Introdução: A automedicação é uma prática frequente em diferentes culturas, que pode ser usada como estratégia para resolução de pequenos problemas de saúde, especialmente em populações cujo acesso a serviços de saúde é restrito. No entanto, essa prática pode, também, ocasionar reações adversas graves, resistência microbiana, interações medicamentosas e gastos desnecessários, especialmente em grupos economicamente desfavorecidos e socialmente excluídos como ocorre com os povos ribeirinhos. Objetivo: Analisar a prática de automedicação e fatores associados entre ribeirinhos da região do Médio Solimões - Amazonas. Método: Estudo transversal de base populacional realizado nas comunidades ribeirinhas do município de Coari - Amazonas. A amostra probabilística foi composta por 492 ribeirinhos adultos. A coleta de dados foi realizada nas comunidades por meio de um questionário composto por variáveis independentes: socioeconômicas, demográficas, de acesso aos serviços de saúde, consumo de drogas lícitas, enfermidades autorrelatadas e informações sobre o consumo de medicamentos. A variável dependente automedicação foi avaliada pelo uso de pelo menos um medicamento sem prescrição médica ou de dentista, nos últimos 30 dias. Na análise dos dados utilizou-se testes do Qui-quadrado ou exato de Fischer, teste t de Student ou de Wilcoxon-Mann-Whitney e regressão logística binária hierarquizada. Resultados: A prevalência da automedicação foi de 76,3%. Dor de diferentes origens (58,1%) foi o principal motivo que levou à automedicação. Analgésicos (57,5%) e antimicrobianos (13,0%) foram os medicamentos mais utilizados. Os fatores associados à automedicação foram sexo masculino (OR=2,20; IC=1,21-4,01), faixa etária entre 18 a 39 anos (OR=2,50; IC=1,06-5,91), não procura por serviços de saúde (OR=2,90; IC=1,66-5,09), tempo de deslocamento da comunidade à zona urbana entre 1 a 4 horas (OR=2,84; IC=1,26-6,41) e maior que 4 horas (OR=5,27; IC=2,18-12,74), ter o hábito de consumo de medicamentos alopáticos por conta própria (OR=3,14; IC=1,49-6,61). Conclusões: Na população ribeirinha, a prática elevada da automedicação reflete a necessidade de busca de autocuidado pelas pessoas, sobretudo decorrente do restrito acesso aos serviços de saúde. / Introduction: Self-medication is a frequent practice in different cultures, and it can be used as a strategy to solve minor health problems, especially among populations with restricted access to health care services. However, such a practice may cause serious adverse reactions, microbial resistance, drug interactions and unnecessary expenses, mainly for economically disadvantaged and socially excluded groups like the riverside communities. Objective: To analyze the self-medication practice and its related factors among riverside communities in the region of the Middle portion of the Solimões River Amazonas State, Brazil. Method: Cross-sectional, population-based study carried out among riverside communities in the municipality of Coari Amazonas State, Brazil. The probability sampling comprised 492 adult riverside dwellers. Data collection was held in the communities by means of a questionnaire including independent variables: socioeconomic, demographic ones, access to health care services, drug therapy, self-reported illnesses, and information on medication use. Medication dependent variable was assessed by the use of at least one drug without medical or dentists prescription in the past 30 days. For the data analysis, Chi-square test or Fischers exact test, Students t or Wilcoxon-Mann-Whitney tests, and hierarchical binary logistic regression were used. Results: Self-medication prevalence was 76.3%. Pain from different origins (58.1%) was the main reason for self-medication. Painkillers (57.5%) and antimicrobial medication (13.0%) were the most used drugs. Self-medication related factors were males (OR=2.20; CI=1.21-4.01), age range between 18 and 39 years (OR=2.50; CI=1.06-5.91), not search for health care services (OR=2.90; IC=1.66-5.09), travel time from the community to the urban center between 1 and 4 hours (OR=2.84; CI=1.26-6.41), and over 4 hours (OR=5.27; CI=2.18-12.74), habit of self-medication for allopathic drugs (OR=3.14; CI=1.49-6.61). Conclusions: High self-medication practice among the riverside population reflects the need for turning to self-medication, mainly due to the restricted access to health care services.

A quimioterapia é uma das abordagens terapêuticas para o tratamento do câncer e, no caso específico das crianças e adolescentes, a mais frequente, de forma individual ou associada a outras modalidades. Tem sido fonte de preocupações, questionamentos e dúvidas, tanto por parte das crianças e adolescentes quanto de seus familiares, por seus efeitos colaterais físicos e psicológicos. O presente estudo tem por objetivo compreender como as crianças e os adolescentes com câncer vivenciam a experiência da quimioterapia, a partir de seus próprios relatos, visto que, ao conhecer suas demandas e sentimentos, podemos incorporá-los ao plano de cuidados de enfermagem e contribuir para uma assistência qualificada e dirigida à qualidade de vida da criança, do adolescente e de sua família. Exploratório e com análise qualitativa dos dados este estudo contou com a participação de 10 crianças e adolescentes entre oito e 18 anos, em diferentes momentos da terapêutica quimioterápica. Para a coleta dos dados, utilizamos como instrumentos a entrevista semiestruturada e a observação livre, complementadas com dados do prontuário dos sujeitos em questão. A análise do material empírico seguiu a técnica de análise de conteúdo. Após a caracterização dos sujeitos da pesquisa, os resultados foram agrupados ao redor de três grandes temas, seguidos dos respectivos subtemas: a doença, compreendendo a trajetória até o diagnóstico e o conhecimento sobre a doença; a quimioterapia, a partir do impacto do tratamento, as características dos quimioterápicos e a visão do processo e, por fim, a rede de apoio que incluiu a família, os amigos e a religião. O estudo nos permitiu compreender que, para as crianças e adolescentes, a experiência da quimioterapia está intimamente ligada à experiência do câncer, sendo impossível entender a dimensão da terapêutica sem antes compreender a base desta questão, o câncer infanto-juvenil. Lembrada, principalmente por seus efeitos colaterais e o sofrimento, a quimioterapia causa, de imediato, um forte impacto, deixando sobressair o medo. Passado este primeiro impacto, principalmente das alterações físicas, as preocupações dirigem-se à recuperação da doença, ou seja, à cura. Mencionam que o câncer interrompe uma vida até então normal e provoca dúvidas quanto ao futuro e mesmo o presente. Em contrapartida, com o tempo, relatam que o processo terapêutico, incluindo a quimioterapia, levou-os a valorizar mais a vida. Brincar, ter a família e os amigos por perto, buscar Deus, conhecer a doença e enfrentá-la, se envolver em todo o processo e, acima de tudo, acreditar no sucesso foram estratégias utilizadas durante a quimioterapia, terapêutica sofrida, restritiva, mas acima de tudo, responsável pela cura da criança e do adolescente. / Chemotherapy is one of the therapies used in cancer treatment. Separately or associated to other therapies, it is the most frequently used to treat children and adolescents. Due to its physical and psychological collateral effects, it has been source of preoccupations, questions and doubts, both for children and adolescents as well as their relatives. This exploratory and qualitative study aimed to understand how children and adolescents with cancer experience chemotherapy, from their own reports. Knowing their demands and feelings permits to incorporate them to the nursing care plan and contributes to a quality care, targeting the quality of life of children, adolescents and their families. Participants were 10 children and adolescents between 8 and 18 years of age, on different moments of chemotherapy. Data collection was done through semi-structured interview and free observation, added by data from subjects patient files. Analysis of the empirical material was done through content analysis. After characterization of the research subjects, results were grouped into three themes and their respective subthemes: disease, understanding the trajectory to diagnosis and knowledge about the disease; chemotherapy, the treatment impact, characteristics of chemotherapeutic drugs and the view of the process and, lastly, the support network, which includes family, friends and religion. The study permitted to understand that, for children and adolescents, the chemotherapy experience is closely related to the cancer experience, and it is impossible to understand the dimension of the therapy without previously understanding the basis of the issue: child and juvenile cancer. Chemotherapy is mainly reminded by its collateral effects and suffering. It has a strong impact on participants, showing the fear caused by it. After the initial impact, mainly due to physical changes, preoccupations are related to disease recovery, that is, cure. They mention that cancer interrupts what was so far a normal life and causes doubts regarding the future and even present life. On the other hand, according to their reports, treatment, including chemotherapy, made them value life more. Playing, being close to family and friends, searching for Good, knowing and facing the disease, getting involved in the process and, above all, believing in success, were the strategies used during chemotherapy, which is a restrictive therapy, that causes suffering, but which is primarily responsible for children and adolescent cure.

Introdução: O câncer infantil é uma enfermidade complexa que requer tratamento prolongado e demandas hospitalares. A quimioterapia é a terapêutica mais utilizada, apesar de apresentar diversos efeitos colaterais e exigir internações hospitalares, o que causa impacto na vida da criança. Brincar é uma atividade inerente e essencial na vida da criança, independentemente de sua idade e condição clínica, sendo o brincar de faz de conta um recurso importante para expressão e elaboração de vivências traumáticas. Neste sentido, o Brinquedo Terapêutico Dramático (BTD) permite a compreensão dos sentimentos e reações emocionais da criança, auxiliando na dramatização das vivências com as doenças, procedimentos invasivos e a situação da hospitalização. Objetivo: Compreender como o tratamento quimioterápico repercute no brincar de faz de conta de crianças com câncer que se submetem ao procedimento. Materiais e Métodos: Tratou-se de um estudo descritivo exploratório utilizando como estratégia a metodologia de estudos de casos múltiplos com crianças de 4 a 12 anos de idade. Participaram 5 crianças que realizaram tratamento quimioterápico em um hospital universitário do interior de São Paulo, no período de abril a setembro de 2016. O recurso utilizado foi o BTD, com a utilização de brinquedos imaginativos convencionais e simbólicos gerais, materiais imaginativos convencionais e simbólicos relacionados a temática da hospitalização. As sessões foram filmadas e se iniciaram com a seguinte questão norteadora: \"Vamos brincar de uma criança que fez quimioterapia?\". Os vídeos foram assistidos por duas avaliadoras independentes visando maior fidedignidade na transcrição dos dados. Resultados e Discussão: A partir das descrições das unidades de significados encontrados nos comportamentos e discursos, emergiram por cinco categorias temáticas: exploração e escolha dos materiais, presença de distratores, reação frente à modelagem, brincar de faz de conta com tema doméstico e brincar de faz de conta com o tema relacionado à hospitalização. De modo geral, as crianças apresentavam clareza com o que iriam brincar e, a brincadeira de faz de conta com o tema hospitalização esteve presente em todas as sessões de BTD. Todas as crianças brincaram sobre o leito, entretanto mesmo que possuía alguma limitação como acesso venoso, alarmes de dispositivos, presença de profissionais de saúde, isto não impediu de as mesmas brincarem e se envolverem no faz de conta. De modo geral, as crianças observavam a modelagem e se engajavam na brincadeira, sem imitar o que a avaliadora estava fazendo. Conclusão: Apesar das limitações impostas pelo contexto (brincar sobre o leito, acesso venoso, ruídos externos), as crianças demonstraram grande engajamento na brincadeira. O brincar ainda é visto por muitos profissionais de saúde como sendo algo de menor importância no cuidado da criança e, por isto, pode ser interrompido para avisos ou procedimentos clínicos que poderiam aguardar ao término da sessão de BTD. A escolha principal por parte das crianças foi a brincadeira de faz de conta com o tema relacionado à hospitalização, demonstraram grande riqueza de detalhes e grande conhecimento sobre os procedimentos clínicos aos quais vivenciam, auxiliando na elaboração de suas vivências / Childhood cancer is a complex disease that requirest prolonged treatment, hospital demands. Chemotherapy is the most used treatment of childhood cancer, although is has several side effects and requires hospitalization wich has an impact on the child\'s life. Playing is an inherent and essential activity in the child\'s life, regardless of age and clinical condition, and play is an important resource for the expression and elaboration of traumatic experiences. In this sense, the Dramatic Therapeutic Toy (DTT) is a resource that allows the understanding of the feelings and emotional reactions of the child, helping in the dramatization of the experiences with the diseases, invasive procedures and the hospitalization situation. Objective: To understand how the chemotherapy treatment repercussions in the play of pretends of children with cancer who undergo this procedure. Materials and Methods: It was performed an descriptive exploratory study as carried out using as methodology the methodology of multiple case studies with children from 4 to 12 years of age. Five children who underwent chemotherapy treatment in a university hospital in the interior of São Paulo, from april to september, 2016, participated in the study. The data collection resource was DTT, using conventional and symbolic general and symbolic toys. Conventional and symbolic imaginative materials related to hospitalization. The sessions were filmed and began with the following guiding question: \"Let\'s play a child who had chemotherapy?\" The videos were assisted by two independent evaluators aiming for greater trust in the transcription of the data. Results and discussion: From the descriptions of the units of meanings found in the behaviors and discourses, emerged by five thematic categories: exploration and choice of materials, presence of distractors, reaction to modeling, play pretend with domestic theme and play pretend with the topic related to hospitalization. In general, the children were clear about what they were going to play with, and the play on the topic related to hospitalization was present in all DTT sessions. All children played on the bed, however, it had some limitations such as venous access, device alarms, presence of health professionals in the bed, this did not prevent them from playing and getting involved. In general, the children observed modeling and engaged in play, without imitating what the evaluator was doing. Conclusion: Despite the limitations imposed by the context (playing on the bed, venous access, external noise) the children showed great commitment in the game. To play is still seen by many health care professionals as being of minor importance in the care of the child and therefore may be disrupted to warnings or clinical procedures that could await the end of the DTT session. The main choice on the part of the children was the play of pretends to the theme related to the hospitalization, which demonstrated great richness of detail and great knowledge on the part of the children on the clinical procedures to which they live, thus aiding in the elaboration of their experiences

O objetivo deste estudo foi interpretar os significados atribuídos à qualidade de vida pelo paciente com câncer colorretal no contexto da quimioterapia antineoplásica. Utilizamos o referencial teórico da antropologia médica, derivada da antropologia interpretativa, que conceitualmente integra cultura e doença, com utilização do método etnográfico, e análise temática indutiva. Realizaram-se entrevistas em profundidade (CEP-EERP-USP 1412/2011) com dezesseis participantes com câncer colorretal, que realizavam quimioterapia antineoplásica em um hospital público universitário. Foram construídas três unidades de sentidos e dois núcleos temáticos. As unidades de sentido \"Itinerário terapêutico: do diagnóstico aos tratamentos\", \"A quimioterapia antineoplásica e seus efeitos adversos\" e \"Qualidade de vida durante a quimioterapia antineoplásica\", mostraram que a construção do itinerário terapêutico perpassa pelo reconhecimento da anormalidade do corpo, busca pelo sistema profissional de saúde e pela necessidade de tratamentos especializados. A primeira indicação terapêutica é a cirurgia, que traz sofrimento e solução parcial do problema, logo substituída pela quimioterapia. A doença é percebida como uma dimensão incontrolável, e os acontecimentos vivenciados fornecem uma nova identidade social, as marcas corporais representam sua vulnerabilidade e os efeitos adversos denunciam sua condição de doente oncológico. Há o sofrimento social, a necessidade de ter resiliência para aderir ao tratamento, de adaptações e transformações individuais, familiares e sociais, que resultaram na adoção de novas ideias, conceitos, valores e crenças, acrescentando novos elementos na sua identidade social, pois percebe a perda de suas capacidades e a impossibilidade de cura. A esperança da retomada da normalidade da vida anterior é prejudicada pela confirmação da impossibilidade de cura, sendo substituída pelo direito de uma morte digna. A pessoa tem a sua condição oncológica visivelmente denunciada e, apesar da consciência de sua finitude, não abre mão da sua esperança de cura. Nos núcleos temáticos \"A experiência moral atribuída ao câncer colorretal e a quimioterapia antineoplásica\" e \"Qualidade de vida de pessoas com câncer colorretal em quimioterapia antineoplásica - a retomada da normalidade\" foi evidenciada que a quimioterapia é uma etapa liminar para a cura, no processo da experiência moral de ter câncer colorretal, que está relacionada às consequências das atitudes morais e sociais no cotidiano, com busca da preservação de sua autoestima e do senso de normalidade, rejeitando que as possibilidades de cura acabaram. O significado de qualidade de vida é construído, de acordo com as relações desenvolvidas com as pessoas, incluindo o julgamento pessoal sobre sua vida, experiências e expectativas de futuro, relacionados ao contexto de adoecimento, onde a quimioterapia é mais uma etapa do tratamento, que mesmo com suas reações limitantes, ainda é a expectativa de alcance de cura. Há evidências que os participantes não possuem qualidade de vida, pois ocorreu a \"perda do controle da vida\", a percepção que a terapêutica não garante a sua cura, permanecendo a incerteza do futuro, mesmo com o sofrimento e a experiência moral. Deve ocorrer a ampliação do foco da qualidade de vida pelos enfermeiros, incluindo as referências socioculturais das pessoas que vivem o processo de adoecimento e do tratamento, ultrapassando a dimensão biológica e tecnológica do cuidar / The aim of this study was to interpret the meanings attributed to quality of life for patients with colorectal cancer in the context of antineoplasic chemotherapy. We use the theoretical framework of medical anthropology, derived from interpretive anthropology, which conceptually integrates culture and disease with use of ethnographic methods, and inductive thematic analysis. There were in-depth interviews (CEP- EERP- USP 1412/2011) with sixteen participants with colorectal cancer who were undergoing cancer chemotherapy in a public university hospital. Three units of meaning and two thematic groups were constructed. The units of \"Therapeutic itinerary meaning: from the diagnosis to treatment\",\"The antineoplasic chemotherapy and its adverse effects\" and \"Quality of life during cancer chemotherapy\", showed that the construction of the therapeutic itinerary runs through the recognition of body abnormality, the search for professional health care system and the need for specialized treatments. The first therapeutic indication is the surgery, which brings suffering and partial solution of the problem, soon replaced by chemotherapy. The disease is perceived as an uncontrollable dimension, and the experienced events provide a new social identity, the body marks represent their vulnerability and the adverse effects report their condition of cancer patients. There is the social suffering, the need for resilience to adhere to treatment, individual, familiar and social adaptations and transformations, which resulted in the adoption of new ideas, concepts, values and beliefs, adding new elements in their social identity, because they realize the loss of their capabilities and the healing impossibility. The hope of normality of life recovery is impaired by the confirmation of the healing impossibility, being replaced by the right of a dignified death. The person has their oncologic condition visibly exposed and, despite the knowledge of their finitude, does not give up their hope of cure. In thematic groups \"The moral experience attributed to colorectal cancer and cancer chemotherapy\" and \"Quality of life of people with colorectal cancer receiving antineoplasic chemotherapy - normality recovery\" was evidenced that chemotherapy is a preliminary step to healing in the process of moral experience of having colorectal cancer, which is related to the consequences of moral and social attitudes in everyday, with the pursuit of preserving their self-esteem and sense of normality, rejecting that the possibilities of cure have ended. The meaning of quality of life is constructed according to the relations developed with people, including personal judgment about life, experiences and expectations of future related to the context of disease where chemotherapy is one more step of the treatment, that even with their limiting reactions, is still the expectation to reach the cure. There is evidence that participants do not have quality of life, because of the \"loss of control of their lives,\" the perception that the therapy does not ensure healing, remaining the uncertainty of the future, even with the suffering and moral experience. Expanding the focus of quality of life should occur by nurses, including socio-cultural references of people who live the process of illness and treatment, exceeding the biological and technological dimension of care

A following study on vancomycin demonstrated the differing pharmacokinetics during the course of a septic insult, day 2 pharmacokinetics differing from day 7. / An important study showed that some septic patients with "normal" serum creatinines can have very high creatinine clearances. It follows that drugs which are renally excreted will have high clearances and illustrates why many of the above patients had low serum levels of antibiotic, a reason why some ICU patients require different dosing to ward patients. / Due to the required fluid loading and inotropic use in septic patients, creatinine clearances and drug clearances are often raised. This results in low serum concentrations at the end of a standard dosing interval. / My beta-lactam antibiotic work has repeatedly demonstrated low serum levels at the end of the standard dosing interval. In view of beta-lactam time-dependent kill characteristics we designed a continuous infusion protocol which we validated in a follow-up paper. / The inflammatory response of infections involves endothelial damage and capillary permeability. With associated fluid shifts of severe sepsis and treatment thereof, the volume of distribution (Vd) of antibiotics that distribute into the extracellular space (aminoglycosides, glycopeptides) is high. Peak serum levels for these antibiotics are therefore lower than those found in non-critically ill and in normal volunteers. It is noteworthy that this change in Vd is not apparent with drugs that have good tissue penetration (e.g. ciprofloxacin). / This thesis is a compilation of 11 of my prospectively designed studies plus extracts from 5 published reviews, focusing on pharmacokinetic (PK) aspects of antibiotics in ICU patients, all published in internationally peer-reviewed journals. / Two large PK studies on ciprofloxacin (a drug that has excellent tissue penetration) designed to address possible PK differences over time, could not demonstrate this difference in adults nor in two groups of paediatric patients where differences in body water are significant. / Two papers investigated the pharmacokinetics of amicakin in adult and paediatric patients documenting the benefit of extended interval dosing. / We automatically assume that antibiotic prescribing data, collated from healthy volunteers and not so ill patients, can be transcribed into the Intensive Care Unit. This is not so. / Jeffrey Lipman. / "April 2005." / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1548. / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 235-254). / 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, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

Ding Baoguo. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 225-247). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

To Kin Wah. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 293-345). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Metabolic syndrome refers to clusters of risk factors (e.g. obesity, hyperlipidemia, insulin resistance, non-alcoholic fatty liver and hypertension) that would lead to development of cardiovascular disease. The prevalence of this disease is high and the therapeutic approaches are insufficient. Potential use of Chinese herbal medicines to target on metabolic syndrome has attracted great attention. Erigerontis Herba (EH) is a Chinese herb that is traditionally used to treat cardiovascular and cerebrovascular diseases. Its effect on diet-induced metabolic syndrome has not been previously investigated. The present study was the first investigation of the effects of Erigerontis Herba, Erigerontis containing herbal formulae and its polyphenol-enriched fraction (EHP) on diet-induced metabolic syndrome. / To determine the effects of EH, EH-containing herbal formulae and EHP on obesity, hyperlipidemia, hepatic steatosis and hypertension, in vitro, ex vivo and in vivo models were used. For in vitro studies, cholesterol uptake inhibition and adipogenesis differentiation assays were performed using Caco-2 cells and 3T3-L1 adipocytes, respectively. Ex vivo organ bath studies were performed to determine the vasodilative effects, and respective underlying mechanisms were determined via inhibition of different pathways using corresponding blockers. In vivo animal model of high-fat diet-induced metabolic syndrome was performed using C57Bl/6 mice. Preventive effects of these herbal extracts were determined by supplementation of extract to high-fat diet for 8 weeks, followed by measurement of body weight, liver and adipose tissues weight, plasma lipid, plasma glucose and liver lipid. Proteins and genes expressions related to lipid metabolism were also determined using Western blotting and RT-PCR. Bioavailability of these herbal extracts were investigated using human intestinal Caco-2 cells monolayer. / Among all tested, EHP demonstrated most prominent effects in the inhibition of both cholesterol uptake and adipogenesis in vitro; and possessed significant vasodilative effects ex vivo, and also significant beneficial effects on obesity and hepatic steatosis in mice, but not on hyperlipidemia. EH-containing herbal formulae exhibited significant inhibitory effects on cholesterol uptake in Caco-2 cells. Among all tested, only DZ4 showed inhibitory effect on adipogenesis. EH, on the other hand, significantly inhibited adipogenesis but exerted no effect on cholesterol uptake. EH and EH-containing herbal formulae showed significant vasodilative effects in ex vivo studies. For in vivo studies, only DZ6 showed mild beneficial effects on diet-induced obesity (inguinal fat/body weight and peri-renal fat/body weight), hepatic steatosis and hyperlipidemia. EH alone showed no significant beneficial effects on high-fat diet-induced metabolic syndrome in mice. Preliminary bioavailability experiments suggested that all herbal preparations had relatively low bioavailability, although EHP had a comparative higher permeation ability through Caco-2 monolayer. / In conclusion, this is the first comprehensive study of the effects of EH (with or without other herbs) on diet-induced metabolic syndrome. EHP, a polyphenol-enriched fraction isolated from EH showed potent beneficial effect on diet-induced obesity and hepatic steatosis both in vitro and in vivo, as well as significant vasodilative effects ex vivo. These data suggested the potential for EHP to be developed as dietary supplementation for metabolic syndrome. The effects will be further determined in clinical trials in the future. / 代謝綜合癥是多種心血管危險因子異常聚集的病理狀態，其病癥包括肥胖，高血脂，胰岛素抗性，高血糖，脂肪肝和高血壓等。它的發病率很高，但是目前治療以及預防這一疾病的措施尚不完善。近年來，用中藥治疗這一疾病引起人们廣大關注。燈盞細辛作為傳統中草藥經常用於心血管和腦血管疾病，但其對於代謝綜合癥是否有效有待研究發現。本課題組建立了高脂餵食引起代謝綜合癥模型，并探討了燈盞細辛，燈盞細辛複方，以及燈盞細辛你酚類對此疾病的療效及作用機制。 / 我們用體內，體外及離體模型研究了燈盞細辛，燈盞細辛複方以及燈盞細辛酚對於肥胖，高血脂，脂肪肝和高血壓的作用。我們用3T3-L1和Caco-2細胞模型研究了燈盞細辛相關提取物對於膽固醇吸收和脂肪生成的作用，用大鼠離體血管環體外實驗，研究了他們對於血管擴張的作用及其機制。另外，本課題組建立了高脂餵食小鼠代謝綜合癥模型，并探討了這些中藥提取物作為食物補充劑對於代謝綜合癥的作用。我們用實時定量PCR技術和蛋白質印跡技術測量了各種相關蛋白和基因的表達。此外，我們還用人的腸細胞單層轉運模型研究了這些中藥提取物的生物利用度。 / 體外實驗結果表明，四個燈盞細辛複方都有明顯抑制膽固醇吸收的作用，但是對於脂肪生成，只有複方DZ4有明顯抑制作用。燈盞細辛提取物可以明顯抑制脂肪生成，但是對膽固醇吸收卻沒有明顯作用。燈盞細辛酚對於兩者都具有明顯的抑制作用。另外，大鼠離體動血管環研究結果顯示，燈盞細辛複方，燈盞細辛提取物以及燈盞細辛酚都有明顯的擴張血管的作用。高脂餵食小鼠代謝綜合癥實驗結果結果顯示四個燈盞細辛複方中只有複方DZ6對於肥胖，脂肪肝和高血脂有作用。燈盞細辛對代謝綜合癥無明顯作用，但是燈盞細辛酚對于肥胖和脂肪肝卻有明顯抑制作用對於此代謝綜合癥小鼠模型。生物利用度相關研究結果顯示，燈盞細辛，燈盞細辛複方以及燈盞細辛酚的生物利用度都相對較低。 / 總括來說，我們綜合研究了燈盞細辛對於代謝綜合癥的藥效。燈盞細辛酚對於肥胖和脂肪肝在體內體外模型都顯示了較好的抑製作用。再加上其對於擴張血管有非常明顯的作用，它有潛能被發展為代謝綜合癥的治療預防方法。 / Wang, Yanping. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 243-256). / Abstracts also in Chinese. / Title from PDF title page (viewed on 01, November, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Colon cancer, a disease in which malignant tumors form in the tissues of colon, is the first commonest cancer and the second leading cause of cancer-related deaths in Hong Kong. The standard treatment options for colon cancer include surgery and chemotherapy. However, multidrug resistance (MDR) develops in nearly all patients with colon cancer. In fact, most of the cancer-related deaths are due to chemotherapy failure caused by MDR, which occurs during the course of cancer progression and chemotherapy. Thus, the reversal of MDR plays an important role in the successful chemotherapy for colon cancer. This study investigated such a pharmacological action in reversing MDR in colon cancer cells by tanshinones, targeting the two common mechanisms responsible for MDR, i.e. overexpression of ATP-binding cassette (ABC) transporters and suppression of apoptosis. / Overexpression of P-glycoprotein (P-gp), one of the most important ABC transporters, can mediate the efflux of drugs out of cancer cells, leading to MDR and chemotherapy failure. The reversal of P-gp-mediated MDR by five tanshinones including tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone and miltirone was evaluated in colon cancer cells. Bi-directional transport assay showed that only cryptotanshinone and dihydrotanshinone decreased the P-gp-mediated digoxin efflux in Caco-2 cells. The two tanshinones potentiated the cytotoxicities of doxorubicin and irinotecan in P-gp overexpressing colon cancer SW620 Ad300 cells. Moreover, these two tanshinones also increased intracellular accumulation of P-gp substrate in SW620 Ad300 cells, presumably by down-regulating P-gp mRNA and protein levels, as well as inhibiting P-gp ATPase activity. / Suppression of apoptosis can lead to MDR in cancer cells to anticancer agents with pro-apoptotic property. Hence, this study also investigated the circumvention of resistance to apoptosis in drug resistant colon cancer cells by cryptotanshinone and dihydrotanshinone, two potential MDR-reversing tanshinones. The drug resistant SW620 Ad300 cells were still sensitive to both cryptotanshinone and dihydrotanshinone in the promotion of cell death. When compared with the parental SW620 cells, the two tanshinones induced less apoptosis but more autophagy in the drug resistant cells. Further studies showed that cell viability was increased after inhibition of autophagy by siRNA interference or autophagy inhibitor. Thus, autophagy induced by the two tanshinones was pro-cell death in SW620 Ad300 cells, which could overcome resistance to apoptosis. / In addition, suppression of apoptosis can be caused by p53 defects/mutations, which were found in more than 50% of all human cancers. Our results also showed that apoptosis and autophagy induced by cryptotanshinone and dihydrotanshinone were independent of the status of p53 in colon cancer cells. The p53-independent cytotoxic actions of the two tanshinones could be useful in overcoming resistance to apoptosis in cancer cells caused by p53 defects/mutations. / Taken together, the current findings indicate a great potential of cryptotanshinone and dihydrotanshinone in the reversal of MDR caused by P-gp overexpression and suppression of apoptosis. They are promising candidates to be further developed as therapeutic agents in the adjuvant therapy for colon cancer, especially for the multidrug resistant cancer types. / 結腸癌是指形成在結腸組織的惡性腫瘤，在香港常見的癌症中排第一位，亦是香港排第二位的致死癌症。結腸癌的標準治療方案主要包括手術和化療。然而，多藥耐藥是結腸癌成功化療的一個障礙。事實上，大多數癌症引起的死亡都和在癌症的發展和化療的過程中產生的多藥耐藥有關。因此，多藥耐藥的逆轉對於結腸癌的成功化療非常重要。本研究旨在通過針對多藥耐藥兩種常見的機制ABC跨膜蛋白的過表達和抑制的細胞凋亡來探討丹參酮對結腸癌細胞多藥耐藥的逆轉。 / P-gp的過表達可介導藥物排出癌細胞，從而導致多藥耐藥和化療失敗。本研究評價了tanshinone I，tanshinone IIA，cryptotanshinone，dihydrotanshinone和miltirone對P-gp介導的結腸癌細胞多藥耐藥的逆轉。雙向轉運實驗表明，只有cryptotanshinone和dihydrotanshinone可以減少P-gp介導的digoxin外排。這兩個丹參酮可以增加doxorubicin和irinotecan在P-gp過表達的結腸癌SW620 Ad300細胞中的毒性。此外，這兩個丹參酮也增加P-gp底物在SW620 Ad300細胞內的積累，推測是通過下調P-gp的mRNA和蛋白水平，以及抑制P-gp的ATP酶活性。 / 抑制的細胞凋亡可導致腫瘤細胞對促凋亡的抗癌藥物产生多藥耐藥。因此，本研究也探討了cryptotanshinone和dihydrotanshinone能否克服結腸癌細胞的凋亡耐受。結果表明cryptotanshinone和dihydrotanshinone仍然能够杀死耐藥的SW620 Ad300細胞。當與SW620細胞相比，這兩個丹參酮在耐藥細胞中誘導的細胞凋亡較少，但自噬增多。進一步研究表明，這兩個丹參酮誘導的自噬是促進細胞死亡的，從而可以克服細胞的凋亡耐受。 / 此外，p53的缺陷/突變存在於50%以上的人類癌症中，并可以抑制細胞產生凋亡。結果表明，cryptotanshinone和dihydrotanshinone誘導的凋亡和自噬與p53在結腸癌細胞中的表達無關。這兩個丹參酮不依賴於p53的細胞毒性可以用於克服p53缺陷/突變引起的凋亡耐受。 / 綜上所述，本研究結果表明cryptotanshinone和dihydrotanshinone在逆轉P-gp的過表達和抑制的細胞凋亡引起的多藥耐藥中具有巨大潛力。它們可以進一步發展為有前途的治療劑并用於結腸癌的輔助治療，尤其是用於多藥耐藥的結腸癌。 / Hu, Tao. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 163-182). / Abstracts also in Chinese. / Title from PDF title page (viewed on 06, December, 2016). / Hu, Tao. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

A pilot clinical trial was conducted after the in-vivo and in-vitro studies: Eight subjects fulfilled the inclusion criteria were recruited. However, the liver function tests of three subjects out of eight were found to be abnormal with elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level, which was not reported in previous toxicity test. The trial was suspended immediately and a follow-up test showed that the elevated AST and ALT level had reverted back to normal within one month after termination of OPR intake. Although we could not accomplish a RCT, the pilot study revealed potential hepatotoxicity of OPR on human beings and it would raise the safety awareness of investigators on the use of herbal remedies in future clinical studies. / After the in-vivo and in-vitro studies, a double-blinded, randomized, placebo-controlled clinical trial (RCT) was planned. Due to a lack of a Chinese version of instrument to measure osteoporosis-specific quality of life, an English version of the Osteoporosis-Targeted Quality of Life Questionnaire (OPTQoL) was translated into Chinese and linguistically validated according to the standard guideline. The newly formed Chinese OPTQoL can be used to assess the impact of new interventions on quality of life among Chinese osteoporosis patients. / Association of the incidence of postmenopausal osteoporosis and Kidney-Vacuity Syndromes in TCM was investigated with the aid of a Kidney-Vacuity Syndromes scoring questionnaire. In the study, postmenopausal women, who suffered from deficiency of kidney "qi" and kidney "essence", had a significantly higher incidence of osteoporosis. These findings strongly supported that replenishing kidney qi and kidney essence was a logical therapeutic principle in the formulation of OPR. / In conclusion, this study investigated the use of TCM on the treatment of postmenopausal osteoporosis in a systematic manner. It started from herbal formulation, basic science studies to clinical trial. It revealed beneficial effects of OPR on bones through in-vivo and in-vitro studies and demonstrated certain possible mechanism behind. On the other hand, the hepatotoxicity of OPR on human beings was also exposed and had not been reported in previous toxicity tests. The study provided valuable clinical data for other investigators on the potential hazards of herbal remedies although they had been validated as safe and effective in pre-clinical stage. / In search for safe, effective and low-priced medicine, the public have turned their attention to Traditional Chinese Medicine (TCM). Extensive experience has been accumulated in TCM regarding the diagnosis and treatment of osteoporosis, which often involves the prescription of kidney-tonifying herbs. Therefore, the aim of the study, firstly, was to explore the association of the incidence of postmenopausal osteoporosis and Kidney-Vacuity Syndromes in TCM, so as to formulate a rational kidney-tonifying herbal formula for osteoporosis research (OPR). Secondly, the effect of the formula was evaluated by in-vitro and in-vivo studies. Thirdly, the Osteoporosis-Targeted Quality of Life Questionnaire was linguistically validated from English to Chinese, which was expected to be one of the outcome measurement tools in future clinical trials. Lastly, a pilot clinical study was performed, which revealed some potential hazards of the formula on human beings which have not been shown in previous works. / Osteoporosis is a skeletal disorder which leads to an increased risk of bone fracture, disability or even death. It has become a major public health threat and the worldwide incidence of osteoporotic fracture is projected to increase two fold within the next 50 years. Postmenopausal women, being affected by a lack of estrogen, face a much higher risk of the disease. This study would therefore focus on type I osteoporosis (i.e. postmenopausal osteoporosis). Although current medications can slow down the bone deterioration process, their side effects and high cost had impaired patients' compliance with long term treatment. / The effect of OPR for the treatment of postmenopausal osteoporosis was then evaluated by in-vitro and in-vivo studies. In the in-vivo study, an osteoporosis model was established by performing ovariectomy on the four-week-old C57BL/6 mice. A high bone turnover rate was induced and OPR successfully slowed down the high turnover rate of bones by decreasing bone formation and resorption process without increasing the uterine linings. However, its beneficial effect on bones could not be detected on bone mineral density measurement. / The potential mechanism of action of OPR on bones was explored by in-vitro study. OPR was shown to induce cell proliferation and differentiation of osteoblast-like UMR 106 cells. Furthermore, the estrogenic activity of OPR was detected by MCF-7 cell line, which has been stably transfected with estrogen responsive elements (ERE). OPR was shown to possess an estrogenic activity in a dose dependent manner and was comparable to the positive control at a concentration of 200 and 1000 mug/ml. The induced estrogenic activity by OPR may be associated with the presence of phytoestrogen within the herbal formula. These findings suggested that the beneficial effect of OPR on bones might relate to its direct positive effect on osteoblast and its estrogenic-like activity. / Liong, Ching. / Adviser: Chun-tao Che. / Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves ). / 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.