O Brasil é um dos maiores produtores mundiais de mel, no qual sua produção é baseada principalmente na criação da espécie exótica Apis mellifera. A produção de mel da Apis mellifera é cerca de 10 vezes maior que das espécies de abelhas sem ferrão, contudo, o mel de abelhas nativas possui maior valor comercial. Embora pouco explorado, o mel de abelhas sem ferrão desperta interesse em indústrias de cosméticos e medicinas naturais. A sua produção se apresenta como uma ferramenta com grande potencial para agregar valor econômico aos ecossistemas brasileiros, em especial os florestais, de forma sustentável e com menor potencial de influências de contaminantes traços. A qualidade química do mel é um importante requisito comercial, principalmente o destinado à exportação. Como exemplo, a União Européia em 2006 decidiu suspender a importação do mel produzido no Brasil sob alegação de que o país não possuía equivalência ao bloco quanto as diretrizes para o controle de resíduos e qualidade do produto. Diante do potencial de produção comercial sustentável do mel de abelhas nativas brasileiras e a falta de conhecimento sobre possíveis resíduos encontrados em sua composição, em especial os elementos traços, como objetivo principal deste trabalho pretendeu-se caracterizar a composição de elementos químicos do mel de abelhas sem ferrão, comparar com o de Apis mellifera e verificar as possíveis variações causadas pelo ambiente. Este estudo investigou a composição química dos méis de abelhas sem ferrão de cinco estados brasileiros: Bahia, Minas Gerais, Rio Grande do Norte, Santa Catarina e São Paulo; compreendendo um total de 70 colméias de diferentes espécies: Melipona quadrifasciata, Melipona scutelaris, Melipona mandacaia, Melipona capixaba, Melipona rufiventris, Melipona compressipes, Melipona bicolor, Nannotrigona testaceicornis, Tetragona clavipes, Tetragonisca angustula e Scaptotrigona sp.. Pólen, a principal fonte de minerais para a colméia, e as próprias abelhas foram também coletadas para estudos de composição e correlação com os méis. A análise por ativação neutrônica instrumental permitiu a determinação de Br, Ca, Co, Cs, Fe, La, Na, Rb, Sc e Zn nos méis, Br, Ca, Co, Cs, Fe, K, La, Na, Rb, Sc, Se e Zn nas amostras de pólen e As, Br, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Se e Zn em abelhas. Méis das abelhas da subtribo trigonina apresentaram maiores concentrações dos elementos alcalinos. Alta razão K/Na foram observadas nas amostras de mel e pólen. Pólen se apresentou como uma grande fonte de P e Se. Análises quimiométricas indicaram os méis e abelhas como bons indicadores de atividades antrópicas. Arsênio apareceu nas abelhas coletadas em áreas de maior atividade antrópica. Como resultado, este estudo tem demonstrado o potencial nutracêutico do mel e pólen meliponícola e o potencial das abelhas nativas como ferramentas de avaliação da qualidade ambiental. A proximidade a atividades antrópicas mostrou-se fator decisivo para concentrações mais elevadas de As mas abelhas / Brazil is one of the largest producers of honey, which production is based mainly on the creation of exotic species Apis mellifera. Honey production of Apis mellifera hives is about 10 times higher than the stingless bees species, however, the native bees honey has greater commercial value in Brazil. Although the little exploitation, honey of stingless bees arouses interest in cosmetic industries and natural medicines. The honey production of stingless bees can represents an important tool to add economic value to Brazilian ecosystems, especially forests, sustainably and with less influence of contaminants. The chemical quality of honey is an important business requirement, mainly for exportaition. As an example, in 2006 the EU decided to suspend the importation of honey produced in Brazil alleging that the country had no equivalence to the european guidelines for honey quality control. Given the potential for sustainable commercial production of honey of Brazilian native bees and lack of knowledge about possible residues found in its composition, particularly the trace elements , the main objective of this work was intended to characterize the composition of chemical elements in stingless bees honey, comparing with that of Apis mellifera and assessing the possible variation caused by the environment. This study investigated the chemical composition of stingless bees honeys from five Brazilian states: Bahia, Minas Gerais, Rio Grande do Norte, Santa Catarina and São Paulo, comprising a total of 70 beehives of different species: Melipona quadrifasciata Melipona scutelaris, Melipona mandacaia, Melipona capixaba, Melipona rufiventris, Melipona compressipes, Melipona bicolor, Nannotrigona testaceicornis, Tetragona clavipes, Tetragonisca angustula and Scaptotrigona sp. Pollen, the main source of minerals to the bee hives, and the bees themselves were also collected for studies of chemical composition and correlation with their honeys . The instrumental neutron activation analysis allowed the determination of Br, Ca, Co, Cs, Fe, La, Na, Rb , Sc and Zn in honey, Br, Ca, Co, Cs, Fe, K, La, Na, Rb, Sc, Se and Zn in pollen samples and As, Br, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Se and Zn in bees. Honey of the subtribe trigonina bees had higher concentrations of alkali elements. High ratio K/Na were observed in samples of honey and pollen. Pollen samples presented as an important source of P and Se. Chemometric analysis indicates the stingless bee honeys as good indicators of anthropogenic activities. Arsenic appeared in bees collected in areas of high human activity. As a result, this study has demonstrated the potential of honey and pollen of stingless bees as nutraceutical application and native bees as tools for assessment of environmental quality. The proximity to anthropic activies showed to be a decisive factor for higher concentrations of As in the bees

O Brasil é um dos maiores produtores mundiais de mel, no qual sua produção é baseada principalmente na criação da espécie exótica Apis mellifera. A produção de mel da Apis mellifera é cerca de 10 vezes maior que das espécies de abelhas sem ferrão, contudo, o mel de abelhas nativas possui maior valor comercial. Embora pouco explorado, o mel de abelhas sem ferrão desperta interesse em indústrias de cosméticos e medicinas naturais. A sua produção se apresenta como uma ferramenta com grande potencial para agregar valor econômico aos ecossistemas brasileiros, em especial os florestais, de forma sustentável e com menor potencial de influências de contaminantes traços. A qualidade química do mel é um importante requisito comercial, principalmente o destinado à exportação. Como exemplo, a União Européia em 2006 decidiu suspender a importação do mel produzido no Brasil sob alegação de que o país não possuía equivalência ao bloco quanto as diretrizes para o controle de resíduos e qualidade do produto. Diante do potencial de produção comercial sustentável do mel de abelhas nativas brasileiras e a falta de conhecimento sobre possíveis resíduos encontrados em sua composição, em especial os elementos traços, como objetivo principal deste trabalho pretendeu-se caracterizar a composição de elementos químicos do mel de abelhas sem ferrão, comparar com o de Apis mellifera e verificar as possíveis variações causadas pelo ambiente. Este estudo investigou a composição química dos méis de abelhas sem ferrão de cinco estados brasileiros: Bahia, Minas Gerais, Rio Grande do Norte, Santa Catarina e São Paulo; compreendendo um total de 70 colméias de diferentes espécies: Melipona quadrifasciata, Melipona scutelaris, Melipona mandacaia, Melipona capixaba, Melipona rufiventris, Melipona compressipes, Melipona bicolor, Nannotrigona testaceicornis, Tetragona clavipes, Tetragonisca angustula e Scaptotrigona sp.. Pólen, a principal fonte de minerais para a colméia, e as próprias abelhas foram também coletadas para estudos de composição e correlação com os méis. A análise por ativação neutrônica instrumental permitiu a determinação de Br, Ca, Co, Cs, Fe, La, Na, Rb, Sc e Zn nos méis, Br, Ca, Co, Cs, Fe, K, La, Na, Rb, Sc, Se e Zn nas amostras de pólen e As, Br, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Se e Zn em abelhas. Méis das abelhas da subtribo trigonina apresentaram maiores concentrações dos elementos alcalinos. Alta razão K/Na foram observadas nas amostras de mel e pólen. Pólen se apresentou como uma grande fonte de P e Se. Análises quimiométricas indicaram os méis e abelhas como bons indicadores de atividades antrópicas. Arsênio apareceu nas abelhas coletadas em áreas de maior atividade antrópica. Como resultado, este estudo tem demonstrado o potencial nutracêutico do mel e pólen meliponícola e o potencial das abelhas nativas como ferramentas de avaliação da qualidade ambiental. A proximidade a atividades antrópicas mostrou-se fator decisivo para concentrações mais elevadas de As mas abelhas / Brazil is one of the largest producers of honey, which production is based mainly on the creation of exotic species Apis mellifera. Honey production of Apis mellifera hives is about 10 times higher than the stingless bees species, however, the native bees honey has greater commercial value in Brazil. Although the little exploitation, honey of stingless bees arouses interest in cosmetic industries and natural medicines. The honey production of stingless bees can represents an important tool to add economic value to Brazilian ecosystems, especially forests, sustainably and with less influence of contaminants. The chemical quality of honey is an important business requirement, mainly for exportaition. As an example, in 2006 the EU decided to suspend the importation of honey produced in Brazil alleging that the country had no equivalence to the european guidelines for honey quality control. Given the potential for sustainable commercial production of honey of Brazilian native bees and lack of knowledge about possible residues found in its composition, particularly the trace elements , the main objective of this work was intended to characterize the composition of chemical elements in stingless bees honey, comparing with that of Apis mellifera and assessing the possible variation caused by the environment. This study investigated the chemical composition of stingless bees honeys from five Brazilian states: Bahia, Minas Gerais, Rio Grande do Norte, Santa Catarina and São Paulo, comprising a total of 70 beehives of different species: Melipona quadrifasciata Melipona scutelaris, Melipona mandacaia, Melipona capixaba, Melipona rufiventris, Melipona compressipes, Melipona bicolor, Nannotrigona testaceicornis, Tetragona clavipes, Tetragonisca angustula and Scaptotrigona sp. Pollen, the main source of minerals to the bee hives, and the bees themselves were also collected for studies of chemical composition and correlation with their honeys . The instrumental neutron activation analysis allowed the determination of Br, Ca, Co, Cs, Fe, La, Na, Rb , Sc and Zn in honey, Br, Ca, Co, Cs, Fe, K, La, Na, Rb, Sc, Se and Zn in pollen samples and As, Br, Co, Cr, Cs, Fe, K, La, Na, Rb, Sb, Sc, Se and Zn in bees. Honey of the subtribe trigonina bees had higher concentrations of alkali elements. High ratio K/Na were observed in samples of honey and pollen. Pollen samples presented as an important source of P and Se. Chemometric analysis indicates the stingless bee honeys as good indicators of anthropogenic activities. Arsenic appeared in bees collected in areas of high human activity. As a result, this study has demonstrated the potential of honey and pollen of stingless bees as nutraceutical application and native bees as tools for assessment of environmental quality. The proximity to anthropic activies showed to be a decisive factor for higher concentrations of As in the bees

Intakes of the highly unsaturated fatty acids (HUFA, ≥20 Carbons, ≥3 double bonds) eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3, DHA) greater than 0.25 g/d are currently recommended for health benefits. Targets for omega-3 blood biomarkers have also been proposed based on associations with protection against coronary heart disease mortality. The relationship between diet intakes and blood biomarkers is not well defined, particularly differences between men and women. North American intakes and blood biomarkers of EPA and DHA are typically below recommendations and targets. To address this disparity, adherence to dietary advice strategies to increase EPA + DHA intake was investigated over one year. Adherence was sustained up to 12 weeks and long-term adherence was well characterized by the % of DHA in erythrocytes. For women, n-3 HUFA blood biomarkers increased following nutraceutical or combined strategy dietary advice but not seafood or functional food advice. To assist in the assessment of EPA + DHA intakes, food sources of EPA and DHA in Canada were incorporated into a semi-quantitative, nutrient-specific food frequency questionnaire (FFQ) and validated. The FFQ is an adequate tool for estimating habitual EPA and DHA intake and ranking Canadian adults by their intakes. The blood biomarker response to recommended intakes of 0.25, 0.5 and 1 g/d EPA + DHA was also characterized in adult men and women. Blood n-3 HUFA biomarkers increased in a dose-dependent manner and aligned with blood targets associated with primary cardiac arrest risk reduction. Sex differences in the DHA:EPA ratio in blood observed with low intakes at baseline disappeared following 0.25 g/d EPA + DHA. These findings are applicable towards informing achievable dietary guidelines for EPA + DHA intake and improving measurement of EPA + DHA intake in relation to blood n-3 HUFA biomarkers.

There is heightened interest to diversify the range of crystal forms exhibited by active pharmaceutical ingredients (APIs) in the pharmaceutical industry. The crystal form can be regarded as the Achilles' heel in the development of an API as it directly impacts the physicochemical properties, performance and safety of the API. This is of critical importance since the crystal form is the preferred method of oral drug delivery by industry and regulatory bodies. The ability to rationally design materials is a lucrative avenue towards the synthesis of functional molecular solids with customized physicochemical properties such as solubility, bioavailability and stability. Pharmaceutical cocrystals have emerged as a new paradigm in pharmaceutical solid form development because they afford the discovery of novel, diverse crystal forms of APIs, generate new intellectual property and modify physicochemical properties of the API. In addition, pharmaceutical cocrystals are amenable to design from first principles of crystal engineering. This dissertation focuses on the crystal engineering of multi-component crystal forms, in particular pharmaceutical cocrystals and crystalline hydrates. It addresses: (i) the factors involved in the selection of cocrystal formers (ii) design strategies for APIs that exhibit complexity, (iii) the role of water molecules in the design of multi-component crystal forms and (iv) the relationship between the crystal structure and thermal stability of crystalline hydrates. In general, cocrystal former libraries have been limited to pharmaceutically acceptable substances. It was investigated to expand this library to include substances with an acceptable toxicity profile such as nutraceuticals. In other words, can nutraceuticals serve as general purpose cocrystals formers? The model compounds, gallic acid and ferulic acid, were selected since they possess the functional moieties carboxylic acids and phenols, that are known to form persistent supramolecular synthons with complementary functional groups such as basic nitrogen and amides. The result yielded pairs of cocrystals and revealed the hierarchical nature of hydrogen bonding between complementary functional groups. In general, pharmaceutical cocrystals have been designed by determining the empirical guidelines regarding the hierarchy of supramolecular synthons. However, this approach may be inadequate when considering molecules that are complex in nature, such as those having a multiplicity of functional groups and/or numerous degrees of conformational flexibility. A crystal engineering study was done to design multi-component crystal forms of the atypical anti-psychotic drug olanzapine. The approach involved a comprehensive analysis and data mining of existing crystal structures of olanzapine, grouped into categories according to the crystal packing exhibited. The approach yielded isostructural, quaternary multi-component crystal forms of olanzapine. The crystal forms consist of olanzapine, the cocrystal former, a water molecule and a solvate. The role of water molecules in crystal engineering was addressed by investigating the crystal structures of several cocrystals hydrates and their related thermal stability. The cocrystal hydrates were grouped into four categories based upon the thermal stability they exhibit and it was concluded that no structure/stability correlations exist in any of the other categories of hydrate. A Cambridge Structural Database (CSD) analysis was conducted to examine the supramolecular heterosynthons that water molecules exhibit with two of the most relevant functional groups in the context of active pharmaceutical ingredients, carboxylic acids, and alcohols. The analysis suggested that there is a great diversity in the supramolecular heterosynthons exhibited by water molecules when they form hydrogen bonds with carboxylic acids or alcohols. This finding was emphasized by the discovery of two polymorphs of gallic acid monohydrate to it the first tetramorphic hydrate for which fractional coordinates have been determined. Analysis of the crystal structures of gallic acid monohydrate polymorphs revealed that forms I and III exhibit the same supramolecular synthons but different crystal packing and forms II and IV exhibit different supramolecular synthons. Therefore, the promiscuity of water molecules in terms of their supramolecular synthons and their unpredictable thermal stability makes them a special challenge in the context of crystal engineering.

Hypercholesterolemia, a condition of high cholesterol levels in the circulation, poses a major risk for developing cardiovascular disease, such as atherosclerosis. A common method of reducing plasma cholesterol levels relies on the administration of drugs that limit cholesterol synthesis or uptake, many of which have undesirable side effects. Thus, some patients are turning to an alternative treatment, namely natural health products. Natural health products are often equally or even more effective at treating illness than synthetic drugs and may produce fewer side effects. The goal of this study was to identify a natural health product that regulates hepatic cholesterol synthesis by inhibiting HMG-CoA reductase, the enzyme which catalyzes the rate-limiting step of the cholesterol synthesis pathway. Several natural compounds were screened using the human hepatoma cell line HepG2. One compound, berberine, showed great potential as a regulator of cholesterol synthesis and so became the subject of this investigation. Berberine inhibited HMG-CoA reductase activity and decreased cellular accumulation of cholesterol. Berberine was shown to regulate HMG-CoA reductase through activation of metabolic regulator AMP-activated protein kinase, which modifies HMG-CoA reductase post-translationally and thereby decreases its activity. In conclusion, this study demonstrates that the natural health product berberine decreases cholesterol synthesis by activating a cellular signalling pathway to bring about post-translational modification of HMG-CoA reductase, and in doing so, inhibits this enzyme. This novel mechanism supports berberine’s potential for a cholesterol-lowering therapy and its role in reducing the risk for cardiovascular disease.

Hypercholesterolemia, a condition of high cholesterol levels in the circulation, poses a major risk for developing cardiovascular disease, such as atherosclerosis. A common method of reducing plasma cholesterol levels relies on the administration of drugs that limit cholesterol synthesis or uptake, many of which have undesirable side effects. Thus, some patients are turning to an alternative treatment, namely natural health products. Natural health products are often equally or even more effective at treating illness than synthetic drugs and may produce fewer side effects. The goal of this study was to identify a natural health product that regulates hepatic cholesterol synthesis by inhibiting HMG-CoA reductase, the enzyme which catalyzes the rate-limiting step of the cholesterol synthesis pathway. Several natural compounds were screened using the human hepatoma cell line HepG2. One compound, berberine, showed great potential as a regulator of cholesterol synthesis and so became the subject of this investigation. Berberine inhibited HMG-CoA reductase activity and decreased cellular accumulation of cholesterol. Berberine was shown to regulate HMG-CoA reductase through activation of metabolic regulator AMP-activated protein kinase, which modifies HMG-CoA reductase post-translationally and thereby decreases its activity. In conclusion, this study demonstrates that the natural health product berberine decreases cholesterol synthesis by activating a cellular signalling pathway to bring about post-translational modification of HMG-CoA reductase, and in doing so, inhibits this enzyme. This novel mechanism supports berberine’s potential for a cholesterol-lowering therapy and its role in reducing the risk for cardiovascular disease.

Intakes of the highly unsaturated fatty acids (HUFA, ≥20 Carbons, ≥3 double bonds) eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3, DHA) greater than 0.25 g/d are currently recommended for health benefits. Targets for omega-3 blood biomarkers have also been proposed based on associations with protection against coronary heart disease mortality. The relationship between diet intakes and blood biomarkers is not well defined, particularly differences between men and women. North American intakes and blood biomarkers of EPA and DHA are typically below recommendations and targets. To address this disparity, adherence to dietary advice strategies to increase EPA + DHA intake was investigated over one year. Adherence was sustained up to 12 weeks and long-term adherence was well characterized by the % of DHA in erythrocytes. For women, n-3 HUFA blood biomarkers increased following nutraceutical or combined strategy dietary advice but not seafood or functional food advice. To assist in the assessment of EPA + DHA intakes, food sources of EPA and DHA in Canada were incorporated into a semi-quantitative, nutrient-specific food frequency questionnaire (FFQ) and validated. The FFQ is an adequate tool for estimating habitual EPA and DHA intake and ranking Canadian adults by their intakes. The blood biomarker response to recommended intakes of 0.25, 0.5 and 1 g/d EPA + DHA was also characterized in adult men and women. Blood n-3 HUFA biomarkers increased in a dose-dependent manner and aligned with blood targets associated with primary cardiac arrest risk reduction. Sex differences in the DHA:EPA ratio in blood observed with low intakes at baseline disappeared following 0.25 g/d EPA + DHA. These findings are applicable towards informing achievable dietary guidelines for EPA + DHA intake and improving measurement of EPA + DHA intake in relation to blood n-3 HUFA biomarkers.

O interesse no desenvolvimento de filmes biodegradáveis tem aumentado ao longo dos anos, devido às preocupações ambientais com o descarte de materiais não renováveis de embalagens para alimentos. O destino final dos resíduos de indústrias é apresentado como um problema bastante representativo, devido ao fato de que os mesmos, muitas vezes não podem ser reaproveitados pela própria indústria, e exigem custos altos para serem descartados. Neste trabalho, verificou-se a capacidade de desenvolver filmes biodegradáveis, pela técnica de casting, a partir de resíduos da fabricação de cápsulas nutracêuticas de óleo de cártamo, óleo de coco e óleo de coco e cártamo (compostos por gelatina, glicerol e água), bem como o efeito da adição em diferentes proporções (20:4, 30:4, 40:4 e 50:4) de resíduos de cápsulas de óleo de cártamo em soluções filmogênicas de 4% de amido de milho, através de análises físico-químicas, mecânicas, estruturais, de barreira, térmicas e morfológicas. Os filmes elaborados a partir dos resíduos de cápsulas nutracêuticas, apresentaram baixa permeabilidade ao vapor d’água, solubilidade em água intermediária, baixa resistência à tração e módulo de Young e alta elongação na ruptura. Estes resultados demonstram que os filmes possuem aptidão para serem aplicados em alimentos mais secos, e possuem boas características mecânicas que podem favorecer sua aplicação como embalagem para alimentos. A adição de maiores quantidades de resíduo (gelatina e glicerol) na solução filmogênica de amido de milho interferiu nas características, diminuindo a resistência à tração e módulo de Young, e aumentando a elongação na ruptura, permeabilidade ao vapor d’água e solubilidade em água. Estes resultados demonstram que a adição dos resíduos aumentou a elasticidade e flexibilidade dos filmes, possibilitando a aplicação em diferentes embalagens para alimentos, de acordo com suas características. Todos os filmes apresentaram uma boa estabilidade térmica e propriedades morfológicas adequadas, visto que, foram obtidos filmes sem rachaduras e bolhas. Em relação à cor, todos os filmes apresentaram coloração mais amarelada, devido às características do resíduo, e também apresentaram alta transparência. Além disso, os filmes demonstraram excelentes propriedades de proteção contra a radiação UV, indicando que estes filmes podem proteger os alimentos embalados pelos mesmos. Diante do exposto, pode-se observar que é viável a utilização de resíduos da fabricação de cápsulas nutracêuticas para utilização no desenvolvimento de filmes biodegradáveis, sendo que estes resíduos podem ser utilizados separadamente ou em combinação com outros ingredientes. / The interest in developing biodegradable films has increased over the years due to the environmental concerns about the disposal of non-renewable materials for food packaging. The final destination of industrial wastes is presented as a problem fairly represented because seldom can these wastes be reused in industry and requires high costs to be discarded. In this work, the ability to develop biodegradable films was observed, by the casting technique, from manufacture wastes of nutraceutical capsules of safflower oil, coconut oil and coconut and safflower oil (composed of gelatin, glycerol and water), and the effect of the addition of different proportions (20:4, 30:4, 40:4 and 50:4), of safflower oil nutraceutical capsules waste in filmogenic solution of 4% corn starch by physico-chemical, mechanical, structural, barrier, thermal and morphological analyses. The films made from nutraceutical capsule wastes showed low water vapor permeability, intermediate water solubility, low tensile strength and Young’s modulus and high elongation at break. These results demonstrate that the films have the potential to be applied in dry foods and have good mechanical characteristics that can favor its application as packaging for food. The addition of large amounts of waste (gelatin and glycerol) in the filmogenic solution of corn starch changed the characteristics, decreasing the tensile strength and Young’s modulus and increasing elongation at break, water vapor permeability and water solubility. These results demonstrate that the addition of waste increased the flexibility and elasticity of the films, allowing its use in different food packaging, according to their characteristics. All films showed good thermal stability and adequate morphological properties where obtained films were without cracks or bubbles. All films were yellowish in color due to the characteristics of waste and also showed high transparency. Moreover, the films had excellent absorption of UV radiation, indicating that these films may have the ability to protect foods that will be packaged hereafter. This study demonstrates the possibility to utilize nutraceutical capsules waste for the development of biodegradable films, and these wastes can be used separately or in combination with other ingredients.

Submitted by Maria Suzana Diniz (msuzanad@hotmail.com) on 2015-10-26T13:14:18Z No. of bitstreams: 1 arquivototal.pdf: 1564125 bytes, checksum: a78fa0ea3146f9e196d44276fc232beb (MD5) / Made available in DSpace on 2015-10-26T13:14:18Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1564125 bytes, checksum: a78fa0ea3146f9e196d44276fc232beb (MD5) Previous issue date: 2015-10-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Anxiety disorders are the most prevalent and economically costly in the context of mental disorders, yet they are among the most commonly underdiagnosed and undertreated. Anxiety in its "natural" way, is considered as a normal emotional reaction in people's lives, serving as protective action, while in his pathological presentation, is characterized by a feeling of persistent concern that hinders the ability of the individual relax . This study aimed to investigate the effects of a single dose and multiple doses (500 mg) of the encapsulated dry extract of the whole plant Passiflora incarnata L. on anxiety in humans. The study is characterized as clinical trial, randomized, double-blind, placebo-controlled. The subjects were randomly assigned to one of the following groups: Placebo or Experimental, n = 30, single dose and placebo or experimental, n = 15, multiple doses. The experimental human anxiety was induced by simulated public speaking test in the following phases: Basal (B), stressful (A), speech 1 (S1), speech 2 (S2) and Final (F); evaluated by through physiological measurements (systolic and diastolic blood pressure, heart rate, Electrical skin conductance and extremities temperature and psychological (State-trait anxiety inventory). In the design of single administration, the physiological and psychological parameters were compared between the placebo and experimental groups by test t (Student) or nonparametric corresponding (Mann-Whitney U). Between phases of each group for these same parameters we used the repeated measures ANOVA of a factor, with post hoc Bonferroni or nonparametric corresponding (Friedman ANOVA) with post hoc Dunn's. We adopted the significance level of 5% (P <0.05). During the single administration in relation to physiological parameters HR was increased in stressful phase (78 ± 3.0 bpm) in the experimental group compared to the placebo group (68 ± 3.0 bpm) (p <0.05), however decreased throughout the speech (92 ± 3.0 to 80 ± 2.0 bpm and 86 ± 2.2 to 74 ± 3.0 bpm, S1 and S2, respectively) in the experimental group compared to the placebo group (p <0.05); psychological measures have not changed. In the design of multiple doses, SBP was reduced in mmHg, in the experimental group compared to the placebo group during all phases. Experimental: 106 ± 1.0 (B) 111 ± 1.0 (A) 121 ± 2.0 (S1) 115 ± 3 (S2) 104 ± 2.0 (F) and Placebo: 121 ± 3 0; 127 ± 3.0; 130 ± 3.0; 130 ± 4.5; 117 ± 3.0 (p <0.05). Between phases in the experimental group there was a reduction in TE in phase F (29.7 ± 0.7 ° C) in relation to the phases A (30.5 ± 0.5 ° C) and S1 (30.6 ± 0 6 ° C). In the experimental group there was a reduction of STAI scores during the second part of speech (42 (39-44 points)) and phase F (41 (40-45 points)) in relation to the baseline phase (45 (42-48 points )). It is suggested that supplementation using Passiflora incarnata L. capsules (500 mg) cardiovascular signals decreased in both single dose and multiple doses, associated with the stress of public speaking. / Os transtornos da ansiedade são os mais prevalentes e economicamente dispendiosos no âmbito dos transtornos mentais, contudo estão entre os mais comumente subdiagnosticados e subtratados. A ansiedade, em sua forma ―natural‖, é considerada como uma reação emocional normal na vida das pessoas, servindo como ação protetora, enquanto que, em sua apresentação patológica, é caracterizada por um sentimento de preocupação persistente que dificulta a capacidade do indivíduo relaxar. Este estudo teve como objetivo investigar os efeitos de uma única dose e de doses múltiplas (500 mg) do extrato seco encapsulado da planta inteira da Passiflora incarnata L. sobre a ansiedade em humanos. O estudo se caracteriza como sendo ensaio clínico, randômico, duplo-cego, placebo-controlado. Os sujeitos foram aleatoriamente distribuídos a um dos seguintes grupos: Placebo ou Experimental, n =30, única administração, bem como Placebo ou Experimental, n =15, doses múltiplas. A ansiedade humana experimental foi induzida pelo Teste de Simulação de Falar em Público (TSFP) sob as fases: Basal (B), Estressora (A), Discurso 1(S1), Discurso 2(S2) e Final (F) e avaliada por meio de medidas fisiológicas (Pressão arterial sistólica e diastólica, Frequência Cardíaca, Condutância Elétrica da Pele e Temperatura das Extremidades) e psicológicas (Inventário de ansiedade Traço-Estado). No delineamento de única administração, os parâmetros fisiológicos e psicológicos foram comparados entre os grupos Placebo e Experimental pelo teste t (Student) ou correspondente não-paramétrico (U Mann-Whitney). Entre as fases de cada grupo para esses mesmos parâmetros foi utilizado o ANOVA de medidas repetidas de um fator, com post hoc de Bonferroni ou correspondente não-paramétrico (ANOVA de Friedman), com post hoc de Dunn’s. Adotou-se o nível de significância de 5% (P<0,05). Durante a única administração, em relação aos parâmetros fisiológicos a FC foi aumentada na fase Estressora (78±3,0 bpm) do grupo experimental em relação ao grupo placebo (68±3,0 bpm) (p<0,05), entretanto apresentou redução durante todo o discurso (92±3,0 para 80±2,0 bpm e 86±2,2 para 74±3,0 bpm, S1 e S2, respectivamente) no grupo experimental em relação ao grupo placebo (p<0,05); as medidas psicológicas não sofreram alterações. No delineamento de múltiplas doses, a PAS foi reduzida, em mmHg, no grupo experimental em relação ao grupo placebo durante todas as fases. Experimental: 106±1,0 (B), 111±1,0 (A), 121±2,0 (S1), 115±3 (S2), 104±2,0 (F) e Placebo: 121±3,0; 127±3,0; 130±3,0; 130±4,5; 117±3,0 (p<0,05). Entre as fases, no grupo experimental houve uma redução da TE na fase F (29,7±0,7°C) em relação às fases A (30,5±0,5°C) e S1 (30,6±0,6°C). No grupo experimental houve uma redução dos escores do IDATE durante a segunda parte do discurso (42 (39-44 pontos)) e na fase F (41(40-45 pontos)) em relação à fase Basal (45(42-48 pontos)). Sugere-se que a suplementação utilizando cápsulas da Passiflora incarnata L. (500 mg) diminuiu os sinais cardiovasculares, tanto em dose única como em doses múltiplas, associados ao estresse de falar em público.

Submitted by Maike Costa (maiksebas@gmail.com) on 2017-02-13T13:24:03Z No. of bitstreams: 1 arquivototal.pdf: 1564135 bytes, checksum: eaa31bb20fdb563ee216aff4e321eb45 (MD5) / Made available in DSpace on 2017-02-13T13:24:04Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1564135 bytes, checksum: eaa31bb20fdb563ee216aff4e321eb45 (MD5) Previous issue date: 2015-06-19 / Anxiety disorders are the most prevalent and economically costly in the context of mental disorders, yet they are among the most commonly underdiagnosed and undertreated. Anxiety in its "natural" way, is considered as a normal emotional reaction in people's lives, serving as protective action, while in his pathological presentation, is characterized by a feeling of persistent concern that hinders the ability of the individual relax . This study aimed to investigate the effects of a single dose and multiple doses (500 mg) of the encapsulated dry extract of the whole plant Passiflora incarnata L. on anxiety in humans. The study is characterized as clinical trial, randomized, double-blind, placebo-controlled. The subjects were randomly assigned to one of the following groups: Placebo or Experimental, n = 30, single dose and placebo or experimental, n = 15, multiple doses. The experimental human anxiety was induced by simulated public speaking test in the following phases: Basal (B), stressful (A), speech 1 (S1), speech 2 (S2) and Final (F); evaluated by through physiological measurements (systolic and diastolic blood pressure, heart rate, Electrical skin conductance and extremities temperature and psychological (State-trait anxiety inventory). In the design of single administration, the physiological and psychological parameters were compared between the placebo and experimental groups by test t (Student) or nonparametric corresponding (Mann-Whitney U). Between phases of each group for these same parameters we used the repeated measures ANOVA of a factor, with post hoc Bonferroni or nonparametric corresponding (Friedman ANOVA) with post hoc Dunn's. We adopted the significance level of 5% (P <0.05). During the single administration in relation to physiological parameters HR was increased in stressful phase (78 ± 3.0 bpm) in the experimental group compared to the placebo group (68 ± 3.0 bpm) (p <0.05), however decreased throughout the speech (92 ± 3.0 to 80 ± 2.0 bpm and 86 ± 2.2 to 74 ± 3.0 bpm, S1 and S2, respectively) in the experimental group compared to the placebo group (p <0.05); 10 psychological measures have not changed. In the design of multiple doses, SBP was reduced in mmHg, in the experimental group compared to the placebo group during all phases. Experimental: 106 ± 1.0 (B) 111 ± 1.0 (A) 121 ± 2.0 (S1) 115 ± 3 (S2) 104 ± 2.0 (F) and Placebo: 121 ± 3 0; 127 ± 3.0; 130 ± 3.0; 130 ± 4.5; 117 ± 3.0 (p <0.05). Between phases in the experimental group there was a reduction in TE in phase F (29.7 ± 0.7 ° C) in relation to the phases A (30.5 ± 0.5 ° C) and S1 (30.6 ± 0 6 ° C). In the experimental group there was a reduction of STAI scores during the second part of speech (42 (39-44 points)) and phase F (41 (40-45 points)) in relation to the baseline phase (45 (42-48 points )). It is suggested that supplementation using Passiflora incarnata L. capsules (500 mg) cardiovascular signals decreased in both single dose and multiple doses, associated with the stress of public speaking. / Os transtornos da ansiedade são os mais prevalentes e economicamente dispendiosos no âmbito dos transtornos mentais, contudo estão entre os mais comumente subdiagnosticados e subtratados. A ansiedade, em sua forma ―natural‖, é considerada como uma reação emocional normal na vida das pessoas, servindo como ação protetora, enquanto que, em sua apresentação patológica, é caracterizada por um sentimento de preocupação persistente que dificulta a capacidade do indivíduo relaxar. Este estudo teve como objetivo investigar os efeitos de uma única dose e de doses múltiplas (500 mg) do extrato seco encapsulado da planta inteira da Passiflora incarnata L. sobre a ansiedade em humanos. O estudo se caracteriza como sendo ensaio clínico, randômico, duplo-cego, placebo-controlado. Os sujeitos foram aleatoriamente distribuídos a um dos seguintes grupos: Placebo ou Experimental, n =30, única administração, bem como Placebo ou Experimental, n =15, doses múltiplas. A ansiedade humana experimental foi induzida pelo Teste de Simulação de Falar em Público (TSFP) sob as fases: Basal (B), Estressora (A), Discurso 1(S1), Discurso 2(S2) e Final (F) e avaliada por meio de medidas fisiológicas (Pressão arterial sistólica e diastólica, Frequência Cardíaca, Condutância Elétrica da Pele e Temperatura das Extremidades) e psicológicas (Inventário de ansiedade Traço-Estado). No delineamento de única administração, os parâmetros fisiológicos e psicológicos foram comparados entre os grupos Placebo e Experimental pelo teste t (Student) ou correspondente não-paramétrico (U Mann-Whitney). Entre as fases de cada grupo para esses mesmos parâmetros foi utilizado o ANOVA de medidas repetidas de um fator, com post hoc de Bonferroni ou correspondente não-paramétrico (ANOVA de Friedman), com post hoc de Dunn’s. Adotou-se o nível de significância de 5% (P<0,05). Durante a única administração, em relação aos parâmetros fisiológicos a FC foi aumentada na fase Estressora (78±3,0 bpm) do grupo experimental em relação ao grupo placebo (68±3,0 bpm) (p<0,05), entretanto apresentou redução durante todo 8 o discurso (92±3,0 para 80±2,0 bpm e 86±2,2 para 74±3,0 bpm, S1 e S2, respectivamente) no grupo experimental em relação ao grupo placebo (p<0,05); as medidas psicológicas não sofreram alterações. No delineamento de múltiplas doses, a PAS foi reduzida, em mmHg, no grupo experimental em relação ao grupo placebo durante todas as fases. Experimental: 106±1,0 (B), 111±1,0 (A), 121±2,0 (S1), 115±3 (S2), 104±2,0 (F) e Placebo: 121±3,0; 127±3,0; 130±3,0; 130±4,5; 117±3,0 (p<0,05). Entre as fases, no grupo experimental houve uma redução da TE na fase F (29,7±0,7°C) em relação às fases A (30,5±0,5°C) e S1 (30,6±0,6°C). No grupo experimental houve uma redução dos escores do IDATE durante a segunda parte do discurso (42 (39-44 pontos)) e na fase F (41(40-45 pontos)) em relação à fase Basal (45(42-48 pontos)). Sugere-se que a suplementação utilizando cápsulas da Passiflora incarnata L. (500 mg) diminuiu os sinais cardiovasculares, tanto em dose única como em doses múltiplas, associados ao estresse de falar em público.