application --- p.42 / Chapter 2.3.3.3 --- Electrofocusing --- p.42 / Chapter 2.3.3.4 --- Western blotting of the protein --- p.43 / Chapter 2.3.3.5 --- Detection methods --- p.45 / Chapter 2.4 --- METHOD OF STATISTICAL ANALYSIS --- p.48 / Chapter CHAPTER THREE : --- RESULTS --- p.49 / Chapter 3.1 --- QUANTITATIVE MEASUREMENT OF PLASMA AND TISSUE BONE SPECIFIC ALKALINE PHOSPHATASE --- p.50 / Chapter 3.1.1 --- General Information of the patients monitoring --- p.50 / Chapter 3.1.2 --- Pretreatment evaluation --- p.52 / Chapter 3.1.3 --- Correlation between the pretreatment plasma ALP levels and prognosis in the osteosarcoma patient group --- p.57 / Chapter 3.1.4 --- "Correlation between the pre-operational, post- operational plasma ALP levels and the prognosis of osteosarcoma" --- p.59 / Chapter 3.1.5 --- Analysis of plasma ALP levels at the time of relapse in osteosarcoma patients --- p.61 / Chapter 3.1.6 --- Usefulness of the plasma ALP levels for monitoring the effectiveness of chemotherapy --- p.62 / Chapter 3.1.7 --- Correlation between the ALP levels in the tumor extract and the prognosis of the osteosarcoma --- p.64 / Chapter 3.2 --- QUALITATIVE ANALYSIS OF THE PLASMA AND TISSUE ALKALINE PHOSPHATASE LEVEL --- p.67 / Chapter 3.2.1 --- Comparison of the result of Isoelectric focusing of the plasma ALP of the osteosarcoma patients and the normal subjects --- p.67 / Chapter 3.2.1 --- Result of Isoelectric focusing of the ALP isoenzymes in the tissue extract of the osteosarcoma and normal bone --- p.70 / Chapter CHAPTER FOUR : --- DISCUSSION --- p.72 / Chapter 4.1 --- USE OF QUANTITATIVE MONITORING OF PLASMA ALP AND MEASURING TISSUE ALP IN OSTEOSARCOMA PATIENTS --- p.73 / Chapter 4.2 --- ISOELECTRIC FORCUSING AS A TECNIQUE FOR QUALITATIVE MEASUREMENT OF PLASMA AND TISSUE ALKALINE PHOSPHATASE --- p.80 / Chapter CHAPTER FIVE : --- CONCLUSION --- p.83 / Chapter CHAPTER SIX : --- BIBILOGRAPHY --- p.85

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 90-109).

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 60-77).

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 112-123).

Introdução: A anemia é uma complicação comum em pacientes com câncer, especialmente naqueles em quimioterapia (QT). Existem poucas estratégias de tratamento para combater a anemia associada ao câncer (AAC). No entanto, pouco tem sido explorado em relação ao efeito do ferro intravenoso (IV) como uma estratégia única para o controle e tratamento da anemia. Objetivos: avaliar a efetividade da suplementação de ferro IV na prevenção da anemia em pacientes submetidos à QT para câncer de mama (CM) não metastático. O objetivo secundário foi a eficácia do Fe IV na redução da necessidade de uso de agentes estimuladores de eritropoiese (AEE) e transfusão de sangue. Métodos: Estudo prospectivo, randomizado, aberto, que incluiu 45 pacientes com CM submetidas a quimioterapia neo ou adjuvante. As pacientes foram selecionadas para o grupo de tratamento com Fe IV nos primeiros 4 ciclos de QT ou para o grupo controle (GC), de maio/10 a setembro/15. Resultados: Todos os parâmetros basais, como nível de hemoglobina (Hb), funções hepática e renal e do metabolismo do ferro, estavam dentro dos valores de referência. Houve redução da Hb inicial em 70% dos pacientes no grupo do Fe e em 82,6% nos pacientes no GC (p não significativo). No entanto, embora a queda de Hb tenha ocorrido, o nível mais baixo foi de 9,4, e nenhuma transfusão de sangue ou o uso de AEE foi necessário. Além disso, houve um bom perfil de tolerância no braço investigacional. Conclusão: A suplementação de Fe IV não foi eficaz na prevenção de AAC no presente estudo. No entanto, esse resultado não invalida novos estudos em diferentes populações e/ou com diferentes esquemas que explorem essa estratégia de tratamento / Introduction: Anemia is a common complication in cancer patients, especially those on chemotherapy (CT). There are few treatment strategies to combat cancer-associated anemia (CAA). However, little has been explored regarding the effect of intravenous (IV) iron as a unique strategy for the control and treatment of anemia. Objectives: to evaluate the effectiveness of iron supplementation in the prevention of anemia in patients undergoing CT for non-metastatic breast cancer. The secondary endpoint was the effectiveness of iron in reducing the need for ESA use and blood transfusion. Methods: A prospective, randomized, open-label study including 45 BC patients undergoing neo or adjuvant chemotherapy. Patients were selected for the IV iron treatment group in the first 4 cycles of CT or for the control group, from May/10 to September/15. Results: All baseline parameters as hemoglobin (Hb) level, liver functions and renal and the iron metabolism, were within normal reference values. There was a reduction in initial Hb in 70% of patients in the iron group and in 82.6% in patients without iron. However, even though the Hb drop occurred, the lowest level was 9.4, and no blood transfusion or ESA was required in any of the cases. In addition, there was a good tolerance profile in the investigation arm. Conclusion: IV iron supplementation was not effective in the prevention of CAA in the present study. However, this result does not invalidate further studies in different populations and with different schedules that explore this treatment strategy

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 4 uppsatser.

Os episódios depressivos constituem a principal causa de morbidade e disfuncionalidade para indivíduos acometidos de transtorno bipolar (TB) ao longo do curso da doença. Os tratamentos disponíveis atualmente para esta fase do transtorno possuem eficácia limitada, o que implica na necessidade de pesquisas que busquem novas opções terapêuticas. Os prejuízos cognitivos presentes em todas as fases do TB, incluindo as depressivas, e associados em seu curso evolutivo a neuroprogressão consistem noutra dimensão psicopatológica que não é beneficiada pelos tratamentos farmacológicos atualmente empregados. Uma mudança de paradigma temse delineado na literatura nos últimos anos a partir do modelo de pesquisa translacional, na qual novas substâncias, incluindo nutracêuticos, têm sido propostas ou estudadas em ensaios clínicos no tratamento da depressão bipolar. Destacam-se entre estes compostos aqueles que atuam no metabolismo energético e na modulação de funções mitocondriais, em vista de extensa linha de evidências que aponta para a existência no TB de alterações fisiopatológicas nestes aspectos da neurobiologia. Escolhemos o monoidrato de creatina como suplemento alimentar a ser estudado como candidato a terapia adjuvante da depressão bipolar, especialmente em razão de sua atuação na bioenergética celular e na potencialização da cognição. Método: Conduzimos um ensaio clínico duplo-cego em que trinta e cinco (35) pacientes portadores de TB do tipo I ou II em episódio depressivo pelos critérios do DSM-IV e que se encontravam em uso de medicamentos preconizados para o tratamento desta fase da doença foram randomicamente alocados em dois grupos de tratamento adjuvante durante 6 semanas: monoidrato de creatina 6 gramas/dia (N=17) ou placebo (N=18). As comparações entre os grupos para as medidas de desfecho escolhidas, sendo determinada como primária a alteração na pontuação na MADRS (Montgomery-Asberg Depression Rating Scale) após 6 semanas, foram realizadas considerando em uma análise principal por intenção-de-tratar os 27 sujeitos (N=16 no grupo creatina; N=11 no grupo placebo) reavaliados em pelo menos uma ocasião ao longo do ensaio clínico, utilizando-se o método da last-observation-carried-forward (LOCF). Procedemos também a análises secundárias que avaliaram os desfechos clínicos de 23 pacientes (N=12 no grupo creatina; N=11 no grupo placebo) que completaram as 6 semanas e os desfechos cognitivos de 18 sujeitos (N=9 no grupo creatina; N=9 no grupo placebo) que foram submetidos a uma bateria de testes neuropsicológicos antes e após o tratamento de 6 semanas. Resultados: Não foram encontradas diferenças estatisticamente significativas entre os grupos de tratamento após 6 semanas nas variáveis clínicas analisadas por intençãode- tratar ou por-protocolo. O grupo creatina apresentou melhora significativa (p < 0,05) em comparação ao grupo placebo do desempenho no teste de fluência verbal após as 6 semanas de tratamento. Conclusão: O presente estudo, ressalvadas suas limitações metodológicas, não corrobora a hipótese de eficácia do monoidrato de creatina como terapia adjuvante da depressão bipolar, mas pode encorajar ensaios clínicos de duração mais prolongada e com amostras maiores que procurem confirmar o efeito potencializador da cognição da creatina nos indivíduos portadores de TB / Depressive episodes are a major cause of morbidity and dysfunction in individuals suffering from bipolar disorder (BD) throughout the course of the disease. The currently available treatments for bipolar depression have limited efficacy, which implies the need for research on new therapeutic options. The cognitive deficits presented in all stages of BD including depressive and that are associated to neuroprogression consist in another psychopathological dimension which is not affected by current pharmacological treatments. A paradigm shift inspired by the translational research approach has been outlined in the literature in recent years, in which new substances, including nutraceuticals, have been proposed or studied in clinical trials for the therapy of bipolar depression. Prominent among these compounds are those that work in energy metabolism and modulation of mitochondrial function in view of extensive line of evidence pointing to the existence in BD of pathophysiological changes in these aspects of neurobiology. We chose to study the dietary supplement creatine monohydrate as a candidate for adjunctive therapy in bipolar depression, especially due to its role in cellular bioenergetics and enhancement of cognition. Methods: We conducted a double-blind trial in which thirty-five (35) patients with BD type I or II in a depressive episode by DSM-IV criteria and in use of regular medication for the treatment of this phase of the disease were randomly allocated into two adjunctive treatment groups for 6 weeks: creatine monohydrate 6 grams daily (N =17) or placebo (N = 18). Comparisons between groups for the chosen outcome measures, being determined as primary the change in score on the MADRS (Montgomery- Asberg Depression Rating Scale) after 6 weeks, were performed considering in a major analysis by intention-to-treat 27 subjects (N=16 in the creatine group; N=11 in the placebo group) reassessed on at least one occasion during the clinical trial using the method of the last-observation-carriedforward (LOCF). We also proceed to a secondary analysis that evaluated the clinical outcomes of 23 patients (N=12 in the creatine group; N=11 in placebo group) who completed the 6 weeks and the cognitive outcomes of 18 subjects (N=9 in the creatine group; N=9 in the placebo group) who were subjected to a battery of neuropsychological tests before and after the 6- week treatment. Results: There were no statistically significant differences between treatment groups after 6 weeks in the clinical variables analyzed by intention-to-treat and per-protocol. The creatine group showed significant improvement (p < 0.05) in the performance in the verbal fluency test when compared to the placebo group after the 6-week treatment. Conclusion: This study, although subject to methodological limitations, does not support the hypothesis of efficacy of creatine monohydrate as adjunctive therapy for bipolar depression, but it can encourage the execution of clinical trials of longer duration and with larger samples that seek to confirm the cognitiveenhancing effect of creatine in individuals with BD