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DESENVOLVIMENTO DE FORMULAÇÕES NANOTECNOLÓGICAS PARA O TRATAMENTO DA CANDIDÍASE VULVOVAGINAL / DEVELOPMENT OF NANO-SCALE FORMULATIONS FOR THE TREATMENT OF VULVOVAGINAL CANDIDIASISSantos, Sara Saurin dos 21 August 2012 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work aimed the preparation of clotrimazole-loaded nanocapsule suspensions for vulvovaginal fungal infections treatment. For the first time, virgin coconut oil and medium chain triglycerides were used as an oil core of polymeric nanocapsules containing clotrimazole. The analytical method for quantification of this drug into nanoparticles was developed and validated. The method proved to be selective, linear, precise, accurate and robust. Using the method of interfacial deposition of preformed polymer, the nanoparticles were successfully prepared at three different concentrations of clotrimazole (1, 2 and 3 mg/mL). The physicochemical parameters measured were pH, particle diameter, polydispersity index, drug content, encapsulation efficiency, zeta potential and stability in storage during 60 days. The encapsulation efficiency was near to 100%, zeta potential was positive due to the cationic polymer employed, the pH was around 5.6 and drug contents were close to the theoretical values. The size distribution was nanometer (140-200 nm) with polydispersity index lower than 0.2. The formulations had adequate physicochemical characteristics and were stable during storage. Photodegradation studies have shown that the nanoencapsulation improved the stability of clotrimazole against UVC radiation compared to free drug solution after 14 hours of experiment. The in vitro drug release using the dialysis bag technique was characterized by a prolonged release. No burst effect was observed. Profilesare based on an anomalous transport and first order kinetics, regardless of the oil used. The in vitro microbiological test of nanocapsules suspensions was performed against Candida albicans and Candida glabrata susceptible and resistant to fluconazole by microdilution method. In combination with clotrimazole into nanoparticles, medium chain triglycerides was reported to have similar MICs of methanolic solution containing the oil and the drug. In addition to the antifungal activity in solution, coconut oil did not lose its activity after incorporation into the nanostructures and, in combination with drug, showed greater inhibition of microbial growth than the nanocapsules of medium chain triglycerides with clotrimazole. Finally nanoparticle suspensions were incorporated into hydrogels containing polymers with mucoadhesive properties, Pemulen® and Pullulan, which presented appropriate drug content, pH and spreadability. The formulations developed in this study represent promising alternatives for treatment of vulvovaginal candidiasis. / Este trabalho objetivou a preparação de suspensões de nanocápsulas contendo clotrimazol para o tratamento de infecções fúngicas vulvovaginais. Pela primeira vez, o óleo de coco virgem e os triglicerídeos de cadeia média foram empregados como núcleo oleoso de nanocápsulas poliméricas contendo clotrimazol. A metodologia analítica para a quantificação do fármaco nas nanopartículas foi desenvolvida e validada. O método mostrou-se seletivo, linear, preciso, exato e robusto. A partir do método de deposição interfacial do polímero pré-formado, as nanopartículas foram preparadas com sucesso em três concentrações diferentes de clotrimazol (1, 2 e 3 mg/mL). Os parâmetros físico-químicos avaliados foram pH, diâmetro de partícula, índice de polidispersão, teor, eficiência de encapsulamento, potencial zeta e estabilidade frente ao armazenamento por 60 dias. A eficiência de encapsulamento foi próxima a 100%, o valor do potencial zeta foi positivo devido ao polímero catiônico empregado, valor de pH em torno de 5,6 e teores de fármaco próximos aos teóricos. A distribuição de tamanho foi nanométrica (140-200 nm), com índice de polidispersão menor que 0,2. As formulações apresentaram características físico-químicas adequadas e foram estáveis durante o armazenamento. Estudos de fotodegradação mostraram que o nanoencapsulamento melhorou a estabilidade do clotrimazol sob radiação UVC, em comparação com a solução do fármaco livre, após 14 horas de experimento. A liberação do fármaco in vitro, a partir da técnica de sacos de diálise, foi caracterizada como uma liberação prolongada sem efeito burst, que foi mediada por transporte anômalo e seguiu cinética de primeira ordem, independente do óleo utilizado. As suspensões foram capazes de diminuir a velocidade de liberação do clotrimazol nas 24 horas de experimento. A partir do método de microdiluição, procedeu-se a avaliação microbiológica in vitro das suspensões de nanocápsulas contra Candida albicans e Candida glabrata sensíveis e resistentes ao fluconazol. Em combinação com o clotrimazol nas nanopartículas, os triglicerídeos de cadeia média apresentaram valores de CIMs semelhantes à solução metanólica contendo o óleo e o fármaco. Além de apresentar atividade antifúngica em solução, o óleo de coco não perdeu sua atividade após a incorporação na nanoestrutura e, em associação com o fármaco, apresentou maior inibição do crescimento microbiano do que as nanocápsulas de triglicerídeos de cadeia média com clotrimazol. Por fim, as suspensões nanoparticuladas foram incorporadas em hidrogéis contendo polímeros com propriedades mucoadesivas, Pemulen® e Pullulan, que apresentaram teor, pH e espalhabilidade adequados. As formulações desenvolvidas neste estudo representam alternativas promissoras para o tratamento da candidíase vulvovaginal.
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Óleo de coco virgem reduz o estresse oxidativo e melhora a sensibilidade do barorreflexo quando associado ao treinamento físico em ratos hipertensos / Virgin Coconut oil reduces oxidative stress and improves baroreflex sensitivity when combined with exercise training in spontaneously hypertensive ratsAlves, Naiane Ferraz Bandeira 10 December 2015 (has links)
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Previous issue date: 2015-12-10 / The hypothesis that oral supplementation with virgin coconut oil (Cocos nucifera L.) and exercise training would improve impaired baroreflex sensitivity (BRS) and reduce oxidative stress in spontaneously hypertensive rats (SHR) was tested. Furthermore, the effects caused by lauric acid (LA) on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats (SHR) were evaluated. In the first stage of the study, SHR and Wistar Kyoto rats (WKY) were used and divided in five groups: WKY + saline (n = 8); SHR + saline (n = 8); SHR + coconut oil (2 mL·day -1, n = 8); SHR + training (n = 8); and SHR + training + coconut oil (n = 8). The swimming protocol under 4% body weight workload lasted 60 minutes. Mean arterial pressure (MAP) was recorded and BRS was tested using phenylephrine (8 μg.kg-1, iv) and sodium nitroprusside (25 μg·kg-1, iv). Oxidative stress was measured using dihydroethidium by microscopy fluorescence in tissue sections from heart and aorta samples. SHR + coconut oil, SHR + training and SHR + training + coconut oil groups presented lower MAP compared to SHR + saline (148 ± 6, 147 ± 7, 134 ± 8 vs. 175 ± 6 mmHg, P < 0.05). Coconut oil combined with exercise training improved BRS in SHR compared with SHR + saline group (-2.47 ± 0.3 vs. -1.39 ± 0.09 ± bpm-1·min-1·mmHg, p <0.05). SHR + saline group showed higher superoxide levels when compared with WKY + saline (774 ± 31 vs. 634 ± 19 arbitrary units (AU), respectively; p <0.05). SHR + training + coconut oil group presented a reduction in oxidative stress compared with SHR + saline in heart (622 ± 16 vs. 774 ± 31 AU, p <0.05). Moreover, coconut oil reduced oxidative stress in SHR compared with SHR + saline in aorta (454 ± 33 vs. 689 ± 29 AU, p <0.05). In the second stage of thestudy, LA reduced blood pressure at 3, 4, 8 and 10 mg/kg doses compared with vehicle (-41±9.4;-41±6;-51.7±8.1;-61±11 vs. -1,3±0.4 mmHg, n = 6). LA (10-8 to 3x10-3M) induced vasorelaxation in isolated cranial mesenteric artery rings in the presence or absence of functional endothelium (Emax=104,1 ± 2,8% e pD2= 4,1 ± 1,4; n=7 vs. Emax= 103,5 3,7 pD2 = 3,3 ± 0,5; n=8, respectively). LA (10-3 M) reduced superoxide levels similar to Tempol, a superoxide anion scavenger, compared to tissue containing only NADPH oxidase in the heart (18.1 ± 0.7; 9.5 ± 0.3 vs. 25.3 ± 0.4 UML / min / ug protein, respectively) and kidney (81.9 ± 2.8, 79 ± 1.3, 99 ± 4.3 vs. UML / min / ug protein, respectively). In conclusion, coconut oil combined with exercise training reduced oxidative stress and improved BRS in SHR. Those effects seem to be, at least in part, to its major component (Lauric acid). / Testamos a hipótese de que a suplementação com óleo de coco virgem (OCV) associada ao treinamento físico é capaz de melhorar a sensibilidade do barorreflexo (SBR) e de reduzir o estresse oxidativo (EO). Além disso, os efeitos promovidos pelo ácido láurico (AL), um dos constituintes majoritários do OCV, nos parâmetros cardiovasculares e EO em ratos espontaneamente hipertensos (SHR) também foram testados. Na primeira etapa do estudo utilizamos animais SHR e Wistar Kyoto (WKY) adultos, divididos em cinco grupos: WKY + salina (n = 8); SHR + salina (n = 8); SHR + óleo de coco (2 mL·dia-1, n = 8); SHR + treinamento (n = 8); e SHR + treinamento + óleo de coco (n = 8). O protocolo de natação teve duração de 60 minutos e sobrecarga de 4% da massa corporal dos animais. A pressão arterial média (PAM) foi registrada e a SBR foi testada usando fenilefrina (8 μg.kg-1, i.v) e nitroprussiato de sódio (25 μg·kg-1, i.v). O EO foi quantificado utilizando dihidroetídio por microscopia de fluorescência no coração e aorta. Os grupos SHR + Óleo de coco, SHR+ treinamento e SHR + treinamento + óleo de coco apresentaram menores níveis de PAM, comparado ao grupo SHR + salina (148 ± 6, 147 ± 7, 134 ± 8 vs. 175 ± 6 mmHg; p <0,05). O OCV associado ao treinamento físico melhorou a SBR em SHR em comparação com o grupo SHR + salina (-2,47 ± 0,3 vs. -1,39 ± 0,09 bpm·min-1·mmHg-1; p<0,05). O grupo SHR + salina apresentou níveis elevados de superóxido, quando comparados com WKY + salina (774 ± 31 vs. 634 ± 19 unidades arbitrárias (u.a), respectivamente; p <0,05). O grupo SHR + treinamento + óleo de coco apresentou redução do EO em comparação com SHR + salina no coração (622 ± 16 vs. 774 ± 31 u.a, p <0,05). Em tecidos de aorta, o óleo de coco reduziu o EO em SHR em comparação com SHR + salina (454 ± 33 vs. 689 ± 29 u.a, p <0,05). Na segunda etapa do trabalho, observamos que o AL promoveu hipotensão a partir das doses de 3, 4, 8 e 10 mg/kg, quando comparado com o veículo (-41 ± 9,4; -41±6; -51,7 ± 8,1; -61 ± 11 vs. -1,3 ± 0,4 mmHg; n=6, respectivamente). O AL (10-8 a 3x10-3 M) induziu vasorrelaxamento em anéis de artéria mesentérica cranial isolada de SHR, na presença ou na ausência do endotélio funcional (Emax = 104,1 ± 2,8% e pD2= 4,1 ± 1,4; n=7 vs. Emax =103,5 3,7 pD2=3,3 ± 0,5; n=8, respectivamente). O AL (10-3 M) reduziu a produção de ânion superóxido no tecido cardíaco e renal respectivamente, quando comparados com tecidos apenas na presença de NADPH oxidase, (18,1 ± 0,7; 9,5 ± 0,3 vs. 25,3 ± 0,4 UML/min/μg proteína, respectivamente) e (81,9 ± 2,8; 79 ± 1,3; vs. 99 ± 4,3 UML/min/μg proteína, respectivamente). Concluímos que a suplementação com OCV associada ao treinamento físico reduziu o EO e melhorou a SBR que estava reduzida durante a hipertensão arterial. Além disso, os efeitos benéficos do OCV alcançados parecem ser oriundos do AL presente no óleo vegetal.
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OPTIMIZING DETECTION AND CONTROL OF CLOSTRIDIUM DIFFICILE AND ITS TOXINSShilling, Michael 06 August 2013 (has links)
No description available.
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Effect of Coconut Oil on Ulcerative Colitis in the Mouse ModelAlok, Pranav Chandra 01 May 2013 (has links)
Ulcerative colitis (UC) is a chronic disease of the colon or large intestine that causes inflammation and ulceration of the inner lining of the colon and rectum. In patients with ulcerative colitis, the body’s immune system overreacts and the body mistakes food, bacteria or other internal materials in the colon for an invading substance. The immune system attacks the material, thus irritating the colon. Limited knowledge of inflammatory conditions coupled with a narrow range of therapeutic options necessitates investigating the role of natural products. This study describes the effect of natural coconut oil on chemically-induced acute and chronic disease in mice. Ulcerative colitis was induced in four groups (5 mice per group) of 10-week-old female C57BL/6 mice by exposing them to 2.5-3% dextran sulfate sodium (DSS) for 5 and 29 days in the acute and chronic models, respectively. Coconut oil treatment was given via food containing 5% coconut oil to three diseased groups in three different regimens: one, preventive group receiving treatment prior to disease induction (14 d in acute; 28 d in chronic); two, simultaneous group receiving treatment simultaneous to disease induction; and three, regular treatment group receiving treatment after the disease induction –until termination of the experiment (14 d in acute; 60 d in chronic). Coconut food was replaced by the regular chow in the disease and water control groups. Clinical symptoms (diarrhea, occult blood, anal bleeding and body weight change) and the size of the isolated colon were recorded for comparison between experimental and control groups. Groups receiving coconut food displayed remissions in clinical markers of the disease. Improvements in clinical symptoms, histopathology, as well as cytokine activities were observed in both models, but the effects were more significant on the basis of standard error in the chronic model.
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