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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Prevalência e validação dos testes para diagnóstico de Trichomonas vaginalis em mulheres grávidas, não grávidas e portadoras do HIV / Prevalence and validity of techniques for the diagnosis of Trichomonas vaginalis in pregnant, non-pregnant and HIV positive women

Lemos, Patrícia Abreu Pinheiro de 04 February 2017 (has links)
Submitted by JÚLIO HEBER SILVA (julioheber@yahoo.com.br) on 2017-02-09T16:33:20Z No. of bitstreams: 2 Tese - Patrícia Abreu Pinheiro de Lemos - 2017.pdf: 4158494 bytes, checksum: 4b77e3a773c3ae35ad05d2c25c885673 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-02-13T09:52:59Z (GMT) No. of bitstreams: 2 Tese - Patrícia Abreu Pinheiro de Lemos - 2017.pdf: 4158494 bytes, checksum: 4b77e3a773c3ae35ad05d2c25c885673 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-02-13T09:52:59Z (GMT). No. of bitstreams: 2 Tese - Patrícia Abreu Pinheiro de Lemos - 2017.pdf: 4158494 bytes, checksum: 4b77e3a773c3ae35ad05d2c25c885673 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-04 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Introduction Trichomonas vaginalis is a flagelate protozoa found in genital human secretions. Tricomoniasis is considered the most prevalent non viral sexually transmitted disease worldwide. Pregnant women and population with immunossupression had the highest frequencies in accord with literature. Purposes The presente study aimed firstly at the systematic review “Trichomonas vaginalis, genetic variation, and HIV-positive women” and secondly focused at the original article “ Association between T. vaginalis in pregant, non-pregnant and HIV-positive women” in order to: a) establish the prevalence of diagnostic techniques in 3 groups of women; b) verify whether imunossupression and/or coinfection conditions represents a risk fator for acquiring T. vaginalis; d) evaluate the accuracy of diagnostic techniques taking PCR as gold standard. Methods The study population included 309 women receiving care at 3 referral public healthcare centers in Goiânia. Pregnant women (100) at Dona Iris Maternity and General Hospital, non-pregnant women at Federal University of Goiás’ Teaching Hospital and 103 HIV-positive women in heathcare at an outpatient clinic of the Tropical Diseases Hospital in Goiânia, Goiás, Brazil. The parasite has been detected comparatively through 4 diagnostic techniques: wet mount, culture, Papanicolaou’s smear and PCR. Accuracy from all techniques was performed in the three women population and PCR was considered gold standard. Results The present study found a positive association between T. vaginalis’ frequency in HIV positive compared with non-pregnant women (ODDS RATIO (OR) 2,26). Comparisom between pregnant women and the non-pregnant women control group demonstrated no association (OR 1,07). PCR technique and wet mount presented the most elevated percentage in the pregnant and HIV positive groups correlated with the women control group. Culture presented almost the same acuracy percentages in the three groups (sensibiity) and the stainning techniques were the most sensibles however with the lowest specificities due to the vast number of false positives (FP). Precancerous lesions were associated with T. vaginalis’ presence both in pregnant and HIV positive women (OR=4,53 and OR-2,12). Conclusion T. vaginalis’ frequency in non- Abstract xvi pregant-women was 18%, in pregnant women was 19% and in HIV positive was 33%. Physiological immunossupression (pregnancy) did not represent risk factor for T. vaginalis’ infection however coinfection for HIV represented risk factor. Accuracy of diagnostic techniques (wet mount and culture) presented higher sensitivitie rates in HIV-positive women (54% e 70%). Cultured T. vaginalis stained by Quick Panoptic presented lower specificity rates in the 3 study groups. / Introdução Trichomonas vaginalis é um protozoário flagelado encontrado em secreções genitais humanas. A Tricomoníase é considerada a doença sexualmente transmissível não viral mais frequente no mundo. Gestantes e portadoras do vírus da imunodeficiência são as que têm apresentado frequências mais elevadas. Objetivos O presente estudo realizou uma revisão sistemática “Trichomonas vaginalis, genetic variation, and pathogenicity” e um artigo original intitulado “Association between T. vaginalis in pregnant, non-pregnant and HIV-positive women” no intuito de: a) estabelecer a frequência dos testes de diagnóstico para detecção do parasito nos 3 grupos de mulheres; b) verificar se as condições de imunossupressão ou coinfecção são fatores de risco para T. vaginalis; c) avaliar a acurácia das técnicas de diagnóstico tendo como padrão-ouro a reação em cadeia da polimerase (PCR). Métodos A população do estudo foi constituída por 309 mulheres atendidas em três hospitais de referência de Goiânia: gestantes no Hospital e Maternidade Dona Iris (HMDI), 106 não gestantes atendidas no Hospital das Clínicas/ Universidade Federal de Goiás, e 103 HIV-positivas atendidas no Hospital de Doenças Tropicais da secretaria estadual de saúde, Goiânia, Goiás, Brasil. A detecção do parasito foi realizada comparativamente através de quatro técnicas de diagnóstico: exame a fresco, cultura, citologia de Papanicolaou e PCR. A acurácia das técnicas foi realizada para as três populações de mulheres onde a PCR foi considerada o padrão ouro. Resultados O presente estudo encontrou chance significativa de associação entre a frequência de T. vaginalis em HIV positivas e a sua frequência em não grávidas representada pelo ODDS RATIO (OR) 2,26. A comparação entre gestantes e o grupo controle de não gestantes não apresentou chance significativa (OR=1,07). A PCR e o exame a fresco apresentaram os percentuais mais elevados no grupo das gestantes e das HIV positivas e a sensibilidade de ambas foi também mais elevada nos dois grupos em relação ao grupo de não grávidas. A cultura apresentou percentuais de acurácia quase que semelhante nos 3 grupos (sensibilidade) e as técnicas coradas foram as mais sensíveis, porém as menos específicas devido ao elevado Resumo xiv número de falsos positivos (FP). A presença de lesões pré-cancerígenas esteve associada à presença de T. vaginalis tanto no grupo das grávidas quanto no das HIV positivas (OR= 4,65 e OR= 2,14). Conclusão A frequência de T. vaginalis em mulheres não grávidas foi 18%, em gestantes foi 19% e em portadoras do HIV foi 33%. A imunossupressão fisiológica (gravidez) não é fator de risco para T. vaginalis, sendo que a co-infecção pelo HIV é fator de risco. No teste de acurácia o exame a fresco e a cultura apresentaram taxas de sensibilidade maior no grupo das HIV-positivas (54% e 70%). Os percentuais de especificidade da cultura corada apresentaram-se baixos nos 3 grupos.
42

Analysis of trichomonas vaginalis antigen by gel diffusion method

Osei, Anthony K. 01 August 1979 (has links)
The antigens of Trichomonas vaginal is grown jn Diamond 1 s medium modified by Klass were analyzed by gel diffusion methods. Three methods were employed in the extraction of the antigens. They were Genetron extract, Borate Buffer Saline extract, and alcohol extract. The alcohol extract was made up of four fractions (TF1 , TF2, TF3, TF4). The antisera used as analytic agents were made in two rabbits obtained from the Center for Disease Control Breeding Colony. All the antigens were compared to show bands of identity, non-identity, and partial identity, and to determine the number of bands produced by each extract. Genetron extract antigen and Borate Buffer Saline extract antigen reacted strongly with the homologous antiserum made in rabbit 3 (R3), producing 4 bands each, while alcohol extract reacted minimally. Fractions TF1 and TF4 produced 3 bands each and fraction TFz and TF3 produced 2 bands each Two bands of precipitate were found to be common to all the antigens, suggesting the similarity of the antigens. In rabbit 4 (R4), 3 bands were produced by each antigen and they were all identical, confirming the similarity of the antigens. Rabbit 3 antiserum reacted more strongly than rabbit 4, even though all the rabbits were inoculated on the same dates with the same number of live Trichomonas vaginalis antigens under the same conditions.
43

Homology pyruvát:feredoxin oxidoreduktázy z hydrogenosomů Trichomonas vaginalis / Pyruvate:ferredoxin oxidoreductase homologues from Trichomonas vaginalis hydrogenosomes

Zedníková, Věra January 2012 (has links)
Oxidative decarboxylation of pyruvate is a fundamental reaction of living organisms in general, leading to energy conservation. In some anaerobic or microaerophilic eukaryotic or prokaryotic organisms pyruvate decarboxylation is carried out by a single enzyme, pyruvate:ferredoxin oxidoreductase (PFO). PFO contains Fe-S clusters and thiamin pyrophosphate cofactor (TPP). In the reaction catalyzed by PFO, from pyruvate and Co-A arise acetyl-CoA, CO2, and two electrons are released. Those electrons are accepted by low molecular carrier proteins. Most frequently these proteins are ferredoxins or flavodoxins such as in nitrogen fixating bacteria. PFO can perform a reversible reaction. Trichomonads are mostly parasitic or endosymbiotic organisms with mitochondria-like organelles, hydrogenosomes. These organelles possess PFO which is one of the key enzymes in the metabolism of Trichomonas vaginalis hydrogenosomes. PFO of T. vaginalis, a sexually transmitted pathogen of man, plays also a role in a term of medical importance. PFO is, by a universally accepted concept, one of the key proteins acting in the activation of antimicrobial drugs against trichomoniasis 5-nitroimidazoles, including metronidazole. In the genome of T. vaginalis seven PFO genes were identified. They were named PFO A, B1, B2, C, D, E and...
44

Reduktivní Evoluce Organel Mitochondriálního Původu u Anaerobních Protist / Reductive Evolution of Mitochondria - Related Organelles in Anaerobic Protist

Rada, Petr January 2011 (has links)
Charles University in Prague, Faculty of Science Department of Parasitology Ph.D. study program: Parasitology Abstract of the Ph.D. Thesis Reductive Evolution of Mitochondria - Related Organelles in Anaerobic Protist Petr Rada Supervisor: Prof. RNDr. Jan Tachezy,Ph.D. Advisor: Doc. RNDr. Ivan Hrdý, Ph.D. Praha, 2011 1 ABSTRACT Trichomonas vaginalis and Giardia intestinalis are parasitic protists of the Excavata group. Both contain anaerobic forms of mitochondria called hydrogenosomes (Trichomonas) and mitosomes (Giardia). Hydrogenosomes produce hydrogen and ATP by substarte level phosphorylation and mitosomes represent the highly-reduced form of mitochondria that do not participate in cellular energy metabolism and ATP generation. Both types of organelles lost the majority of mitochondrial pathways and their genomes during the mitochondrion to hydrogenosome transition. Consequently, hydrogenosomes and mitosomes facilitate translocation of nuclearly encoded proteins into the matrix of the organelle as well as exchange of metabolites and ions across their membranes. Little is known about the membrane machineries required for the biogenesis of the organelle and metabolite exchange and the limited knowledge of mitosomal proteomes has been mostly gained from genomic analysis and localization studies of a few...
45

Potencial anti-trichomonas vaginalis de Manilkara rufula análise fitoquímica, semissíntese e mecanismo de morte do parasito / Manilkara rufula anti-Trichomonas vaginalis potential : phytochemistry analysis, semi-synthesis and mechanism of death of the parasite

Vieira, Patrícia de Brum January 2015 (has links)
Embora seja uma das áreas mais ameaçadas na Terra, há poucos estudos sobre o potencial farmacológico da Caatinga. Este bioma é exclusivamente brasileiro e as plantas encontradas na região apresentam características únicas que as tornam fontes imensuráveis de compostos ativos. O parasito Trichomonas vaginalis é o agente etiológico da tricomoníase, a doença sexualmente transmissível não viral mais comum no mundo. A infecção está associada a sérias consequências em saúde e casos de resistência ao fármaco de escolha, metronidazol, estão em constante crescimento. Desta forma, a necessidade por alternativas para o tratamento da tricomoníase é evidente. O objetivo desta tese foi avaliar o potencial anti-T. vaginalis de plantas oriundas da Caatinga. A planta Manilkara rufula apresentou a mais potente atividade frente ao parasito e um fracionamento bioguiado foi realizado. Triterpenos pentacíclicos (caproato de α- e β-amirina, acetato de β-amirina e lupeol) foram identificados nas frações apolares de M. rufula, porém com baixa atividade antiparasitária. Derivados triterpênicos semissintéticos, frações contendo flavonoides, taninos e saponinas também foram testados. Nossos resultados demonstraram que o ácido ursólico e a fração H100 apresentaram potente atividade anti-T. vaginalis e ambos afetaram o crescimento e viabilidade dos trofozoítos. Além disso, o ácido ursólico e a fração H100 induziram importantes alterações na ultraestrutura dos organismos, indicando que o mecanismo de morte do parasito ocorreu por danos na membrana. A fração H100 induziu a lise total de eritrócitos e reduziu a adesão dos parasitos às células epiteliais, sugerindo, novamente, a ação sobre membrana. A fração H100 não apresentou citotoxicidade às células epiteliais. Os resultados apresentados demonstraram o potencial da planta M. rufula contra T. vaginalis e contribuem para o entendimento das propriedades farmacológicas das plantas da Caatinga, bem como para o desenvolvimento racional de alternativas para o tratamento da tricomoníase. / Although it is one of the most endangered areas on Earth, there are few studies on the pharmacological potential of the Caatinga. This is an exclusively Brazilian biome and its plants present unique characteristic that make them an immeasurable source of active compounds. The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. The infection has been associated with serious consequences in health and cases of resistance to metronidazole are constantly increasing. Then, the necessity of new alternatives to the treatment of trichomoniasis is evident. The aim of this thesis was to evaluate the anti-T. vaginalis potential of plants from Caatinga. The Manilkara rufula plant showed the most potent activity against the parasite and bioguided fractionation was performed. Pentacyclic triterpenes (α- and β-amyrin caproate and β-amyrin and lupeol acetate) were identified in the nonpolar fractions of M. rufula, however, low antiparasitic activity was observed. Triterpenic semisynthetic derivatives, fractions containing flavonoids, tannins and saponins were also tested. Our results showed that ursolic acid and H100 fraction exhibited potent anti-T. vaginalis activity and both affect growth and viability of trophozoites. In addition, ursolic acid and H100 fraction induced significant alterations in the ultrastructure of the parasite, indicating that the mechanism of death is by membrane damage. The H100 fraction induced complete lysis of erythrocytes and reduced the parasites adhesion to epithelial cells, once again, suggesting that the H100 action was on parasite membrane. The fraction H100 showed no cytotoxicity to epithelial cells. The results demonstrated the potential of the plant M. rufula against T. vaginalis and contributed to the understanding of the pharmacological properties of the Caatinga plants, as well as for the rational development of alternatives for trichomoniasis treatment.
46

Síntese e atividade anti-Trichomonas vaginalis de chalconas

Trein, Marcia Rodrigues January 2017 (has links)
Tricomoníase é a doença sexualmente transmissível não-viral mais comum no mundo e pode gerar sérias consequências na saúde reprodutiva, câncer e transmissão e aquisição do HIV. Por esta razão, esta infecção resulta em um pesado fardo para os sistemas de saúde pública. O único tratamento aprovado para esta infecção, que consiste nos 5-nitromidazois metronidazol e tinidazol, apresenta efeitos adversos e há uma subestimada taxa de resistência da infecção, atualmente considerada uma doença negligenciada, a estes fármacos. Portanto, há uma necessidade urgente de novas alternativas terapêuticas para a tricomoníase. Chalconas são uma família de moléculas que apresenta várias aplicações biológicas, como atividade contra diversos patógenos, incluindo protozoários patogênicos. Este trabalho apresenta o potencial anti-Trichomonas vaginalis de derivados de chalcona sintetizados e seus efeitos sobre os trofozoítos. Os valores de IC50 dos compostos mais ativos variaram de 27,5 a 76,4 μM, e as moléculas 4’-hidroxichalcona e 3’-aminochalcona apresentaram os valores mais baixos (27,5 e 28,9 μM). Estes dois compostos foram citotóxicos contra a linhagem de células epiteliais vaginais HMVII, consequentemente apresentaram baixos Índices de Seletividade; contudo, ao se utilizar larvas de Galleria mellonella, como modelo de toxicidade in vivo, não foi observada diminuição da viabilidade após o tratamento. As moléculas também não provocaram hemólise em eritrócitos humanos em 1 e 24 horas. Os compostos não induziram significativa produção de espécies reativas de oxigênio (EROs) nos trofozoítos. Neutrófilos humanos apresentaram aumento na produção de EROs quando coincubados com trofozoítos tratados com os compostos. Os resultados indicam que as chalconas são uma família de moléculas com potencial atividade contra T. vaginalis. / Trichomoniasis is the most common non-viral sexually transmitted disease worldwide and can lead to serious consequences in reproductive health, cancer and HIV acquisition. For this reason, this infection results in a heavy burden for public health systems. Current approved treatment, which consists in 5-nitromidazole drugs, metronidazole and tinidazole, present adverse effects and there is underestimate drug resistance data on this parasitic infection, currently considered a neglected disease. Therefore, there is an urgent need for new alternatives for trichomoniasis treatment. Chalcones are a family of molecules that present various biological applications, such as activity against many pathogenic organisms including protozoan pathogens. This study presents the anti-Trichomonas vaginalis potential of synthetized chalcone derivatives and their effects on the trophozoites. IC50 values of the most active compounds ranged from 27.5 to 76.4 μM, and 4’-hydroxychalcone and 3’- aminochalcone presented the lowest values of IC50 (27.5 and 28.9 μM). These two compounds showed cytotoxicity against HMVII vaginal epithelial cells, thus presenting a low Selectivyty Index; however, when Galleria mellonella larvae were used as model for in vivo toxicity no significant decrease in viability after treatment was observed. The chalcones also did not induce hemolysis in human erythrocytes The compounds did not induce significant reactive oxygen species (ROS) production in the trophozoites. Human neutrophils have increased ROS production when exposed to treated trophozoites. Results indicate that chalcones are a family of molecules with potential activity against T. vaginalis.
47

Pathogenic effect of Trichomonas vaginalis on various cell lines in vitro.

Bhojraj, Neetha. January 2010 (has links)
Trichomoniasis has been linked to pelvic inflammatory disease, cervical cancer, increased HIV transmission, infertility as well as co-infections with other STIs. In 2002, an association was found with Trichomonas vaginalis and PID in HIV positive women. Therefore, the question arose whether T. vaginalis is able to invade the upper genital tract of HIV infected women. A prerequisite for invasion of the upper genital tract is the capability of the organism to adhere to the cells of the organs involved. This study therefore investigated the interaction between T. vaginalis and vaginal, cervical and endometrial cells. In comparing adhesion and cytotoxicity of T. vaginalis to cells of the upper and lower genital tract at different pH, immortalized vaginal (VK2), cervical (ME 180) and endometrial (KLE) cells were exposed to a standardized inoculum of trichomonads at pH 4.5 to 7.0. Adhesion was measured microscopically after acridine orange staining and cytotoxicity was established by measuring LDH release using a commercial kit. Adhesion of the ME-180 and VK2 cell lines was found to be pH dependent. However, the KLE cell line was not. As the pH increased, adherence to the vaginal and cervical cells decreased. Adhesion to endometrial cells was minimal at neutral pH but marked adhesion was found at lower pH. For the vaginal cell line, cytotoxicity was minimal at pH 4.5 but substantial (30 to 60%) at higher pH. In contrast, cytotoxicity on cervical and endometrial cells was highest at lower pH. The pronounced toxicity of vaginal epithelial cells at pH 5 and pH 5.5 is in keeping with the pH range found in patients with vaginitis. The observations on the cervical epithelium suggest toxic effect on the ecto-cervical epithelium immediate after acquisition of the infection. Adhesion of trichomonads to the endometrial cell line suggests that T. vaginalis is capable of colonization of the upper genital tract. At pH values applicable to the in vivo situation, toxicity was very low. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2010.
48

Characterization of the Trichomonas Vaginalis AP65 adhesin and effects of polyamine depletion on cytoadherence and cytotoxicity : a dissertation /

Garcia, Ana Fernanda. January 2007 (has links)
Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2007. / Vita. Includes bibliographical references.
49

Potencial anti-trichomonas vaginalis de Manilkara rufula análise fitoquímica, semissíntese e mecanismo de morte do parasito / Manilkara rufula anti-Trichomonas vaginalis potential : phytochemistry analysis, semi-synthesis and mechanism of death of the parasite

Vieira, Patrícia de Brum January 2015 (has links)
Embora seja uma das áreas mais ameaçadas na Terra, há poucos estudos sobre o potencial farmacológico da Caatinga. Este bioma é exclusivamente brasileiro e as plantas encontradas na região apresentam características únicas que as tornam fontes imensuráveis de compostos ativos. O parasito Trichomonas vaginalis é o agente etiológico da tricomoníase, a doença sexualmente transmissível não viral mais comum no mundo. A infecção está associada a sérias consequências em saúde e casos de resistência ao fármaco de escolha, metronidazol, estão em constante crescimento. Desta forma, a necessidade por alternativas para o tratamento da tricomoníase é evidente. O objetivo desta tese foi avaliar o potencial anti-T. vaginalis de plantas oriundas da Caatinga. A planta Manilkara rufula apresentou a mais potente atividade frente ao parasito e um fracionamento bioguiado foi realizado. Triterpenos pentacíclicos (caproato de α- e β-amirina, acetato de β-amirina e lupeol) foram identificados nas frações apolares de M. rufula, porém com baixa atividade antiparasitária. Derivados triterpênicos semissintéticos, frações contendo flavonoides, taninos e saponinas também foram testados. Nossos resultados demonstraram que o ácido ursólico e a fração H100 apresentaram potente atividade anti-T. vaginalis e ambos afetaram o crescimento e viabilidade dos trofozoítos. Além disso, o ácido ursólico e a fração H100 induziram importantes alterações na ultraestrutura dos organismos, indicando que o mecanismo de morte do parasito ocorreu por danos na membrana. A fração H100 induziu a lise total de eritrócitos e reduziu a adesão dos parasitos às células epiteliais, sugerindo, novamente, a ação sobre membrana. A fração H100 não apresentou citotoxicidade às células epiteliais. Os resultados apresentados demonstraram o potencial da planta M. rufula contra T. vaginalis e contribuem para o entendimento das propriedades farmacológicas das plantas da Caatinga, bem como para o desenvolvimento racional de alternativas para o tratamento da tricomoníase. / Although it is one of the most endangered areas on Earth, there are few studies on the pharmacological potential of the Caatinga. This is an exclusively Brazilian biome and its plants present unique characteristic that make them an immeasurable source of active compounds. The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. The infection has been associated with serious consequences in health and cases of resistance to metronidazole are constantly increasing. Then, the necessity of new alternatives to the treatment of trichomoniasis is evident. The aim of this thesis was to evaluate the anti-T. vaginalis potential of plants from Caatinga. The Manilkara rufula plant showed the most potent activity against the parasite and bioguided fractionation was performed. Pentacyclic triterpenes (α- and β-amyrin caproate and β-amyrin and lupeol acetate) were identified in the nonpolar fractions of M. rufula, however, low antiparasitic activity was observed. Triterpenic semisynthetic derivatives, fractions containing flavonoids, tannins and saponins were also tested. Our results showed that ursolic acid and H100 fraction exhibited potent anti-T. vaginalis activity and both affect growth and viability of trophozoites. In addition, ursolic acid and H100 fraction induced significant alterations in the ultrastructure of the parasite, indicating that the mechanism of death is by membrane damage. The H100 fraction induced complete lysis of erythrocytes and reduced the parasites adhesion to epithelial cells, once again, suggesting that the H100 action was on parasite membrane. The fraction H100 showed no cytotoxicity to epithelial cells. The results demonstrated the potential of the plant M. rufula against T. vaginalis and contributed to the understanding of the pharmacological properties of the Caatinga plants, as well as for the rational development of alternatives for trichomoniasis treatment.
50

Síntese e atividade anti-Trichomonas vaginalis de chalconas

Trein, Marcia Rodrigues January 2017 (has links)
Tricomoníase é a doença sexualmente transmissível não-viral mais comum no mundo e pode gerar sérias consequências na saúde reprodutiva, câncer e transmissão e aquisição do HIV. Por esta razão, esta infecção resulta em um pesado fardo para os sistemas de saúde pública. O único tratamento aprovado para esta infecção, que consiste nos 5-nitromidazois metronidazol e tinidazol, apresenta efeitos adversos e há uma subestimada taxa de resistência da infecção, atualmente considerada uma doença negligenciada, a estes fármacos. Portanto, há uma necessidade urgente de novas alternativas terapêuticas para a tricomoníase. Chalconas são uma família de moléculas que apresenta várias aplicações biológicas, como atividade contra diversos patógenos, incluindo protozoários patogênicos. Este trabalho apresenta o potencial anti-Trichomonas vaginalis de derivados de chalcona sintetizados e seus efeitos sobre os trofozoítos. Os valores de IC50 dos compostos mais ativos variaram de 27,5 a 76,4 μM, e as moléculas 4’-hidroxichalcona e 3’-aminochalcona apresentaram os valores mais baixos (27,5 e 28,9 μM). Estes dois compostos foram citotóxicos contra a linhagem de células epiteliais vaginais HMVII, consequentemente apresentaram baixos Índices de Seletividade; contudo, ao se utilizar larvas de Galleria mellonella, como modelo de toxicidade in vivo, não foi observada diminuição da viabilidade após o tratamento. As moléculas também não provocaram hemólise em eritrócitos humanos em 1 e 24 horas. Os compostos não induziram significativa produção de espécies reativas de oxigênio (EROs) nos trofozoítos. Neutrófilos humanos apresentaram aumento na produção de EROs quando coincubados com trofozoítos tratados com os compostos. Os resultados indicam que as chalconas são uma família de moléculas com potencial atividade contra T. vaginalis. / Trichomoniasis is the most common non-viral sexually transmitted disease worldwide and can lead to serious consequences in reproductive health, cancer and HIV acquisition. For this reason, this infection results in a heavy burden for public health systems. Current approved treatment, which consists in 5-nitromidazole drugs, metronidazole and tinidazole, present adverse effects and there is underestimate drug resistance data on this parasitic infection, currently considered a neglected disease. Therefore, there is an urgent need for new alternatives for trichomoniasis treatment. Chalcones are a family of molecules that present various biological applications, such as activity against many pathogenic organisms including protozoan pathogens. This study presents the anti-Trichomonas vaginalis potential of synthetized chalcone derivatives and their effects on the trophozoites. IC50 values of the most active compounds ranged from 27.5 to 76.4 μM, and 4’-hydroxychalcone and 3’- aminochalcone presented the lowest values of IC50 (27.5 and 28.9 μM). These two compounds showed cytotoxicity against HMVII vaginal epithelial cells, thus presenting a low Selectivyty Index; however, when Galleria mellonella larvae were used as model for in vivo toxicity no significant decrease in viability after treatment was observed. The chalcones also did not induce hemolysis in human erythrocytes The compounds did not induce significant reactive oxygen species (ROS) production in the trophozoites. Human neutrophils have increased ROS production when exposed to treated trophozoites. Results indicate that chalcones are a family of molecules with potential activity against T. vaginalis.

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