26 research outputs found

    Efeitos de combinações entre o ácido anacárdico derivado da casca da castanha do caju (Anacardium occidentale) e o óleo de açaí (Euterpe oleracea Mart.), livres ou nanoestruturados, no tratamento de células de câncer de pele não melanoma, in vitro

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    Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Pós-Graduação em Nanociência e Nanobiotecnologia, 2017.O Câncer de Pele Não Melanoma (CNPM) o tipo de câncer que possui maior incidência no Brasil e no mundo. O ácido anacárdico (AA) é um composto proveniente da casca da castanha do caju (Anacardium occidentale) que vem atraindo grande interesse nos últimos anos devido ás suas propriedades antitumorais, antibióticas, gastroprotetoras e antioxidantes. O açaí (Euterpe oleracea Mart.) também vem atraindo a atenção de pesquisadores, por ser rico em polifenóis com atividades como supressão tumoral, antiproliferativo e pró-apoptótica. Grande parte desses fitoquímicos que possuem atividades terapêuticas são pouco solúveis em soluções aquosas, o que dificulta sua administração e absorção no organismo. Desta forma, a encapsulação desses compostos em nanoestruturas se torna uma alternativa plausível para potencializar seus efeitos biológicos. Diante do exposto, o presente projeto de pesquisa tem como objetivo avaliar os efeitos de combinações entre o ácido anacárdico (AA) derivado da casca da castanha do caju (Anacardium occidentale) e o óleo de açaí (Euterpe oleracea Mart.), livres ou nanoestruturados, no tratamento de câncer de pele não melanoma in vitro. Os testes de estabilidade mostraram que a nanoemulsão à base de óleo de açaí (AçNE) apresentaram gotículas com diâmetro hidrodinâmico de ± 140 nm, com índice de polidespersão de 0,229, potencial de superfície de ± 17,6 mV e pH 7 por 120 dias. Foi possível modificar a superfície das AçNE adicionando polímeros de quitosana (CH), polietileno glicol (PEG) e fosfolipídios catiônicos DOTAP (1,2-Dioleoiloxi-3-(trimetilamónio) propano). Tais formulações não apresentaram efeito citotóxico nas linhagens A431 e HaCaT, independentemente do tipo de superfície. Os tratamentos AçNE associado ao AA provocaram uma significativa redução na viabilidade das células A431, porém não foi observado efeito de sinergismo entre os mesmos. Em contrapartida, quando ambos compostos foram adicionados na forma não-nanoestruturada, observou-se redução de 90% da viabilidade de células A431 em 24 horas. Dados de citometria de fluxo indicam que a combinação dos compostos livres resulta em morte celular por apoptose e bloqueio do ciclo celular. O presente estudo sugere que a combinação de óleo de açaí e AA é uma promissora alternativa terapêutica antitumoral a ser mais explorada em estudos futuros.Non-Melanoma Skin Cancer (CNPM) is the type of cancer that has the highest incidence in Brazil and worldwide. Anacardic acid (AA) is a compound derived from cashew nuts (Anacardium occidentale) that has attracted great interest in recent years due to its antitumor, antibiotic, gastroprotective and antioxidant properties. Açaí (Euterpe oleracea Mart.) has also attracted the attention of researchers, because it is rich in polyphenols which shows great activity as a tumor suppressor, antiproliferative and pro-apoptotic. Most of these phytochemicals that have therapeutic activities are poorly soluble in aqueous solutions, which hinders their administration and absorption in the body. In this way, the encapsulation of these compounds in nanostructures becomes a plausible alternative to enhance their biological effects. Thus, the present research project has the objective of evaluating the effects of anacardic acid (AA) derived from cashew nut shell (Anacardium occidentale) and açaí oil (Euterpe oleracea Mart.), free or nanostructured, in the treatment of non-melanoma skin cancer in vitro. The stability tests showed that the açaí oil-based nanoemulsion (AçNE) showed droplets with a hydrodynamic diameter of ± 140 nm, with a polydispersion index of 0.229, surface potential of ± 17.6 mV and pH 7 for 120 days. It was possible to modify the surface of the AçNE by adding polymers of chitosan (CH), polyethylene glycol (PEG) and cationic phospholipids DOTAP (1,2-Dioleoyloxy-3- (trimethylammonium) propane). Such formulations showed no cytotoxic effect on the A431 and HaCaT cell lines, regardless of surface type. The AçNE treatments associated with AA caused a significant reduction in the viability of A431 cells, but no synergism was observed between them. On the other hand, when both compounds were added in the non-nanostructured form, a 90% reduction in the viability of A431 cells was observed in 24 hours. Flow cytometry data indicate that the combination of the free compounds results in cell death by apoptosis and cell cycle block. The present study suggests that the combination of acai oil and AA is a promising alternative antitumor therapy to be further explored in future studies

    Observed distributions of the susceptibility parameter <i>α</i> for those infected in simulated populations HP1 and HP2.

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    <p>Observed distributions of the susceptibility parameter <i>α</i> for those infected in simulated populations HP1 and HP2.</p

    Percentiles of the population HP2 detected as infected or the percentiles of total population egg excretion, EPG, accounted for by upper percentiles of the distributions of susceptibility, <i>α</i><sub><i>i</i></sub>, number of exposure episodes, <i>n</i><sub><i>i</i></sub>, cumulative water contact, <i>n</i><sub><i>i</i></sub><i>s</i><sub><i>i</i></sub>, and cumulative cercarial exposure, .

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    <p>Percentiles of the population HP2 detected as infected or the percentiles of total population egg excretion, EPG, accounted for by upper percentiles of the distributions of susceptibility, <i>α</i><sub><i>i</i></sub>, number of exposure episodes, <i>n</i><sub><i>i</i></sub>, cumulative water contact, <i>n</i><sub><i>i</i></sub><i>s</i><sub><i>i</i></sub>, and cumulative cercarial exposure, .</p

    Repeated <em>Schistosoma japonicum</em> Infection Following Treatment in Two Cohorts: Evidence for Host Susceptibility to Helminthiasis?

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    <div><p>Background</p><p>In light of multinational efforts to reduce helminthiasis, we evaluated whether there exist high-risk subpopulations for helminth infection. Such individuals are not only at risk of morbidity, but may be important parasite reservoirs and appropriate targets for disease control interventions.</p> <p>Methods/Principal Findings</p><p>We followed two longitudinal cohorts in Sichuan, China to determine whether there exist persistent human reservoirs for the water-borne helminth, <i>Schistosoma japonicum</i>, in areas where treatment is ongoing. Participants were tested for <i>S. japonicum</i> infection at enrollment and two follow-up points. All infections were promptly treated with praziquantel. We estimated the ratio of the observed to expected proportion of the population with two consecutive infections at follow-up. The expected proportion was estimated using a prevalence-based model and, as highly exposed individuals may be most likely to be repeatedly infected, a second model that accounted for exposure using a data adaptive, machine learning algorithm. Using the prevalence-based model, there were 1.5 and 5.8 times more individuals with two consecutive infections than expected in cohorts 1 and 2, respectively (p<0.001 in both cohorts). When we accounted for exposure, the ratio was 1.3 (p = 0.013) and 2.1 (p<0.001) in cohorts 1 and 2, respectively.</p> <p>Conclusions/Significance</p><p>We found clustering of infections within a limited number of hosts that was not fully explained by host exposure. This suggests some hosts may be particularly susceptible to <i>S. japonicum</i> infection, or that uncured infections persist despite treatment. We propose an explanatory model that suggests that as cercarial exposure declines, so too does the size of the vulnerable subpopulation. In low-prevalence settings, interventions targeting individuals with a history of <i>S. japonicum</i> infection may efficiently advance disease control efforts.</p> </div

    The marginal distributions of exposure and host susceptibility, together with contours of their joint distribution.

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    <p>The y-axis shows exposure, <i>E</i>, and the x-axis shows host susceptibility, <i>α</i>. The line <i>w<sub>T</sub> = αE</i> describes the threshold of detectable infections: the minimum worm burden in an individual detectable by currently available assays. The shaded area depicts those combinations of <i>α</i> and <i>E</i> producing infection intensities above this lower limit of detection, w<sub>t</sub>. The fraction of the population susceptible to infection at or above this threshold is that lying to the right of the line <i>α</i> = <i>α</i>*.</p

    Description of the two cohorts at enrollment (<i>T<sub>0</sub></i>).

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    *<p>Cohort 1 is composed of 424 residents from 10 villages in Xichang County, Sichuan, China where schistosomiasis was endemic, monitored from 2000 to 2006.</p>†<p>Cohort 2 is composed of 400 residents from 27 villages in two counties in Sichuan, China where schistosomiasis reemerged following reduction of <i>S. japonicum</i> infection prevalence below 1%, monitored from 2007 to 2010.</p>‡<p>Prevalence and infection intensity estimates include all participants in village-wide infection surveys conducted at cohort enrollment: 1,801 individuals in 10 villages in cohort 1, 1,608 individuals in 27 villages in cohort 2.</p>**<p>Participants were asked about water contact behaviors from the start of the rice planting season. In Xichang County (from which cohort 1 participants were drawn) rice planting begins in April, whereas in the two reemerging counties (from which cohort 2 participants were drawn) rice planting begins in May.</p

    Distribution of incident <i>S. japonicum</i> infections by age in cohorts 1 (top) and 2 (bottom).

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    <p>Incident <i>S. japonicum</i> infections were measured at two follow-up points (2002 and 2006 in cohort 1, 2008 and 2010 in cohort 2). All participants were tested for <i>S. japonicum</i> at enrollment (2000 in cohort 1, 2007 in cohort 2) and all infections were promptly treated with praziquantel.</p

    <i>S. japonicum</i> infection prevalence and intensity at follow-up.

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    *<p>Cohort 1 is composed of people from 10 villages where schistosomiasis is endemic. Participants were tested for <i>S. japonicum</i> infection in 2000 (<i>T<sub>0</sub></i>), 2002 (<i>T<sub>1</sub></i>) and 2006 (<i>T<sub>2</sub></i>).</p>†<p>Cohort 2 is composed of people from 27 villages in two counties where schistosomiasis reemerged following reduction of <i>S. japonicum</i> infection prevalence below 1%. Participants were tested for <i>S. japonicum</i> infection in 2007 (<i>T<sub>0</sub></i>), 2008 (<i>T<sub>1</sub></i>) and 2010 (<i>T<sub>2</sub></i>).</p>‡<p>Infection prevalence and intensity were estimated for the source population, accounting for the stratified sampling used in enrolling cohort participants. Each individual in the cohort was assigned a weight equal to the inverse probability of being sampled.</p

    The observed and predicted proportion of the population with two consecutive <i>S. japonicum</i> infections.

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    *<p>The expected prevalence of two consecutive infections was estimated based on the prevalence of infections at <i>T<sub>1</sub></i> and <i>T<sub>2</sub></i>.</p>†<p>The expected prevalence of two consecutive infections was estimated accounting for <i>S. japonicum</i> exposure. The infection prediction model included water contact minutes by month and activity for all measures for which at least 20% of cohort participants reported exposure, age, sex, baseline village infection prevalence, county and year of infection test. Prediction models were fit separately for each cohort.</p>‡<p>P-values were estimated assuming the number of individuals with two consecutive infections follows a binomial distribution, where is equal to the expected prevalence of two consecutive infections and is equal to the number of individuals in the full population. Thus the p-value is that of a two-sided, one-sample test assuming the probability of double-infections is equal to <i>P<sub>DI</sub></i>.</p

    Associations between Schistosomiasis and the Use of Human Waste as an Agricultural Fertilizer in China

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    <div><p>Background</p><p>Human waste is used as an agricultural fertilizer in China and elsewhere. Because the eggs of many helminth species can survive in environmental media, reuse of untreated or partially treated human waste, commonly called night soil, may promote transmission of human helminthiases.</p><p>Methodology/Principal Findings</p><p>We conducted an open cohort study in 36 villages to evaluate the association between night soil use and schistosomiasis in a region of China where schistosomiasis has reemerged and persisted despite control activities. We tested 2,005 residents for <i>Schistosoma japonicum</i> infection in 2007 and 1,365 residents in 2010 and interviewed heads of household about agricultural practices each study year. We used an intervention attributable ratio framework to estimate the association between night soil use and <i>S. japonicum</i> infection. Night soil use was reported by half of households (56% in 2007 and 46% in 2010). Village night soil use was strongly associated with human <i>S. japonicum</i> infection in 2007. We estimate cessation of night soil use would lead to a 49% reduction in infection prevalence in 2007 (95% CI: 12%, 71%). However, no association between night soil and schistosomiasis was observed in 2010. These inconsistent findings may be due to unmeasured confounding or temporal shifts in the importance of different sources of <i>S. japonicum</i> eggs on the margins of disease elimination.</p><p>Conclusions/Significance</p><p>The use of untreated or partially treated human waste as an agricultural fertilizer may be a barrier to permanent reductions in human helminthiases. This practice warrants further attention by the public health community.</p></div
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