Bakgrund: Svampinfektion i underlivet drabbar oftast kvinnor vid fertila ålder, ungefär 75% av kvinnor får det någon gång i livet. Svampinfektioner behandlas med antimykotika framförallt receptfria läkemedel, problemet med frekvent användning av receptfria läkemedel är att svampen kommer tillbaka inom kort igen eller förorsakar att det blir svårare att bli av med svampen. Syftet med studien är att sammanfatta och värdera kvalitén av de tillgängliga randomiserade kontrollerade studier samt avgöra om oral eller lokal antimykotika behandling är effektivast vid genital candidainfektion? Metod: Databassökning av studier genomfördes i både Pubmed och Cochrane Library för att söka efter systematiska reviews, reviews och RCT studier. RCT studierna värderades med CONSORTstatement och bedömdes antingen med låg, medel eller hög kvalité. Studierna sammanställdes i tabeller för att jämföra skillnaden i effektiviteten mellan oral eller lokal behandling. Resultat: Sökningen identifierade 190 studier varav fyra betraktades som relevanta. Bedömningen presenterade en av studierna som hög kvalité och resten medelkvalité. Tre av fyra studier visade ingen skillnad på effektiviteten mellan oral och lokal antimykotika behandling, medan endast en studie visade signifikant skillnad som gynnade den orala behandlingen. Slutsats: Generellt erhöll studier som var inkluderade i denna litteraturstudie bra kvalité vid bedömningen. Dessutom visade majoriteten av undersökningarna från både gamla och nya studier att det inte finns någon skillnad i effektivitet hos orala och intravaginala antimykotika behandling. / Background: Vaginal yeast infections usually affect women at fertile age, about 75% of women get it at some point in their lives. Vaginal yeast infections are treated with antimycotics, primarily with non-prescription drugs, the issue with frequent use of non-prescription drugs is that the fungus comes back shortly again, or it becomes difficult to get rid of. The aim of the study is to summarize and evaluate the quality of available randomized controlled trials and determine if oral or local antimycotics treatment is effective in genital candidiasis? Method: Database search of studies was conducted in both PubMed and Cochrane Library to search for systematic reviews, reviews, and RCT studies. RCT studies were evaluated with CONSORT statement and assessed with low, medium or high quality. The studies were compiled in tables to compare the difference in efficacy between oral or local treatment. Result: The search identified 190 studies, of which four were considered relevant. The assessment presented one of the studies as high quality and the rest medium quality. Three out of four studies showed no difference in efficacy between oral and local antifungal therapy, while only one study showed significant difference, which favored the oral treatment. Conclusion: Overall, studies that were included in this literature study were of good quality when assessing. Moreover, most of the researches from both old and new studies showed that there is no difference in the efficacy of oral and intravaginal antifungal therapy.

Orientador: Taís Maria Bauab / Resumo: A candidíase vulvovaginal (CVV) é uma infecção fúngica oportunista que ocasiona relevante problema à saúde da mulher, visto os desagradáveis sintomas desta afecção, somada às dificuldades terapêuticas dos fármacos da prática clínica e ao surgimento de cepas resistentes. Neste sentido, as plantas medicinais associadas a alternativas que melhorem o potencial antifúngico, como o emprego da nanotecnologia, despontam como uma importante fonte no controle e erradicação de infecções fúngicas. Deste modo, o objetivo deste trabalho foi avaliar a atividade antifúngica do óleo essencial (OE) de Cymbopogon nardus (L.) Rendle, em forma livre e incorporado em microemulsão lipídica (ME+OE) frente cepas ATCC e clínicas de C. albicans, C. glabrata e C. krusei. O OE foi obtido por hidrodestilação. A análise química do OE foi realizada por cromatografia gasosa acoplada a espectrofotômetro de massas (CG-EM). As microemulsões lípidicas (ME) foram desenvolvidas e um diagrama de fases foi construído. A ME e ME+OE foram caracterizados por dispersão de luz dinâmica, análise do potencial zeta, microscopia de luz polarizada, ensaios reológicos, força mucoadesiva e microscopia eletrônica de transmissão (MET). A potencialidade antifúngica do OE e ME+OE foi avaliada pela determinação da concentração inibitória mínima (CIM), concentração fungicida mínima (CFM) por microdiluição, ensaio de interação sorbitol e ergosterol. O ensaio de inibição da formação de hifas de C. albicans em presença de probiótico e p... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Vulvovaginal candidiasis (VVC) is an opportunistic fungal infection that causes relevant problem to woman’s health, due to unpleasant symptoms, difficulties of the therapy and the emergence of resistant strains. In this context, the medicinal plants associated to alternatives that improve the antifungal potential, such as the nanotechnology, is an important source in the eradication and control of fungal infections. Thus, the objective of this study was to evaluate the antifungal activity of the essential oil (EO) of Cymbopogon nardus (L.) Rendle, free form and loaded into a lipid microemulsion (ME+EO) against ATCC and clinical strains of C. albicans, C. glabrata and C. krusei. The EO was obtained by hydrodistillation. The chemical analysis of the EO was performed by gas chromatography-mass spectrometry (GC-MS). The lipid microemulsions (ME) were developed and a phase diagram was constructed. The ME and ME+EO were characterized by scattering, zeta potential, polarized light microscopy, rheological assays, bioadhesiveness and transmission electronic microscopy (TEM). The antifungal activity of the EO and ME+EO were evaluated by determination of minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) by microdilution, sorbitol and ergosterol assay. The inhibition of C. albicans hyphae formation in presence of probiotic and vaginal pathogen was carried out by transwells® system. Moreover, the coated and clean surfaces were characterized by contact angle... (Complete abstract click electronic access below) / Doutor

Orientador: Juliana Campos Junqueira / Banca: Antonio Olavo Cardoso Jorge / Banca: Graziella Nuernberg Back Brito / Resumo: Estudos realizados in vitro tem demonstrado que Streptococcus mutans podem produzir metabólitos capazes de inibir Candida albicans, tornando interessante a identificação e desenvolvimento de novas substâncias para o tratamento da candidose bucal. Assim, o objetivo desse estudo foi extrair, fracionar e identificar as substâncias produzidas por S. mutans e avaliar seus efeitos sobre a patogenicidade de C. albicans e na resposta imunológica em modelos de estudo in vivo. As substâncias do sobrenadante da cultura de S. mutans foram extraídas com acetato de etila e posteriormente fracionadas em coluna de sílica derivatizada C-18 (150 g, Φ = 3,5 cm) utilizando diferentes soluções de MeOH:H2O (36:64, 49:51, 60:40, 76:24, 100:0) como eluente, obtendo cinco diferentes frações (SM-F1, SM-F2, SMF3, SM-F4 e SM-F5). A identificação das substâncias contidas no extrato bruto e frações foi realizada por cromatografia gasosa acoplada a espectrometria de massas. Foram testados os efeitos do extrato bruto e frações do sobrenadante da cultura de S. mutans sobre a candidose experimental induzida em modelo invertebrado de Galleria mellonella e em camundongos imunossuprimidos. Para a escolha da concentração a ser testada nos modelos in vivo foi realizada a determinação da Concentração Inibitória Mínima do extrato bruto e frações sobre C. albicans. No modelo de infecção experimental com G. mellonella, os efeitos do extrato e frações foram analisados pelos testes de curva de sobrevivência, quantificaç... (Resumo completo, clicar acesso eletrônico abaixo) / In vitro studies have shown that Streptococcus mutans can produce metabolites capable of inhibiting Candida albicans, becoming interesting the identification and development of new substances for the treatment of oral candidiasis. Thus, the objective of this study was to extract, fractionate and identify the substances produced by S. mutans and evaluate their effects on the pathogenicity of C. albicans and on the immune response in in vivo study models. Substances from the S. mutans culture supernatant were extracted with ethyl acetate and subsequently fractionated on a C-18 derivatized silica column (150 g, Φ = 3.5 cm) using different solutions of MeOH:H2O (36:64, 49:51, 60:40, 76:24, 100:0) as eluent, obtaining five different fractions (SM-F1, SM-F2, SM-F3, SM-F4 and SM-F5). The identification of the substances contained in the crude extract and fractions was performed by gas chromatography coupled to mass spectrometry (GC-MS). The crude extract products and the fractions of the supernatant of the S. mutans culture were assessed on experimental candidiasis induced in invertebrate model of Galleria mellonella and in immunosuppressed mice. For a choice of the concentration to be tested in the in vivo models, a determination of the Minimum Inhibitory Concentration (MIC) of the crude extract and fractions on C. albicans was performed. In the model of experimental infection with G. mellonella, the effects of extract and fractions were analyzed by the survival curve test, (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I) is exceptionally common in Finland. Most patients have chronic oral candidiasis since childhood. Thus, most patients receive repeated courses of antifungals throughout their life. Eleven of our patients (31.4%) have become colonized with Candida albicans with decreased sensitivity to fluconazole. A total of 43 isolates of C. albicans from 23 APECED patients isolated during the years 1994 to 2004 were divided into 2 groups: fluconazole-susceptible dose-dependent (MIC, 16-32 μg/mL, 18 isolates) and fluconazole-susceptible (MIC ≤8 μg/mL, 25 isolates) groups. Antifungal activity of amphotericin B, echinocandins, and azoles was determined by the Clinical and Laboratory Standards Institute M27-A2 methodology. All isolates were highly susceptible to amphotericin B and echinocandins. Posaconazole and voriconazole were active against all isolates. Our data suggest that topical amphotericin B could continue to be a safe and active drug for daily administration for APECED patients. Posaconazole, voriconazole, and echinocandins may be useful in some complicated cases.

Diagnostics serve as the frontline defense for the containment and mitigation of infectious diseases. The emerging synthetic biology field established numerous useful applications of engineered biological systems and networks that led to the development of living biosensors. Significant effort has been made to develop G-coupled protein receptor (GPCR)-based yeast biosensors for applications in drug discovery, environmental monitoring, and clinical diagnostics of small molecules and fungal pathogens. Of the living biosensor chassis, yeast-based biosensors offer exceptional advantages over other in vitro diagnostics, such as long-term storage in a reagent-free and dried dormant state, an engineered colorimetric readout for yes/no result interpretation, and high scalability through industrial fermentation. These advantages could be the next innovation as a low-cost, low-tech, and reliable diagnostic alternative in point-of-care and at-home contexts. Chapter 1 provides background information related to synthetic biology, living biosensors, direction evolution, and point-of-care diagnostics. Chapter 2 covers the development of engineered living yeast as a diagnostic tool for viral infections by tailoring the biosensing recognition element to sense any amino acid-based biomarker of choice via directed evolution. Chapter 3 describes the development of living yeast biosensor for the detection of the pathogenic fungus, Aspergillus fumigatus, in clinical supernatants and patient samples. Chapter 4 describes the progression of a living yeast biosensor for the multi-drug resistant pathogenic fungus, Candida auris, and its detection in clinical culture supernatants and samples.

No description available.

El objetivo general de esta tesis fue avanzar en el estudio de la relación patógeno-hospedador-ecosistema de la infección por C. trachomatis en mujeres de la ciudad de Bahía Blanca, para poder favorecer medidas de control y prevención eficaces. Las poblaciones estudiadas fueron mujeres sintomáticas y asintomáticas atendidas en un hospital público (n=295), trabajadoras sexuales (n=143) y jóvenes ingresantes universitarios de ambos sexos (n=204). La prevalencia de infección por C. trachomatis fue mayor en las trabajadoras sexuales que en las estudiantes universitarias (6,29 % y 5,88 % respectivamente). La menor prevalencia se observó en las mujeres sintomáticas y asintomáticas atendidas en un hospital público (3,05 %). En este grupo, la frecuencia de infección fue mayor en las mujeres asintomáticas (4,35 %) que en las sintomáticas (2,65 %). Entre las muestras positivas para C. trachomatis el genotipo E fue el de mayor circulación, seguido por el D y el F. La presencia de C. trachomatis se asoció significativamente con la menor edad, el mayor número de parejas sexuales, el cambio reciente de pareja, la alteración de la microbiota habitual vaginal y la presencia de reacción inflamatoria vaginal. En las trabajadoras sexuales y en las mujeres sintomáticas y asintomáticas, la vaginosis bacteriana fue el estado patológico más frecuente y la trichomonosis la ITS más prevalente. La frecuencia de otras infecciones genitales como candidiasis y sífilis fue baja. No se detectaron casos de infección por N. gonorrhoeae ni serología positiva para HIV. En las jóvenes universitarias, los factores de riesgo para la adquisición de ITS fueron el inicio temprano de las relaciones sexuales, la baja utilización del preservativo y la falta de consulta a los profesionales especializados, los cuales alertan sobre la necesidad de incrementar la vigilancia en esta población. Los resultados muestran la necesidad de profundizar el estudio de las infecciones genitales, y en particular las causadas por C. trachomatis, en las mujeres jóvenes, independientemente de la sintomatología, y encarar programas de prevención de ITS, especialmente en las poblaciones más vulnerables. Palabras clave: Chlamydia trachomatis, ITS, trichomonosis, vaginosis bacteriana, candidiasis, sífilis, HIV, trabajadoras sexuales, jóvenes universitarios. / The general aim of this thesis was to advance in the study of the pathogen-host-ecosystem relation of infection by C. trachomatis in women of the city of Bahía Blanca, to promote effective control and prevention measures. The studied populations were symptomatic and asymptomatic women treated in a public hospital (n=295), female sex workers (n=143) and young college students of both sex (n=204). The prevalence of infection by C. trachomatis was higher in female sex workers than in college students (6.29% y 5.88 % respectively). The lower prevalence was observed in symptomatic and asymptomatic women treated in a public hospital (3.05%). In this group, the frequency of infection was higher in asymptomatic women (4.35%) than in the symptomatic women (2.65%). Between the positives samples for C. trachomatis, the E genotype was the one with most circulation, followed by genotypes D and F. The presence of C. trachomatis was significantly associated with lower ages, bigger number of sexual partners, therecent change of partner, the alteration of the normal vaginal microbiota and the presence of vaginal inflammatory reaction. In female sex workers, and in symptomatic and asymptomatic women, the bacterial vaginosis was the most frequent pathological state and the trichomonosis was the most prevalent STI. The frequency of other genital infections such as candidiasis and syphilis was low. There were no cases detected of infection by N. gonorrhoeae or positive serology for HIV. In young college students, the risks factors for the acquisition of STI were the early beginning of sexual intercourse, low utilization of condom and the lack of consultation to specialized professional, which alert about the need of increase the surveillance in this population. The results show the need of deepen the study of genital infections, and particularly the ones caused by C. trachomatis, in young women, independently of the symptomatology, and encourage STI prevention programs, especially in the most vulnerable populations. Key words: Chlamydia trachomatis, STI, trichomonosis, bacterial vaginosis, candidiasis, syphilis, HIV, female sex workers, young college students.

Baicalein is known to be a potent antifungal agent and induces programmed cell death in Candida albicans. In the present study, we found that baicalein also inhibited the growth of C. krusei isolates. The minimal inhibitory concentrations of baicalein against eight C. krusei isolates were 1.35--2.70 microg/ml. One-hour exposure to baicalein elicited a consistent and moderate post-antifungal effect on the C. krusei isolates. Further flow cytometric study demonstrated a depolarization of mitochondrial membrane potential. However, both the levels of reactive oxygen species and DNA fragmentation were not significantly changed after baicalein treatment in C. krusei. It can be concluded that the antifungal activity of baicalein was mitochondria-dependent in both C. krusei and C. albicans, but the antifungal mechanism was different. Reactive oxygen species may not play a direct role and baicalein does not initiate programmed cell death or apoptosis in C. krusei. The structure-activity relationship study showed that the three hydroxyl groups in baicalein were essential for its antifungal potency. / Candidiasis has become a serious infection with very high mortality and morbidity in the world if not providing effective treatments. However, due to clinical limitation and resistance of the current antifungal agents, there is an urgent need to search for novel antifungals. In this study, after screening a compound library (n=400) for antifungal activity, three members (metergoline, purpurin and baicalein) were chosen for further study. Their antifungal characteristics and the antifungal mechanisms were investigated. / Metergoline, a serotonin receptor antagonist, was found to have potent antifungal activity against the intrinsically fluconazole-resistant human fungal pathogen Candida krusei. The minimal inhibitory concentration and minimal fungicidal concentration of metergoline against C. krusei were 4 microg/ml and 8 microg/ml respectively. Metergoline induced post-antifungal effect. Significant synergism was found in combination of metergoline with amphotericin B by a checkerboard assay, which may be due to the perturbation of cell permeability and increase in the intracellular accumulation of antifungal agents. Metergoline also inhibited extracellular phospholipase production in C. krusei. To gain insights into the mechanisms, intracellular changes that accompany apoptosis were examined by flow cytometry and spectrophotometry. The results showed an increase in the level of reactive oxygen species, depolarization of mitochondrial membrane potential, phosphatidylserine externalization, and positive terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labelling in the metergoline-treated C. krusei . Taken together, we conclude that metergoline may promote apoptosis in C. krusei through reactive oxygen species production and perturbation in mitochondrial homeostasis, implying its antifungal potential to treat candidiasis. / The antifungal activity of purpurin, a natural red anthraquinone pigment in madder root (Rubia tinctorum L.), was evaluated against Candida isolates by a broth microdilution assay. The minimal inhibitory concentrations of purpurin against Candida species isolates were 1.28--5.12 microg/ml. Mechanistic studies indicated that purpurin inhibited energy-dependent efflux pumps of Candida isolates. Furthermore, purpurin demonstrated a depolarization of mitochondrial membrane potential, suggesting a possible linkage of the antifungal mechanism of purpurin to Candida apoptosis. / Kang, Kai. / Adviser: Fong Wing Ping. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 98-123). / 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, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

No description available.

La candidose oropharyngée (COP) constitue l’infection fongique opportuniste la plus fréquente chez les patients infectés au VIH-1. Malgré la profonde immunosuppression causée par le VIH-1, l’infection à Candida albicans demeure confinée au niveau de la muqueuse buccale sans dissémination aux organes profonds. La souris transgénique (Tg) CD4C/HIVMut exprimant le génome tronqué du VIH-1 présente, suite à l’inoculation orale de C. albicans, une COP chronique reproduisant fidèlement l’infection chez les patients séropositifs. Cette souris Tg a donc été utilisée afin de déterminer si les macrophages contribuent au confinement de C. albicans à la muqueuse buccale. Cette étude a permis de démontrer que i) les macrophages sont recrutés aux muqueuses buccale et gastrique en réponse au champignon malgré l’expression du transgène, ii) les macrophages de ces souris Tg présentent une polarisation vers un phénotype d’activation alternative et iii) la production de monoxyde d’azote par les macrophages des souris Tg n’est pas requise pour limiter la prolifération de Candida à la muqueuse buccale et pour restreindre sa dissémination aux organes profonds. Les macrophages ne semblent donc pas directement responsables de l’établissement de l’infection chronique à Candida chez la souris Tg CD4C/HIVMut. / Oropharyngeal candidiasis (OPC) is the most frequent opportunistic fungal infection among HIV-infected patients. Despite the profound immunosuppression caused by HIV-1, Candida albicans infection is limited to the oral epithelium and rarely disseminates to deep organs. The CD4C/HIVMut transgenic (Tg) mice, which expresses the truncated HIV-1 genome, developed a chronic OPC after oral inoculation with C. albicans that closely reproduces infection in seropositive patients. Here, we used this Tg mouse to investigate the contribution of macrophages in limiting candidiasis to the oral mucosa. This study shows that i) macrophages are recruited to the oral and gastric mucosa in response to C. albicans despite transgene expression, ii) the macrophages of this Tg mouse exhibited a polarization toward an alternatively activated phenotype and iii) nitric oxide production by these macrophages is dispensable for limiting chronic oral carriage and for preventing systemic dissemination of the fungi in these Tg mice. Overall, these result indicate that macrophage do not directly determine the susceptibility to chronic carriage of Candida in these CD4C/HIVMut Tg mice.