The present study covers the causes of victory and defeat in the light of chapter eight of the Holy Qur'an. It has been prompted by the current situation facing Muslims in many parts of the world, which is characterized by despair, reversals and loss, This study is thus reflexive in nature. In order to obtain a satisfactory response to this predicament, the relevant text in addition to several of its commentaries were scrutinized. The latter search remained unsatisfactory since their focus of inquiry was merely exegetical and failed to reveal any didactic element, which is crucial for obtaining guidance. This work has successfully managed to deduce this aspect from the text which amplifies the importance of extensive sacrifice for gaining glory. / Religious Studies and Arabic / M.A. (Islamic studies)

BK channels are well studied targets of acute ethanol action. They play a prominent role in neuronal excitability and have been shown to play a significant role in behavioral ethanol tolerance in invertebrates. The focus of my work centers on the effects of alcohol on the BK channel and comprises studies that examine how subcellular location affects acute ethanol sensitivity and how duration of acute alcohol exposure impacts the development of rapid tolerance. My results also provide potential mechanisms which underlie acute sensitivity and rapid tolerance. I first explore BK channel sensitivity to ethanol in the three compartments (dendrite, cell body, and nerve terminal) of magnocellular neurons in the rat hypothalamic-neurohypophysial (HNS) system. The HNS system provides a particularly powerful preparation in which to study the distribution and regional properties of ion channel proteins because the cell bodies are physically separated from the nerve terminals. Using electrophysiological and immunohistochemical techniques I characterize the BK channel in each of the three primary compartments and find that dendritic BK channels, similar to somatic channels, but in contrast to nerve terminal channels, are insensitive to alcohol. Furthermore, the gating kinetics, calcium sensitivity, and iberiotoxin sensitivity of channels in the dendrite are similar to somatic channels but sharply contrast terminal channels. The biophysical and pharmacological properties of somatodendritic vs. nerve terminal channels are consistent with the characteristics of exogenously expressed αβ1 vs. αβ4 channels, respectively. Therefore, one possible explanation for my findings is a selective distribution of β1 subunits to the somatodendritic compartment and β4 subunits to the terminal compartment. This hypothesis is supported immunohistochemically by the appearance of distinct punctate β1 or β4 channel clusters in the membrane of somatodendritic or nerve terminal compartments, respectively. In conclusion, I found that alcohol sensitivity of BK channels within the HNS system is dependent on subcellular location and postulate that β-subunits modulate ethanol sensitivity of HNS BK channels. In the second and primary focus of my thesis I explore tolerance development in the striatum, a brain region heavily implicated in addiction. Numerous studies have demonstrated that duration of drug exposure influences tolerance development and drug dependence. To further elucidate the mechanisms underlying behavioral tolerance I examined if BK channel tolerance was dependent on duration of alcohol exposure using patch clamp techniques in cultured striatal neurons from P8 rats. I found that persistence of rapid tolerance is indeed a function of exposure time and find it lasts surprisingly long. For example, after a 6 hr exposure to 20 mM ethanol, acute sensitivity was still suppressed at 24 hrs withdrawal. However, after a 1 or 3 hr exposure period, sensitivity had returned after only 4 hrs. I also found that during withdrawal from a 6 hr but not a 3 hr exposure the biophysical properties of BK channels change and that this change is correlated with an increase in mRNA levels of the alcohol insensitive STREX splice variant. Furthermore, BK channel properties during withdrawal from a 6 hr exposure to alcohol closely parallel the properties of STREX channels exogenously expressed in HEK293 cells. In conclusion I have established that BK channels develop rapid tolerance in striatal neurons, that rapid tolerance is dependent upon exposure protocol, and is surprisingly persistent. These findings present another mechanism underlying BK channel tolerance and possibly behavioral tolerance. Since these phenomena are dependent on duration of drug exposure my results may find relevance in explaining how drinking patterns impact the development of alcohol dependence in humans.

The body of work presented here is a compendium of the multiple steps required for an investigator initiated trial of an existing medication (Valproic Acid- VPA) for a new indication (Retinitis Pigmentosa – RP). The chapters are listed in logical and chronological order of the process. In order to access patient records an expedited Institutional Review Board (IRB) application for retrospective chart review was submitted (Chapter 1). These records enabled the statistical analysis which not only laid the framework for the trial design, but also became the basis for two manuscripts (Chapter 2). Protocol development informed by the preliminary human studies (Chapter 3) was an instrumental part of the Investigational New Drug (IND) application (Chapter 3.5). This protocol along with the extensive case report forms that detail the intended data to be collected are included in the IND application. Because the Phase II clinical trial proposed attempting to identify the specific RP mutations of the subjects utilizing a National Eye Institute (NEI) study that enabled free genotyping services, two IRB applications were submitted (Chapter 3.6). The first was for approval of the NEI genotyping protocol, the second involved the VPA intervention. Two very different sources of funding for this trial were attempted (Chapter 4) – the NIH via the Challenge Grant mechanism and a private eye disease foundation (Foundation Fighting Blindness). In Chapter 5 I detail the alternate study designs that were considered and developed for this trial (and ultimately abandoned). Finally, in Chapter 6, I formally detail my suggestions to aid in the development of a comprehensive investigator initiated core facility at UMMMC. The goal of this project was two-fold. The first was to learn the entire process of trial and protocol design both from a Umass Institutional perspective as well as from the perspective of the FDA. The second goal was the very real prospect of helping patients with a blinding disease. This work was successful on both counts. IRB approval was received for all the submitted applications. The complexity and uniqueness of many aspects of these submissions culminated in a comprehensive learning experience. The process of working with the Umass Research Pharmacy as well as developing the industry contacts and know-how to develop a workable and financially feasible placebo were both particularly important learning experiences. FDA approval of the IND submission was also received, and the process of pre-communication and delving into the considerable and ever-changing rules and regulations resulted in an extensive and valuable knowledge base. While the practicality of funding has limited the ability of this trial to move forward at this point, given the extensive framework laid by this body of work, we are actively pursuing other opportunities. The third outcome of this work, while not as intentional, was the considerable process of determining the specific competencies and infrastructure that exist at UMMMC to enable investigator initiated drug intervention studies. While this institution is clearly moving rapidly in the direction of translational research, the many needs of these studies are often only clearly understood when the process is specifically undertaken. In completing the approval of this Phase II clinical trial, I was not only able to better understand and define the existing capabilities of UMMMC for this kind of research, I was able to add to that infrastructure when the existing knowledge or skill set was not available. In this manner, I was able to inform and guide many of the support personnel who guided me and have become a part of the strategic direction of UMMMC towards clinical translational research.

Made available in DSpace on 2014-06-11T19:28:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-21Bitstream added on 2014-06-13T18:32:33Z : No. of bitstreams: 1 pereira_slg_me_arafcf.pdf: 629055 bytes, checksum: 4c92bb2be28496297c6aee8cad01e39a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / Na sua quase totalidade, as formas farmacêuticas líquidas apresentam agentes conservantes em suas fórmulas visando a proteção contra o desenvolvimento microbiano. Entretanto, pesquisas indicam que conservantes são substâncias tóxicas, pois dependendo da concentração administrada podem provocar reações adversas ou intoxicações. A inclusão desses agentes na fórmula de um medicamento deve seguir rigorosamente os parâmetros de eficácia e segurança, garantindo assim proteção antimicrobiana máxima sem provocar danos aos usuários. Por essas razões, este estudo teve como objetivo analisar os possíveis impactos na qualidade das dispersões moleculares de uso oral comercializadas no Brasil em decorrência das alterações na concentração de excipientes no pós-registro de medicamentos, em especial a modificação “moderada” de conservantes (5 – 10%). Foram analisadas as fórmulas de todas as dispersões moleculares de uso oral, de referência, registradas na ANVISA em março de 2009, e os respectivos sistemas conservantes foram identificados. A elaboração de uma matriz “medicamentos versus sistemas conservantes” propiciou a definição dos principais sistemas conservantes empregados industrialmente e sua inserção em oito fórmulas de bancada. Os testes de efetividade antimicrobiana realizados nestas fórmulas indicaram que metade delas não atendeu aos critérios de aceitação propostos na monografia oficial (USP 32), além de outras duas que apresentaram frágil proteção antimicrobiana, pois nelas o crescimento microbiano esteve muito próximo do limite máximo permitido. Em se tratando dos riscos que tais alterações possam provocar na conservação de um medicamento, estes valores são preocupantes, especialmente em escala industrial e, no mínimo, as fórmulas não aprovadas deveriam ser retestadas / Almost all liquid dosage forms have preservative agents in their formulas in order to protect against microbial growth. However, researches indicate that preservatives are toxic, because depending on the administered concentration they can cause adverse reactions or intoxications. The inclusion of these agents in the formulation of a product should strictly follow the parameters of efficacy and safety, thus ensuring maximum antimicrobial protection without causing harm to users. For these reasons, this study aimed to examine the possible impacts on the quality of molecular dispersions for oral administration commercialized in Brazil as a result of changes in the concentration of excipients in the post-registration of medicines, particularly the “moderate” modification of preservative agents (5 – 10%). All formulas of molecular dispersions for oral use, as reference drugs, recorded at ANVISA in March 2009 were analyzed and the preservative agents were identified. The development of a matrix drugs versus preservative systems led to the definition of major preservative systems used industrially and their inclusions in eight formulas studied. The antimicrobial effectiveness tests conducted on these formulas indicated that half of them did not meet the acceptance criteria proposed in the official monograph (USP 32), beyond two other formulas that presented weak antimicrobial protection, because microbial growth in them was very close to the maximum allowed. Considering the risks that such changes may result in the conservation of a drug these negative values are worrisome, especially on an industrial scale and, at least, the formulas not approved should be retested

Made available in DSpace on 2016-12-08T16:44:38Z (GMT). No. of bitstreams: 1 PGPV08MA075.pdf: 2514308 bytes, checksum: 5a0e94495b6093ef64517b7c72d7304f (MD5) Previous issue date: 2008-12-16 / The Santa Catarina s plateau has a vast variety of different plants that still little known by its inhabitants. The domestication and intensive cultivation of certain native plants species has stimulated the adoption of conventional techniques like the use of organic pesticides that because of its intensive application causes environmental contamination and human intoxication. The objectives of this research were to study the occurrence of Hypericum species at the region of Santa Catarina s plateau and the viability of homeopathic preparations to grow Hypericum species. The studies of Hypericum species occurrence were conducted by 26 field expeditions and consisted of sampling plants in 9 different places. The survey showed the occurrence of four Hypericum species identified as: Hypericum connatum, Hypericum carinatum, Hypericum brasiliense and Hypericum ternum. The effect evaluation of homeopathic preparations in the control of pests and diseases of Hypericum perforatum and Hypericum inodorum Androsaemum was carried out by experiments conducted under greenhouse and field conditions. To test the effects of the treatments on plants of H. inodorum the field experiment was carried on in completely randomized blocks with five replicates and seven treatments (no spray, Cuprum metallicum 30CH, Staphysagria 30CH, Carbo vegetabilis 30CH, Arnica Montana 30CH, rust nosode 30DH and Bordeaux mixture (0,3%). The experimental unit consisted of a plot with 10 H. inodorum Androsaemum plants. The greenhouse experiment was conducted in a completely randomized design with five replicates and eight treatments (Staphysagria 30CH, Cuprum metallicum 30CH, Hypericum connatum macerated 30CH, Calcarea sulphurica 30CH, Bordeaux mixture 30CH, water 30CH, rust nosode 30DH and pure water). Each pot with one H. inodorum Androsaemum plant was considered an experimental unit. At the greenhouse conditions Cuprum metallicum, Staphysagria and Hypericum connatum macerated reduced the rust (Melampsora hypericorum) severity and the treatment with Bordeaux mixture 30CH reduced the population of whitefly nymphs. In the field experiment the treatments rust nosode and Carbo vegetabilis reduced the rust incidence, and the Bordeaux mixture (0,3%) reduces the rust severity. The experiments with the medicinal specie Hypericum perforatum under the field conditions was carried on in randomized blocks with 5 replicates and 9 treatments (pure water, Corralium, Staphysagria, Nitricum acidum, Arnica montana, Lycopodium clavatum, Hypericum connatum and Hypericum perforatum macerate, all of them at 8CH). Each experimental unit consisted of a plot with 8 plants. In the greenhouse the experiemt was carryed on in a completely randomized design with 5 replicates and 11 treatments (Arnica montana, Carbo vegetabilis, Phosporus, Hypericum perforatum, Magnesia carbonica, water, Nitricum acidum, Staphysagria, Lycopodium clavatum e macerado de Hypericum perforatum, all of them at 8CH and pure water). Each experimental plot was composed by one H. perforatum plant planted in vase. At greenhouse conditions plants of H. perforatum treated with Carbo vegetabilis 12CH showed the lowest trips population, Hypericum perforatum macerated 12CH showed to increase the biomass production and Staphysagria 12CH increased the production of hipericin glands. In the field experiment there were no significant differences among the treatments. However it was observed that H. perforatum is a promising green soil cover species / O Planalto Serrano Catarinense possui uma rica flora ainda pouco conhecida por sua população. A domesticação e o cultivo intensivo de certas espécies nativas tem incentivado contraditoriamente a utilizaçao de técnicas convencionais como o uso de agroquímicos que por serem utilizados de modo indiscriminado causam problemas de intoxicação humana e contaminação ambiental. Neste trabalho foi realizado um estudo de ocorrência de espécies do genero Hypericum no Planalto Serrano Catarinense, e o efeito de preparados homeopáticos no controle de pragas e doenças em plantas de Hypericum perforatum e Hypericum inodorum Androsaemum . O levantamento foi realizado por 26 expedições técnicas com coletas e identificação de plantas em 9 municípios da região. Verificou-se a presença de 4 diferentes espécies - Hypericum connatum, Hypericum carinatum, Hypericum brasiliense e Hypericum ternum. Os experimentos envolvendo a espécie Hypericum inodorum Androsaemum , foram realizados em casa-de-vegetação e a campo. A campo utilizou-se delineamento de blocos ao acaso com 5 repetições e 7 tratamentos (testemunha sem intervenção, Cuprum metallicum, Staphysagria, Carbo vegetabilis e Arnica montana na 30CH, nosódio da ferrugem 30DH e Calda bordalesa a 0,3%). A unidade experimental era constituída de uma parcela com 10 plantas de H. inodorum Androsaemum . O experimento em casa-de-vegetação foi conduzido em delineamento inteiramente casualizado com 5 repetições e 8 tratamentos (Staphysagria, Cuprum metallicum, macerado de Hypericum connatum, Calcarea sulphurica, calda bordalesa e água na 30CH, nosódio da ferrugem na 30DH e testemunha água pura). A unidade experimental era de um vaso com uma planta de hipérico. Verificou-se que os preparados homeopáticos Cuprum metallicum, Staphysagria e macerado de Hypericum connatum diminuiram a severidade da ferrugem (Melampsora hypericorum), o tratamento calda bordalesa na 30CH diminui a população de ninfas de mosca-branca em plantas de H. inodorum Androsaemum , em casa-de-vegetação. A campo os tratamentos nosódio da ferrugem e Carbo vegetabilis diminuiram a incidência da ferrugem, e a calda bordalesa a 0,3% diminui a severidade de M. hypericorum. O experimento realizado a campo com a espécie medicinal Hypericum perforatum era de blocos ao acaso com 5 repetições e 9 tratamentos (água pura, Corralium, Staphysagria, Nitricum acidum, Arnica montana, Lycopodium clavatum, macerado de Hypericum connatum e de Hypericum perforatum, todos na potência 8CH). Cada unidade experimental era composta por uma parcela com 8 plantas. No experimento em casa-de-vegetação utilizou-se delineamento inteiramente casualizado com 5 repetições e 11 tratamentos (Arnica montana, Carbo vegetabilis, Phosporus, Hypericum perforatum, Magnesia carbonica, água, Nitricum acidum, Staphysagria, Lycopodium clavatum e macerado de Hypericum perforatum, todos na potência 12CH e água pura). A parcela experimental era composta por um vaso com uma planta de H. perforatum. Verificouse que as plantas tratadas com Carbo vegetabilis apresentaram uma população menor de trips, o tratamento macerado de Hypericum perforatum aumentou a produçao de biomassa e Staphysagria aumentou a produção de glândulas de hipericina. Durante o experimento realizado a campo verificou-se que nao houve differença entre os tratamentos na produçao de biomassa ou na produçao de glandulas de hiperecina. Entretanto, observou-se que a espécie Hypericum perforatum é promissora quanto a sua utilização como cobertura verde do solo

Neste trabalho, é proposto o desenvolvimento de instrumentação e procedimentos analíticos automáticos empregando fotometria em fase sólida para determinação de zinco em produtos farmacêuticos e água. Para implementação do procedimento analítico, todo o sistema foi acoplado a um computador através de uma interface eletrônica. Um software escrito em linguagem QuickBASIC 4.5 permite que o computador efetue o controle da adição das soluções da amostra e do eluente e faça aquisição de dados. O sistema de detecção é constituído de uma cela de fluxo contendo, um LED e um fotodiodo. A geometria da cela de fluxo possibilitava variar o comprimento do caminho óptico. O procedimento para determinação do zinco foi baseado na retenção do analito na fase sólida (TAN-C18), previamente inserida na cela de fluxo, seguido de uma etapa de eluição. Com os parâmetros analíticos otimizados obteve-se resposta linear na faixa de 0,05 a 0,85 mg L-1 (R=0,995), limite detecção de 9,3 \'mü\'g L-1, coeficiente de variação de 1,4% (n=10) e frequência de amostragem de 36 det h-1. O módulo de análise foi aplicado em amostras de produtos farmacêuticos e a exatidão dos resultados foi averiguada comparando com os resultados obtidos por espectrometria de emissão óptica com plasma acoplado indutivamente ICP-OES. Aplicando-se tratamento estatístico apropriado, observou-se que não havia diferença significativa ao nível de confiança de 95 %. Estes resultados comprovam a viabilidade do emprego de fotômetro de LED em fotometria em fase sólida / In this work, it is propose the instrumentation and automatic analytic procedures development using solid phase spectrophotometry for determination of zinc in pharmaceutical preparations and water. For analytic procedure implementation, the whole system was coupled to a computer through an electronic interface. A written software in language QuickBASIC 4.5 allows the computer makes the sample solutions addition control and of eluent and do data acquisition. The detection system is constituted of a flow cell contend, a LED and a photodiode. The flow cell geometry enabled vary the length of the optical path. The procedure for zinc determination was going based in analyte retention in the solid phase (TAN-C18), previously inserted in the flow cell, followed by an elution stage. With the optimized analytic parameters it btained lineal answer in the band of 0,05 to 0,85 mg L-1 (R=0,995), limit detection of 9,3 \'mü\'g L-1, variation coefficient of 1,4% (n=10) and sampling throughput of 36 det h-1. The analysis module was going applied in pharmaceutical preparations samples and the exactness of the results was going ascertained comparing with the results obtained for inductively coupled plasma optic emission spectrometry of with ICP- its. Applying appropriated statistical treatment, it observed that there wasn\'t significant difference to the reliable level of 95 %. These results prove photometer job viability of LED in photometry in solid phase

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-03-10T14:07:49Z No. of bitstreams: 1 rafaelpimentelpinheiro.pdf: 5642312 bytes, checksum: c0018e11016a4083a03c156be84fe1ad (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-03-13T19:16:19Z (GMT) No. of bitstreams: 1 rafaelpimentelpinheiro.pdf: 5642312 bytes, checksum: c0018e11016a4083a03c156be84fe1ad (MD5) / Made available in DSpace on 2017-03-13T19:16:19Z (GMT). No. of bitstreams: 1 rafaelpimentelpinheiro.pdf: 5642312 bytes, checksum: c0018e11016a4083a03c156be84fe1ad (MD5) Previous issue date: 2015-07-30 / Palicourea rigida Kunth, pertencente à família Rubiaceae, tem sido utilizada na medicina popular para o tratamento de inflamações e infecções do trato urinário, do aparelho reprodutor feminino e para doenças da pele. Do ponto de vista químico, triterpenos, iridoides, flavonoides e alcaloides têm sido identificados na espécie. O objetivo do presente trabalho foi realizar uma caracterização química e avaliar as atividades anti-inflamatória tópica e cicatrizante de P. rigida. Folhas secas e pulverizadas foram extraídas em etanol P.A. por maceração estática seguida de rota-evaporação para obtenção do extrato etanólico (EEPR). EEPR foi submetido à partição líquido/líquido, adquirindo as frações hexânica, diclorometânica, em acetato de etila e butanólica. EEPR foi analisado por CLUE-UV-EM, enquanto a fração hexânica por CG-EM. A fração em acetato de etila foi fracionada por cromatografia em coluna de Sephadex LH-20 e a substância isolada foi elucidada por RMN 1H e 13C e espectrometria de massas. A partir de EEPR, foi desenvolvido uma formulação de creme à base Lanette® (cEEPR). A atividade antiinflamatória tópica de EEPR foi avaliada pelos modelos de edema de orelha em camundongos Swiss empregando óleo de cróton, ácido araquidônico, capsaicina e fenol. A atividade cicatrizante de EEPR e cEEPR foi investigada em ratos Wistar através do modelo de lesões por excisão cutânea. Análises histopatológicas e as atividades das enzimas mieloperoxidase (MPO) e N-acetil-β-d-glucoronidase (NAG) foram também determinadas. Loganina e quercetina 3-6- O-acetil-β-glicosídeo foram identificadas no EEPR por CLUE-UV-EM, enquanto ácido palmítico, fitol, ácido linoleico, esqualeno, gama tocoferol, vitamina E, campesterol, estigmasterol e gama sitosterol foram caracterizadas na fração hexânica por CG-EM. A partir da fração em acetato de etila, o flavonoide quercetina 3-O-β-D-glicosídeo foi isolado e sua estrutura elucidada. EEPR apresentou atividade anti-inflamatória tópica nos diferentes modelos através da redução da massa e espessura do edema, assim como pela diminuição do processo inflamatório observado pelas análises histopatológicas e inibição das atividades de MPO e NAG. EEPR e cEEPR demonstraram atividade cicatrizante pela diminuição da área da lesão e aumento do grau de contração, bem como pela estimulação do processo de cicatrização e redução das atividades de MPO e NAG. Os resultados indicam que P. rigida é rica em substâncias bioativas que podem ser responsáveis pelas atividades anti-inflamatória e cicatrizante. / Palicourea rigida Kunth, belonging to the Rubiaceae family, has been used in folk medicine for the treatment of inflammation and infections of the urinary tract, female reproductive tract and skin conditions. From the chemical point of view, triterpenes, iridoids, flavonoids and alkaloids have been identified in species. The aim of this study was to perform a chemical characterization and evaluate the topical anti-inflammatory and wound healing activities of P. rigida. Dried and powdered leaves were extracted in ethanol PA by static maceration followed by rota-evaporation for obtaining ethanol extract (EEPR). EEPR was subjected to partition liquid/liquid to obtain the hexane, dichloromethane, ethyl acetate and butanol fractions. EEPR was analyzed by UPLC-UV-MS, while the hexane fraction by GC-MS. The ethyl acetate fraction was separated by column chromatography with Sephadex LH-20 and the isolated compound was elucidated by 1H and 13C NMR and mass spectrometry. From the EEPR, a dermatological formulation was developed using the cream-based Lanette® (cEEPR). The topical anti-inflammatory activity of EEPR was evaluated by the ear edema models in mice Swiss using croton oil, arachidonic acid, capsaicin and phenol. The wound healing activity of EEPR and cEEPR was investigated in Wistar rats through the model of skin lesions. Histopathological analysis and activity of the enzyme myeloperoxidase (MPO) and N-acetyl- β-D-glucuronidase (NAG) were also determined. Loganin and quercetin 3-6-O-acetyl-β- glucoside were identified in EEPR by UPLC-UV-MS, while palmitic acid, phytol, linoleic acid, squalene, gamma tocopherol, vitamin E, campesterol, stigmasterol and sitosterol were characterized in the hexane fraction by GC-MS. From the fraction in ethyl acetate, the flavonoid quercetin 3-O-β-D-glucoside was isolated and its structure elucidated. EEPR showed topical anti-inflammatory activity in different models by reducing the the mass and thickness of the edema, as well as through the decrease in the inflammatory process observed by histopathological analysis and inhibition of the MPO and NAG activities. EEPR and cEEPR demonstrated wound healing activity by decrease the area of lesion and increase the contraction degree, as well as stimulate the healing process and reduce the MPO and NAG activities. The results indicate that P. rigida is rich in bioactive substances which may be responsible for the anti-inflammatory and wound healing activities.

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-12T12:13:46Z No. of bitstreams: 1 milenemachadominateli.pdf: 5060284 bytes, checksum: 446ee2d6824758d7358e4ba2cb4f755a (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-12T15:46:30Z (GMT) No. of bitstreams: 1 milenemachadominateli.pdf: 5060284 bytes, checksum: 446ee2d6824758d7358e4ba2cb4f755a (MD5) / Made available in DSpace on 2017-05-12T15:46:30Z (GMT). No. of bitstreams: 1 milenemachadominateli.pdf: 5060284 bytes, checksum: 446ee2d6824758d7358e4ba2cb4f755a (MD5) Previous issue date: 2015-07-13 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Vernonia polyanthes Less, família Asteraceae, popularmente conhecida no Brasil como assa-peixe, tem sido utilizada no tratamento de afecções do aparelho respiratório, problemas renais e gastrointestinais, feridas, fraturas e torções, contusões e luxações e, ainda, indicada como tônica, emenagoga, diurética e cicatrizante. O objetivo deste trabalho foi avaliar o potencial toxicológico e as atividades anti-inflamatória tópica e cicatrizante e desenvolver um creme dermatológico a partir do extrato etanólico das folhas de V. polyanthes Less. Folhas secas e pulverizadas foram submetidas à extração em etanol PA por maceração estática seguida de rotaevaporação para obtenção do extrato etanólico de V. polyanthes (EEVP). Parâmetros bioquímicos, hematológicos, morfológicos e histopatológicos foram determinados em ratos Wistar após 15 e 30 dias de tratamento por via oral com 100, 200 e 400 mg/kg de EEVP. O creme dermatológico do extrato etanólico de V. polyanthes (cEEVP) foi desenvolvido nas concentrações 0,10, 0,25 e 0,50% seguido de estudo de estabilidade. A atividade anti-inflamatória tópica de cEEVP foi avaliada pelos métodos de edema de orelha induzido por óleo de cróton, fenol e ácido araquidônico, enquanto EEVP e cEEVP foram usados no ensaio da atividade cicatrizante através de induções de lesões cutâneas. Análises histopatológicas e avaliação da atividade das enzimas mieloperoxidase (MPO) e N-Acetil-β-D-glicorominidase (NAG) complementaram os ensaios farmacológicos. Na avaliação da toxicidade, EEVP não alterou os parâmetros bioquímicos, hematológicos e histopatológicos, mas promoveu modificações nos níveis lipídicos e enzimas hepáticas nos grupos tratados com EEVP. O cEEVP apresentou conformidades adequadas no estudo de estabilidade e juntamente com o EEVP demonstrou efeitos anti-inflamatório tópico e cicatrizante. Os resultados poderão contribuir com a Política Nacional de Plantas Medicinais e Fitoterápicos através da difusão do conhecimento e da comprovação científica das aplicações terapêuticas de V. polyanthes. / Vernonia polyanthes Less, Asteraceae family, popularly known in Brazil as assa-peixe, has been used to treat diseases of the respiratory tract, kidney and gastrointestinal problems, wounds, fractures and sprains, bruises and dislocations, and also indicated as tonic, emmenagogue, diuretic and healing. The aim of this work was to investigate the toxicological potential and topical anti-inflammatory and healing activities and develop a dermatological cream from the ethanol extract of V. polyanthes leaves. Dried and powdered leaves were extracted in ethanol PA by static maceration for obtaining dry ethanol extract (EEVP) using a rotaevaporator. Parameters Biochemical, hematologic, morphological and histopathological were determined in Wistar rats after 15 and 30 days of treatment orally with 100, 200 and 400 mg/kg EEVP. Dermatological cream of EEVP (cEEVP) was developed at the concentrations of 0.10, 0.25 and 0.50% and evaluated through stability study. The topical anti-inflammatory activity of cEEVP was assessed by ear edema induced by croton oil, phenol and arachidonic acid, while the wound healing activity was performed by cutaneous lesions test using EEVP and cEEVP. Histopathological analysis and evaluation of the myeloperoxidase (MPO) and N-acetyl-β-D-glicorominidase (NAG) activities were also determined. In the evaluation of toxicity, EEVP did not modify the biochemical, hematological and histopathological parameters, but promoted alterations in lipid and liver enzymes levels. The cEEVP showed adequate conformities in the stability study and together with the EEVP demonstrated topical anti-inflammatory and wound healing effects. The results may contribute to the National Policy of Medical Plants and Herbal through the dissemination of knowledge and scientific evidence of the therapeutic applications of V. polyanthes.

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Platelet preparations are a source of various autologous growth factors and have numerous applications in tissues engineering. The aim of this work was to development electrospun nanofiber scaffolds with platelet preparations. Scaffolds based on the adhesion of platelets on nanofiber meshes were developed. The scaffolds were able to enhance chondrocyte proliferation in vitro. The main disadvantage of this system is the burst release of growth factors immediately after adhesion. To overcome this, we developed coaxially electrospun scaffolds with incorporated alpha granules. Alpha granules are novel platelet preparations with high amounts of growth factors. This system was able to stimulate chondrocyte proliferation and maintain TGF- 1 concentrations for 7 days. Additionally, a novel drug delivery system with coaxially incorporated liposomes was developed. Liposomes incorporated into nanofibers remain intact and can be used for the delivery of various molecules. The ability to maintain HRP activity was compared to systems based on coaxial electrospinning with liposomes, coaxial electrospinning without liposomes and blend electrospinning. When compared to other systems, coaxial electrospinning with liposomes preserves enzyme activity twice as long. These results clearly indicate the potential of...