Yam Wing Sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 154-160). / Abstracts in English and Chinese. / Abstract English --- p.i / Chinese --- p.iii / Acknowledgments --- p.v / Table of contents --- p.vii / List of Tables --- p.x / List of Figures --- p.xi / List of Abbreviations --- p.xvi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Chinese Medicine and Western Medication --- p.1 / Chapter 1.2 --- Chinese Medicine and Compound Formula --- p.2 / Chapter 1.3 --- Cardiovascular disease (CVD) and atherosclerosis --- p.6 / Chapter 1.4 --- General Research Objectives --- p.19 / Chapter Chapter 2 --- Establishment of compound formulation and Extract Preparation --- p.21 / Chapter 2.1 --- Formulation searched from Chinese Pharmacopoeia --- p.21 / Chapter 2.2 --- Aqueous extract preparation --- p.25 / Chapter 2.2.1 --- Materials and Methods --- p.25 / Chapter 2.2.2 --- Discussion --- p.27 / Chapter Chapter 3 --- Vasodilation study --- p.28 / Chapter 3.1 --- Vascular Smooth Muscle Contraction and Relaxation --- p.28 / Chapter 3.2 --- Endothelium and Vasodilation --- p.30 / Chapter 3.3 --- Vasodilation in organ bath --- p.32 / Chapter 3.3.1 --- Materials and Methods --- p.32 / Chapter 3.3.2 --- Results --- p.35 / Chapter 3.3.3 --- Discussion --- p.40 / Chapter 3.4 --- Endothelium dependent vasodilation --- p.40 / Chapter 3.4.1 --- Materials and Methods --- p.43 / Chapter 3.4.2 --- Results --- p.45 / Chapter 3.4.3 --- Discussion --- p.54 / Chapter 3.5 --- Adrenoceptor and vasodilation --- p.55 / Chapter 3.5.1 --- Materials and Methods --- p.57 / Chapter 3.5.2 --- Results --- p.58 / Chapter 3.5.3 --- Discussion --- p.62 / Chapter 3.6 --- Potassium Channels and Vasodilation --- p.63 / Chapter 3.6.1 --- Materials and Methods --- p.65 / Chapter 3.6.2 --- Results --- p.67 / Chapter 3.6.3 --- Discussion and Summary --- p.77 / Chapter 3.7 --- Potential active components from Fenge and Danshen --- p.82 / Chapter 3.7.1 --- Materials and Methods --- p.82 / Chapter 3.7.2 --- Results --- p.83 / Chapter 3.7.3 --- Discussion --- p.87 / Chapter Chapter 4 --- Comparison of Fenge and Yege --- p.88 / Chapter 4.1 --- Vasodilative effects of Fenge and Yege --- p.89 / Chapter 4.1.1 --- Materials and Methods --- p.89 / Chapter 4.1.2 --- Results --- p.89 / Chapter 4.1.3 --- Discussion --- p.101 / Chapter 4.2 --- The comparison of antioxidative effect between Yege and Fenge --- p.104 / Chapter 4.2.1 --- Red blood cell hemolysis model --- p.106 / Chapter 4.2.1.1 --- Materials and Methods --- p.106 / Chapter 4.2.1.2 --- Results --- p.108 / Chapter 4.2.1.3 --- Discussion --- p.110 / Chapter 4.2.2 --- Ischemia-reperfusion on Langendroff --- p.112 / Chapter 4.2.2.1 --- Materials and Methods --- p.114 / Chapter 4.2.2.2 --- Results --- p.117 / Chapter 4.2.2.3 --- Discussion --- p.125 / Chapter Chapter 5 --- Comparison of Chemical Profiles of Fenge and Yege --- p.127 / Chapter 5.1 --- The application of HPLC --- p.127 / Chapter 5.2 --- HPLC standardization --- p.129 / Chapter 5.2.1 --- Materials and Methods --- p.132 / Chapter 5.2.2 --- Results --- p.133 / Chapter 5.2.3 --- Discussion --- p.144 / Chapter Chapter 6 --- "Summaries, Discussion and prospects" --- p.146 / Chapter 6.1 --- Summaries and Discussion --- p.146 / Chapter 6.2 --- Prospects --- p.148 / Chapter 6.2.1 --- "Cardiovascular tonic effect of pure compounds, extracts with difference solvents and their vasodilative mechanism." --- p.148 / Chapter 6.2.2 --- Macrophage Foam Cell and Atherosclerosis --- p.149 / Chapter 6.2.3 --- The D:F (7:3) and D:Y (7:3) compound formulae capsule with GMP --- p.152 / References --- p.154

EGb761 consists of two major groups of substances, flavonoids and terpenoids. Using human neuroblastoma SH-SY5Y cells, the present study demonstrated that, EGb761 could block Abeta-42 (a 42-amino acid cytoxic form of beta amyloid protein)-induced cell apoptosis, reactive oxygen species (ROS) accumulation, mitochondrial dysfunction and activation of c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt signaling pathways, possibly via its antioxidant and platelet activating factor (PAF) antagonizing activities. Two active constituents of EGb761, quercetin (a flavonoid) and ginkgolide B (a terpenoid) might contribute to the protective effects of EGb761. Quercetin but not ginkgolide B might be responsible for the antioxidant action of EGb761. Both compounds might be involved in the PAF antagonist activity of EGb761. / EGb761, a Ginkgo biloba extract, is a medicinal product for the treatment and prevention of cardiovascular and neuronal diseases, including Alzheimer's disease (AD). While considerable researches have documented its neuroprotective effects, its clinical effect is inconclusive and the precise neuroprotective mechanisms are not clearly known. / In conclusion, EGb761 may have beneficial effects in treatment and prevention of neurodegenerative diseases like AD. Its neuroprotective effects may be associated with constituent multiplicity, the dosage and BBB permeability. / The ability of EGb761 to cross the blood brain barrier (BBB) is unclear. In this study, the ability of EGb761 to cross the BBB was speculated through comparison of the effects of EGb761 on mitochondrial function between platelets and central nervous system in two animal models, the senescence accelerated prone 8 (SAMP8) mouse strain and ovariectomized rats. Mitochondrial function was evaluated as cytochrome c oxidase (COX) activity, mitochondrial ATP content and mitochondrial glutathione (GSH) content. SAMP8 mice have been widely used as a model of age-related cognitive decline with relevance to biochemical and genetic alterations in AD. Using two age groups (3-week-old and 40-week-old) of SAMP8 mice, this study found that, EGb761 protected against mitochondrial dysfunction in both platelets and hippocampi of old mice, but only showed protective effects on platelet mitochondria of young mice. Estrogen withdrawal was suggested to play a primary role in the onset of post-menopausal AD. Using ovariectomized middle-aged rats to mimic the post-menopausal pathophysiological changes, this study also demonstrated that, EGb761 protected against mitochondrial dysfunction in both platelets and hippocampi of ovariectomized rats. In contrast, in sham-operated rats, EGb761 increased mitochondrial GSH content in platelets but failed to show similar effect on hippocampi. These results suggested that the effects of EGb761 on the brain might be interfered by the BBB permeability. / The effective dosage of EGb761 in the brain remains undetermined. Using SH-SY5Y cells, this study demonstrated that low doses of EGb761 (50--100 mug/ml) inhibited hydrogen peroxide (H2O2)-induced cell apoptosis via inactivation of Alet, JNK and caspase 3 while high doses of EGb761 (250--500 flg/ml) enhanced H2O2 toxicities via inactivation of Akt and enhancement of activation of JNK and caspase 3. Additional experiments suggested that the dosage effect of EGb761 on apoptotic signaling proteins might be correlated with regulation of the cell redox state. / Shi, Chun. / Adviser: Lee Ka Ho Kenneth. / Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 81-99). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Introduction: The public health system is of central importance in efforts to reduce the burden of chronic disease, yet there are no national data on organizational capacity (OC) or dissemination practices pertaining to chronic disease prevention (CDP) programming in the public health system. The aim of this thesis is to investigate OC and dissemination practices within the Canadian public health system. Two new conceptual models pertaining to these constructs were developed, and a survey of all public health organizations across Canada engaged in CDP was conducted in 2004-5. / Method: Data were collected in telephone interviews with persons most knowledgeable about CDP programming in 77 "resource" organizations that develop and transfer CDP innovations to other organizations, and 216 "user" organizations that adopt and deliver CDP programs in specific populations. Reliable measures of the constructs of interest were developed using principal components analyses. Levels of OC, its potential determinants, and involvement in CDP programming were compared across three types of organizations and across Canada. In addition, levels of 13 dissemination-related practices were compared across organizations and independent correlates of dissemination were identified in multiple linear regression. / Results: Levels of skill and involvement were highest for tobacco control and healthy eating programming; lowest for stress management, social determinants of health, and program evaluation. Any notable differences in skill levels favoured central Canada. Resource adequacy was low overall; lowest in eastern Canada and within formal public health organizations. Supports for OC were highest in central Canada and in grouped organizations. Dissemination practices most heavily engaged in included: Identification of barriers to adoption/implementation of the innovation, tailoring dissemination strategies and design of dissemination plan. There was little coherence across organizations in the number or types of dissemination practices engaged in. Skill at planning/implementing dissemination, external sources of funding, type of resource organization, attitude toward the process of collaboration, and user-centeredness were all positively associated with dissemination (R2=0,42; F value 8.20, p<0.0001). / Conclusions: These results provide a backbone for organizational research in public health systems. Strengths and gaps identified in OC and dissemination practices will guide strategic investment in the public health system.

Nível elevado de homocisteína (Hcy) no plasma é considerado fator de risco de doença cardiovascular. Consumo reduzido de vitaminas B6, B12 e ácido fólico tem sido relacionado com hiperhomocisteinemia. O objetivo desse estudo foi verificar o consumo de vitaminas B6, B12 e ácido fólico nas populações urbana e rural, bem como a correlação dos níveis plasmáticos dessas vitaminas com os níveis plasmáticos de Hcy. Também determinamos os níveis séricos de lipídeos e avaliamos o risco cardiovascular das populações frente a hiperlipemia. O consumo de B6 e ácido fólico é maior na população urbana, com p=0,00 e p=0,04 respectivamente, sendo o consumo de B12 maior na população rural, com p=0,47. As correlações são significativamente negativa entre Hcy e as vitaminas B12 e ácido fólico . A população rural apresenta Hcy com valor médio de 16,5±9,2µmol/L, classificada como hiperhomocisteinemia moderada, e a população urbana 12,8±5,5 µmol/L, o qual está dentro da faixa de referência. O valor médio de LDL sérica é maior na população urbana (3,4±0,8mmoI/L) do que na população rural (2,8±0,9mmoI/L), com valor de p=0,00. Como fator de risco cardiovascular, consideramos Hcy plasmática >14µmol/L e LDL sérica >3,38mmol/L. Neste caso, 41,4% da população rural e 7,4% população urbana apresentam Hcy maior que 14µmol/L. O inverso ocorre em relação a LDL, onde 43,2% da população urbana e 11% na população rural apresentam níveis acima de 3,38mmol/L. Concluímos que o risco cardiovascular decorrente de hiperhomocisteinemia é maior na população rural que na urbana e este risco poderia reduzir mediante o consumo de vitaminas. / Elevated levels of plasma homocysteine (Hey) are considered a risk factor for cardiovascular diseases. Low intake of vitamins 86, 812 and folic acid have been related to hyperhomocysteinemia. The purpose of the present study is to determine the consumption of the vitamins B6, B12 and folic acid in two Brazilian urban and rural populations, along with the plasmatic levels of these vitamins and plasmatic homocysteine. In addition, the serum levels of lipids have been determined to evaluate the cardiovascular risk in the two populations regarding their hyperlipidemie comdition. The consumption of B6 and folic acid is higher in the urban population (p=0.00 and p=0.04 respective/y), while the consumption of B12 is not significantly different (p=0.47). There is a negative correlation between B12 and folic acid with Hcy. The rural population shows mean Hcy value of 16.5±9.2µmol/L and is classified as having moderate hyperhomocysteinemia, while for the urban population, the mean value is 12.8±5.5µmol/L and is well within the normal range. The mean value of the serum LDL is higher in the urban population (3.4±0.8mmol/L) compared to the rural population (2.8±0.9mmol/lL) with a significance of p=0.00. Plasma Hcy values >14µmol/L and serum LDL >3.38mmol/L were considered as the risk factors for cardiovascular disease. With in the reference values, 41.4% of the rural population and 7.4% of the urban population showa Hcy as a risk factor. For LDL, the inverse is true, i.e 43.2% of urban and 11% of the rural population are at risk. We conclude that the cardiovascular risk arising from hyperhomocysteinemia is higher in the rural population and that this can be reduced by increased consumption of vitamins.

No description available.

Background / Hand, foot, and mouth disease (HFMD), in particular those associated with enterovirus 71 (EV71), has caused large outbreaks in the Western Pacific and Southeast Asian countries in the past three decades. There is currently no effective chemoprophylaxis or vaccination for HFMD or EV71 infection. Public health strategies rest on good understanding of the epidemiological features of HFMD. The present series of studies examined the epidemiological characteristics of HFMD in Hong Kong, with a view to better understand the disease epidemiology so as to guide public health actions. / Methods and results of individual studies / Study (1)--characterizing the changing epidemiological features identified from various surveillance systems for HFMD / The trend of HFMD activities from 2001-2009 was analyzed using the sentinel surveillance statistics and HFMD outbreaks. The type of institutions reporting HFMD over time, incidences of outbreaks in 18 districts, and age and sex distribution of affected persons of HFMD outbreaks were analyzed. The clinical presentation, hospitalization rate, complication rate and case fatality of outbreaks were examined. The circulating enterovirues each year were determined by laboratory surveillance findings from 2001-2009 and test for morbidity caused by EV71. Seasonal peak was detected from warmer months of May through July but a smaller winter peak was found from October to December since 2006. An increasing trend of more older children aged above 5 years were infected, from 25.4% in 2001 to 33.0% in 2009 (p=0.01, Mantel-Haenszel Chi-square test). Laboratory surveillance detected a cyclical high activity of EV71 in every 3 to 4 years, which was associated with a higher average hospitalization rate among patients of the HFMD outbreaks reported in corresponding year, although it was only marginally significant (p=0.09, linear regression test). / Study (2)--analyzing the characteristics of EV71 epidemic in 2008 / All EV71 cases diagnosed by PHLC from 1998-2008 were analyzed. The complication and case fatality rates, percentage requiring hospitalization, median duration of hospital care, and the likelihood of being associated with an HMFD outbreak in institution in 2008 were compared with the corresponding rates calculated from cases reported from 1998-2007. Phylogenetic tree was constructed by using the neighbour-joining method and the molecular epidemiology of EV71 detected in 2008 was compared with the past years’ trends. Ninety-eight EV71 cases were reported in 2008, highest in the past decade. The annual incidence was 1.4/100 000 in general population, with highest incidence reported in children aged 0-4 years old (27.9/100 000). 11.2% had complications including meningitis or encephalitis (6.1%), pneumonia (3.1%), acute flaccid paralysis (1.0%), and shock (1.0%). There was only one fatal case (CFR: 1.0%) attributed to interstitial pneumonitis. 45.9% had concurrent HFMD outbreaks in their schools or institutions, and six schools required temporarily class suspension for 14 days. Both the complication rate and CFR werenot significantly different from the corresponding rates of the past 10 years (p=0.12 and 1.00 respectively). Phylogenetic analysis found that most cases reported in 2008 were C4 strains, which were the predominant circulating strains in the past ten years. / Study (3)--examining the association between meteorological parameters and HFMD activity / The sentinel consultation rate of HFMD was tested for any association with the meteorological parameters obtained from the Hong Kong Observatory from 2000-2004. Different regression models were examined to find the best model for predicting HFMD consultation rates from 2005-2009. In multivariate regression analysis, model M2 (in which mean temperature, diurnal difference in temperature, relative humidity and wind speed were positively associated with HFMD) was found to have a higher R2 (0.119) than M0 and M1 models with an R2 of 0.079 and 0.062 respectively, indicating that HFMD consultation rates were better explained using meteorological parameters measured 2 weeks earlier. The predicted trend of HFMD consultation rates for 2005 to 2009 matched well with the observed one (Spearman’s rank correlation coefficient=0.276, P=0.000). Sensitivity analysis showed that the estimated HFMD consultation rates were mostly affected by varying the relative humidity and least affected by wind speed. / Study (4)--determining the basic reproduction number of coxsackievirus A16 and enterovirus 71 using mathematical model / The basic reproduction numbers (R0) of EV71 and CoxA16 from laboratory confirmed HFMD outbreaks reported to DH from 2004-2009 were determined using mathematical model. Thirty four outbreaks were analyzed, 27 due to CoxA16 and seven due to EV71. The median R0 of EV71 was 5.48 with an inter-quartile range of 4.206.51 while median R0 of CoxA16 was 2.50 with an inter-quartile range of 1.963.67. In the sensitivity analysis, R0 of EV71 was significantly higher than that of CoxA16 in whole range of incubation periods, p≦0.025. R0was not associated with outbreak setting, size of the institution or number of persons affected. / Study (5)--assessing the impact of SARS and pandemic influenza H1N1 on transmission of HFMD in Hong Kong / I compared the observed HFMD consultation rates and the projected rates, which were constructed using mathematical model, in defined periods of 2003 and 2009 during which territory-wide public health interventions (including school closure) against Severe Acute Respiratory Syndrome (SARS) and pandemic influenza H1N1 were implemented. There was a reduction of 57.2% (95% C.I.:53.0-60.7%) in observed HFMD consultation rates during SARS period in 2003 and a reduction of 26.7% (95% C.I.:19.5-32.7%) during pandemic influenza H1N1 period in 2009. In 2003, the projected rates were still lower than the observed rates beyond week 31 until almost the end of the year. On the contrary, in 2009, the observed HFMD consultation rates became comparable to that of the projected rates in August, before the end of the defined intervention period. / Conclusions / This thesis bridges the knowledge gaps regarding epidemiological characteristics of HFMD. The changing epidemiology of HFMD, including the cyclical high activity of EV71 warrants vigilant surveillance of its activity in order to guide preventive measures. I have demonstrated that climate parameters may help predict HFMD activity, which could assist in explaining the winter peak detected in recent years and issuing early warning in the future. The R0 of EV71 and CoxA16 were first determined in the literature and I found that R0 of EV71 was higher than R0 of CoxA16. The reduction of transmission of HFMD during the SARS and H1N1 periods suggested that public health measures are effective in reducing the transmission of enteroviruses. / Ma, Siu Keung. / Thesis (M.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 121-149). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Table of content --- p.ii / Acknowledgements --- p.iv / Abbreviations --- p.v / Caption for Tables --- p.vi / Caption for Figures --- p.viii / Précis --- p.1 / Chapter PART I: --- LITERATURE REVIEW ON HFMD --- p.5 / Chapter Chapter 1. --- Current Understanding of Epidemiology of HFMD --- p.6 / Chapter 1.1 --- Causative agents and virology --- p.6 / Chapter 1.2 --- Clinical presentation and management --- p.8 / Chapter 1.3 --- Geographical distribution and past epidemics --- p.14 / Chapter 1.4 --- Host susceptibility and molecular determinants of neruovirulence --- p.26 / Chapter 1.5 --- Routes of transmission and transmission dynamics --- p.27 / Chapter 1.6 --- Knowledge gap identified from literature review --- p.29 / Chapter PART II: --- STUDIES ON EPIDEMIOLOGY OF HFMD IN HONG KONG --- p.33 / Chapter Chapter 2. --- Study Objectives and Main data source for analysis --- p.34 / Chapter 2.1 --- Aim and objectives of this thesis --- p.34 / Chapter 2.2 --- Sentinel surveillance system for monitoring HFMD activity --- p.35 / Chapter 2.3 --- Institutional outbreaks of HFMD reported to DH . --- p.37 / Chapter 2.4 --- EV 71 infection reported to Department of Health --- p.37 / Chapter 2.5 --- Laboratory surveillance for monitoring enteroviruses --- p.37 / Chapter Chapter 3. --- Study (1)--Characterizing the changing epidemiological features identified from various surveillance systems for HFMD --- p.38 / Chapter Chapter 4. --- Study (2)--Analyzing the epidemic of enterovirus 71 in 2008 and its public health implication to Hong Kong --- p.52 / Chapter Chapter 5. --- Study (3)--Examining the association between meteorological parameters and HFMD activity --- p.67 / Chapter Chapter 6. --- Study (4)--Determining the basic reproduction number of coxsackievirus A16 and enterovirus 71 using mathematical model --- p.85 / Chapter Chapter 7. --- Study (5)--Impact of SARS and Pandemic Influenza H1N1 on transmission of HFMD in Hong Kong --- p.100 / Chapter Chapter 8. --- Conclusion --- p.111 / List of publications related to this thesis --- p.119 / References --- p.121

O lítio é freqüentemente utilizado no tratamento do Transtorno Bipolar, doença associada a um risco aumentado para demência. Evidências experimentais sugerem efeitos neuroproterores do lítio. O lítio inibe a amiloidogênese e a fosforilação da proteína tau tanto in vitro como in vivo. Estes são processos importantes na patogênese da doença de Alzheimer. O objetivo este estudo foi a investigação do efeito do lítio na prevalência de Transtorno Cognitivo Leve e doença de Alzheimer em 114 bipolares idosos eutímicos. Todos os sujeitos completaram uma avaliação catamnéstica, psicopatológica e cognitiva que incluía o mini-exame do estado mental (Mini-mental), o teste cognitivo de Cambridge (CAMCOG) e o questionário do informante sobre o declínio cognitivo do idoso (IQCODE). Foi feita uma comparação da prevalência de Transtorno Cognitivo Leve e doença de Alzheimer entre pacientes em uso de lítio e pacientes em uso de outros estabilizadores de humor. Os sujeitos que entraram na pesquisa tinham em média 68,2 ± 5,0 anos e preenchiam os critérios da Décima Revisão da Classificação Internacional de Doenças e Problemas de Saúde Relacionados (CID-10) para o transtorno bipolar. Durante a avaliação os bipolares estavam eutímicos. Eutimia foi definida como uma pontuação máxima de 7 pontos na escala de Hamilton de 21 pontos para Depressão e 4 na escala de Young para mania. 66 pacientes em uso contínuo do lítio por 6 anos em média foram comparados com 48 pacientes em tratamento com outros estabilizadores de humor. O diagnóstico de Transtorno Cognitivo Leve foi feito de acordo com os critérios de Petersen(1999) e de doença de Alzheimer de acordo com o critério do “National Institute for Communicative Disorders and Stroke - Alzheimer’s Disease and Related Disorders Association" (NINCDS/ADRDA). A prevalência de demência nesta amostra (19,4%) foi mais elevada do que o esperado para uma população comparável (7,1%). A prevalência de doença de Alzheimer entre aqueles com lítio foi 4,5% quando comparada com 33,3% entre aqueles sem lítio. Controlando idade e outras variáveis relacionadas ao curso da doença, o efeito do lítio na prevalência de doença de Alzheimer permaneceu significativo (OR = 0,079; p < 0,001). Nenhuma associação foi encontrada com Transtorno Cognitivo Leve. A alta da prevalência de doença de Alzheimer neste estudo está de acordo com as evidências de risco aumentado para demência em pacientes bipolares. Nesta amostra o tratamento com lítio reduziu a prevalência de Alzheimer aos níveis da população idosa em geral. Estes achados estão de acordo com os efeitos neuroprotetores do lítio em eventos cruciais para a patologia da doença de Alzheimer. Estudos prospectivos são necessários para avaliar se o lítio também pode ser efetivo na prevenção de doença de Alzheimer em outras populações. / Lithium is widely used in the treatment of bipolar disorder, a condition associated with an increased risk for dementia. Experimental evidence suggests that lithium has a neuroprotective effect. Both in vitro and in vivo, lithium inhibits amyloidogenesis and phosphorilation of tau protein, which are two crucial processes in the pathogenesis of Alzheimer’s disease. The objective of this study was to investigate the effect of lithium on the prevalence of Mild Cognitive Impairment and Alzheimer’s disease in 114 elderly euthymic bipolar patients. Subjects completed a thorough catamnestic, psychopathological and cognitive tests evaluation including the Mini-mental state evaluation, Cambridge cognitive test (CAMCOG) and the informant questionnaire on cognitive decline in the elderly (IQCODE). The prevalence of Mild Cognitive Impairment and Alzheimer’s disease between patients on lithium therapy and patients on treatment with other mood-stabilizing drugs was compared. Patients were 68.2 ± 5.0 years old and fulfilled of the International Classification of Diseases - 10th Revision (ICD-10) diagnosis for bipolar disorder. At the time of the evaluation patients were euthymic, as defined by a maximum score of 7 in the 21-item Hamilton Rating Scale for Depression, and 4 in the Young Mania Rating Scale. Sixty-six patients were continuously being treated with lithium for six years, on average, and 48 patients were receiving other mood-stabilizing drugs. Diagnosis of Mild Cognitive Impairment was made according to Petersen (1999) and of Alzheimer’s disease was made according to the National Institute for Communicative Disorders and Stroke - Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria. The overall prevalence of dementia in our sample (19.4%) was higher than the prevalence expected in the age-comparable general population (7.1%). The prevalence of Alzheimer’s disease among lithium users was 4.5% as compared to 33.3% among non-users. After controlling for age and other variables related to the clinical course of the bipolar disorder, the effect of lithium on Alzheimer’s disease prevalence remained significant (OR = 0.079; p < 0.001). No association was found with Mild Cognitive Impairment. The higher prevalence of Alzheimer’s disease in our study supports the reports of increased risk for dementia in bipolar patients. In our sample, lithium treatment reduced the prevalence of Alzheimer’s disease to the levels of the general elderly population. This finding is in line with the neuroprotective effects of lithium on crucial events for the pathology of Alzheimer’s disease. Further prospective studies are needed to clarify whether lithium may also be effective in the prevention of Alzheimer’s disease in the general population.

A Doença de Alzheimer é uma doença neurodegenerativa progressiva e de início tardio, que compromete principalmente as areas da cognição, julgamento e estabilidade emocional. Esta doença se caracteriza por dois tipos de lesões cerebrais características: emaranhados neurofibrilares e placas senis. Os emaranhados neurofibrilares são compostos por uma proteína do citoesqueleto (proteína tau) hiperfosforilada e agregada. As placas senis são formadas por agregados da proteína &#946;-amilóide. A doença de Alzheimer é resultado dainteração de vários fatores ainda incompletamente elucidados; não obstante, o estresse oxidativo e os processos inflamatórios ocupam posição de destaque dentre esses fatores. Neste trabalho, avaliamos as atividades das enzimas eritrocitárias superóxido dismutase, catalase e glutationa peroxidase, assim como o conteúdo plasmático de glutationa total, vitamina C, &#945;-tocoferol, &#946;-caroteno, licopeno e coenzima Q10. A esses parâmetros antioxidantes foram contrapostas medidas de oxidação de lipídios e proteínas plasmáticas. Adicionalmente, efetuamos a avaliação das expressões monocitárias de HLADR e CD-11b, e das citocinas IL-6, IL-1&#945; e TNF-&#945;. Nossos resultados mostram que os pacientes de doença de Alzheimer possuem níveis circulantes de atocoferol inferiores aos pacientes controles, e possuem monócitos que apresentam maior expressão basal de HLA-DR e maior produção de IL-1&#945; quando estimulados por LPS. Esses resultados fortalecem a hipótese inflamatória na doença de Alzheimer, de acordo com trabalhos recentes que apontam bons resultados com o a-tocoferol na sua prevenção e tratamento. / Alzheimer\'s disease is a late-onset, progressive degenerative disease that affects mainly the judgement, emotional stability and memory domains. This disease is characterized by two telltale cerebral lesions: neurofibrillary tangles and senile plaques. Neurofibrillary tangles are constituted by hyperphosphorylated cytoskeleton protein tau aggregates, while senile plaques are mainly composed by &#946;-amyloid protein aggregates. Alzheimer\'s disease is the outcome of a complex interaction among several factors which are not fully understood yet; nevertheless it is clear thar oxidative stress and inflammatory pathways rate high among these factors. In this work, we evaluated the erythrocytic acitivities of superoxide dismutase, catalase and glutathione peroxidase, as well as the plasma levels of total glutathione, &#945;-tocopherol, &#945;-carotene, lycopene, and coenzyme Q10. These antioxidant parameters were confronted with plasmatic levels of protein and lipid oxidation products. Additionally, we measured the basal expression of monocyte HLA-DR and CD-11b, as well as the monocyte production of the cytokines IL1-&#945;, IL-6 and TNF-&#945;. Our results show that Alzheimer\'s Disease patients show lower plasmatic levels of &#945;-tocopherol when compared to control patients, and have higher basal monocyte HLA-DR expression associated with higher IL-1&#945; production when stimulated by LPS. These results lend support to the inflammatory theory of Alzheimer\'s disease, according to recent works that indicate good results of &#945;-tocopherol administration in both its prevention and treatment.

Tam Wing Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 82-100). / Abstracts in English and Chinese. / English abstrac --- p.I / 中文摘要 --- p.VI / Glossary --- p.X / Chapter Chapter 1. --- Background: / Chapter 1.1. --- Coronary heart disease in Hong Kong --- p.1 / Chapter 1.2. --- Coronary heart disease and atherosclerosis --- p.2 / Chapter 1.3. --- Pathogenesis of atherosclerosis --- p.2 / Chapter 1.4. --- Risk factors for atherosclerosis --- p.5 / Chapter 1.5. --- Homocysteine --- p.6 / Chapter 1.6. --- Folate --- p.10 / Chapter 1.7. --- Vitamin B12 --- p.13 / Chapter 1.8. --- Adhesion Molecules --- p.14 / Chapter 1.9. --- Phytoestrogen --- p.17 / Chapter 1.10. --- Secondary prevention of coronary artery disease --- p.20 / Chapter Chapter 2. --- "Heart disease, Danshen and Gegen in Chinese medicine" / Chapter 2.1. --- The record of Cardiac symptoms in Chinese Medicine --- p.24 / Chapter 2.2. --- Danshen (Salvia Miltriorrhiza) --- p.25 / Chapter 2.3. --- Gegen (Radix Pueraria) --- p.28 / Chapter Chapter 3. --- Surrogate atherosclerotic markers / Chapter 3.1. --- Flow-mediated dilatation of brachial artery (FMD) --- p.31 / Chapter 3.2. --- Carotid intima media thickness (IMT) --- p.32 / Chapter Chapter 4. --- Method / Chapter 4.1. --- Rational of the study --- p.33 / Chapter 4.2. --- Clinical protocol --- p.35 / Chapter 4.3. --- Measurement of plasma homocysteine --- p.38 / Chapter 4.4. --- Measurement of folate and vitamin B12 --- p.40 / Chapter 4.5. --- Measurement of soluble cellular adhesion molecules (CAMs) --- p.41 / Chapter 4.6. --- Measurement of plasma enterolactone --- p.43 / Chapter 4.7. --- Measurement of plasma hs-C-reactive protein --- p.44 / Chapter 4.8. --- Other laboratory tests --- p.45 / Chapter 4.9. --- High resolution ultrasound imaging --- p.46 / Chapter 4.10. --- Statistical analysis --- p.49 / Chapter 4.11. --- My contribution to this joint project --- p.49 / Chapter Chapter 5. --- Results / Chapter 5.1. --- Recruitment and outcomes of subjects --- p.51 / Chapter 5.2. --- Baseline characteristics --- p.53 / Chapter 5.3. --- Medical history and treatment received in the study subjects --- p.54 / Chapter 5.4. --- Safety profiles --- p.55 / Chapter 5.5. --- Severe adverse events --- p.56 / Chapter 5.6. --- Lipid profiles --- p.57 / Chapter 5.7. --- Secondary endpoints --- p.58 / Chapter 5.8. --- Primary endopoints --- p.59 / Chapter 5.9. --- The effect of statin usage on the primary endpoints / Chapter 5.10. --- The major determinant of the change in FMD by multivariate logistic regression / Chapter 5.11. --- Progress of lipid profiles and primary endpoints in the open label phase / Chapter Chapter 6. --- Discussion / Chapter 6.1. --- Brachial FMD --- p.66 / Chapter 6.2. --- Carotid IMT --- p.69 / Chapter 6.3. --- Brachial GTN --- p.70 / Chapter 6.4. --- Lipid-lowering effect --- p.72 / Chapter 6.5. --- Phytoestrogen --- p.72 / Chapter 6.6. --- Folate --- p.73 / Chapter 6.7. --- Vitamin B12 and glucose --- p.76 / Chapter 6.8. --- Summary of possible anti-atherogenic mechanism of D&G --- p.76 / Chapter 6.9. --- Placebo effect --- p.77 / Chapter 6.10. --- Safety profile --- p.77 / Chapter 6.11. --- Limitation of the study and suggestion of solution --- p.77 / Chapter 6.12. --- Suggestions and ummary of the future work --- p.79 / Chapter Chapter 7. --- Conclusions --- p.81 / References --- p.82

A Doença de Alzheimer é uma doença neurodegenerativa progressiva e de início tardio, que compromete principalmente as areas da cognição, julgamento e estabilidade emocional. Esta doença se caracteriza por dois tipos de lesões cerebrais características: emaranhados neurofibrilares e placas senis. Os emaranhados neurofibrilares são compostos por uma proteína do citoesqueleto (proteína tau) hiperfosforilada e agregada. As placas senis são formadas por agregados da proteína &#946;-amilóide. A doença de Alzheimer é resultado dainteração de vários fatores ainda incompletamente elucidados; não obstante, o estresse oxidativo e os processos inflamatórios ocupam posição de destaque dentre esses fatores. Neste trabalho, avaliamos as atividades das enzimas eritrocitárias superóxido dismutase, catalase e glutationa peroxidase, assim como o conteúdo plasmático de glutationa total, vitamina C, &#945;-tocoferol, &#946;-caroteno, licopeno e coenzima Q10. A esses parâmetros antioxidantes foram contrapostas medidas de oxidação de lipídios e proteínas plasmáticas. Adicionalmente, efetuamos a avaliação das expressões monocitárias de HLADR e CD-11b, e das citocinas IL-6, IL-1&#945; e TNF-&#945;. Nossos resultados mostram que os pacientes de doença de Alzheimer possuem níveis circulantes de atocoferol inferiores aos pacientes controles, e possuem monócitos que apresentam maior expressão basal de HLA-DR e maior produção de IL-1&#945; quando estimulados por LPS. Esses resultados fortalecem a hipótese inflamatória na doença de Alzheimer, de acordo com trabalhos recentes que apontam bons resultados com o a-tocoferol na sua prevenção e tratamento. / Alzheimer\'s disease is a late-onset, progressive degenerative disease that affects mainly the judgement, emotional stability and memory domains. This disease is characterized by two telltale cerebral lesions: neurofibrillary tangles and senile plaques. Neurofibrillary tangles are constituted by hyperphosphorylated cytoskeleton protein tau aggregates, while senile plaques are mainly composed by &#946;-amyloid protein aggregates. Alzheimer\'s disease is the outcome of a complex interaction among several factors which are not fully understood yet; nevertheless it is clear thar oxidative stress and inflammatory pathways rate high among these factors. In this work, we evaluated the erythrocytic acitivities of superoxide dismutase, catalase and glutathione peroxidase, as well as the plasma levels of total glutathione, &#945;-tocopherol, &#945;-carotene, lycopene, and coenzyme Q10. These antioxidant parameters were confronted with plasmatic levels of protein and lipid oxidation products. Additionally, we measured the basal expression of monocyte HLA-DR and CD-11b, as well as the monocyte production of the cytokines IL1-&#945;, IL-6 and TNF-&#945;. Our results show that Alzheimer\'s Disease patients show lower plasmatic levels of &#945;-tocopherol when compared to control patients, and have higher basal monocyte HLA-DR expression associated with higher IL-1&#945; production when stimulated by LPS. These results lend support to the inflammatory theory of Alzheimer\'s disease, according to recent works that indicate good results of &#945;-tocopherol administration in both its prevention and treatment.