Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-18T12:20:42Z No. of bitstreams: 1 jessicacorreabezerra.pdf: 4319197 bytes, checksum: 86d9f6d6b75d5c485d7ca71acb154e85 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-18T12:49:51Z (GMT) No. of bitstreams: 1 jessicacorreabezerra.pdf: 4319197 bytes, checksum: 86d9f6d6b75d5c485d7ca71acb154e85 (MD5) / Made available in DSpace on 2017-05-18T12:49:51Z (GMT). No. of bitstreams: 1 jessicacorreabezerra.pdf: 4319197 bytes, checksum: 86d9f6d6b75d5c485d7ca71acb154e85 (MD5) Previous issue date: 2015-03-13 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Incidência de disruptores endócrinos sobre o desenvolvimento gonadal é a causa de muitas anomalias do sistema reprodutor masculino (SRM), principalmente aqueles com ação estrogênica. O Ginkgo biloba é um disruptor endócrino, que possui afinidade por receptores β estrogênicos, importantes no desenvolvimento do SRM. A proposta deste estudo foi avaliar o efeito do Ginkgo biloba, após exposição materna, sobre os parâmetros reprodutivos dos machos F1. Ratas Wistar prenhes receberam 25, 50 ou 100 mg/Kg/dia de Ginkgo biloba, por gavagem, do 16° ao 20º dias de prenhez. As fêmeas prenhes foram avaliadas quanto ao consumo diário de ração, peso corporal e sinais clínicos de toxicidade. Nos machos F1 foram analisados a descida testicular, morfologia da glande do pênis, concentração e morfologia espermática, peso dos órgãos reprodutores e viscerais, níveis séricos de testosterona, e a organização estrutural do tecido testicular e epididimário. Não foram observadas diferenças estatísticas significativas nas variáveis analisadas, com exceção da morfologia espermática, onde houve aumento de espermatozoides anormais em todos os grupos tratados em comparação com o grupo controle. O numero de espermatozoides anormais nos grupos C, T1, T2 e T3 foi, espectivamente, 19,90± 3,53, 29,0± 7,01, 26,05± 3,72 e 30,05± 6,53 (Média ± DP), contando-se 200 espermatozoides/lâmina. A maioria das anomalias concentrou-se na cauda do espermatozoide, totalizando 13,35± 2,42, 18,45± 6,87, 16,15± 4,31 e 19,55± 5,43(Média ± DP) nos grupos C, T1, T2 e T3, respectivamente. Estes resultados indicam que o Ginkgo biloba não causa alterações na toxicidade materna, no desenvolvimento fetal, pósnatal e na data da puberdade, mas induz o aumento da anomalia espermática. / Incidence of endocrine disruptors on the gonadal development is the cause of many anomalies of the male reproductive system (MRS), especially those with estrogen action. Ginkgo biloba is an endocrine disruptor, which has affinity for β estrogen receptors, important in the development of MRS. The purpose of this study was to evaluate the effect of Ginkgo biloba, after maternal exposure on the reproductive parameters of F1 males. Pregnant Wistar rats received 25, 50 or 100 mg /kg/day of Ginkgo biloba, by gavage, from the 16th to 20th days of pregnancy. Pregnant animals were evaluated for daily feed intake, body weight and clinical signs of toxicity. In F1 males were analyzed testicular descent, morphology of the glans penis, sperm concentration, sperm morphology, weight of reproductive and visceral organs, seric concentrations of testosterone, and the structural organization of testicular tissue and epididymis. No statistically significant differences were observed in the analyzed variables, except for sperm morphology, where there was an increase of abnormal sperm in all treated groups compared with the control group. The number of abnormal sperm in groups C, T1, T2 and T3 were, respectively, 19.90 ± 3.53, 29.0 ± 7.01, 26.05 ± 3.72 and 30.05 ± 6.53 (mean ± SD), counting 200 sperm / stain. Most anomalies concentrated in the sperm tail, totaling 13.35 ± 2.42, 18.45 ± 6.87, 16.15 ± 4.31 and 19.55 ± 5.43 (mean ± SD) in groups C, T1, T2 and T3, respectively. These results indicate that Ginkgo biloba does not alter the maternal toxicity, fetal development, postnatal and puberty date, but induces the increase of sperm abnormality.

<p>U okviru ove disertacije izvr&scaron;eno je preparatvno izolovanje etarskog ulja li&scaron;ća ginka (<em>Ginkgo biloba</em> L.) destilacijom pomoću vodene pare, u cilju određivanja pojedinih fizičko-hemijskih parametara. Oficinalnim postupkom određen je sadržaj etarskog ulja u li&scaron;ću ginka i iznosi 0,0083%. Li&scaron;će ginka je ekstrahovano klasičnim rastvaračima tj. sme&scaron;om alkohol-voda, pri čemu je koncentracija alkohola iznosila 40% (m/m). Primenom navedenog rastvarača, izvr&scaron;ena je vi&scaron;estupna protivstrujna ekstrakcija (u pet stupnjeva) pri čemu je dobijen tečni ekstrakt (<em>Extracta fluida</em>) sa relativno visokim sadržajem ekstraktivnih materija (17,06%). Tečni ekstrakt je direktno kori&scaron;ćen za dobijanje suvog ekstrakta li&scaron;ća ginka (<em>Extracta sicca</em>)primenomvsu&scaron;nie sa raspr&scaron;ivanjem (spray dryer). Kvalitativna i kvantitativna karakterzacija izvr&scaron;ena je primenom postupka tečne hromatografije na tankom sloju (HPTLC) i određen sadržaj ukupnih flavonoida sračunatih na rutin, a i na katehin, a određen je i sadržaj ukupnih fenola sračunatih na hlorogensku kiselinu. Glavni deo doktorske disertacije predstavlja ekstrakcija sistema li&scaron;će ginka-ugljenik (IV)-oksid pod pritiskom, pri čemu je ispitivan uticaj stepena usitnjenosti droge na prinos ekstrakcije, i kori&scaron;ćen koeficijent brze i spore ekstrakcije kao mera kinetičkog pona&scaron;anja ekstrakcije. Dobijeni rezultati ispitivanja su pokazali značajan uticaj stepena usitnjenosti droge na brzinu ekstrakcije, pogotovo, kod ekstrakcije natkritičnim ugljenik (IV) oksidom. Radi izbora optimalnog protoka ekstragensa ispitivani su sledeći protoci 0,095, 0,194 i 0,277 kg/h . Na osnovu prinosa ekstrakcije usvojeno je da je protok ekstragensa od 0,194 kg/h optimalan. Prinos ekstrakcije je ispitivan kori&scaron;ćenjem dva postupka ekstrakcije, i to: ekstrakcija tečnim ugljenik (IV) -oksidom (temperatura ispod kritične temperature Tc= 31,1^oC, a pritisak ne&scaron;to ispod ili iznad kritičnog pritiska p_c=73,8 bar), i ekstrakcija natkritičnim ugljenik (IV)- oksidom (pritisak i temperatura iznad kritičnih vrednosti pritiska i temperature). U natkritičnoj oblasti promenom pritiska se značajno menjaju svojstva ekstragensa, povećava se sposobnost rastvaranja, dielektrična konstanta i dr. Ispitivan je uticaj temperature na prinos ekstrakcije (izotermni proces), pri čemu se dobijaju rezultati koji se ne mogu objasniti jednostavno, analizirajući samo uticaj gustine rastvarača na moć rastvaranja, već se za obja&scaron;njenje dobijenih rezultata uključuje i uticaj napona pare ekstrahovane komponente, tako da rastvorljivost komponente može da se poveća, smanji ili ostane ista sa povećanjem temperature na konstantnom pritisku, u zavisnosti koji uticaj je dominantniji. Kod izotermnih postupaka prinos ekstrakcije raste sa povećanjem pritiska ekstrakcije, &scaron;to je u saglasnosti sa teoretskim principima. S druge strane, ekstrakti dobijeni pri vi&scaron;im pritiscima imaju manji sadržaj etarskog ulja &scaron;to se obja&scaron;njava činjenicom da veći pritisci imaju veću moć rastvaranja glavnih komponenata kao i komponenata kao &scaron;to su smole, voskovi i masna ulja. Kvalitativnom i kvantitativnom analizom selektovanih ekstrakata dobijenih tečnim (130 bar, 20^oC, 3 h) i natkritičnim (100 bar, 40^o C, 4 h) ugljenik (IV)-oksidom, kao i etarska ulja izolovana iz ovih ekstrakata nađeno je da ispitivani uzorci sadrže nalkane, račvaste alkane i jedinjenja sa kiseonikom, među kojima posebno mesto zauzimaju fenoli sa zasićenim i nezasićenim alkil ostacima.<br />Izvr&scaron;ena je uporedna anliza etarskog ulja dobijenog destilacijom li&scaron;ća ginka pomoću vodene pare i etarskih ulja dobijenih iz selektovanih ekstrakata. Interesantan je podatak koji se odnosi na sadržaj etarskog ulja u drogi određen direktnom destilacijom droge pomoću vodene pare i izdvajanjem etarskih ulja iz ekstrakata takođe destilacijom pomoću vodene pare. U ovom drugom slučaju dobija se, preračunavanjem, sadržaj etarskog ulja u drogi vi&scaron;estruko veći (4-10 puta) od sadržaja, određenog oficinalnim postupkom, u drogi. Ova pojava se obja&scaron;njava uvođenjem pojma &bdquo;vezano&ldquo; etarsko ulje i &bdquo;slobodno&ldquo; etarsko ulje. Ekstrakcijom ugljenik (IV)-oksidom pod pritiskom tzv. vezano etarsko ulje se oslobađa voskova i masnog ulja &scaron;to se odražava na njegovu povećanu količinu u CO₂-ekstraktima. Na kraju u ovoj disertaciji izvr&scaron;eno je modelovanje ekstrakcionog sistema li&scaron;će <em>Ginkgo biloba</em> &ndash; ugljenik (IV)-oksid pod pritiskom kori&scaron;ćenjem model jednačine Naika i saradnika, modifikovane model jednačine Reverchon i Sesti-Osseo kao i model, če&scaron;će kori&scaron;ćen, koji je predložila Sovov&aacute;. Kori&scaron;ćeni modeli mogu relativno uspe&scaron;no da se koriste za opisivanje ekstrakcionog sistema li&scaron;će <em>Ginkgo biloba</em> &ndash; ugljenik (IV)-oksid pod pritiskom. Radi iznalaženja najpovoljnijih uslova ekstrakcije primenjen je metod odzivne povr&scaron;ine variranjem parametra ekstrakcije (pritisak, temperatura i vreme ekstrakcije). Na osnovu eksperimentalnih rezultata dobijen je polinom drugog reda za izračunavanje optimalnog prinosa ekstrakcije i određeni su najpovoljniji uslovi ekstrakcije kao i međusobni uticaji pojedinih parametra.</p> / <p>Within this thesis preparative isolation of essential oil from leaves of ginkgo (<em>Ginkgo biloba</em> L.) by steam distillation was carried out, in order to determine some physico-chemical parameters. The essential oil content in the leaves of ginkgo wass determined by an officinal procedure and its value is 0.0083%. Ginkgo leaves were extracted with conventional solvents, i.e. alcohol-water mixture, where the alcohol concentration was 40% (w/w). The forementioned solvent was used to carry out a multistage counter-current extraction (five stages) by which the liquid extract (<em>Extracta fluida</em>) with a relatively high content of extracts (17.06%) was obtained. The liquid extract was directly used to obtain a dry extract of ginkgo leaves (<em>Extracta sicca</em>) by spay drying. The qualitative and quantitative characterisation was based on the proceedings of liquid thin layer chromatography (HPTLC), the content of total flavonoids expressed as rutin, and as catechin, and the total phenol content expressed as chlorogenic acid was determined. The main part of the doctoral thesis is the extraction system of ginkgo leaves-carbon (IV) oxide under pressure, in which the effect of the drug particle size on the extraction yield was studied, and as a measure of the kinetic behavior of extraction the coefficient of fast and slow extraction was used. The obtained results showed a significant effect of the drug particle size on the speed of extraction, particularly, the extraction with supercritical carbon (IV) oxide. For the purpose of selecting the optimal flow of the solvent several flowrates were investigated 0.095, 0.194 and 0.277 kg/h. Based on the yield of extraction the solvent flowrate of 0.194 kg/h was assumed as optimal. The extraction yield was investigated using two extraction procedures: extraction with liquid carbon (IV) oxide (temperature below the critical temperature Tc = 31.1 ⁰C and pressure slightly below or above the critical pressure p_c = 73.8 bar), and extraction with supercritical carbon (IV) oxide (pressure and temperature above the critical values of pressure and temperature). In the supercritical area the change in pressure significantly the influences the properties of the solvent, increases the ability of dissolving, dielectric constant, etc. The effect of temperature on extraction yield was examined (isothermal process), where the obtained results can not be explained simply by analyzing only the effect of solvent density on the power of dissolution, but to explain these results the effect of vapor pressure of the extracted components must be included, so that the solubility of the component may increase, decrease or remain the same with increasing temperature at constant pressure, depending on which influence is dominant. In isothermal processes the extraction yield increases with increasing pressure of extraction, which is consistent with theoretical principles. On the other hand, extracts obtained at high pressures have a lower content of essential oils which can be explained by the fact that higher pressures have a greater power of dissolution of the main components as well as components such as resins, waxes and fatty oils. The qualitative and quantitative analysis of the selected extracts obtained with liquid (130 bar, 20 ⁰C, 3 h) and supercritical (100 bar, 40 ⁰C, 4 h) carbon (IV) oxide, and essential oils isolated from these extracts showed that the studied samples contain n-alkanes, branched alkanes and compounds with oxygen, including phenols with saturated and unsaturated alkyl residues. A comparative analysis of the essential oil obtained by distillation of ginkgo leaves by steam and essential oil obtained from selected extracts was carried out. An interesting fact concerning the essential oil content in the drug determined by direct distillation of drugs by steam and separating the essential oils from extracts also produced by steam distillation. In the other case, by calculation, the obtained essential oil content in the drug is several times higher (4-10 times) of content, determined by an fficinal procedure, in the drug. This phenomenon is explained by introducing the notion of &quot;linked&quot; essential oil and &quot;free&quot; essential oil. The extraction with carbon (IV) oxide under pressure the so called linked essential oil is released from waxes and fatty oils which is reflected in its increased amount in CO₂-extracts. At the end of this dissertation the modeling of the extraction system leaves of <em>Ginkgo biloba</em> - carbon (IV) oxide under pressure was carried out using the model equation of Naik and associates, the modified model equation of Reverchon and Sesti Osseo and also like a frequently used model proposed Sovov&aacute;. The mentioned models can be relatively used to describe the extraction system leaves of <em>Ginkgo biloba</em> - carbon (IV) oxide under pressure. In order to find the most favorable conditions of extraction, the response surface methodology varying extraction parameters was used (pressure, temperature and extraction time). Based on the experimental results a second order polynom for the calculation of the optimum yield of extraction was obtained and the extraction conditions and the mutual influence of some parameters were determined.</p>

Rhabdoviridae family viruses attacking the plant hosts were only described at the angiosperms. In this work, a gymnosperm rhabdoviridae infection was described for the first time ever ? specifically at Ginkgo biloba. Even though there were not observed any kinds of obvious infection symptoms on any of randomly chosen plant samples, through the molecular methods and detection primers the rhabdoviridae infection was proved at six of the plant samples. The acquired nucleotide and amino acid sequences, which were compared with the GenBank sequences, confirm the Rhabdoviridae family viruses occurrence. These given sequences demonstrated a certain analogy with a Strawberry crinkle virus assigned to the genus of Cytorhabdoviruses. The analyses proved a different reciprocal homology among the nucleotide sequences of the individual isolates, and in all likelihood an occurrence of two up to now unknown viruses in the Ginkgo biloba samples was proved for the first time. A definite categorization will be dependent on an acquisition and comparison of other sequences from the isolates genome and also on certain biological characteristics observation.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2017-03-31T10:25:55Z No. of bitstreams: 2 Dissertação - Daniela Cristina da Silva - 2017.pdf: 3223777 bytes, checksum: 67c2832449d10a3a2590e8a834f55b10 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-31T10:44:27Z (GMT) No. of bitstreams: 2 Dissertação - Daniela Cristina da Silva - 2017.pdf: 3223777 bytes, checksum: 67c2832449d10a3a2590e8a834f55b10 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-03-31T10:44:27Z (GMT). No. of bitstreams: 2 Dissertação - Daniela Cristina da Silva - 2017.pdf: 3223777 bytes, checksum: 67c2832449d10a3a2590e8a834f55b10 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-09 / Entomopathogenic fungi combined with plant extracts may have their development in vitro and their insecticidal activity modified. There are many reports on the activity of entomopathogenic fungi and extracts in insects, but few studies on fungi combined with plant extracts. The objective of this study was to evaluate in vitro the effect of crude ethanol extracts of Artemisia annua, Andrographis paniculata, Curcuma zedoaria, Ginkgo biloba and Rosmarinus officinalis on the Metarhizium anisopliae s.l. IP 46 by the diffusion disc test, to evaluate in vivo susceptibility of Aedes aegypti larvae to extracts by determination the cumulative emergence of adults, development and mortality of larvae for 15 days, then to select the extracts and combine them with IP 46 at 3.3 x 105 conidia.mL-1. There was no significant inhibition germination of IP 46. On the fifteenth day there was a significant effect on cumulative emergence of adults and development of larvae for A. annua at 10 ppm, 33 ppm and 1000 ppm and C. zedoaria at 100 ppm and 333 ppm. There was also a significant effect on accumulated mortality of larvae exposed to G. biloba at 10000 ppm.These extracts with in these concentrations were selected and combined with IP 46 at 3.3 x 105 conidia.mL-1, minus G. biloba which was combined at 5000 ppm after the LC50 and LC90 calculations. These combinations, except for A. annua at 1000 ppm, exhibited a significant increase in larval mortality and/ or showed an effect on development, indicating that combined methods may be more effective in controlling A. aegypti than isolated methods. / Fungos entomopatogênicos combinados a extratos de plantas podem ter o seu desenvolvimento in vitro e sua atividade inseticida in vivo modificada. Existem muitos relatos sobre a atividade de fungos entomopatogênicos e extratos em insetos, porém são poucos os estudos sobre fungos combinados a extratos de plantas. O objetivo do trabalho foi avaliar in vitro o efeito de extratos brutos etanólicos de Artemisia annua, Andrographis paniculata, Curcuma zedoaria, Ginkgo biloba e Rosmarinus officinalis em isolado de Metarhizium anisopliae s.l. IP 46 por meio do teste de disco difusão, avaliar in vivo a suscetibilidade de larvas de Aedes aegypti expostas a esses extratos por meio da avaliação da emergência acumulada de adultos, do desenvolvimento e da mortalidade de larvas, durante 15 dias, para então selecionar os extratos e combiná-los com IP 46 a 3,3 x 105 conídios.mL-1. Observou-se que não houve inibição significativa de IP 46 pelos extratos. No décimo quinto dia houve efeito significativo na emergência acumulada de adultos e no desenvolvimento de larvas expostas a A. annua a 10 ppm, 33 ppm e 1000 ppm e de C. zedoaria a 100ppm e 333 ppm. Também houve efeito significativo na mortalidade acumulada de larvas exposta a G. biloba a 10000 ppm. Esses extratos nessas concentrações foram selecionados e combinados com IP 46 a 3,3 x 105 conídios.mL-1, menos o de G. biloba que foi combinado a 5000 ppm após cálculos da CL50 e CL90. Essas combinações, exceto para A. annua a 1000 ppm, exibiram aumento significativo na mortalidade larval e/ou apresentararam efeito sobre o desenvolvimento, indicando que métodos combinados podem ser mais efetivos no controle de A. aegypti do que métodos isolados.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-06-20T20:06:17Z No. of bitstreams: 1 leonardotoshiooshio.pdf: 6184732 bytes, checksum: 2ae5dded31a5fbae3336c3f4555afe20 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-13T15:26:54Z (GMT) No. of bitstreams: 1 leonardotoshiooshio.pdf: 6184732 bytes, checksum: 2ae5dded31a5fbae3336c3f4555afe20 (MD5) / Made available in DSpace on 2016-07-13T15:26:54Z (GMT). No. of bitstreams: 1 leonardotoshiooshio.pdf: 6184732 bytes, checksum: 2ae5dded31a5fbae3336c3f4555afe20 (MD5) Previous issue date: 2012-08-31 / O Extrato de Ginkgo biloba (EGb) é um dos fitoterápicos mais consumidos no mundo e tem sido utilizado no tratamento da disfunção erétil e como afrodisíaco. O presente trabalho teve como objetivo avaliar a toxicidade sistêmica do EGb e o efeito sobre o sistema reprodutor masculino de ratos Wistar. Oitenta animais de três meses de idade foram tratados com água destilada (Grupo Controle) e extrato aquoso de Ginkgo biloba nas seguintes doses: 3,5 (EGb 3,5); 7,0 (EGb 7,0) e 14,0 mg/kg (EGb 14,0) uma vez ao dia, por 56 dias consecutivos. Foram avaliados o peso corporal, estimativa de consumo diário de ração, indícios de sinais clínicos de toxicidade, peso de órgãos e glândulas acessórias do sistema reprodutor masculino e dados histométricos testiculares. Espermatozoides foram coletados da cauda do epidídimo e foram submetidos à contagem e avaliados quanto à vitalidade e morfologia. Foram realizados hemograma completo, dosagem bioquímica sérica de ureia, creatinina e alanina aminotransferase (ALT) e concentração de testosterona total sérica. Não foram observados nos animais sinais clínicos de toxicidade sistêmica e mortes. Apesar de ter ocorrido diferenças estatísticas significativas na estimativa de consumo de ração, hemoglobinometria, concentração de hemoglobina globular média e volume das células de Leydig, concluise que o EGb no presente trabalho, e com as doses utilizadas, não causou toxicidade sistêmica nem promoveu alteração na morfometria testicular e qualidade espermática de ratos Wistar. / Ginkgo biloba Extract (GBE) is one of the most consumed herbal medicines in the world and it has been used in the treatment of erectile dysfunction and as an aphrodisiac. The present study had as objective to evaluate the GBE systemic toxicity and its effect on male reproductive system of Wistar rats. Eighty animals of threemonth- old age were treated with distilled water (Control Group) and aqueous extract of Ginkgo biloba in the following doses: 3.5 (GBE 3.5); 7.0 (GBE 7.0) and 14.0 mg/kg (GBE 14.0) once per day, for 56 consecutive days. Body weight, daily food consumption estimation, toxicity clinical signs evidences, male reproductive system organs and accessory glands weights and testis histometric analysis data were evaluated. Spermatozoa were collected from the cauda epididymis and were subjected to counting and evaluations of vitality and morphology. Complete blood count test, serum biochemistry test of urea, creatinine and alanine aminotransferase (ALT) and total serum testosterone levels were realized. Clinical signs of systemic toxicity and deaths were not seen. In spite of it had had significant statistical differences on daily food consumption estimation, hemoglobinometry, mean corpuscular hemoglobin concentration and Leydig cell volume, it was concluded that GBE in the present study and with the doses used, did not cause systemic toxicity nor promoted alterations on testicular morphometry and spermatic quality of Wistar rats.

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-07-04T10:50:02Z No. of bitstreams: 1 eduardosiqueiraferandes.pdf: 2252400 bytes, checksum: 56e960a38ee98a43aa5d60c466f2b6e8 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-08T14:07:24Z (GMT) No. of bitstreams: 1 eduardosiqueiraferandes.pdf: 2252400 bytes, checksum: 56e960a38ee98a43aa5d60c466f2b6e8 (MD5) / Made available in DSpace on 2017-08-08T14:07:24Z (GMT). No. of bitstreams: 1 eduardosiqueiraferandes.pdf: 2252400 bytes, checksum: 56e960a38ee98a43aa5d60c466f2b6e8 (MD5) Previous issue date: 2009-08-13 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O extrato de Ginkgo biloba (EGb) é usado no tratamento e prevenção de doenças neurodegenerativas, como antiinflamatório, no tratamento da vertigem, na perda de memória relacionada a idade. Efeitos do extrato de ginkgo na reprodução demonstraram que ele inibia a fertilização por reduzir a viabilidade de espermatozóides e degenerar o oócito. Administrado a camundongos alterou o peso de órgãos como a próstata e alterou o perfil reprodutivo desses animais – levando a uma menor taxa de prenhez e aumento das mortes embrionárias. Em ratas, o EGb demonstrou causar crescimento intra-uterino restrito, aventando-se a possibilidade do efeito ter sido causado por sua atividade estrogênica. Outros trabalhos também demonstraram efeito estrogênico do Ginkgo biloba. Sabe-se que os níveis adequados de estrogênio, progesterona e de prostaglandinas são cruciais para o transporte do concepto pela tuba uterina e sua implantação uterina, portanto existe a possibilidade da administração do EGb no início da prenhez causar alterações no desenvolvimento embrionário, sendo esse o propósito do presente trabalho. Para o estudo foram usadas 68 ratas Wistar, adultas, nulíparas, prenhes, provenientes do Biotério do Centro de Biologia da Reprodução, Universidade Federal de Juiz de Fora. As ratas foram distribuídas aleatoriamente em quatro grupos experimentais (n=17): Controle e tratados Gb 3.5, Gb 7 e Gb 14, que receberam, respectivamente, 3,5, 7 e 14mg/Kg/dia do extrato de Ginkgo biloba em 1mL de suspensão aquosa, via intragástrica, uma vez ao dia, durante os oito primeiros dias de prenhez. As ratas do grupo controle receberam pelo mesmo esquema 1mL de água destilada. As ratas foram eutanasiadas, no 15o dia de prenhez, por exsanguinação total sob anestesia. Foram avaliados: sinais clínicos indicativos de toxicidade materna – entre outros, alteração do consumo de ração e de água, alteração do peso corporal, hiper ou hipoatividade, piloereção, estereotipia, perfil bioquímico e hematológico e morte –; número de corpos lúteos; peso de órgãos maternos (ovários, fígado e rins); perfil hematológico e bioquímico maternos; peso de fetos e de placentas; número de fetos viáveis, reabsorvidos e mortos; malformações fetais em membros superiores e inferiores, fechamento de tubo neural e morfologia de face. Com exceção do perfil bioquímico materno em que houve aumento do nível de colesterol e decréscimo dos níveis de ALT, uréia e creatinina, significativamente relevantes, nos animais tratados com 7 e 14mg/Kg/dia de EGb, nenhuma outra alteração significativa foi encontrada nos parâmetros maternos ou fetais avaliados. De forma geral, o tratamento com EGb em ratas Wistar, durante o período de trânsito tubário e implantação, não causou efeito tóxico no organismo materno, tampouco induziu mortes, crescimento intrauterino retardado ou malfomações fetais. Há ainda indícios de que o EGb poderia agir de forma hepatoprotetora e nefroprotetora quando administrado a ratas Wistar durante o período de prenhez quando usado nas doses 7 e 14 mg/Kg/dia. / The Ginkgo biloba extract (EGb) is mainly used in the treatment for and in the prevention of neurodegenerative diseases. It is also used in the treatment for dizziness, age-related memory loss and as an anti-inflammatory. Effects of EGb on reproduction include fertilization inhibition through the reduction of spermatozoa viability and oocyte degeneration. When administered to male mice, EGb led to alterations in the weight of organs such as the prostate, and in the reproductive behavior of these animals (leading to lower pregnancy rates and embryo death increase). In female rats, EGb was proved to cause intra-uterine growth retardation, this effect being thought to be related to its estrogenic activity. Other studies have also shown EGb estrogenic effects. Adequate levels of estrogen, progesterone and prostaglandins are known to be very important to tubal transit and uterine implantation. Hence, there is the possibility of EGb causing embryonic development alterations when administered in the beginning of pregnancy. Investigating this possibility is the aim of this thesis. In order to achieve that, the following experimental protocol was carried out with 68 nulliparous pregnant Wistar rats. The rats were randomly distributed into four experimental groups (n=17): Control, Gb 3.5, Gb 7 and Gb 14, which were treated, respectively, with zero, 3.5, 7.0 and 14.0mg/Kg/Day of EGb diluted in 1mL of distilled water through gavage, once a day, during the first eight days of pregnancy. Rats were euthanized in the 15th day of pregnancy, through total exsanguination under anesthesia. The following parameters were assessed: clinical signs of maternal toxicity – such as feed and water intake alterations, body weight alterations, hyper or hypoactivity, piloerection, stereotypy, biochemical and hematological profile and death –; number of corpora lutea; maternal organs (ovaries, liver and kidneys) weight; maternal hematological and biochemical profiles; fetuses and placentas weight; number of viable, resorpted and dead fetuses; fetal malformations in both superior and inferior members, neural tube closure and facial morphology. Amongst the parameters evaluated, alterations were found only in the maternal hematological profile. There was significant raise in the cholesterol level and reduction in the levels of ALT, urea and creatinine for the animals treated with 7 and 14mg/Kg/day of EGb. No significant alteration was found for other maternal and fetal parameters evaluated. Hence, it seems that treatment with EGb during both tubal transit and implantation periods did not cause toxic effects to the maternal organism of Wistar rats. Neither did it induce deaths, intra-uterine growth retardation or fetal malformation. There is also evidence that EGb could present hepatoprotective and nephroprotective effects when administered to Wistar rats during pregnancy in the dosages of 7 and 14 mg/Kg/day.

Sun Huimin. / Thesis submitted in: December 2002. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 77-89). / Abstracts in English and Chinese. / TITLE PAGE --- p.i / ACKNOWLEDGEMENTS --- p.ii / ABSTRACT --- p.iii / ABSTRACT IN CHINESE --- p.v / LIST OF PUBLICATIONS --- p.vii / ABBREVIATIONS --- p.viii / TABLE OF CONTENTS --- p.ix / Chapter CHAPTER 1. --- General Introduction --- p.1 / Chapter 1.1 --- Current Status of Herbal Product Use --- p.1 / Chapter 1.2 --- Herb-drug interactions --- p.2 / Chapter 1.2.1. --- Mechanisms of herb-drug interaction --- p.3 / Chapter 1.2.2. --- Pharmacodynamic interaction --- p.3 / Chapter 1.2.3. --- Pharmacokinetic interaction --- p.4 / Chapter 1.2.4. --- Herb-drug interaction involving drug metabolizing enzymes --- p.5 / Chapter 1.3 --- Methodologies for studying herb-drug interactions involving CYP enzymes --- p.7 / Chapter 1.3.1. --- Animal studies (Ex vivo approach) --- p.7 / Chapter 1.3.2. --- In vitro inhibition/induction studies --- p.8 / Chapter 1.3.3. --- Clinical studies --- p.9 / Chapter CHAPTER 2. --- Effect of flavonoid-containing herbs on CYP 450 enzyme activities: a screening study in rat --- p.11 / Chapter 2.1 --- Introduction --- p.11 / Chapter 2.2 --- Materials and Methods --- p.12 / Chapter 2.2.1. --- Chemicals --- p.12 / Chapter 2.2.2. --- Herbs --- p.12 / Chapter 2.2.3. --- Preparation of herbal extracts --- p.13 / Chapter 2.2.3.1. --- Preparation of Green Tea extract --- p.13 / Chapter 2.2.3.2. --- Preparation of Decaffeinated Green Tea (DGT) and its extracts --- p.13 / Chapter 2.2.3.3. --- "Preparation of extracts of Huang Qin, Ge Gen and Huai Mi" --- p.14 / Chapter 2.2.3.4. --- Preparation of Ginkgo biloba extract suspension --- p.14 / Chapter 2.2.4. --- Animal treatment --- p.14 / Chapter 2.2.5. --- Preparation of rat liver microsomes --- p.15 / Chapter 2.2.6. --- Determination of protein content of liver microsomes --- p.16 / Chapter 2.2.7. --- Determination of microsomal CYP content --- p.17 / Chapter 2.2.8. --- Statistical analysis --- p.19 / Chapter 2.3 --- Results --- p.19 / Chapter 2.4 --- Discussion --- p.24 / Chapter 2.5 --- Conclusion --- p.25 / Chapter CHAPTER 3 --- Rationale of the clinical study --- p.26 / Chapter CHAPTER 4 --- Development of HPLC methods for simultaneous determination of multiple probe drugs and their metabolites in human plasma or urine --- p.30 / Chapter 4.1 --- Introduction --- p.30 / Chapter 4.2 --- Materials and Methods --- p.33 / Chapter 4.2.1. --- Chemicals and reagents --- p.33 / Chapter 4.2.2. --- Preparation of stock and working solutions --- p.33 / Chapter 4.2.3. --- Equipment and chromatographic conditions --- p.34 / Chapter 4.2.4. --- Treatment of plasma and urine samples with β-glucuronidase --- p.35 / Chapter 4.2.5. --- Extraction procedures --- p.36 / Chapter 4.2.6. --- Preparation of working solutions for calibration curve --- p.37 / Chapter 4.3 --- Results --- p.39 / Chapter 4.3.1. --- Separation of the analytes --- p.39 / Chapter 4.3.2. --- Calibration and linearity --- p.39 / Chapter 4.3.3. --- Sensitivity --- p.39 / Chapter 4.3.4 --- Accuracy and precision --- p.50 / Chapter 4.4 --- Discussion --- p.52 / Chapter 4.5 --- Conclusions --- p.53 / Chapter CHAPTER 5 --- Stability study of probe drugs --- p.54 / Chapter 5.1 --- Introduction --- p.54 / Chapter 5.2 --- Materials and Methods --- p.54 / Chapter 5.2.1. --- Preparation of standard solutions of probe drugs --- p.54 / Chapter 5.2.2. --- Preparation of stability study mediums --- p.54 / Chapter 5.2.2.1. --- Gastric juice (pH=1.2) --- p.54 / Chapter 5.2.2.2. --- Intestine fluid (pH=6.8) --- p.54 / Chapter 5.2.2.3. --- Human plasma (pH=7.4) --- p.55 / Chapter 5.2.2.4. --- Phosphate buffer (pH=7.4) --- p.55 / Chapter 5.2.3. --- Incubation --- p.55 / Chapter 5.2.4. --- Determination of probe drug concentrations in incubation samples --- p.56 / Chapter 5.3 --- Results --- p.57 / Chapter 5.4 --- Discussion --- p.59 / Chapter 5.5 --- Conclusion --- p.59 / Chapter CHAPTER 6 --- Effect of the extract of Ginkgo biloba leaf (761) on CYP isozymes in human subjects --- p.60 / Chapter 6.1 --- Introduction --- p.60 / Chapter 6.2 --- Materials and Methods --- p.60 / Chapter 6.2.1. --- Drugs --- p.60 / Chapter 6.2.2. --- Subjects --- p.61 / Chapter 6.2.3. --- Study design --- p.62 / Chapter 6.2.4. --- Determination of probe drugs/metabolites in the plasma and urine --- p.63 / Chapter 6.2.5. --- Data analysis --- p.65 / Chapter 6.2.6. --- Statistical analysis --- p.66 / Chapter 6.3 --- Results --- p.66 / Chapter 6.3.1. --- Effect of EGb761on CYP1A2 activity --- p.66 / Chapter 6.3.2. --- Effect of EGb761on CYP2E1 activity --- p.67 / Chapter 6.3.3. --- Effect of EGb761 on CYP450 3A activity --- p.68 / Chapter 6.3.4. --- Effect of EGb761 on NAT2 activity --- p.69 / Chapter 6.3.5. --- Effect of EGb761 on CYP2D6 activity --- p.70 / Chapter 6.3.6. --- Effects of EGb761 on CYP2C19 activity --- p.71 / Chapter 6.4 --- Discussion --- p.72 / Chapter 6.5 --- Conclusion --- p.76 / References --- p.77 / Appendix --- p.90

published_or_final_version / abstract / toc / Anatomy / Master / Master of Philosophy

Vieni populiariausių vaistinių preparatų Europoje yra dviskiaučių ginkmedžių (Ginkgo biloba L.) lapų preparatai. Nors Ginkgo biloba lapų ekstraktai pasižymi plačiu farmakologiniu pritaikymu, tačiau nėra daug duomenų apie jų poveikį mitochondrijoms. Todėl darbo tikslas buvo ištirti dviskiaučių ginkmedžių lapų ekstraktų poveikį žiurkės širdies ir kepenų mitochondrijų oksidacinio fosforilinimo sistemai. Darbo uždaviniai: 1. Ištirti dviskiaučių ginkmedžių lapų ekstraktų poveikį žiurkės širdies permeabilizuotų skaidulų bei izoliuotų širdies ir kepenų mitochondrijų kvėpavimui. 2. Ištirti dviskiaučių ginkmedžių lapų tinktūros poveikio oksidaciniam fosforilinimui širdies mitochondrijose mechanizmą. 3. Įvertinti dviskiaučių ginkmedžių lapų tinktūros poveikį izoliuotos žiurkės širdies elektromechaniniam aktyvumui ir nustatyti kaip greit tinktūros komponentai patenka į ląstelę ir mitochondrijas. 4. Ištirti ar dviskiaučių ginkmedžių lapų tinktūra apsaugo širdies mitochondrijas nuo žalingo išemijos/reperfuzijos poveikio. 5. Ištirti dviskiaučių ginkmedžių lapų tinktūros poveikį mitochondrijų oksidacinio fosforilinimo sistemai in vivo, įvedant ją per os. / Ginkgo biloba-derived preparations have become widely used in medical practice. Thougt extracts of Ginkgo biloba leaves have a wide pharmacological application, little is known about extract effects on mitochondria. Therefore, the aim of this study was to investigate the influence of extracts of Ginkgo biloba leaves on mitochondrial oxidative phosphorylation system. The tasks of the study were following: 1. To investigate the effects of extract of Ginkgo biloba leaves on the respiration of isolated heart and liver mitochondria and permeabilized heart fibers. 2. To analyze the mechanism(s) of extract of Ginkgo biloba leaves on mitochondrial oxidative phosphorylation system. 3. To determine the effect of extract of Ginkgo biloba leaves on perfused rat heart electromechanical activity and to analyze how GBE given to isolated perfused rat hearts readily can penetrate into the heart cells and mitochondria. 4. To test whether perfusion with Ginkgo biloba extract protects heart mitochondria against ischemia/reperfusion damage. 5. To investigate the effect of extract of Ginkgo biloba leaves on mitochondrial oxidative phosphorylation system in vivo.

Thesis (Ph. D. (Pharmacy))--Rhodes University, 2006.