Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Hui, Lai Shan. / Thesis (M.Sc.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 83-87.

by Kwok-cheong Chung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1983. / Bibliography: leaves 194-221.

by Ng, Shuet Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 118-137. / ACKNOWLEDGEMENTS --- p.i / ABSTRACT --- p.ii / CONTENTS --- p.iv / Chapter CHAPTER 1: --- GENERAL INTRODUCTION / Chapter I. --- The History of Gossypol --- p..4 / Chapter II. --- The Chemistry of Gossypol --- p..7 / Chapter A. --- Enantiomers of Gossypol --- p.10 / Chapter B. --- Analysis of Gossypol --- p.11 / Chapter III. --- Metabolism and Distribution of Gossypol in Body --- p.12 / Chapter IV. --- The Effect of Gossypol --- p.14 / Chapter A. --- Effect of Gossypol on Different Animal Species --- p.14 / Chapter B. --- Effect of Gossypol on Male Reproductive Organs --- p.16 / Chapter 1. --- Testis and Epididymis --- p.16 / Chapter 2. --- Spermatozoa and Spermatogenic Cells --- p.18 / Chapter C. --- Effect of Gossypol on Reproductive Hormones --- p.20 / Chapter D. --- Effect of Gossypol on Enzymes --- p.22 / Chapter 1. --- Enzymes in Capacitation --- p.23 / Chapter 2. --- The Metabolic Enzymes --- p.24 / Chapter a. --- On Glycolysis --- p.24 / Chapter b. --- On TCA Cycle --- p.26 / Chapter c. --- On Oxidative Phosphorylation --- p.26 / Chapter 3. --- Adenyl Cyclase --- p.26 / Chapter 4. --- Na+/K+-ATPase --- p.28 / Chapter E. --- Other Effects of Gossypol --- p.29 / Chapter V. --- Toxicity of Gossypol --- p.30 / Chapter A. --- General Toxic Effect --- p.30 / Chapter B. --- The Mutagenicity --- p.32 / Chapter VI. --- Clinical Trials of Gossypol --- p.33 / Chapter VII. --- The Purpose of This Study --- p.35 / Chapter A. --- Gossypol and LDH-X --- p.35 / Chapter B. --- Effect of Gossypol on Antioxidant Defense Systems / Chapter C. --- The Influence of Gossypol on Zinc Metabolism --- p.37 / Chapter CHAPTER 2: --- EFFECT OF GOSSYPOL ON LDH-X OF COCK AND DRAKE / Chapter I. --- Introduction --- p.39 / Chapter A. --- General Description of Lactate Dehydrogenase --- p.39 / Chapter B. --- Discovery of LDH-X --- p.40 / Chapter C. --- Properties of LDH-X --- p.41 / Chapter D. --- Role of LDH-X in the Spermatozoa --- p.42 / Chapter E. --- Gossypol and LDH-X --- p.43 / Chapter II. --- Materials and Methods --- p.44 / Chapter A. --- Reagents --- p.45 / Chapter B. --- Methods --- p.45 / Chapter 1. --- The Effect of Gossypol on the Spermatozoa of Cock and Drake --- p.45 / Chapter 2. --- "Measurement of LDH-X Activities in Cock, Drake, Mouse and Rat" --- p.46 / Chapter a. --- Preparation of Samples --- p.46 / Chapter b. --- Enzyme Assay --- p.47 / Chapter III. --- Results / Chapter A. --- Effect of Gossypol on the Spermatozoa of Cock and Drake --- p.48 / Chapter 1. --- Cock --- p.48 / Chapter 2. --- Drake --- p.49 / Chapter B. --- "The LDH-X Activities of Cock, Drake, Rat and Mouse" --- p.51 / Chapter IV. --- Discussion --- p.54 / Chapter CHAPTER 3: --- "THE EFFECT OF GOSSYPOL ON THE METABOLISM OF ZINC IN THE TESTIS, HAIR AND RETINA OF HAMSTER AND MOUSE" / Chapter I. --- Introduction --- p.57 / Chapter A. --- The Physiological Role of Zinc in Animals --- p.57 / Chapter B. --- The Relationship Between Gossypol and Divalentions --- p.58 / Chapter II. --- Materials and Methods --- p.60 / Chapter A. --- Reagents --- p.60 / Chapter B. --- Treatment of Animals for the Zinc Content Study / Chapter 1. --- Detection of Zinc Content in Hamster Hair --- p.61 / Chapter 2. --- "Detection of Zinc Distribution in the Hair, Testis, and Retina in Hamster and Mouse" --- p.62 / Chapter C. --- Determination of Zinc and Iron --- p.63 / Chapter III. --- Results --- p.63 / Chapter A. --- Amount of Zinc in Hamster's Hair --- p.63 / Chapter B. --- "The Distribution of Zinc Content in Hair, Testis and Retina of Hamster and Mouse" --- p.69 / Chapter IV. --- Discussion --- p.71 / Chapter CHAPTER 4: --- EFFECT OF GOSSYPOL ON THE ANTIOXIDANT DEFENSE SYSTEM IN THE TESTIS OF HAMSTER / Chapter I. --- Introduction --- p.73 / Chapter A. --- Oxygen Radicals in Living Cells --- p.75 / Chapter B. --- Oxygen Damage of Spermatozoa --- p.76 / Chapter C. --- Antioxidant Defense System --- p.77 / Chapter 1. --- Enzymatic Antioxidants --- p.78 / Chapter 2. --- Non-Enzymatic Antioxidants --- p.78 / Chapter II. --- Materials and Methods --- p.81 / Chapter A. --- Reagents --- p.81 / Chapter B. --- Experimental Animals --- p.82 / Chapter C. --- The Effect of Scavengers on the Antifertility of Gossypol --- p.83 / Chapter 1. --- Vitamin C --- p.83 / Chapter 2. --- Selenium --- p.84 / Chapter 3. --- Vitamin E --- p.85 / Chapter D. --- Chemical Interaction of Gossypol with Vitamin C and Sodium Selenite --- p.85 / Chapter E. --- Malonaldehyde Assay --- p.85 / Chapter F. --- The Effect of Gossypol on the Antioxidant Defense Enzymes --- p.86 / Chapter 1. --- Drug Treatment --- p.86 / Chapter 2. --- Preparation of Samples for Enzyme Determination --- p.87 / Chapter 3. --- Enzyme Assays --- p.87 / Chapter a. --- Se-GSH-Px --- p.88 / Chapter b. --- Glutathione-S-Transf erase --- p.88 / Chapter c. --- Catalase --- p.89 / Chapter d. --- Superoxide Dismutase --- p.90 / Chapter III. --- Results --- p.90 / Chapter A. --- The Effect of Scavengers on the Antifertility of Gossypol --- p.90 / Chapter B. --- Chemical Interaction of Gossypol with Vitamin C and sodium selenite --- p.91 / Chapter C. --- The MDA Concentration of the Testis of Hamster after Gossypol and Scavengers Injection --- p.101 / Chapter D. --- The Antioxidant Defense Enzymes --- p.101 / Chapter IV. --- Discussion --- p.109 / Chapter CHAPTER 5: --- CONCLUSION AND GENERAL DISCUSSION --- p.113 / REFERENCES --- p.118 / Chapter APPENDIX I --- THE INFLUENCE OF DIETARY LARD ON THE ANT I FERTILITY EFFECT OF GOSSYPOL --- p.138 / Chapter APPENDIX II --- PROTOCOL FOR GOSSYPOL DETERMINATION --- p.158

L-lactate dehydrogenase (LDH) cDNAs encoding for LDH-A4 (muscle) and LDH-B4 (heart) isozymes from caiman (Caiman crocodilus apaporiensis) belonging to the order Crocodilia were sequenced. The phylogenetic relationships of the newly determined cDNA and their deduced protein sequences, as well as the previously published sequences of vertebrate LDH isozymes were analyzed by various phylogenetic tree construction methods. These results indicated that Chelonia is indeed more closely related to Crocodilia. The divergent times between caiman and alligator, Chelonia and Crocodilia, were estimated to be approximately 36, 177 million years, respectively. £`-crystallin/Lactate dehydrogenase B cDNA from caiman (Caiman crocodilus apaporiensis), Pekin duck (Anas platyrhynchos), Muscovy duck (Cairina moschata) and Greylag goose (Anser anser) eye lens were sequenced. Accorcding to cDNA sequences, duck lens £`¡Vcrystallin and heart LDH-B are the products of the same gene. In amino acid sequences, two residues Asn-114 and Phe-118 are well conserved in£`-crystallin/ LDH-B among caiman, Muscovy duck and Greylag goose except in Pekin duck which are replaced by glycine residues. The lens protein composition, LDH activity and£`-crystallin/ LDH B4 protein structure of caiman and three avians were analyzed and compared. The results show no significant differences in conformational or enzymatic properties between Pekin duck £`-crystallin and caiman, Muscovy duck and Greylag goose £`-crystallin. The unique replacement of both Asn-114 and Phe-118 by Gly residues in Pekin duck £`-crystallin amino acid sequence might therefore be due to the selective pressure during the recruitment processes of active enzyme into avian lens£`-crystallins.

Akademisk avhandling--Copenhagen. / Bibliography: p. 102-109.

Akademisk avhandling--Copenhagen. / Bibliography: p. 102-109.

INTRODUÇÃO: A resposta do osteossarcoma (OS) à quimioterapia (QT) préoperatória é atualmente o indicador mais sensível para o prognóstico de sobrevida dos pacientes diagnosticados com OS. Esta resposta é avaliada mediante a porcentagem de necrose encontrada pelo patologista após a extração da peça na cirurgia, utilizando- se o índice de necrose tumoral de Huvos, no qual a necrose é expressada percentualmente. Existem estudos correlacionando os valores da fosfatase alcalina (FA) e da desidrogenase lática (DHL) com a sobrevida do paciente. Neste trabalho foi pesquisada a relação que existe entre os valores sanguíneos, pré e pós QT, de FA e DHL, com a porcentagem de necrose tumoral encontrada na peça cirúrgica após a realização da QT pré-operatória. MÉTODOS: Foram estudados 647 prontuários de pacientes tratados pelo Grupo de Oncologia Ortopédica do Instituto de Ortopedia e Traumatologia do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, no período de 1990 até o inicio de 2013, com diagnóstico anatomopatológico de OS. Destes, 510 foram excluídos por não apresentarem dados completos para a análise posterior. Foram incluídos um total de 137 prontuários. Os valores da FA e da DHL dos pacientes incluídos foram obtidos da realização do estadiamento, antes da QT pré-operatória e dos valores reportados após a finalização da QT pré-operatória. Também foi coletado o grau de necrose tumoral de cada peça extraída na cirurgia de cada paciente. Classificamos os resultados da FA e DHL obtidos em dois grupos. No grupo I os pacientes com valores normais de FA e DHL, no grupo II, os pacientes com valores acima do limite de normalidade. A classificação utilizada para agrupar os valores de sorológicos em investigação foi adaptado do trabalho realizado por Bramer et. al. Foi reportada a porcentagem de necrose tumoral descrita pelos patologistas, obtida das peças extraídas nas cirurgias realizadas pós QT. Esta porcentagem foi classificada de acordo com a classificação de Huvos. Foram calculadas as correlações da necrose da peça cirúrgica (Huvos) com as enzimas pré, pós e alteração (pós-pré) QT e também entre as enzimas, com uso de correlações de Spearman para verificar a existência de correlação entre elas. RESULTADOS: Tanto a FA como a DHL diminuíram nos pacientes estudados, quando comparados os valores pré QT e pós QT. A média da diferença da FA obtida pré QT e pós QT foi de 795,12 U/L sendo o valor pré QT maior ao valor pós QT. A diferença entre os valores da DHL pré QT e pós QT foi em média de 437,40 U/L, sendo o valor pré QT maior ao valor pós QT. Não houve correlação estatisticamente significativa entre o índice de Huvos e os valores de FA e DHL. A ausência da relação foi observada tanto com os valores pré-quimioterapia, quanto com os valores pós-quimioterapia, não obtendo correlação com a alteração das enzimas após a quimioterapia (p < 0,05). CONCLUSÃO: A medição de FA e da DHL não são fatores preditivos sobre a resposta tumoral à quimioterapia préoperatória em pacientes portadores de osteossarcoma / BACKGROUND AND AIMS: The osteosarcoma´s (OS) response to pre surgical chemotherapy (CT) is actually the most sensible predictor for life prognosis in patients diagnosed with OS. This response is evaluated by the chemotherapy-induced necrosis percentage found by the pathologist after the removal of the surgical piece, using the Huvos tumor necrosis (TN) index, in which the necrosis is expressed in percentage. There are studies that correlate the alkaline phosphatase (AP) and the lactate deshydrogenase (LDH) with the patient\'s life prognosis. In this study we researched the relationship between the serum levels of pre and post CT of AP and LDH and the percentage of TN found in the surgical piece after the pre surgical CT. METHODS: This is a retrospective study in which we studied 647 medical history files with anatomopathologic diagnosis of OS, treated by the Orthopedic oncology group of the Orthopedic and Traumatology Institute of the Hospital das Clinicas of the Medical School of the University of São Paulo between 1990 and 2013. Out of these, 510 were excluded for not having complete data for posterior analyses. We included 137 files in the study. The AP and the LDH values were obtained before and after pre surgical CT. We also obtained the degree of chemotherapy-induces TN obtained from the surgical piece. We classified the AP and the LDH into two groups. In the first group the patients with normal AP and LDH values and in the second group those with values above normal limit. This classification was adapted from the study published by Bramer et al. We classified the percentage of TN obtained from the removed surgical pieces after CT, using the Huvos index. We calculated the correlation between the TN with the pre, post and pre-post difference CT enzymes, using the Spearman correlation. RESULTS: The AP and the LDH decreased when comparing the pre CT values to the post CT values. The mean of the difference was of 795.12 U/L, the pre CT value being higher than the post CT. The difference between the LDH values pre and post CT was of 437.40 U/L, being the pre CT higher than the post CT. There was no statistically significant correlation between the Huvos index and the AP and LDH values. This was observed with the pre CT as well as with the post CT values (p < 0,05). CONCLUSIONS: The values of AP and LDH are not predictors for the tumor\'s chemotherapy-induced necrosis to pre surgical CT in patients with osteosarcoma

INTRODUÇÃO: A resposta do osteossarcoma (OS) à quimioterapia (QT) préoperatória é atualmente o indicador mais sensível para o prognóstico de sobrevida dos pacientes diagnosticados com OS. Esta resposta é avaliada mediante a porcentagem de necrose encontrada pelo patologista após a extração da peça na cirurgia, utilizando- se o índice de necrose tumoral de Huvos, no qual a necrose é expressada percentualmente. Existem estudos correlacionando os valores da fosfatase alcalina (FA) e da desidrogenase lática (DHL) com a sobrevida do paciente. Neste trabalho foi pesquisada a relação que existe entre os valores sanguíneos, pré e pós QT, de FA e DHL, com a porcentagem de necrose tumoral encontrada na peça cirúrgica após a realização da QT pré-operatória. MÉTODOS: Foram estudados 647 prontuários de pacientes tratados pelo Grupo de Oncologia Ortopédica do Instituto de Ortopedia e Traumatologia do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, no período de 1990 até o inicio de 2013, com diagnóstico anatomopatológico de OS. Destes, 510 foram excluídos por não apresentarem dados completos para a análise posterior. Foram incluídos um total de 137 prontuários. Os valores da FA e da DHL dos pacientes incluídos foram obtidos da realização do estadiamento, antes da QT pré-operatória e dos valores reportados após a finalização da QT pré-operatória. Também foi coletado o grau de necrose tumoral de cada peça extraída na cirurgia de cada paciente. Classificamos os resultados da FA e DHL obtidos em dois grupos. No grupo I os pacientes com valores normais de FA e DHL, no grupo II, os pacientes com valores acima do limite de normalidade. A classificação utilizada para agrupar os valores de sorológicos em investigação foi adaptado do trabalho realizado por Bramer et. al. Foi reportada a porcentagem de necrose tumoral descrita pelos patologistas, obtida das peças extraídas nas cirurgias realizadas pós QT. Esta porcentagem foi classificada de acordo com a classificação de Huvos. Foram calculadas as correlações da necrose da peça cirúrgica (Huvos) com as enzimas pré, pós e alteração (pós-pré) QT e também entre as enzimas, com uso de correlações de Spearman para verificar a existência de correlação entre elas. RESULTADOS: Tanto a FA como a DHL diminuíram nos pacientes estudados, quando comparados os valores pré QT e pós QT. A média da diferença da FA obtida pré QT e pós QT foi de 795,12 U/L sendo o valor pré QT maior ao valor pós QT. A diferença entre os valores da DHL pré QT e pós QT foi em média de 437,40 U/L, sendo o valor pré QT maior ao valor pós QT. Não houve correlação estatisticamente significativa entre o índice de Huvos e os valores de FA e DHL. A ausência da relação foi observada tanto com os valores pré-quimioterapia, quanto com os valores pós-quimioterapia, não obtendo correlação com a alteração das enzimas após a quimioterapia (p < 0,05). CONCLUSÃO: A medição de FA e da DHL não são fatores preditivos sobre a resposta tumoral à quimioterapia préoperatória em pacientes portadores de osteossarcoma / BACKGROUND AND AIMS: The osteosarcoma´s (OS) response to pre surgical chemotherapy (CT) is actually the most sensible predictor for life prognosis in patients diagnosed with OS. This response is evaluated by the chemotherapy-induced necrosis percentage found by the pathologist after the removal of the surgical piece, using the Huvos tumor necrosis (TN) index, in which the necrosis is expressed in percentage. There are studies that correlate the alkaline phosphatase (AP) and the lactate deshydrogenase (LDH) with the patient\'s life prognosis. In this study we researched the relationship between the serum levels of pre and post CT of AP and LDH and the percentage of TN found in the surgical piece after the pre surgical CT. METHODS: This is a retrospective study in which we studied 647 medical history files with anatomopathologic diagnosis of OS, treated by the Orthopedic oncology group of the Orthopedic and Traumatology Institute of the Hospital das Clinicas of the Medical School of the University of São Paulo between 1990 and 2013. Out of these, 510 were excluded for not having complete data for posterior analyses. We included 137 files in the study. The AP and the LDH values were obtained before and after pre surgical CT. We also obtained the degree of chemotherapy-induces TN obtained from the surgical piece. We classified the AP and the LDH into two groups. In the first group the patients with normal AP and LDH values and in the second group those with values above normal limit. This classification was adapted from the study published by Bramer et al. We classified the percentage of TN obtained from the removed surgical pieces after CT, using the Huvos index. We calculated the correlation between the TN with the pre, post and pre-post difference CT enzymes, using the Spearman correlation. RESULTS: The AP and the LDH decreased when comparing the pre CT values to the post CT values. The mean of the difference was of 795.12 U/L, the pre CT value being higher than the post CT. The difference between the LDH values pre and post CT was of 437.40 U/L, being the pre CT higher than the post CT. There was no statistically significant correlation between the Huvos index and the AP and LDH values. This was observed with the pre CT as well as with the post CT values (p < 0,05). CONCLUSIONS: The values of AP and LDH are not predictors for the tumor\'s chemotherapy-induced necrosis to pre surgical CT in patients with osteosarcoma