Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-08-22T12:37:56Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Thalita Pedon de Araujo.pdf: 2526779 bytes, checksum: a40c82344a005b431aae114c685b4df6 (MD5) / Made available in DSpace on 2016-08-22T12:37:56Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Thalita Pedon de Araujo.pdf: 2526779 bytes, checksum: a40c82344a005b431aae114c685b4df6 (MD5) Previous issue date: 2016-02-26 / CAPEs / A bioequivalência de três formulações de metronidazol (MTZ) 0,75% sendo uma delas disponível no Brasil, Rozex® (Galderma, Brasil, produto de referência) e duas formulações geleificadas (Teste 01 e Teste 02) desenvolvidas em nosso laboratório contendo os mesmos excipientes do produto referência foram avaliadas por meio de um estudo aberto, randomizado, de dois períodos e cruzado, realizado em 14 voluntários brasileiros saudáveis. Uma dose única de 143,5 mg de formulação tópica foi aplicada em duplicata em cada braço do voluntário e o estrato córneo foi coletado em período de 6 e 12 horas após a aplicação correspondente ao tempo de absorção e eliminação respectivamente. O perfil de concentração do metronidazol (MTZ) no estrato córneo (EC) após a aplicação foi determinado pela remoção sequencial das camadas de EC utilizando fita adesiva (Scotch Tape Livro, 3M, St. Paul, MN). Cada local de aplicação foi tratado com 30 fitas. Todas as fitas foram pesadas antes e depois do procedimento de tape stripping em balança (Sartorius®) para posterior cálculo da quantidade de EC extraída. Após o procedimento de extração do fármaco das fitas as concentrações do MTZ no estrato córneo foram determinadas utilizando cromatografia líquida de alta eficiência – CLAE e a avaliação dos dados foi realizada de duas diferentes formas seja considerando ou não o volume de estrato córneo coletado. A análise da bioequivalência tópica in vivo dos produtos contendo metronidazol através da dermatofarmacocinética (DPK) demonstrou com confiança de 95% no intervalo de 80% - 125% que o produto Teste 01 é bioequivalente ao produto de referência Rozex e que o produto Teste 02 é bioinequivalente ao produto de referência Rozex, considerando ou não a quantidade de estrato córneo coletado. Conclui-se assim que, apenas 0,5% a mais de agente espessante no Teste 2 foi suficiente para aumentar a viscosidade em 1,4 vezes e para diminuir a espalhabilidade em 3 vezes deste produto, levando a uma não-bioequivalência entre o teste 2 e o produto de referência que continham os mesmos constituintes. Resultado que demostra a necessidade de mudança na legislação brasileira atual. / The bioequivalence of three formulations of metronidazole (MTZ) 0.75% being one available in Brazil, Rozex® (Galderma, Brazil, reference product) and two formulations (Test 01 and Test 02) developed in our laboratory, containing the same excipients reference product were evaluated using an open, randomized, two-period, crossover healthy Brazilian performed in 14 volunteers. A single dose of 143.5 mg of topical formulation was applied in duplicate on each of the volunteer arm and the stratum corneum was collected in a period of 6 and 12 hours after the application corresponding to the time of absorption and elimination, respectively. The concentration profile of metronidazole (MTZ) in the stratum corneum (SC) after application was determined by sequential removal of the EC layers using adhesive tape (Scotch Book Tape, 3M, St. Paul, MN). Each application site was treated with 30 tapes. All tapes were weighed before and after the tape stripping procedure on scale (Sartorius®) for subsequent calculation of the amount of EC extracted. After the drug extraction procedure ribbons concentrations of MTZ in the stratum corneum have been determined using high-performance liquid chromatography - HPLC and data evaluation was done in two ways considering whether or not the volume of the stratum corneum collected. The analysis of topical bioequivalence in vivo products containing metronidazole by dermatofarmacocinética (DPK) has shown with 95% confidence in the 80% range - 125% that the product test 01 is bioequivalent to Rozex reference product and that the product test 02 is bioinequivalente Rozex the reference product, considering or not the amount of stratum corneum collected. It is therefore concluded that only 0.5% more thickener in Test 2 was sufficient to increase the viscosity by 1.4 times and to reduce the spreadability of this product 3 times, leading to a non-bioequivalence between the test 2 and the reference product containing the same constituents. A result that demonstrates the need for change in the current Brazilian legislation.

Orientador: Gilberto De Nucci / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T00:45:29Z (GMT). No. of bitstreams: 1 Cavedal_LuizEduardo_M.pdf: 4045758 bytes, checksum: 5a5eef2831b79d1e23a2a7214378a9ec (MD5) Previous issue date: 2014 / Resumo: O objetivo foi o desenvolvimento de um método rápido, sensível e específico para quantificar clonazepam em plasma humano. Posteriormente esse método foi utilizado em um estudo de bioequivalência para comparar a biodisponibilidade entre duas formulações de clonazepam comprimidos de 2 mg em 40 voluntários saudáveis de ambos os sexos. Materiais e métodos: O estudo foi conduzido em dois períodos de confinamento dos voluntários, com 18 dias de intervalo entre o primeiro período e o segundo. Os plasmas dos voluntários, após a administração dos medicamentos, foram obtidos em diversos pontos de coleta dentro de um intervalo de 72 horas. As concentrações de clonazepam foram analisadas por cromatografia de fase reversa combinada e espectrometria de massas (LC-MS-MS) com eletrospray de ionização positiva usando o método de monitoramento de ion selecionado. Das curvas de concentração plasmática de Clonazepam vs tempo foram obtidos os seguintes parâmetros farmacocinéticos: Cmax e ASC0-72. Resultados: A média geométrica da relação Clonazepam/ Rivotril? 2 mg foi de 100.30% (90% CI=91.59-109.85%) para Cmax e 101.1% (90% CI=97.60-104.72%) para ASC0-72. Conclusão: Considerando que o CI de 90% (intervalo de confiança) para ambos Cmax e ASC0-72 obedeceram ao intervalo proposto pela Agência Nacional de Vigilância Sanitária (ANVISA) de 80-125%, foi concluído que Clonazepam 2 mg comprimido é bioequivalente ao Rivotril? 2 mg / Abstract: The objective was a development of a rapid, sensitive and specific method for clonazepam quantification in human plasma. This method was used in a bioequivalence study to compare the bioavailability of two clonazepam tablet 2 mg formulations in 40 health volunteers of both sexes. Material and methods: The study was conducted in two-period crossover design and an 18 days washout period. The volunteers plasma samples were obtained, after dose, over several times until 72-hour interval. Clonazepam concentrations were analysed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionisation using selected ion-monitoring method. From the Clonazepam plasma concentration vs time curves the following pharmacokinetic parameters were obtained: Cmax and ASClast. Results: Geometric mean of Clonazepam/ Rivotril? 2 mg individual percent ratio was 100.30% (90% CI=91.59-109.84%) for Cmax and 101.1% (90% CI=97.61-104.72%) for ASC0-72. Conclusion: Since the 90% CI (confidence interval) for both Cmax and ASClast were within the 80-125% interval proposed by the Agencia Nacional de Vigilância Sanitária (ANVISA), it was concluded that Clonazepam 2 mg tablets was bioequivalent to Rivotril? 2 mg, according to both the rate and extent of absorption / Mestrado / Farmacologia / Mestre em Farmacologia

Orientador: Ronilson Agnaldo Moreno / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-18T19:06:44Z (GMT). No. of bitstreams: 1 Boldrina_LucasWillianLeal_M.pdf: 4238858 bytes, checksum: f936f1b9588d396ee62a90e197d6665d (MD5) Previous issue date: 2011 / Resumo: O objetivo deste estudo foi avaliar a bioequivalência de Fenoximetilpenicilina comprimido (500.000 UI) da Aché Laboratórios S/A, Meracilina formulação teste e Pen-Ve-Oral®, produzido por Eurofarma Laboratórios Ltda., Brasil, em voluntários sadios de ambos os sexos. O estudo foi do tipo aberto, randomizado, cruzado, com 2 tratamentos, 2 seqüências, 2 períodos, com uma semana de intervalo entre as doses, nos quais os voluntários receberam em cada período a formulação teste e a formulação de referência. Uma única dose de cada formulação foi administrada a 26 voluntários sadios. A seqüência de tratamento foi determinada por uma lista de randomização gerada automaticamente pelo sistema SCPCM (Sistema de Controle de Pesquisas Cínicas de Medicamentos). As amostras de plasma foram coletadas num intervalo de 36 horas. As concentrações de Fenoximetilpenicilina foram analisadas por cromatografia líquida de alta eficiência acoplada a um detector UV-visível. A partir da curva da concentração de Fenoximetilpenicilina no plasma vs tempo foram obtidos os parâmetros farmacocinéticos: ASC0-t,, ASC0-inf, e Cmax. As médias geométricas da Meracilina e Pen-Ve-Oral® foram: 99.89% (90% CI = 94,62%; 105,46%) para ASC0-t 99.76 (90% CI = 94,09%; 105,78%) para ASC0-inf 101.11% (98.61% - 103.37% ) para Cmax,. Diante dos resultados encontrados de Cmax e ASC0-t e estando dentro do intervalo de confiança entre 80% e 125% proposto pela Agência Nacional de Vigilância Sanitária (ANVISA) e pelo Food and Drug Administration (FDA), conclui-se que a Meracilina - comprimidos (500.000 UI) é bioequivalente ao Pen-Ve-Oral®, de acordo com sua taxa de extensão e biodisponibilidade / Abstract: This study aimed to compare the bioequivalence between Phenoxymethylpenicillin tablets (500.000 UI), a test formulation Meracilina by Aché Laboratórios S/A, and the Pen-Ve-Oral® tablet formulation elaborated by Eurofarma Laboratórios Ltda., Brazil, in healthy human volunteers of both sexes. The study was carried out by using an open, randomized-crossover design, consisting of a two-period treatment, in which the volunteers received, in each period, the test formulation or the reference formulation, with a seven-day washout interval. A single dose of each formulation was administered to 26 healthy volunteers. The treatment sequence was determined by a randomization list, automatically produced by the Clinical Trial Medicine Control System. Plasma samples were obtained over a 36-hour period. Phenoxymethylpenicillin concentrations were analyzed by high pressure liquid chromatography and UV-visible detection (HPLC-UV). From the Phenoxymethylpenicillin plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained: ASC0-t, ASC0-inf, and Cmax. The mean of Meracilina/Pen-Ve-Oral® 500.000 UI percent geometric mean was 99.89% for AUC0-t, 100.86% for AUC0-? and 101.11% for Cmax. The 90% confidence intervals were 94.62 - 105.46%, 95.22 - 106.83% and 98.61 - 103.87%, respectively. Considering the results of Cmax. and AUC0-t within the confidence interval between 80% and 125% proposed by the Brazilian National Agency for Sanitary Surveillance (Anvisa) and for the US Food and Drug Administration (FDA), it was concluded that Meracilina tablet (500.000UI) by Eurofarma Laboratórios Ltda. is bioequivalent to Pen-Ve-Oral® tablet for both rate and extent of bioavailability / Mestrado / Farmacologia / Mestre em Farmacologia

A method is presented for the simultaneous identification of nine compounds in samples of A. membranaceus and A. membranaceus var. mongholicus. Compounds identified in the extracts of the two plants included glycosides, saponins and flavonoids. They are identified as Calycosin-7-O-beta-D-glucoside (C1), Ononin (C2), (6aR,11aR)-3-hydroxy- 9,10-dimethoxypterocarpan-3-O-beta-D-glucoside (C3), (3R)-7,2'-dihydr- oxy-3',4'-dimethoxyisoflavan-7-O-beta-D-glucoside (C4), Calycosin (C6), Astragaloside IV (C5 ), Formononetin (C7), (6aR,11a R)-3-hydroxy-9,10-di-methoxypterocarpan (C8), and Isomucronulatol (C9). / An HPLC-DAD-MS method is proposed for the differentiation of Rhizoma Coptidis and Cortex Phellodendri samples. This method can also be used to identify two common species of Rhizome Coptidis, i.e., C. chinensis and C. deltoidea, and two species of Cortex Phellodendri, i.e., P. chinensis and P. amurense. From the experiment results, there are thirteen, twelve and seven common components found in samples Rhizoma Coptidis, P. amurense and P. chinensis, respectively. Nine compounds in Rhizoma Coptidis were identified to be alkaloids. The common components in Cortex Phellodendri included four alkaloids and two lactones, i.e., obaculacotone and obacunone, present in all samples of P. amurense. / High Performance Liquid Chromatography-Atmospheric Pressure Chemical Ionization Mass-Spectrometry has been applied to the analysis and standardization of Chinese Herbal Medicines. The applications included quantitative study of Astragaloside in Radix Astragali, investigation on the chromatographic fingerprint of Radix Astragali, differentiation of Cortex Phellodendri and Rhizoma Coptidis, and identification of constituents in Sanhuang Xiexin Decoction. / In the quantitative study of Astragaloside, an Multiple Reaction Monitoring scan mode was used. The linearity between 2 and 500 mg/L is 0.9996. The precision of injection and reproducibility of method is 1.72% and 3.27% respectively. A total of 20 samples from local market and mainland China were analyzed and the results are comparable to those obtained from HPLC-ELSD analysis. / The present study also proposed a HPLC separation and online identification for the 15 constituents in a composite Chinese herbal formula, the Sanhuang Xiexin Decoction. It provided a possible starting point to evaluate related herbal preparations containing Rhizoma Coptidis, Radix Scutellariae and Rhizoma Rhei. Thirteen constituents in the decoction were identified, including five major alkaloids from Rhizoma Coptidis, five anthraquinones from Rhizoma Rhei and two favonoids and one glycoside from Radix Scutellariae. / "November 2007." / Adviser: Chi Chun Tao. / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4726. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 177-200). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

A epilepsia é a condição crônica mais prevalente dentre as doenças neurológicas graves, associada com taxas significativas de morbidade e mortalidade. Pacientes com epilepsia farmacorresistente possuem uma taxa de mortalidade 2 a 3 vezes maior que indivíduos sem epilepsia. A epilepsia do lobo temporal (ELT) é a principal causa de epilepsia farmacorresistente nos adultos e também o protótipo da epilepsia cirurgicamente tratável, portanto, com maior acessibilidade para estudo de possíveis mecanismos epileptogênicos. Esclerose hipocampal (EH) é o achado neuropatológico mais comum em pacientes com ELT. Evidências, baseadas em experimentos animais e estudos em humanos, sugerem que as vias serotoninérgicas desempenham um importante papel na epileptogênese. Pacientes com ELT, causadas pela EH, apresentam maior prevalência de transtornos do humor e psicose contribuindo para uma pior qualidade de vida, com consequente impacto negativo nas respostas terapêuticas farmacológicas e cirúrgicas. Além disso, alguns estudos sugerem a existência de um mecanismo patogênico operante comum entre estas condições. Portanto, esta é um importante variável para análise. O objetivo desse estudo foi correlacionar as variáveis clínicas da epilepsia e a presença de transtornos psiquiátricos coexistentes com a concentração de serotonina (5-HT), a densidade dos receptores serotoninérgicos e a densidade do transportador serotoninérgico (5-HTT) no hipocampo dos pacientes com ELT-EH, que foram submetidos à cirurgia devido à presença de epilepsia farmacorresistente. Foram avaliadas amostras de 44 hipocampos de pacientes cirurgicamente tratados para ELT-EH. A concentração de 5-HT foi avaliada por cromatografia líquida de alta eficiência (HPLC) com detecção por fluorescência. 5-HTT e os receptores serotoninérgicos 5-HT1A, 5-HT2A, 5-HT6 e 5-HT7 foram avaliados por Western Blot. Níveis mais baixos de concentração de 5-HT estiveram associados com a presença de crises TCG (Wilcoxon-Mann-Whitney; p = 0.019). A densidade aumentada do receptor 5-HT1A esteve associada com maior duração da epilepsia (coeficiente de correlação de Spearman: p = 0.040) e a densidade diminuída do receptor 5-HT6 esteve associado com presença de EME (Wilcoxon-Mann-Whitney: p = 0.0027). A densidade dos receptores 5-HT2A e 5-HT7 e do 5-HTT não estiveram associadas com variáveis clínicas da epilepsia. A concentração de 5-HT, a densidade dos receptores e a densidade de 5-HTT não estiveram associadas à presença dos transtornos psiquiátricos neste grupo de pacientes. Nossos achados sugerem que as vias serotoninérgicas estão associadas com mecanismos de epileptogênese. Não foi evidenciado associações entre as vias serotoninérgicas e a presença de comorbidades psiquiátricas neste grupo de pacientes com ELT-EH / Epilepsy is the most prevalent neurological condition and it is associated with significative morbidities and mortalities rates. Patients with refractory epilepsy have a 2- to 3-fold higher mortality rate than people without epilepsy. Temporal lobe epilepsy (TLE) is the most common form of adult drug-resistant epilepsy. It is also the prototype of a surgically treatable epilepsy and because of that it is the most accessible for studies focused in epileptogenesis. Hippocampal sclerosis (HS) is the most common neuropathological finding in patients with TLE. Evidences from experimental, clinical and image studies suggest that the serotonergic system play an important role in epileptogenesis. Patients with TLE-HS have a higher prevalence of mood disorder and psychosis contributing for a worse quality of life with and consequent negative impact in pharmacological and surgical responses. Furthermore, studies suggest a common pathogenic mechanism operant in both conditions. Therefore, this is an important analytical variable. The objective of this study was to correlate clinical variables of epilepsy and the presence of psychiatric disease with serotonin (5-HT) concentration, serotonergic receptor density and serotonergic transporter (5-HTT) density in the hippocampus of TLE-HS patients submitted for surgery due to refractory epilepsy. It was analyzed 44 hippocampal tissue samples from surgical treated TLE-HS patients. 5-HT concentration was assessed by high pressure liquid chromatography (HPLC) with fluorescence detection. 5-HTT and serotonergic receptors 5-HT1A, 5-HT2A, 5-HT6 and 5- HT7 were assessed by Western Blotting. Lower levels of 5-HT concentration were associated with the presence of generalized tonic-clonic seizures (Wilcoxon-Mann-Whitney; p = 0.019). A higher 5-HT1A receptor density was associated with longer epilepsy duration (Spearman correlation coefficient: p = 0.040). Lower 5-HT6 receptor density was associated with the presence of status epilepticus (Wilcoxon-Mann-Whitney: p = 0.0027). 5-HT2A receptor, 5- HT7 receptor and 5-HTT densities were not associated with clinical variables of epilepsy. 5-HT concentration, serotonergic receptors and transporter densities were not associated with the presence of psychiatric disease in this group of patients. Our findings suggest that the serotonergic pathways are associated with epileptogenesis mechanisms. It was not evidenced any association between serotonergic pathways and psychiatric comorbidities in this group of TLE-HS patients

<p>Rod Hypericum obuhvata oko 500 različitih vrsta klasifikovanih u 36 sekcija. Najpoznatiji predstavnik roda je kantarion (Hypericum perforatum, Hypericaceae). Hemijska karakterizacija kantariona je bila predmet mnogobrojnih istraživanja koja su pokazala prisustvo različitih klasa jedinjenja, kao i &scaron;irok spektar biolo&scaron;kog potencijala. Međutim, ispitivanja su otkrila prisustvo istih klasa jedinjenja i u drugim predstavnicima roda Hypericum, opravdavajući hemijska istraživanja i određivanje biolo&scaron;kih aktivnosti. S obzirom da se kantarion retko plantažno uzgaja, već uglavnom sakuplja iz prirode, neretko usled nedovoljne obučenosti sakupljača lekovitog bilja dolazi do zamene propisanog biolo&scaron;kog izvora droge Hyperici herba (H. perforatum subsp. perforatum, Hypericaceae) morfolo&scaron;ki sličnim predstavnicima roda, &scaron;to posledično utiče na sadržaj aktivnih principa i biolo&scaron;ki potencijal. Zbog toga su ciljevi ove doktorske disertacije: utvrđivanje uticaja geografskog porekla i stadijuma ontogenetskog razvoja biolo&scaron;kog izvora na kvalitativni i kvantitativni hemijski sastav, biolo&scaron;ki potencijal vodeno-alkoholnog ekstrakta taksona roda Hypericum, kao i utvrđivanje kvaliteta (stepen usitnjenosti, biolo&scaron;ki izvor, hemijski sastav i biolo&scaron;ki potencijal) komercijalno dostupnih čajeva na bazi kantariona koji se nalaze u slobodnoj prodaji. Biljni materijal je obuhvatio uzorke 32 taksona roda Hypericum kao i 51 uzorak monokomponentnih čajeva na bazi kantariona prikupljenih na teritoriji centralnog dela Balkanskog poluostrva, centralne Evrope, Rusije i Turske tokom 2011-2016. godine. U većini ispitanih ekstrakta kvantifikovan je visok sadržaj ukupnih fenola i flavonoida. Rezultati određivanja sadržaja hipericina u ispitivanim ekstraktima pokazali su njegovo prisustvo kod uzoraka svih taksona prikupljenih za vreme cvetanja, pri čemu je to bila i fenofaza u kojoj je dostignut maksimalan sadržaj. Hiperforin je takođe detektovan u većini uzoraka prikupljenih za vreme cvetanja, prateći dinamiku akumulacije sličnu hipericinu. Sa druge strane apigenin i epikatehin nisu detektovani u velikom broju ispitanih ekstrakta, dok je prisustvo naringenina kvantifikovano u manje od 50% uzoraka. Amentoflavon je bio prisutan u manje od 30% ispitanih uzoraka. Visok sadržaj kvercetina i rutina je određen u svim ispitanim ekstraktima, pri čemu u slučaju kvercetina nije zabeleženo značajnije variranje tokom ontogenetskog razvoja, dok je maksimalna koncentracija rutina određena u uzorcima prikupljenim pre, ili za vreme cvetanja. U većini uzoraka detektovane su galna, hlorogenska, kafena i p-hidroksibenzojeva kiselina (naročito u periodu koji prethodi cvetanju), dok ferulna kiselina nije kvantifkovana kod vi&scaron;e od 80% ispitanih ekstrakta. Rezultati su pokazali snažnu antioksidantnu sposobnost ispitivanih ekstrakata. Uočena je snažnija inhibicija monoaminooksidaze A u odnosu na monoaminooksidazu B, kao i vi&scaron;i anti-&alpha;-glukozidazni od anti-&alpha;-amilaznog potencijala. Sposobnost inhibicije acetilholinesteraze je ocenjena kao umerena. Ispitivanje antiproliferativnog potencijala ekstrakata vrsta roda Hypericum, je pokazalo izrazit sinergistički efekat sa antineoplastičnim lekom bleomicinom (radiomimetik) kao i visoku selektivnost prema ćelijama karcinoma cerviksa i melanoma, za razliku od umerenog antiproliferativnog potencijala i niske selektivnosti samih ekstrakata prema malignim ćelijama. Zabeležen je značajan broj neusitnjenih (in toto) komercijalno dostupnih uzoraka čajeva na bazi kantariona, dok su kao biolo&scaron;ki izvor ispitanih uzoraka čajeva identifikovane različite podvrste H. perforatum. Sličnost hemijskog profila i biolo&scaron;kog potencijala velikog broja ispitanih taksona sa H. perforatum ukazuju na mogućnost njihove eksploatacije. Međutim, zavisnost navedenih parametara od geografskog porekla biljnog materijala ističe značajan uticaj abiotičkih ekolo&scaron;kih faktora na kvalitet droge. Hemijski sastav i morfolo&scaron;ko ispitivanje uzoraka monokomponentnih čajeva na bazi kantariona ukazuju na neophodnost kontrole njihovog kvaliteta.</p> / <p>The genus Hypericum includes more than 500 different species classified in 36 sections. The most known representative of genus is St. John&#39;s wort (Hypericum perforatum, Hypericaceae). Chemical characterization of St. John&#39;s wort was the subject of many conducted researches which demonstrated the presence of different classes of compounds, as well as a wide spectrum of biological potential. However, the studies have also shown the presence of the same compounds in other representative of the genus Hypericum, justifying the evaluation of their chemical composition and biological potential. Considering the fact that St. John&#39;s wort is rarely being cultivated, rather collected from nature, unqualified collectors may substitute the official biological source of Hyperici herba (H. perforatum subsp. perforatum, Hypericaceae) for morphologically similar representatives of the genus, consequently affecting the quantities of active principles and biological potential of the drug. The aims of this PhD thesis were to evaluate the influence of geographical origin and stage of ontogenetic development of biological source on qualitative and quantitative chemical composition and biological potential of water - alcoholic extract of different Hypericum taxa, as well as to determine the quality (grinding degree, biological source, chemical composition and biological potential) of commercially available St. John&rsquo;s wort teas on the market. The plant material included samples of 32 taxa of genus Hypericum, as well as 51 commercially available sample of monocomponent teas based on St. John&#39;s wort collected at territory of central part of Balkan Peninsula, central Europe, Russia and Turkey, during period 2011 - 2016. High amounts of total phenolics and flavonoids were quantified in the most of the examined extracts. Quantification of hypericin showed its presence in all of the samples collected during flowering period, while that was also the ontogenetic stage of its maximum accumulation. Hyperforin was also quantified in most of the samples collected during flowering period, following the hypericin trend of accumulation. On the other hand, apigenin and epicatechin were not detected in large number of the examined extracts, while naringenin was detected in less than 50% of samples. Amentoflavone was present in less than 30% of the examined samples. High amounts of quercetin and rutin were determined in all of the examined samples. No significant changes in the amounts of quercetin during ontogenetic development were noticed, while the highest amounts of rutin were determined in samples collected before, or during flowering. Gallic, chlorogenic, caffeic and p-hydroxybenzoic acid were detected in most of the examined samples (especially in period before opening of the flowers), while ferulic acid was not quantified in more than 80% of samples. The results have demonstrated strong antioxidant potential of the examined extracts. Stronger potential of the examined extracts to inhibit monoamine oxidase A than monoamine oxidase B, as well as stronger anti-&alpha;-glucosidase than anti-&alpha;-amylase potential were recorded. The obtained anticholinesterase activity of the examined extracts was moderate. The examination of antiproliferative potential of different Hypericum species extracts has shown additive effects in combination with bleomycin (radiomimetic), as well as high selectivity toward cervix and melanoma cancer cells. On the other hand, moderate antiproliferative potential and low selectivity during treatment of cancer cells only with the examined extracts was recorded. Significant share of in toto commercially available tea samples based on St. John&#39;s wort was noticed, while different subspecies of H. perforatum were identified as biological sources of the examined teas. Chemical profile and biological potential resemblance between a large number of investigated taxa and H. perforatum point to possibilities of their exploitation. However, the dependence of listed parameters from geographical origin of plant material emphasizes the importance of abiotic ecological factors for the quality of herbal drug. Chemical composition and morphological examination of monocomponent teas based on St. John&rsquo;s wort stress the importance of their quality control.</p>

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 4 uppsatser.

A epilepsia é a condição crônica mais prevalente dentre as doenças neurológicas graves, associada com taxas significativas de morbidade e mortalidade. Pacientes com epilepsia farmacorresistente possuem uma taxa de mortalidade 2 a 3 vezes maior que indivíduos sem epilepsia. A epilepsia do lobo temporal (ELT) é a principal causa de epilepsia farmacorresistente nos adultos e também o protótipo da epilepsia cirurgicamente tratável, portanto, com maior acessibilidade para estudo de possíveis mecanismos epileptogênicos. Esclerose hipocampal (EH) é o achado neuropatológico mais comum em pacientes com ELT. Evidências, baseadas em experimentos animais e estudos em humanos, sugerem que as vias serotoninérgicas desempenham um importante papel na epileptogênese. Pacientes com ELT, causadas pela EH, apresentam maior prevalência de transtornos do humor e psicose contribuindo para uma pior qualidade de vida, com consequente impacto negativo nas respostas terapêuticas farmacológicas e cirúrgicas. Além disso, alguns estudos sugerem a existência de um mecanismo patogênico operante comum entre estas condições. Portanto, esta é um importante variável para análise. O objetivo desse estudo foi correlacionar as variáveis clínicas da epilepsia e a presença de transtornos psiquiátricos coexistentes com a concentração de serotonina (5-HT), a densidade dos receptores serotoninérgicos e a densidade do transportador serotoninérgico (5-HTT) no hipocampo dos pacientes com ELT-EH, que foram submetidos à cirurgia devido à presença de epilepsia farmacorresistente. Foram avaliadas amostras de 44 hipocampos de pacientes cirurgicamente tratados para ELT-EH. A concentração de 5-HT foi avaliada por cromatografia líquida de alta eficiência (HPLC) com detecção por fluorescência. 5-HTT e os receptores serotoninérgicos 5-HT1A, 5-HT2A, 5-HT6 e 5-HT7 foram avaliados por Western Blot. Níveis mais baixos de concentração de 5-HT estiveram associados com a presença de crises TCG (Wilcoxon-Mann-Whitney; p = 0.019). A densidade aumentada do receptor 5-HT1A esteve associada com maior duração da epilepsia (coeficiente de correlação de Spearman: p = 0.040) e a densidade diminuída do receptor 5-HT6 esteve associado com presença de EME (Wilcoxon-Mann-Whitney: p = 0.0027). A densidade dos receptores 5-HT2A e 5-HT7 e do 5-HTT não estiveram associadas com variáveis clínicas da epilepsia. A concentração de 5-HT, a densidade dos receptores e a densidade de 5-HTT não estiveram associadas à presença dos transtornos psiquiátricos neste grupo de pacientes. Nossos achados sugerem que as vias serotoninérgicas estão associadas com mecanismos de epileptogênese. Não foi evidenciado associações entre as vias serotoninérgicas e a presença de comorbidades psiquiátricas neste grupo de pacientes com ELT-EH / Epilepsy is the most prevalent neurological condition and it is associated with significative morbidities and mortalities rates. Patients with refractory epilepsy have a 2- to 3-fold higher mortality rate than people without epilepsy. Temporal lobe epilepsy (TLE) is the most common form of adult drug-resistant epilepsy. It is also the prototype of a surgically treatable epilepsy and because of that it is the most accessible for studies focused in epileptogenesis. Hippocampal sclerosis (HS) is the most common neuropathological finding in patients with TLE. Evidences from experimental, clinical and image studies suggest that the serotonergic system play an important role in epileptogenesis. Patients with TLE-HS have a higher prevalence of mood disorder and psychosis contributing for a worse quality of life with and consequent negative impact in pharmacological and surgical responses. Furthermore, studies suggest a common pathogenic mechanism operant in both conditions. Therefore, this is an important analytical variable. The objective of this study was to correlate clinical variables of epilepsy and the presence of psychiatric disease with serotonin (5-HT) concentration, serotonergic receptor density and serotonergic transporter (5-HTT) density in the hippocampus of TLE-HS patients submitted for surgery due to refractory epilepsy. It was analyzed 44 hippocampal tissue samples from surgical treated TLE-HS patients. 5-HT concentration was assessed by high pressure liquid chromatography (HPLC) with fluorescence detection. 5-HTT and serotonergic receptors 5-HT1A, 5-HT2A, 5-HT6 and 5- HT7 were assessed by Western Blotting. Lower levels of 5-HT concentration were associated with the presence of generalized tonic-clonic seizures (Wilcoxon-Mann-Whitney; p = 0.019). A higher 5-HT1A receptor density was associated with longer epilepsy duration (Spearman correlation coefficient: p = 0.040). Lower 5-HT6 receptor density was associated with the presence of status epilepticus (Wilcoxon-Mann-Whitney: p = 0.0027). 5-HT2A receptor, 5- HT7 receptor and 5-HTT densities were not associated with clinical variables of epilepsy. 5-HT concentration, serotonergic receptors and transporter densities were not associated with the presence of psychiatric disease in this group of patients. Our findings suggest that the serotonergic pathways are associated with epileptogenesis mechanisms. It was not evidenced any association between serotonergic pathways and psychiatric comorbidities in this group of TLE-HS patients

<p>Doktorsku disertaciju čine tri celine kojima je zajednički element ispitivanje fenola, u pogledu njihovog sadržaja i dostupnosti u dijetetskim suplementima na bazi grožđa i japanskog troskota, ispitivanja uticaja suplementacije kod eksperimentalnih životinja, odnosno mogućnosti ekstrakcije fenolnih jedinjenja iz komine grožđa. Osnovni ciljevi prvog dela bili su ispitivanje bezbednosti i kvaliteta 14 suplemenata na bazi grožđa i japanskog troskota u pogledu ujednačenosti mase, sadržaja i brzine rastvorljivosti. U drugom delu je radi provere terapijske delotvornosti suplementa koji sadrži čist resveratrol ispitan njegov uticaj na glikemiju i lipidni status eksperimentalnih životinja. Treći deo je obuhvatio analizu pet različitih komina grožđa i razvoj metode ekstrakcije fenola iz odabrane komine kako bi se dobili ekstrakti sa &scaron;to je moguće većim prinosom, koristeći rastvarače koji su bezbedni po ljudsko zdravlje. Rezultati su pokazali da dva od četrnaest suplemenata nisu ispunila zahteve farmakopeje za lekove u pogledu ujednačenosti mase i sadržaja aktivne komponente, dok ni jedan suplement nije ispunio zahteve u pogledu brzine rastvorljivosti aktivne supstance, zbog čega se postavlja pitanje delotvornosti ispitanih suplemenata. Ni kod jednog suplementa nisu kvantifikovani ostaci pesticida ni toksični metali, čime je potvrđena njihova bezbednost. Farmakodinamska ispitivanja na pacovima pokazala su antioksidantna, anti-dijabetska i hipolipidemijska svojstva dijetetskog suplementa na bazi resveratrola, čime je potvrđena njegova delotvornost. Za potvrdu delotvornosti suplementa na ljudima neophodno je sprovesti dobro dizajnirano kliničko ispitivanje na dovoljnom broju ispitanika. Analiza pet različitih komina grožđa pokazala je da ovaj nusprodukt proizvodnje vina sadrži različite fenole, od kojih je samo katehin bio prisutan u značajnoj količini. Kvalitativan i kvantitativan sastav komine značajno varira zavisno od sorte i berbe grožđa, kao i od primenjenog tehnolo&scaron;kog procesa proizvodnje vina. Imajući u vidu sveobuhvatne kriterijume u pogledu efikasnosti ekstrakcije, zaključeno je da su 55% etanol, odnos uzorak / rastvarač 1:40, pH 4,5, T 55&deg;C i vreme od 30 min optimalni eksperimentalni uslovi za ekstrakciju fenola iz komine grožđa. U zavisnosti od osnovnog cilja procesa ekstrakcije ovi parametri se mogu lako modifikovati. Vi&scaron;estruke su mogućnosti za iskori&scaron;ćenje komine grožđa, a jedan od njih bi mogla biti i da se koristi kao sirovina za izradu dijetetskih suplemenata.</p> / <p>The dissertation consists of three parts with a common element &ndash; testing phenols in terms of content and availability in grape and Polygonum cuspidatum-based dietary supplements, testing the supplement&rsquo;s impact on experimental animals and the possibility to extract phenolic compounds from grape pomace. The primary objectives of the first part were testing safety and quality of fourteen grape and Polygonum cuspidatum-based supplements in terms of uniformity of mass, content and dissolution profile. In the second part, to test the therapeutic efficacy of a supplement containing pure resveratrol, its effect on the glycemia and lipid profile of experimental animals was examined. The third part covers the analysis of five different grape pomaces and the development of a phenol extraction method from the selected grape pomace to obtain extracts with the highest possible yield, using solvents that are safe for human health. The results showed that two out of fourteen supplements have not met the Pharmacopoeia requirements in terms of uniformity of mass and active substance content, while no supplement has met requirements in terms of dissolution test of the active substance, which raises the question of the effectiveness of the tested supplements. No pesticide or heavy metal residues were quantified in any of the supplements which confirms their safety. Pharmacodynamic testing on rats has shown antioxidant, antidiabetic and hypolipidemic properties of the resveratrol-based dietary supplement which confirms its efficacy. In order to confirm the supplement efficacy on people, it is necessary to conduct a well-designed clinical trial on a sufficient number of human participants. The analysis of five different grape pomaces revealed that this byproduct of vine production contains different phenols, and only catechin was present in significant amounts. The qualitative and quantitative composition of grape pomace varies significantly depending on grape variety and harvesting as well as on the technological process that was applied in vine production. Considering the comprehensive criteria in terms of extraction efficacy, it was concluded that optimal experimental conditions for the extraction of phenol from grape pomace include 55% ethanol, sample/solvent ratio 1:40, pH 4.5, T 55&deg;C for 30 minutes. Depending on the primary objective in the extraction process, these parameters can be easily modified. There are multiple possibilities for utilizing grape pomace and one of them could be as raw material in production of dietary supplements.</p>