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Atividade toxicol?gica do extrato das folhas de Kalanchoe brasiliensis em camundongos SwissFonseca, Aldilane Gon?alves da 25 September 2014 (has links)
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Previous issue date: 2014-09-25 / As esp?cies do g?nero Kalanchoe (Crassulaceae) s?o bastante utitlizadas em
todo o Brasil, como medicamento para tratar tosse, fur?nculos, gastrite e outras
enfermidades. Nesse cen?rio destaca-se K. brasiliensis, conhecida popularmente
como coirama ou sai?o. Este trabalho tem como proposta a exposi??o por via oral
de camundongos a um extrato hidroalco?lico de folhas de Kalanchoe brasiliensis.
Os animais (total de 100) foram divididos em grupos de 12 (6 machos e 6 f?meas)
para avalia??o aguda; e grupos de 10 para avalia??o subcr?nica.Os grupos teste
foram tratados com doses de 250 mg/Kg, 500 mg/Kg, 1000 mg/Kg e 2000 mg/Kg,
e o grupo controle recebeu solu??o salina 0,9 %. Os animais foram observados
por 14 dias para avalia??o aguda e 30 dias para avalia??o subcr?nica, e nesse
per?odo analisou-se o aparecimento de sinais cl?nicos, altera??es no peso e no
consumo de ?gua e ra??o. Ap?s o per?odo de observa??o, foram realizadas a
an?lise histopatol?gica dos ?rg?os, as concentra??es s?ricas bioqu?micas e
par?metros hematol?gicos para os grupos da avalia??o subcr?nica. N?o foram
observadas diferen?as e altera??o do peso corp?reo entre os grupos, nem de
consumo de ?gua e ra??o, tamb?m n?o houve mortes entre os grupos, nos dois
tipos de ensaios. As an?lises histopatol?gicas demonstraram algumas altera??es
compat?veis com baixa toxicidade aguda hep?tica. Os resultados de glicemia,
triglicer?deos, ALT, ureia e creatinina mostraram diferen?as entre o grupo controle
e os testes nas concentra??es estudadas (p<0,05), por?m estas diferen?as n?o
demonstram mudan?a relevante no quadro cl?nico dos animais. Os resultados
mostraram que o extrato de K. brasiliensis apresenta baixa toxicidade aguda nas
doses utilizadas e n?o apresenta toxicidade quando administrado durante 30 dias.
Isto destaca a import?ncia desta esp?cie como futuro e promissor candidato a
fitoter?pico, assim que tenha seus ensaios farmacol?gicos conclu?dos. / The species of the genus Kalanchoe (Crassulaceae) are widely used in Brazil as a
medicinal product to treat cough, boils, gastritis and other diseases. In this
scenario stands out K. brasiliensis, popularly known as coirama or sai?o. This
paper aims at the oral exposure of mice to a hydroalcoholic extract of leaves of
Kalanchoe brasiliensis. The animals (total of 100) were divided into 12 groups (6
males and 6 females) for the acute assessment; and groups of 10 for subchronic
evaluation. Test groups were treated with doses of 250 mg / kg, 500 mg / kg, 1000
mg / kg and 2000 mg / kg and the control group received 0.9% saline. The animals
were observed for 14 days for acute evaluation and 30 days for subchronic
evaluation, and in that period analyzed the appearance of clinical signs, changes
in weight and consumption of water and food. After the observation period,
histopathological analysis of the organs, biochemical serum and haematological
parameters for the assessment of the subchronic groups were processed.
Differences and changes in body weight were not observed among the groups, nor
consumption of water and food, there were no deaths among the groups in the two
types of assays. Histopathological analysis showed some alterations compatible
with low acute hepatic toxicity. The results of blood glucose, triglycerides, ALT,
urea and creatinine showed differences between the control group and the test
concentrations studied (p <0.05), but these differences do not show relevant
change in the clinical picture of animals. The results showed that the extract K.
brasiliensis has low acute toxicity at the doses used and no toxicity when
administered for 30 days. This highlights the importance of this species as future
and promising candidate for phytotherapics, so has its pharmacological trials
completed.
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Avalia??o da atividade anti-inflamat?ria do extrato aquoso, fra??es e compostos identificados nos frutos de Hancornia Speciosa Gomes (Apocynaceae)R?go, Manoela Torres do 19 June 2015 (has links)
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Previous issue date: 2015-06-19 / Hancornia speciosa Gomes (Apocynaceae), conhecida popularmente
por ?mangabeira?, ? usada na medicina popular para o tratamento de desordens
inflamat?rias, hipertens?o, dermatites, diabetes, doen?as hep?ticas e
desordens estomacais. No que diz respeito aos frutos de H. speciosa, a
etnobot?nica indica o uso principalmente para o tratamento de inflama??o e
tuberculose, entretanto n?o h? relatos de estudos que comprovem sua poss?vel
atividade biol?gica. O estudo tem como objetivo avaliar a atividade antiinflamat?ria
do extrato aquoso dos frutos de H. speciosa Gomes. O extrato
aquoso foi preparado por decoc??o, posteriormente submetido a um
fracionamento por meio de parti??o l?quido-l?quido e os metabolitos
secund?rios identificados por Cromatografia l?quida de alta efici?ncia acoplada
ao detector de arranjos de diodos (CLAE-DAD) e Cromatografia l?quida
acoplada ao detector de arranjo de diodo e ao espectr?metro de massa (CLDAD-EM).
As propriedades anti-inflamat?rias do extrato aquoso, fra??es
diclorometano (CH2Cl2), acetato de etila (AcOEt) e n-butanol (n-BuOH), bem
como a rutina e o ?cido clorog?nico foram investigadas usando modelos in vivo
e in vitro. Testes in vivo compreenderam edema de orelha induzido por xilol,
onde foi mensurado a forma??o do edema; peritonite induzida por carragenina
onde foi avaliado os leuc?citos totais em 4h e bolsa de ar induzida por zimosam
que foi mensurado a contagem total de leuc?citos e contagem diferencial em 6,
24 e 48 horas. Os testes in vitro avaliaram os n?veis de citocinas IL-1?, IL-6, IL-
12 e TNF-? usando ELISA a partir do modelo de peritonite induzido por
carragenina. Os resultados demonstraram a presen?a de rutina e ?cido
clorog?nico no extrato aquoso dos frutos de H. speciosa por CLAE-DAD e CLDAD-EM.
O extrato aquoso e fra??es, bem como a rutina e ?cido clorog?nico
inibiram significativamente o edema de orelha induzido por xilol e reduziram a
migra??o celular em modelos animais, tanto na peritonite induzida por
carragenina como na bolsa de ar induzida por zimosam. Al?m disso, foi
observada a redu??o dos n?veis de express?o de citocinas IL-1?, IL-6, IL-12 e
TNF-?. Este ? o primeiro estudo que demonstra o efeito anti-inflamat?rio do
extrato aquoso dos frutos de Hancornia speciosa contra diferentes agentes
inflamat?rios em modelos animais, sugerindo que suas mol?culas bioativas,
especialmente rutina e ?cido clorog?nico contribuem, em parte, para o efeito
anti-inflamat?rio do extrato aquoso. Estes resultados suportam a utiliza??o de
H. speciosa na medicina popular e revelam que o extrato aquoso apresenta um
potencial terap?utico para o desenvolvimento de uma droga herbal com
propriedades anti-inflamat?rias. / Hancornia speciosa Gomes (Apocynaceae), popularly known as
?mangabeira?, has been used in folk medicine to treat inflammatory disorders,
hypertension, dermatitis, diabetes, liver diseases and stomach disorders.
Regarding the Hancornia speciosa fruits, the ethnobotany indicates its use
especially for treating inflammation and tuberculosis. However, no study has
been done so far to prove such biological activities. The objective was
evaluation anti-inflammatory activity from the fruits of Hancornia speciosa
Gomes (mangabeira). Aqueous extract was prepared by decoction,
subsequently submitted the liquid-liquid fractionation. The secondary
metabolites were identified by high performance liquid chromatography coupled
with detector diode array (HPLC-DAD) and liquid chromatography diode array
detector coupled with mass spectrometry (LC-DAD-MS). The anti-inflammatory
properties of the aqueous extract, dichloromethane (CH2Cl2), ethyl acetate
(EtOAc) and n-butanol (n-BuOH) fractions of the fruits from H. speciosa, as well
as rutin and chlorogenic acid were investigated using in vitro and in vivo
models. In vivo tests comprised the xylene-induced ear edema that was
measured the formation of edema, carrageenan-induced peritonitis was
evaluated the total leukocytes at 4h and zymosan-induced air pouch was
measured the total leukocytes and differential cell count at 6, 24 and 48 hours,
whereas in vitro tests were evaluated levels of cytokines IL-1?, IL-6, IL-12 and
TNF-? using ELISA obtained of carrageenan-induced peritonitis model. The
results showed the presence of rutin and chlorogenic acid were detected in the
aqueous extract from H. speciosa fruits by HPLC-DAD and LC-DAD-ME.
Furthermore, the aqueous extracts and fractions, as well as rutin and
chlorogenic acid significantly inhibited the xilol-induced ear edema and reduced
cell migration in the animal models such as carrageenan-induced peritonitis and
zymosan-induced air pouch. In addition, reduced levels of cytokines IL-1?, IL-6,
IL-12 and TNF-? were observed. This is the first study that demonstrated the
anti-inflammatory effect of aqueous extract from Hancornia speciosa fruits
against different inflammatory agents in animal models, suggesting that their
bioactive molecules, especially rutin and chlorogenic acid contributing, at least
in part, to the anti-inflammatory effect of aqueous extract. These findings
support the widespread use of Hancornia speciosa in popular medicine and
demonstrate that this aqueous extract has therapeutic potential for the
development of a herbal drugs with anti-inflammatory properties.
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Spondias tuberosa Arr. (UMBU): estudo fitoqu?mico e avalia??o do potencial anti-inflamat?rioSiqueira, Emerson Michell da Silva 26 February 2015 (has links)
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Previous issue date: 2015-02-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Spondias tuberosa Arruda (Anacardiaceae) ? uma ?rvore frut?fera conhecida
popularmente no Brasil como umbuzeiro, tapereba ou umbu. A planta ? nativa e
end?mica do Brasil, distribu?da por todos estados do nordeste brasileiro. Essa esp?cie
tem grande import?ncia na medicina popular do semi-?rido nordestino, onde ? utilizada
principalmente para tratar condi??es inflamat?rias, problemas digestivos assim como
infec??es virais e bacterianas. No entanto, apesar da vasta utiliza??o na medicina
tradicional, existem poucos estudos farmacol?gicos e fitoqu?micos que d?em
embasamento cient?fico a sua utiliza??o popular. Diante disto, este trabalho buscou
caracterizar os marcadores qu?micos e avaliar a atividade anti-inflamat?ria do extrato
das folhas de Spondias tuberosa. O extrato das folhas foi preparado por macera??o em
etanol:?gua (70:30, v/v). A avalia??o do perfil fitoqu?mico do extrato foi realizada
preliminarmente por Cromatografia em Camada Delgada e em seguida por
Cromatografia L?quida de Alta Efici?ncia. Na an?lise por Cromatografia em Camada
Delgada foi observada a presen?a dos flavonoides rutina e isoquercitrina, o que foi
corroborado pela an?lise por Cromatografia L?quida de Alta Efici?ncia que ainda
indicou a presen?a dos ?cidos fen?licos, ?cido clorog?nico e ?cido caf?ico.
Adicionalmente, foi desenvolvido e validado um m?todo por Cromatografia L?quida de
Alta Efici?ncia segundo as normas da RDC 899/2003 da ANVISA e ICH Guidelines
2005, para avaliar o teor dos compostos identificados no extrato. Para avalia??o do
efeito anti-inflamat?rio foram utilizados os modelos de peritonite e de edema de pata
induzidos por carragenina, administra??o via intraperitoneal, em camundongos. A
avalia??o do efeito anti-inflamat?rio in vivo demonstrou que o extrato das folhas, nas
concentra??es de 125, 250 e 500 mg/kg, apresentou uma diminui??o do influxo de
leuc?citos para o local da inflama??o, do di?metro do edema e do n?vel da enzima
mieloperoxidase, quando comparado ao f?rmaco utilizado como controle dexametasona
(2 mg/kg, via i.p.). Em suma, em nosso trabalho foi verificado que o extrato
hidroetan?lico das folhas de Spondias tuberosa apresentou atividade anti-inflamat?ria
importante nos dois modelos ensaiados, o que torna a planta uma potencial esp?cie para
este uso, justificando o seu uso popular. No que se refere ? caracteriza??o de
marcadores, os compostos fen?licos, ?cido clorog?nico, ?cido caf?ico, rutina e
isoquercitrina, identificados no extrato hidroetan?lico das folhas de Spondias tuberosa
podem ser utilizados no controle de qualidade da mat?ria-prima e de extratos obtidos
com a esp?cie. / Spondias tuberosa Arruda (Anacardiaceae) is a fruitful tree popularly known as
umbuzeiro, tapereba or umbu. It is a native and endemic species from Brazil,
widespread in Brazilian Northeast. The species is important in folk medicine of the
semi-arid Northeast, where it is mainly used to treat various inflammatory conditions,
digestive problems as well as viral and bacterial infections. However, despite the
common use in folk medicine, there are scarce pharmacological and phytochemicals
studies that afford scientific evidence to its popular use. Therefore, this study aimed to
characterize the chemical markers in S. tuberosa leaves extract, obtained by maceration
ethanol:water (70:30, [v/v]), and evaluate its anti-inflammatory potential in vivo. The
phytochemical profile in TLC analysis suggested the occurence of the flavonoids rutin
and isoquercitrin. HPLC analysis enabled us to confirm the presence of flavonoids and
also, were detected the phenolic acids, chlorogenic acid and caffeic acid. In addition
was developed and validated a HPLC method to evaluate the content of the identified
compounds in S. tuberosa leaves extract according to RDC 899/2003 of ANVISA and
ICH Guidelines 2005. In order to evaluate the anti-inflammatory potential of S.
tuberosa leaves extract, the peritonitis and paw edema models induced by carrageenan
were used, administration i.p. in mice. The results highlighted the anti-inflammatory
property in vivo at 125, 250 and 500 mg/kg since a decrease in leukocyte influx to the
site of inflammation, diameter of the edema and the level of myeloperoxidase were
observed when compared to the drug control dexamethasone (2 mg/kg, i.p. route).
Taken together, the results pointed out S. tuberosa as a potential species for developing
phytotherapic derivatives in according to its popular use. With regard to the
characterization markers, chlorogenic acid, caffeic acid, rutin and isoquercitrin were
identified and quantified in Spondias tuberosa leaves extract so they could be used in
quality control analyses of the raw material and extracts of this species.
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Intera??es da trancinolona com ciclodextrinas em sistemas multicomponentesMedeiros, Arthur S?rgio Avelino de 31 March 2015 (has links)
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Previous issue date: 2015-03-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / A triancinolona (TRI) ? um importante corticoster?ide utilizado na terap?utica
como anti-inflamat?rio e devido ? sua baixa solubilidade em ?gua, ? utilizada
principalmente na forma de suspens?es injet?veis. A associa??o da triancinolona
com ciclodextrinas e co-solventes foi realizada para solubilizar o f?rmaco e explicar
as intera??es envolvidas. Os diagramas de solubilidade de fases mostraram que o
f?rmaco foi solubilizado pelas ciclodextrinas atrav?s da forma??o de um complexo
incrivelmente est?vel, com os melhores resultados obtidos com a aplica??o da
randomil-metil-beta-ciclodextrina (RM?CD) (aumento de solubilidade de 161 vezes).
O f?rmaco tamb?m foi solubilizado pelos co-solventes, com incremento de
solubilidade de 1,4 e 6,7 vezes (trietanolamina, TEA, e N-metilpirrolidona, NMP,
respectivamente). A aplica??o simult?nea dos dois solubilizantes ainda permitiu um
aumento de solubilidade consider?vel, por?m diminuiu a quantidade final
solubilizada e a afinidade entre f?rmaco e ciclodextrinas, o que permitiu uma maior
quantidade de f?rmaco n?o complexado. Os estudos experimentais de resson?ncia
magn?tica nuclear 2D-ROESY e te?ricos por modelagem molecular mostraram
intera??es da TRI com as CDs por complexo de inclus?o, provavelmente entre a
extremidade do anel A do f?rmaco e cavidade das CDs. Os complexos s?lidos
bin?rios e tern?rios puderam ser obtidos por spray drying. Evid?ncias de forma??o
de complexo em fase s?lida foram ainda mostradas atrav?s de FTIR, difra??o de
raios-X e microscopia eletr?nica de varredura. Os estudos de dissolu??o mostraram
que associa??es bin?rias e tern?rias apresentaram maior velocidade de dissolu??o
em compara??o com o f?rmaco puro. Al?m disso, o complexo tern?rio
TRI:RM?CD:TEA apresentou uma maior velocidade de dissolu??o do f?rmaco que o
complexo bin?rio TRI:RM?CD. Portanto, devido ? maior solubilidade e velocidade de
dissolu??o, os complexos bin?rios e tern?rios se apresentam como novos insumos
com grande potencial para a aplica??o farmac?utica da triancinolona. / Triamcinolone is a relevant anti-inflammatory costicosteroid drug, used mainly
by injectable suspensions due its poor water solubility. The association of
triamcinolone with cyclodextrins and co-solvents (triethanolamine TEA and N-methylpirrolidone
NMP) was held to solubilize the drug and explain the involved
interactions. Phase-solubility diagrams showed that triamcinolone was solubilized
forming incredible stable complexes with cyclodextrins, in which bests results were
observed applying randomyl-methylated-beta-cyclodextrin (RM?CD) (161 fold on
increased solubility). The co-solvents TEA and NMP also enhanced drug solubility
1.4 and 6.7 fold, respectively. The association of both co-solvents with CDs seems
decreased complexation stability, but enables higher amount of uncomplexed drug.
Experimental magnetic resonance 2D-ROESY and theoretical molecular modeling
studies demonstrated TRI-CDs interactions and elucidated the structure of formed
complex, which occurred due to the inclusion of ring A of TRI on CDs cavity.
Physicochemical aspects of solid binary and ternary complexes prepared by spray
drying were assessed by using FTIR, X-ray diffraction and SEM photographs.
Dissolution studies showed that binary and ternary associations presented higher
dissolution efficacy in detrimental to pure drug system. In addition, the ternary
complex containing TEA and RM?CD allowed drug dissolution faster than binary
complex with RM?CD. Therefore, given the higher solubility and drug dissolution
rate, binary and ternary complexes are new raw materials with great potential for
pharmaceuticals containing triamcinolone.
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Fatores de virul?ncia, resist?ncia ao estresse osm?tico e susceptibilidade de isolados de Candida tropicalis oriundos de ambiente costeiro do nordeste brasileiroAlves, Diana Luzia Zuza 26 March 2015 (has links)
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Previous issue date: 2015-03-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / V?rios estudos t?m sido desenvolvidos com rela??o aos riscos ? sa?de humana associados ao
uso recreativo de praias contaminadas com esgotos dom?sticos. Esses res?duos cont?m v?rios
micro-organismos, incluindo Candida tropicalis, agente etiol?gico tanto de infec??es
superficiais quanto sist?micas, al?m de indicador de contamina??o fecal do meio ambiente.
Nesse contexto, o presente trabalho teve como objetivo caracterizar isolados de C. tropicalis
oriundos da areia da Praia de Ponta Negra, Natal, Rio Grande do Norte, Brasil, quanto a
express?o de fatores de virul?ncia in vitro, a adapta??o ao estresse osm?tico e a
susceptibilidade ?s f?rmacos antif?ngicos. Foram analisados 62 isolados ambientais de C.
tropicalis, observando-se grande varia??o entre os mesmos para os diversos fatores de
virul?ncia avaliados. Em geral, os isolados ambientais foram mais aderentes a c?lulas
epiteliais bucais humanas (CEBH) do que a cepa de refer?ncia de C. tropicalis ATCC13803,
al?m de serem altamente produtoras de biofilme. Em rela??o ? morfog?nese, a maioria dos
isolados exibiu fen?tipo rugoso em meio Spider (34 isolados, 54,8%). Na avalia??o da
atividade enzim?tica, a maioria dos isolados teve maior produ??o de proteinase do que a cepa
de refer?ncia de C. tropicalis ATCC13803. Adicionalmente, 35 isolados (56,4%) tiveram alta
atividade hem?litica (?ndice de hem?lise > 55). Com rela??o ? resist?ncia de C. tropicalis ao
estresse osm?tico, 85,4% dos isolados foram resistentes em meio contendo 15% de cloreto de
s?dio, o que corrobora com a alta capacidade de sobreviv?ncia descrita para essa levedura no
ambiente mar?timo. Finalmente, no que diz respeito ? sensibilidade aos antif?ngicos foi
observada elevada resist?ncia aos az?licos testados (fluconazol, voriconazol e itraconazol),
com ocorr?ncia do fen?meno ?Low-high? e de efeito semelhante ao crescimento paradoxal
que ocorre para as equinocandinas. As cepas resistentes aos tr?s az?licos testados foram 15
(24,2%). Para a anfotericina B tamb?m ocorreu resist?ncia (14 isolados, 22,6%), ao passo
que para as equinocandinas todas as cepas foram sens?veis. Portanto, nossos resultados
demonstram que isolados de C. tropicalis oriundos da areia de praia do nordeste brasileiro
podem expressar plenamente atributos de virul?ncia e apresentam alta capacidade de
persist?ncia no ambiente costeiro, al?m de serem significativamente resistentes aos
antif?ngicos mais empregados na pr?tica cl?nica atual. Isso constitui potencial risco ? sa?de
dos frequentadores desse ambiente, especialmente indiv?duos imunocomprometidos e em
extremos et?rios. / Several studies have been developed regarding health risks associated with the recreational
use of beaches contaminated with domestic sewage. These wastes contain various microorganisms,
including Candida tropicalis, etiologic agent of both superficial infections such as
systemic, as well as indicator of fecal contamination for the environment. In this context, the
objective of this study was to characterize C. tropicalis isolates from the sandy beach of
Ponta Negra, Natal, Rio Grande do Norte, Brazil, regarding the expression of in vitro
virulence factors, adaptation to osmotic stress and susceptibility to antifungal drugs. We
analyzed 62 environmental isolates of C. tropicalis and observed a great variation between
them for the various virulence factors evaluated. In general, environmental isolates were
more adherent to CEBH than C. tropicalis ATCC13803 reference strain, besides the fact they
were also highly biofilm producers. In relation to morphogenesis, most isolates presented
wrinkled phenotype in Spider medium (34 isolates, 54.8 %). When assessing enzyme
activity, most isolates had higher proteinase production than C. tropicalis ATCC13803
reference strain. In addition, 35 isolates (56.4 %) had high hemolytic activity (hemolysis
index > 55). With regard to C. tropicalis resistance to osmotic stress, 85.4% of the isolates
were able to grow in a liquid medium containing 15% sodium chloride, corroborating to high
survival capacity described for this yeast at marine environment. Finally, with regard to
sensitivity to antifungal drugs, it was observed high resistance to the azoles tested, with the
occurrence of the "Low-high" phenomenon and similar effect to the paradoxical growth
which occurs to the echinocandins. For the three azoles tested we verified that 15 strains were
resistant (24.2 %). Some strains were also resistant to amphotericin B (14 isolates, 22.6 %),
while all of them were sensitive for the echinocandins tested. Therefore, our results
demonstrate that C. tropicalis isolated from the sand of northeast of Brazil can fully express
virulence attributes and showed a high persistence capacity on the coastal environment, in
addition of being significantly resistant to most applied antifungals in current clinical
practice. This constitutes a potential health risk to visitors of this environment, especially
immunocompromised individuals and those with extreme age range.
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Estudo comparativo entre antipsic?ticos at?picos no tratamento da esquizofrenia e sua influ?ncia na qualidade de vida dos pacientes / Comparative study of atypical antipsychotics in the treatment of schizophrenia and its influence on quality of life of patientsRibeiro, Susana Barbosa 31 July 2015 (has links)
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Previous issue date: 2015-07-31 / A esquizofrenia ? um transtorno mental grave e persistente; o diagn?stico ocorre
principalmente na fase da adolesc?ncia. O tratamento farmacol?gico se faz com antipsic?ticos
t?picos e at?picos. Os at?picos apresentam como vantagem os reduzidos efeitos
extrapiramidais, o que os tornam promissores no tratamento da esquizofrenia, por outro lado,
eles t?m apresentado altera??es metab?licas e hormonais significativas. O objetivo deste
estudo foi avaliar a influ?ncia dos antipsic?ticos at?picos, olanzapina e risperidona, sobre a
qualidade de vida, assim como sobre seus efeitos adversos nos pacientes esquizofr?nicos. Para
isto foi analisada a qualidade de vida dos pacientes com aplica??o do instrumento EuroQol-
5D-3L, bem como a realiza??o de exames bioqu?micos e hormonais, aferi??o da press?o
arterial, e medi??o de ?ndices antropom?tricos, al?m da aplica??o das escalas Ugvalg for
Kliniske Undersgelser (UKU) e Simpson-Angus, estas avaliaram os efeitos colaterais
ocasionados pelos medicamentos. Os dados foram analisados utilizando-se o teste t de
Student e teste de qui-quadrado, com n?vel de signific?ncia de 5%. Os resultados do EuroQol
mostraram que o antipsic?tico olanzapina causa preju?zos significativos associados aos
cuidados pessoais (p < 0,001). Comparando os dois grupos de antipsic?ticos, o valor m?dio de
anos de vida ajustados pela qualidade, conhecido por QALY, foi favor?vel para o grupo da
risperidona (p < 0,032). Os demais resultados obtidos dos grupos olanzapina e risperidona
foram comparados entre si. Em rela??o ?s vari?veis socioecon?micas, observou-se que os
homens utilizavam, de forma prevalente, a olanzapina (p < 0,008); este mesmo grupo
apresentou os seguintes resultados, significativamente desfavor?veis, relacionados ?s
seguintes vari?veis antropom?tricas: circunfer?ncia abdominal (p < 0,01), circunfer?ncia do
quadril (p < 0,02) e peso (p < 0,02), al?m da press?o arterial (p < 0,04). As an?lises
bioqu?micas e hormonais mostraram que a olanzapina ocasionou preju?zos relacionados ?s
seguintes vari?veis: triglicer?deos (p < 0,04), HDL colesterol no sexo masculino (p < 0,02) e
cortisol (p < 0,01). Nos usu?rios de risperidona, o ?nico valor desfavor?vel foi o da prolactina
(p < 0,04). Em rela??o ?s an?lises da escala de Simpson-Angus, o grupo tratado com
olanzapina ficou em situa??o desfavor?vel, pois a m?dia dos escores totais para olanzapina foi
de 0,38, enquanto que para risperidona foi de 0,11 (p < 0,02). Na escala UKU, obteve-se os
seguintes resultados, tamb?m desfavor?vel para o grupo olanzapina: fadiga (p < 0,02),
distonia (p < 0,01) e tremor (p < 0,03). De acordo com a escala UKU, os efeitos colaterais
presentes no grupo da risperidona inclu?ram: ginecomastia (p < 0,01), disfun??o ejaculat?ria
(p <0,02) e disfun??o er?til (p <0,02). Conclui-se que os usu?rios de olanzapina apresentaram
o pior escore de qualidade de vida, maiores riscos metab?licos associados ao sobrepeso, e
perfil lip?dico inadequado, al?m de maior tend?ncia a manifesta??o de sintomas
extrapiramidais. Contudo, os usu?rios de risperidona se mostraram mais propensos a rea??es
adversas decorrentes de altera??es hormonais. / Schizophrenia is a severe and persistent mental illness; diagnosis occurs mainly during
adolescence. The pharmacological treatment is done with typical and atypical antipsychotics.
Atypical have the advantage of reduced extrapyramidal effects, which make them promising
for the treatment of schizophrenia, furthermore, they have shown significant metabolic and
hormonal changes. The objective of this study was to evaluate the influence of atypical
antipsychotics, olanzapine and risperidone on the quality of life and on their adverse effects in
schizophrenic patients. For this we analyzed the quality of life of patients with
implementation of EuroQol-5D-3L instrument and performing biochemical and hormonal
tests, blood pressure measurement, and measurement of anthropometric indices, besides the
application of Ugvalg scales for Kliniske Undersgelser (UKU) and Simpson-Angus, who
evaluated the side effects caused by drugs. Data were analyzed using the Student t test and
chi-square test, with 5% significance level. The results showed that the EuroQol the
antipsychotic olanzapine causes significant losses associated with personal care (p <0.001).
Comparing the two groups of antipsychotics, the average years of quality-adjusted life, known
per QALY was favorable for the risperidone group (p <0.032). The results of olanzapine and
risperidone groups were compared. In terms of socioeconomic, it was observed that men used,
the prevalent form, olanzapine (p <0.008); this same group showed the following results
significantly unfavorable, related to anthropometric variables: waist circumference (p <0.01),
hip circumference (p <0.02), weight (p <0.02) and blood pressure (p <0.04). The biochemical
and hormonal analyzes showed that olanzapine resulted in losses related to the following
variables: triglycerides (p <0.04), HDL cholesterol in men (p < 0.02) and cortisol (p < 0.01).
In risperidone users, the only negative value was prolactin (p < 0.04). Regarding the analysis
of the Simpson-Angus scale, the group treated with olanzapine was handicapped because the
average total scores for olanzapine was 0.38, while for risperidone was 0.11 (p < 0.02). In the
UKU scale, the following results were obtained also unfavorable for the olanzapine group:
fatigue (P <0.02), dystonia (p <0.01) and tremor (p <0.03). According to the UKU scale, the
side effects present in the risperidone group included: gynecomastia (p <0.01), ejaculatory
dysfunction (p <0.02) and erectile dysfunction (p <0.02). It was concluded that olanzapine
users had the worst score of quality of life, higher metabolic risks associated with overweight
and inadequate lipid profile and greater tendency to extrapyramidal manifestations. However,
risperidone users were more likely to adverse reactions due to hormonal changes.
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Desenvolvimento biotecnol?gico de uma emuls?o de uso t?pico a base de ?leo de r?-touro Rana catesbeiana ShawMachado, Lucas Amaral 11 March 2015 (has links)
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Previous issue date: 2015-03-11 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O objetivo deste estudo foi realizar a extra??o ?leo de r?-touro ?leo de r?-touro e desenvolver uma emuls?o adequada para uso t?pico do mesmo. Duas amostras de ?leo fora obtidas por diferentes m?todos, sendo uma por extra??o a quente e outra utilizando solvente org?nico. As amostras foram fisioquimicamente caracterizadas por t?cnicas de titula??o e seus compostos identificados atrav?s de cromatografia gasosa acoplada a espectrometria de massas (GC/EM). O equil?brio hidrif?lico-lipof?lico requerido (EHLr) do ?leo de r?-touro foi determinado e em seguida um diagrama de fases constru?do. A estabilidade da emuls?o de uso t?pico contendo diferentes adjuvantes farmac?uticos foi determinada. A an?lise de citotoxicidade do ?leo de r?-touro in natura e na emuls?o de uso t?pico foi realizada atrav?s do ensaio de MTT, utilizando linhagem de fibroblastos normais (3T3) e de melanoma (B16F10). O rendimento da extra??o a quente foi de 60,6%. Os principais compostos insaturados encontrados foram o ?cido eicosapentaen?ico (17,6%) e ?cido araquid?nico (8,4%). O estudo de EHLr demonstrou a presen?a de sistemas est?veis com EHL entre 12 e 13,5 e o diagrama de fases revelou a predomin?ncia de sistemas caracterizados como emuls?o (62%). A emuls?o t?pica apresentou tamanho de got?cula igual a 390 nm, polidispers?o de 0,05, potencial zeta -25 mV e manteve-se est?vel durante os 90 dias avaliados. O ?leo de r?-touro e a emuls?o t?pica n?o apresentaram citotoxicidade frente ? linhagem de c?lulas 3T3. No entanto, estes sistemas inviabilizaram significativamente (p > 0,05) o crescimento das c?lulas B16F10. Em conclus?o, o ?leo de r?-touro apresenta caracter?sticas qu?micas desej?veis para o desenvolvimento de sistemas terap?uticos de uso farmac?utico e/ou cosm?tico. / The skin is one of the largest organs of the human body and accounts for about 16% of body weight. The body protection against the external environment microorganisms is one of its most important functions, however is necessary that the skin remain intact for this function be exercised, so that when there is an injury on the skin, the process of restructuring needs to be starts, however this restructuration may also be compromised due to some diseases, justifying even more the need for the development of topical products that promote or accelerate the skin healing. Thus the aim of this study was to extract bullfrog oil and to develop a suitable topical emulsion. Two different oil samples were extracted by hot or organic solvent process. Titration techniques and gas chromatography- mass spectrometry were used to characterize the bullfrog oil. The required hydrophile-lipophile balance (HLBr) of bullfrog oil was determined and a pseudo-ternary phase diagram was constructed. The stability of the topical emulsion was evaluated. Then, cellular viability was determined by MTT assay using normal fibroblasts (3T3) and melanoma (B16F10) cells lines. The hot extraction yield was 60.6%. The major polyunsaturated compounds found were Eicosapentaenoic acid (17.6%) and Arachidonic acid (8.4%). HLBr study demonstrated the presence of stable systems with HLB ranging from 12.1 to 13.5 and the pseudo-ternary phase diagram showed mainly emulsion systems (62%). Topical emulsion showed 390 nm, polydispersity 0.05, zeta potential -25 mV and remained stable for ninety days. The bullfrog oil and topical emulsion did not showed citotoxicity in normal fibroblasts cells. However, these systems showed significantly inhibition of melanoma cells growth. In conclusion, the bullfrog oil presented desirable chemical characteristics required to be used for the development of a pharmaceutical and cosmetic products.
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Avalia??o dos efeitos t?xicos in vitro e in vivo do extrato hidroetan?lico dos frutos de Genipa americana L. (Rubiaceae) em camundongos SwissAssis, Cinthya Saraiva de 27 October 2015 (has links)
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Previous issue date: 2015-10-27 / O uso terap?utico de plantas medicinais tem contribu?do desde a antiguidade de forma ben?fica para a sa?de. No entanto, muitas esp?cies carecem de evid?ncias cient?ficas que forne?am embasamento para a sua utiliza??o na pr?tica terap?utica. Neste contexto, encontra-se a esp?cie Genipa americana L. (Rubiaceae), conhecida popularmente como jenipapo e utilizada como antissifil?tica, antiulcerosa e anti-hemorr?gica, contra hematomas, como t?nico, afrodis?aco, etc. Visto que, essa esp?cie carece de estudos toxicol?gicos, o objetivo deste trabalho foi avaliar a toxicidade in vivo (toxicidade aguda e subcr?nica) e in vitro (citotoxicidade) do extrato dos frutos da G. americana. O extrato hidroetan?lico dos frutos de G. americana foi preparado por macera??o. Foi realizada uma an?lise fitoqu?mica preliminar para avaliar a presen?a de metab?litos secund?rios no extrato. No estudo da citotoxicidade do extrato (0,1; 1,0; 10; 100 e 1000 ?g/100?L) foram utilizadas linhagens de c?lulas normais (3T3) e tumorais (786-0, HepG2 e B16), analisados pelo ensaio do MTT. Para a avalia??o da toxicidade aguda (dose ?nica de 2000 mg/Kg) e subcr?nica (100, 500 e 1000 mg/Kg por 30 dias) foram utilizados camundongos Swiss de ambos os sexos. Ao final dos experimentos, amostras de sangue e ?rg?os foram coletados para an?lise. Os dados entre os grupos foram comparados pelo test T ou por ANOVA com p?s-teste de Dunnett com n?vel de signific?ncia de 5%. O estudo fitoqu?mico do extrato indicou principalmente a presen?a de irid?ides. Os ensaios de citotoxicidade apresentaram resultados de at? 70% de inibi??o celular frente ? linhagem de B16, na dose de 1000 ?g/100?L, e at? 29% frente ? linhagem 786-0, na dose de 10 ?g/100?L. O extrato n?o promoveu morte nas c?lulas 3T3 e HepG2. Durante as avalia??es in vivo, n?o houve mortes de animais. A an?lise das amostras de sangue revelou que os animais submetidos ? avalia??o da toxicidade aguda apresentaram leves altera??es hep?ticas, e que os animais submetidos ? avalia??o da toxicidade subcr?nica apresentaram altera??es no peso relativo do rim esquerdo e na concentra??o plasm?tica de ur?ia. N?o foram observadas diferen?as entre grupos testes e controles na avalia??o histopatol?gica dos ?rg?os coletados. Apesar das altera??es encontradas nos ensaios de toxicidade in vivo, segundo os crit?rios descritos pelos Guias OECD, sugere-se que o extrato hidroetan?lico dos frutos da G. americana seja classificado como de baixa toxicidade. A citotoxicidade do extrato sugere que omesmo possui potencial contra as linhagens de melanoma (B16) e carcinoma renal (786-0). / The therapeutic use of medicinal plants has contributed since antiquity in a beneficial way for health. However, many species lacks of scientific evidence which provide basis for their use in therapeutic practice. In this context is the Genipa americana L. species (Rubiaceae), popularly known as jenipapo and used to treat syfilis, ulcer and hemorrhagic disturbs. It's also used against bruising, as tonic and as aphrodisiac. Due this species lacks toxicological studies, the aim of this study was to evaluate the toxicity in vivo (acute and sub-chronic toxicity) and in vitro (cytotoxicity) of the hydroethanolic extract from G. americana fruits. The hydroethanolic extract of G. americana fruits was prepared by maceration. A preliminary phytochemical analysis was performed to assess the presence of secondary metabolites in the extract. The cytotoxicity study of the extract (0.1, 1.0, 10, 100 and 1000 mg / 100 ul) were performed against normal cells (3T3) and tumor (786-0, HepG2 and B16), analyzed by the MTT assay. To evaluate the acute (single dose of 2000 mg / Kg) and subchronic (100, 500 and 1000 mg / kg for 30 days) toxicity Swiss mice of both sexes were used. At the end of the experiment, blood samples and organs were collected for analysis. Data between groups were compared by t test or ANOVA with Dunnett's post-test with 5% significance level. The phytochemical study of the extracts mainly indicated the presence of iridoids. Results for cytotoxicity tests showed up to 70% inhibition of B16 cell line at a dose of 1000 mg / 100 ul, and up to 29% inhibition of 786-0 at a dose of 10 ug / 100 ul. The extract did not cause death in 3T3 and HepG2 cells. During the in vivo assays, there were no animal deaths. Analysis of blood samples revealed that the animals submitted to the evaluation of acute toxicity had changes in AST and ALT, and that the animals evaluated for subchronic toxicity showed changes in the relative wet weight of the kidney and plasma urea concentration. No differences were observed between groups on histopathological evaluation of the collected organs. Despite the changes found in the in vivo toxicity tests, using the criteria described by the OECD Guidelines, it is suggested that the hydroethanolic extract of the fruits of the G. americana is classified as low toxicity. The cytotoxicity of the extract suggests that they have potential against melanoma cell lines (B16).
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miRNAS circulantes como biomarcadores para fibrila??o atrial agudaSilva, Anan?lia Medeiros Gomes da 15 December 2015 (has links)
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Previous issue date: 2015-12-15 / A Fibrila??o Atrial (FA) ? a arritmia card?aca sustentada mais comum. Pequenos RNAs n?o codificantes (miRNAs) v?m demonstrando uma atividade regulat?ria na arritmog?nese, atuando em genes alvos que contribuem para o desenvolvimento da FA. Este estudo teve como objetivo avaliar a express?o de miRNAs candidatos em plasma de indiv?duos com FA e com FA aguda e suas futuras aplica??es como marcadores para o diagn?stico e monitoramento desta doen?a. Os miR-21, miR-133a, miR-133b, miR-150, miR-328 e miR-499 foram selecionados para serem alvos do estudo atrav?s de uma pr?via revis?o liter?ria. Eles foram isolados do plasma de indiv?duos com faixa et?ria entre 20 e 85 anos com FA (n=17), FA aguda (n=5) e sem FA (n=15). Os resultados foram analisados atrav?s da t?cnica da PCR em tempo real (RT-PCR) atrav?s do m?todo miScript SYBR Green PCR. Observamos que os miR-21, miR-133b, miR-328 e miR499 foram diferentemente expressos entre os tr?s grupos (p<0,05). A eleva??o da express?o desses miRNAs miR-21 (0.6-fold), miR-133b (1.4-fold), miR-328 (2.0-fold) e miR-499 (2.3-fold) foi maior em pacientes com FA aguda quando comparados aos pacientes com FA e os controles. Os miR-133a e miR-150 n?o apresentaram diferen?as estat?sticas entre os grupos. Nossos dados sugerem que os miR-21, miR-133b, miR-328 e miR-499 podem ser potenciais biomarcadores para FA,bem como para a FA aguda, e para o diagn?stico e acompanhamento da doen?a. Estes resultados podem contribuir para a compreens?o do processo que desencadeia a FA, incentivando o desenvolvimento de novos estudos para avaliar a aplica??o destas mol?culas como futuros biomarcadores para esta doen?a. / Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Some non-coding RNAs (miRNAs) have been involved in regulatory activity in arrhythmogenesis, targeting genes that contribute to the development of AF. The present study aimed to evaluate the expression of candidate miRNAs in plasma from patients with AF and new-onset AF and its application as future markers for diagnosis and monitoring of disease. miR-21, miR-133a, miR-133b, miR-150, miR-328 and miR-499 were selected as targets in this study through a prior literature review. They were isolated from plas-ma of individuals aged from 20 to 85 years old with AF (n = 17), new-onset AF (n = 5) and without AF (n = 15), where the latter was the control group. The results were ana-lyzed by Real-Time PCR (RT-PCR) with miScript SYBR Green PCR. We observed that miR-21, miR-133b, miR-328 and miR-499 had different levels of expression be-tween the three groups (p <0.05). Increased expression of miR-21 (0.6-fold), miR-133b (1.4-fold), miR-328 (2.0-fold) and miR-499 (2.3-fold) in patients with new-onset AF when compared to AF and control subjects. The miR-133a and miR-150 expression did not differ among the groups. miR-21, miR-133b, miR-328 and miR-499 may be potential biomarkers for AF as well as for new-onset AF, for monitoring and for the di-agnosis. These findings may contribute to the understanding of the process that trig-gers AF and suggest application these molecules as future biomarkers for AF.
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Nanopart?culas cati?nicas de poli (?cido l?tico) para libera??o modificada de pept?dios da pe?onha do escorpi?o Tityus serrulatusMesquita, Philippe de Castro 24 July 2015 (has links)
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Previous issue date: 2015-07-24 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Acidentes notificados envolvendo o envenenamento por escorpi?es ainda s?o frequentes no Brasil, ocasionados principalmente pela esp?cie Tityus serrulatus, conhecido como escorpi?o amarelo. Embora os soros antiescorpi?nicos sejam produzidos rotineiramente por diversos laborat?rios oficiais, a efic?cia de sua utiliza??o depende da rapidez com que se inicia o tratamento e da efici?ncia na produ??o de anticorpos pelos animais imunizados. No presente trabalho, o desenvolvimento de nanopart?culas polim?ricas cati?nicas de poli(?cido l?tico) teve como objetivo a busca de um sistema de libera??o modificada para os pept?deos e prote?nas presentes na pe?onha do escorpi?o T. serrulatus, capaz de potencializar a produ??o de anticorpos em soro anti-veneno. As nanopart?culas cati?nicas foram obtidas por nanoprecipita??o, ap?s o estudo do efeito dos par?metros da t?cnica sobre as propriedades f?sico-qu?micas das part?culas, com a otimiza??o de um m?todo de baixa energia. A funcionaliza??o da superf?cie das nanopart?culas com a polietilenoimina hiper-ramificada foi comprovada pela an?lise de potencial zeta e possibilitou a adsor??o por intera??o eletrost?ticade diferentes tipos de prote?nas. A efici?ncia de incorpora??o de 40-80 % de albumina de sorobovino (BSA) e 100 % de pept?deos da pe?onha do escorpi?o avaliadas por espectrofotometria e eletroforese em gel de poliacrilamida, confirmou o sucesso na escolha dos par?metros do m?todo de obten??o das nanopart?culas, produzidas com tamanho entre 100 a 250 nm. A an?lise de microscopia de for?a at?mica e estudos in vitro de libera??o, mostraram que as nanopart?culas esf?ricas fornecem um perfil sustentado de libera??o das prote?nas pelo mecanismo de difus?o, que potencializou a produ??o de anticorpos antiveneno em animais imunizados com as nanopart?culas contendo a pe?onha do escorpi?o, comprovando o potencial para aplica??o in vivo das nanopart?culas. / Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly
caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are
produced routinely by various government laboratories, the effectiveness of its use depends
on how quickly treatment is initiated and efficiency in the production of antibodies by the
immunized animals. In this study, the development of cationic polymeric nanoparticles of
poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T.
serrulatus venom, able to enhance the production of serum antibodies against the scorpion
toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after
study of the parameters? variations effects over the physicochemical properties of the
particles. The surface functionalization of the nanoparticles with the hyperbranched
polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by
electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80
% to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by
spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the
selected parameters established for obtainment of nanoparticles, produced with size between
100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the
spherical nanoparticles provided a sustained release profile of proteins by diffusion
mechanism, demonstrating the potential for application of the nanoparticles in vivo.
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