Thesis (MTech (Biomedical Technology))--Cape Technikon, 2011. / Cancer of the prostate gland is now recognised as one of the principal medical problems in males. In the USA, cancer of the prostate is the second most commonly diagnosed cancer after skin cancer and the second most common cause of death from cancer after lung cancer. In South Africa, prostate cancer is the second most common cancer, with an estimated annual incidence of 19.1 per LOO000 men (Sitas, 1994). However, this incidence is probably under-estimated, due to incomplete records. Comparison of the incidence of prostate cancer in the different racial groups shows that it is the second most common malignancy in the White, Black (African) and Mixed (Coloured) race groups, and the fourth most common malignancy in Asian (Indian) men in South Africa. Metastatic prostate cancer is refractory to hormone therapy and remains incurable. Hence, novel therapeutic approaches are needed. These anticancer drugs can be tested in tumour cell lines, and cell culture methods also permit testing of optimum conditions.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / Este estudo teve como objetivo avaliar a qualidade de vida relacionada à saÃde (QVRS), domÃnios afetados das mulheres com cÃncer de mama em tratamento quimioterÃpico. Estudo exploratÃrio de corte transversal, realizado no Centro Regional Integrado de Oncologia e na Santa Casa da MisericÃrdia de Fortaleza, instituiÃÃes de tratamento para o cÃncer de mama. A coleta de dados foi atravÃs de instrumento de dados sociodemogrÃficos e clÃnicas, a avaliaÃÃo da QV com a aplicaÃÃo dos QuestionÃrios EORTC QLQ â C30 (VersÃo 3.0) e EORTC QLQ BR 23, durante o perÃodo de abril a julho de 2012. Foi utilizado o SPSS 20.0 para a anÃlise dos dados e revisado por um estatÃstico. Sendo os resultados apresentados em forma de tabelas e discutidas a luz da literatura existente. Participaram da amostra 145 mulheres com cÃncer de mama em quimioterapia, a mÃdia de idade encontrada foi 52 anos, 56,6% das mulheres tinham companheiro, 24,1% sÃo domÃsticas ou do lar; 55,9% recebia, pelo menos, um salÃrio mÃnimo. A maioria (86 ou 59,3%) procede do interior do estado, 60,7% mulheres apresentaram atà 8 anos de estudo, caracterizando assim, baixa escolaridade na maioria da amostra estudada. Com relaÃÃo aos dados clÃnicos, 43,4% das pacientes estava realizando a quimioterapia neoadjuvante, o restante adjuvante. O esquema mais utilizado foi TAC- Docetaxel + doxorrubicina + ciclofosfamida, em 37,2% das mulheres, com tempo de tratamento predominante menor do que 6 meses, em 66,9% das mulheres. Destaca-se que o escore da QVG resultou (76,14), o que significa que a QVG foi considerada razoÃvel ou satisfatÃria pelas mulheres. A funÃÃo mais afetada foi a emocional e encontrou-se que condiÃÃo fÃsica e o tratamento provocaram alguma dificuldade financeira (MÃdia= 41,83), na maioria das pacientes. Os sintomas com os maiores escores foram insÃnia (37,93), fadiga (36,01), perda de apetite (33,56). Com relaÃÃo ao instrumento QLQ BR-23, o resultado mostra o escore EC= 50,07, significando que muitas mulheres apresentam efeitos colaterais da QT e a satisfaÃÃo sexual prejudicada. Em suma, os resultados do presente estudo mostram o quÃo importante à avaliar a QV e os domÃnios mais afetados da paciente atendida em instituiÃÃes de Fortaleza. à relevante avaliar o bem-estar fÃsico, psicolÃgico, bem como o fÃsico, o social e o ambiental para a qualidade de vida. Com o estudo, pode-se corroborar com as prÃticas clÃnicas pertinentes e as proposiÃÃes de polÃticas de saÃde que satisfaÃam o paciente como um todo.

Submitted by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-05-24T16:16:21Z No. of bitstreams: 1 Reprodução Não Autorizada.pdf: 47716 bytes, checksum: 0353d988c60b584cfc9978721c498a11 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-05-24T17:49:06Z (GMT) No. of bitstreams: 1 Reprodução Não Autorizada.pdf: 47716 bytes, checksum: 0353d988c60b584cfc9978721c498a11 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-05-24T17:49:24Z (GMT) No. of bitstreams: 1 Reprodução Não Autorizada.pdf: 47716 bytes, checksum: 0353d988c60b584cfc9978721c498a11 (MD5) / Made available in DSpace on 2016-05-24T17:49:24Z (GMT). No. of bitstreams: 1 Reprodução Não Autorizada.pdf: 47716 bytes, checksum: 0353d988c60b584cfc9978721c498a11 (MD5) Previous issue date: 2016-01-29 / FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas / This study aimed to analyze the cytotoxic and antioxidant extracts obtained from 20 plant species in the Amazon. A relationship was shown between Artemia salina mortality with antioxidant activity and cytotoxicity in mouth cancer cells and antioxidant activity by chemical and biological method. Furthermore, it was found cytotoxicity of samples of breast cancer cells, fibroblasts and macrophages. The botanical material was from the Adolpho Ducke Forest Reserve, involving roots, stems and leaves. The most active extracts the high polarity and its fractionation was performed with Sephadex LH20 eluting with methanol plus 50% water in the last two fractions. The methanol extract of Inga cordatolata leaves was the most active antioxidant in tests on chemical and cellular level. Showed higher cytotoxic effect to other samples both in the crude extract, as in its fractions. In spite of the high cytotoxicity observed in mouth cancer cells, this species does not induce killing of macrophages. In small concentrations of this antioxidant extract has been shown, whereas in higher concentrations showed significant cytotoxicity. Chemical analysis by High Performance Liquid Chromatography and Liquid Chromatography Ultra Efficiency suggests the presence of quercetin and isorhamnetin 3-O-glucoside on their constituents. It was concluded that methanol extract of the leaves has Inga cordatolata, associated form, the biological properties investigated in this work. Among all samples, it presents more likely to turn out to be a source of anticancer drugs. However, it is not possible to state that these effects are maintained in vivo. Thus, it is suggested the preparation of nanocapsules to see if there would be selective drug distribution between normal and cancerous tissues, and the activity of this sample would be different in each tissue / Este trabalho objetivou analisar as atividades citotóxica e antioxidante de extratos obtidos de 20 espécies vegetais da Amazônia. Foi demonstrada a relação entre mortalidade de Artemia salina com atividade antioxidante e citotoxicidade em células de cancer de boca e atividade antioxidante por método químico e biológico. Além disso, verificou-se a citotoxicidade das amostras sobre as células de câncer de mama, fibroblastos e macrófagos. O material botânico foi proveniente da Reserva Florestal Adolpho Ducke, envolvendo raízes, caules e folhas. Os extratos mais ativos foram os de elevada polaridade e o seu fracionamento foi realizado com Sefadex LH20 utilizando como eluente o metanol, acrescido de 50% de água nas ultimas duas frações. O extrato metanol das folhas de Inga cordatolata foi a mais ativa nos ensaios antioxidantes em nível químico e celular. Revelou efeito citotóxico superior às demais amostras tanto no extrato bruto, quanto nas suas frações. Apesar da elevada citotoxicidade observada nas células de câncer de boca, esta espécie não induziu a morte de macrófagos. Em pequenas concentrações este extrato se demonstrou antioxidante, ao passo que nas concentrações maiores apresentou citotoxicidade expressiva. A análise química por Cromatografia Líquida de Alta Eficiência e a Cromatografia Líquida de Ultra Eficiência sugere a presença de quercetina e isorhamnetina 3-O-glucosideo nos seus constituintes. Conclui-se que o extrato metanol das folhas de Inga cordatolata detém, de forma associada, as propriedades biológicas investigadas por este trabalho. Dentre todas as amostras analisadas, ela apresenta maiores probabilidades de vir a se tornar uma fonte de medicamentos antineoplásicos. Contudo, não é possível afirmar que esses efeitos sejam mantidos in vivo. Dessa forma, sugere-se a elaboração de nanocápsulas para constatar se haveria distribuição seletiva da droga entre os tecidos normais e cancerosos, e se a atividade desta amostra seria diferenciada em cada tecido

Orientador: Márcio Ajudarte Lopes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-23T01:35:44Z (GMT). No. of bitstreams: 1 Ramos_LaraMariaAlencar_D.pdf: 993265 bytes, checksum: 9da6c3e7c0c22ceebc93d5f7eac147d1 (MD5) Previous issue date: 2013 / Resumo: A quimioterapia é um dos tratamentos utilizados para a cura do câncer, e têm como princípio o uso de drogas que alteram o metabolismo das células neoplásicas levando a morte celular. Apesar dos benefícios do tratamento quimioterápico, as drogas também afetam células normais e geram efeitos colaterais que prejudicam diretamente a qualidade de vida dos pacientes. Tais efeitos na cavidade oral podem ser classificados como agudos (mucosite, hipossalivação, candidose, herpes) ocorrem durante o tratamento, e tardios (hipossalivação) ocorrem após a conclusão do tratamento. A mucosite é o efeito colateral agudo mais importante, e causa principalmente dor e disfagia. Além da alteração na quantidade da saliva os quimioterápicos também alteram os componentes da mesma, predispondo os tecidos orais a alguns efeitos secundários. As proteínas SPLUNC (short palate, lung and nasal epithelium clone) foram identificadas em glândulas salivares, saliva, fluídos das vias aéreas e outros tecidos, com uma possível participação no sistema imune inato dessas regiões. O objetivo desse estudo foi avaliar a correlação entre a expressão das proteínas SPLUNC1 e SPLUNC2A com a presença de efeitos colaterais como mucosite e hipossalivação durante a quimioterapia, assim como a quantificação dessas proteínas antes, durante e após o tratamento. Foram realizadas três coletas de saliva total em 20 pacientes saudáveis, 20 pacientes submetidos à quimioterapia convencional e em 15 pacientes submetidos a regimes de condicionamento prévios ao transplante autólogo de células tronco hematopoiéticas e as proteínas foram avaliadas por meio de western blotting. Foi observada uma significativa mudança na qualidade da saliva durante a quimioterapia, caracterizada pelo aumento na expressão de SPLUNC1, mas não foi comprovado que essa variação esteja associada ao agravamento da mucosite e hipossalivação / Abstract: Chemotherapy is one of the treatments used to cure cancer, and have as a principle the use of drugs that alter the metabolism of neoplastic cells leading to cell death. Despite of the benefits of chemotherapy, the drugs also affect normal cells and cause side effects that directly affect the quality of life of patients. Such effects in the oral cavity can be classified as acute (mucositis, hyposalivation, candidosis, herpes) occur during the treatment, and late (hyposalivation) occur after completion of treatment. Mucositis is the most important acute side effect, and mainly causes pain and dysphagia. Besides the change in the amount of saliva, chemotherapy also alters the saliva composition, predisposing oral tissues to some collateral effects. Proteins SPLUNC (short palate, lung and nasal epithelium clone) were identified in salivary glands, saliva, fluid from the airways and other tissues, with a possible role in the innate immune system in these regions. The aim of this study was to evaluate the correlation between the expression of proteins SPLUNC1 and SPLUNC2A with the presence of side effects such as mucositis and hyposalivation during chemotherapy, as well as the quantification of these proteins before, during and after treatment. Were performed three collections of whole saliva in 20 healthy subjects, 20 patients undergoing conventional chemotherapy and 15 patients undergoing conditioning regimens prior to autologous hematopoietic stem cell transplantation and proteins were evaluated by western blotting. We observed a significant change in the quality of saliva during chemotherapy, characterized by increased expression of SPLUNC1, but it was not observed any association with worsening of hyposalivation and mucositis / Doutorado / Patologia / Doutora em Estomatopatologia

Le cancer est reconnu comme l'un des principaux enjeux de santé actuels. Même si de grands progrès ont été réalisés dans ce domaine, les effets systémiques des chimiothérapies et le caractère invasif des procédures actuelles de potentialisation (agents physiques) sont autant d'éléments limitants. Les ultrasons se démarquent néanmoins par leur faible morbidité. Appliqués de façon extracorporelle, ils peuvent pénétrer en profondeur dans les tissus et y induire effets thermiques et mécaniques, incluant entre autres la cavitation. La cavitation peut se définir comme la formation et l'oscillation de bulles dans le milieu de propagation. Il a été montré de potentiels bénéfices de ce mécanisme dans la potentialisation d'agents thérapeutiques. Bien que la génération de cavitation puisse être aidée par l'ajout d'agents de nucléation extérieurs, le travail présenté ici s'en affranchit afin de rendre la procédure plus versatile. Des simulations ont montré qu'un dispositif ultrasonore basé sur deux faisceaux confocaux permettait des conditions favorables à l'obtention de cavitation dans ces conditions. De plus, études in vivo ont montré l'innocuité du phénomène en regard de la stabilité de la doxorubicine, des effets histologiques sur tissus sains ainsi que sur l'éventuelle diffusion métastatique. L'efficacité du traitement combiné n'a en revanche pas pu être démontrée. Pour investiguer la combinaison de chimiothérapie avec de la cavitation stable, une stratégie de régulation est mise en place. Bien que la synergie ait pu être démontrée in vitro, l'étude préclinique ne permet pas de conclure sur l'effet in vivo. Dans l'hypothèse d'un défaut de localisation du nuage de cavitation, une méthode de localisation spatiale est mise en place et validée / Cancer is recognized as one of the major health issues of this beginning century. Even if great achievements have been performed, chemotherapies induce systemic toxicity and combinable physical agents are invasive. Ultrasound has shown a great potential as an external physical agent. Applied extracorporeally, it can penetrate in depth in tissue and induce various biological effects, mechanical of thermal. Notably, cavitation, which is the formation and oscillatory motion of bubbles in a media, has effects providing the possibility to enhance the delivery of chemotherapeutic agents. This effect can be induced in biological tissues by using external nucleation agents such as ultrasound contrast agents. However, to avoid diffusion issues, this work focuses on cavitation without external nucleation agents. For this purpose, a particular setup based on two confocal transducers was designed. Simulations showed its advantages for cavitation applications. A developed preclinical device demonstrated the safety of using unseeded inertial cavitation for the potentiation of doxorubicin (DOX) regarding the drug stability, the effect on healthy tissues and the metastatic spreading. Unfortunately, no effect of combining inertial cavitation with DOX in could have been demonstrated in vivo. To investigate stable cavitation phenomenon, a control process was developed. It permitted to evidence in vitro the synergistic interaction between DOX and stable cavitation. Again, preclinical studies were not able to prove this synergy in vivo. To assess the correct tissue exposures to stable cavitation, a localization method was developed and validated

M. Tech. / AIM: To determine the efficacy of Astragalus membranaceous tincture at maintaining the circulating white blood cell count (WBC) and absolute neutrophil count (ANC) of breast cancer patients receiving chemotherapy. METHODS: This is an open-label study with an active control group. Both the study and control group consisted of fifteen participants. The participants in the study group each received ten millilitres of Astragalus membranaceous 1:2 tincture daily for the duration of their course of chemotherapy. RESULTS: The overall decrease in the WBC and ANC in the control was 4.9 and 3.13 parts per billion per litre, respectively. The study group showed an overall decrease of 2.7 and 1.9 parts per billion per litre, respectively. The average overall reduction in chemotherapy dose was 4.79 percent in the study group and 20.21 percent in the control. In all of the analyses p > 0.05. The small sample size, poor patient compliance and skewed distribution of the variables hindered the reliability of the results. CONCLUSION: The positive effects observed in the study group cannot be extrapolated to the entire population, however further research is strongly motivated.

Neuropathic pain is a common and dose-limiting adverse effect of several cancer chemotherapeutic agents including paclitaxel. Current treatments for chemotherapy-induced peripheral neuropathy (CIPN) are largely ineffective and the pain can persist long after the cessation of the chemotherapy regimen. Whilst the specific underlying mechanisms are not fully understood, oxidative stress and mitochondrial damage are thought to be involved in the development of CIPN. Antioxidants which protect mitochondria may inhibit oxidative stress and protect mitochondrial function more effectively than antioxidants which do not specifically act within mitochondria, and may attenuate CIPN. The overall aim of the study was therefore to determine the effects of mitochondrial-targeted antioxidants on CIPN. This was addressed in two main parts. Firstly, in vitro studies aimed to determine the effects of paclitaxel alone and in combination with mitochondrial-targeted antioxidants melatonin and MitoVitE, and a non-targeted antioxidant, Trolox, on oxidative stress and mitochondrial function in cells. In vivo studies aimed to determine the effects of melatonin, MitoVitE and Trolox in a preclinical rat model of paclitaxel neuropathic pain. In vitro studies used a dorsal root ganglion (DRG) cell line (50B11). Cells were cultured with a range of concentrations of paclitaxel, with or without the addition of melatonin, MitoVitE or Trolox. Several measures of oxidative stress including free radical production, and glutathione levels, and measures of mitochondrial function, including mitochondrial metabolic rate, membrane potential, mitochondrial pore opening and ATP production were made. In vivo studies used a rat model of paclitaxel-CIPN, and assessed the effects of melatonin, MitoVitE and Trolox on behavioural measures of pain. In vitro studies showed that paclitaxel induced oxidative stress and caused mitochondrial damage in the DRG cell line. Compared to paclitaxel alone, cells co-treated with melatonin and MitoVitE had reduced oxidative stress and mitochondrial damage. Co-treatment of cells with paclitaxel and Trolox did not differ from conditions with paclitaxel only. In vivo studies demonstrated that melatonin and MitoVitE attenuated paclitaxel-induced mechanical hypersensitivity, whilst Trolox did not affect behavioural measures of CIPN. These studies suggest that mitochondrial-targeted antioxidants may be useful as a potential treatment strategy for CIPN.

Until now, emerging viral diseases have been posing ongoing threats to the global public health. Among the notorious viruses, the HIV that causes the AIDS has been spreading continuously since it was first identified in 1981 and is the most quickly spreading disease of the century. Although considerable advance has been made by drug discovery groups, the therapeutic management is still challenged by the rapid mutations of the virus to yield resistant strains, so as the emergence of side effects. Therefore, the development of novel potent anti-HIV agents is urgently sought. Owing to the chemical diversity, we believe that natural products may serve as potential "lead" compounds for discovery of anti-HIV drugs.;In order to search for novel naturally occurring compounds with potent inhibitory effects against HIV, we began with isolation of natural products from two medicinal plants of Justicia by means of silica gel column chromatography, and preparative HPLC, namely, J. gendarussa that displayed potent anti-HIV activity in our initial screening, and J. procumbens, and their chemical structures and determinated by spectroscopic and chemical methods such as IR, UV, HRESIMS, 1H NMR and 13C NMR spectrometry (including DEPT, 1H-1H COSY, and HMBC techniques). Upon the complete identification of compounds, we focused on the synthesis of one potential lead compound isolated from J. gendarussa, patentiflorin A (3). Nevertheless, we evaluated all the isolated natural compounds and synthetic 3 via bioactivity screening for anti-HIV activity.;In the phytochemical investigation of J. gendarussa, a rare, shade-loving, quick-growing, evergreen scented shrub collected in Vietnam, the bioassay-directed fractionation of the methanol extract of the roots and stems of the plant led to the isolation two new arylnaphthalide lignan glycosides, named justiprocumins A and B (1--2), together with a known one, patentiflorin A (3). On the other hand, the phytochemical investigation of the methanol extract of the aerial parts of J. procumbens resulted in the isolation of four novel arylnaphthalide lignans, procumbenosides G (4), H (5), I (6) and J (7), along with 23 known compounds, namely, tuberculatin (8), procumbenoside B (9), procumbenoside E (10), ciliatoside B (11), ciliatoside A (12), 5-methoxy-4, 42-di-O-methylsecolariciresinol (13), secoisolariciresinol dimethyl ether (14), 2, 3-bis(3, 4-dimethoxybenzyl)-4-hydroxybutyl acetate (15), secoisolariciresinol (16), hemiariensin (17), ariensin (18), secoisolariciresinol dimethyl ether diacetate (19), hinokinin (20), justicidin E (21), justicidin D (22), justicidin C (23), cilinaphthalide A (24), 5'-methoxy-4'-O-methyllariciresinol (25), 3, 5, 7, 32, 42, 52-hexamethoxyflavone (26), 3, 5, 7, 8, 32, 42-heptamethoxyflavone (27), 3, 5, 7, 8, 32, 42, 52-heptamethoxyflavone (28), methyl ferulate (29) and loliolide (30). In addition, the compound 3 was totally synthesized with a yield of 68.3%;In the anti-HIV evaluation for all the isolated compounds using the defective HIV-based pseudotyped assay, patentiflorin A (3) was found to have anti-HIV activity with an IC50 value of 26.9 nM, while justicin E (21) showed 65.4 % inhibitory effect against HIV replication at 2.5 μg/mL. In the evaluation for the broadness of the spectrum of anti-HIV activity using a standardized human PBMC assay, 2 gave IC50 values of 14-21, and 3 gave IC50 values 24-37 nM in inhibiting the particle production of all the four HIV-1 isolates [BAL and SF162 (both are M-tropic), LAV0.04 (T-tropic), and 89.6 (dual tropic)], while the synthetic 3 showed quite similar activity as that of natural 3. In the test of cytotoxicity, natural 3 exhibited no apparent cytotoxicity at 19.0 mM in A549 and Hela cells, and the synthetic 3 displayed much lower cytotoxicity (CC50: 75.5 mM) than that of the natural 3 (CC50: 18.4 mM) in PBMC cells. That means 2 and 3 have great potentials as anti-HIV lead compounds for further drug development.;In conclusion, natural compounds isolated from medicinal plants serves as one of the most important sources of potentially anti-HIV compounds, which can be employed as "lead" compounds to develop novel therapeutic drugs against HIV.

Class of 2011 Abstract / OBJECTIVES: To determine the solubility and stability of hydrocortisone in a ‘magic mouthwash; suspension. METHODS: A literature review was conducted to establish the most common ingredients in a ‘magic mouthwash’ suspension It was decided that the test suspension would consist of 75% commercially available diphenhydramine solution, 12.5% nystatin suspension (100,000 units/ml) , and 12.5% lidocaine solution (2% lidocaine). Powdered hydrocortisone was then added to the test suspensions at different concentrations and stored at 27C, 38C, and 48C. Aliquots were taken from each of the test samples at the time of compounding and at 4, 7, 13, 19, and 26 days to be analyzed by HPLC for degradation of hydrocortisone and percent hydrocortisone in suspension. RESULTS: At 27C, 98.5% of hydrocortisone was recovered after 26 days, versus 33.7% at 38C, and 7% at 48C. The solubility of hydrocortisone in the suspension was higher at higher temperatures, with 82% in solution at 48C, 70% at 38C, and 38% at 27C. CONCLUSION: The amount of hydrocortisone recovered deteriorated over time and at higher temperatures, and solubility of hydrocortisone in the suspension was greater at higher temperatures.

Please read the abstract in the section 00front of this document / Thesis (PhD (Chemistry))--University of Pretoria, 2006. / Chemistry / unrestricted