RESUMO
BACKGROUND: Study of in vivo antifungal activity of the hydroalcoholic extract (HE) and n-BuOH extract (BUTE) of Sapindus saponaria against azole-susceptible and -resistant human vaginal Candida spp. METHODS: The in vitro antifungal activity of HE, BUTE, fluconazole (FLU), and itraconazole (ITRA) was determined by the broth microdilution method. We obtained values of minimal inhibitory concentration (MIC) and minimum fungicide concentration (MFC) for 46 strains of C. albicans and 10 of C. glabrata isolated from patients with vulvovaginal candidiasis (VVC). VVC was induced in hyperestrogenic Wistar rats with azole-susceptible C. albicans (SCA), azole-resistant C. albicans (RCA), and azole-resistant C. glabrata (RCG). The rats were treated intravaginally with 0.1 mL of HE or BUTE at concentrations of 1%, 2.5% and 5%; 100 µg/mL of FLU (treatment positive control); or distilled water (negative control) at 1, 24, and 48 h after induction of the infection, and the progress of VVC was monitored by culturing and scanning electron microscopy (SEM). The toxicity was evaluated in cervical cells of the HeLa cell line. RESULTS: The extracts showed in vitro inhibitory and fungicidal activity against all the isolates, and the MIC and MFC values for the C. glabrata isolates were slightly higher. In vivo, the SCA, RCA, and RCG infections were eliminated by 21 days post-infection, with up to 5% HE and BUTE, comparable to the activity of FLU. No cytotoxic action was observed for either extract. CONCLUSIONS: Our results demonstrated that HE and BUTE from S. saponaria show inhibitory and fungicidal activity in vitro, in addition to in vivo activity against azole-resistant vaginal isolates of C. glabrata and azole-susceptible and resistant isolates of C. albicans. Also considering the lack of cytotoxicity and the low concentrations of the extracts necessary to eliminate the infection in vivo, HE and BUTE show promise for continued studies with purified antifungal substances in VVC yeast isolates.
Assuntos
Antifúngicos/farmacologia , Azóis/farmacologia , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sapindus/química , Animais , Brasil , Candida albicans/isolamento & purificação , Candida glabrata/isolamento & purificação , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/microbiologia , Colo do Útero/citologia , Colo do Útero/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Feminino , Fluconazol/farmacologia , Frutas/química , Células HeLa , Humanos , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar , Saponinas/análise , Saponinas/farmacologia , Saponinas/toxicidade , Triterpenos/análise , Triterpenos/farmacologia , Triterpenos/toxicidadeRESUMO
Vulvovaginal candidiasis (VVC) is regarded as an important public health issue, and several aspects of its pathogenesis are not yet sufficiently clear. Experimental in vivo models of vaginal infection with Candida albicans have been extremely useful in the identification of factors concerning hormonal influences on the infection, the virulence of the yeasts, the susceptibility, and the treatment of the infection. The development of easily manageable, reproducible, and economically viable animal models of VVC is highly important. We describe a simple experimental model of VVC in rats, using a pharmaceutical brand of estradiol hexa-hydrobenzoate for human treatment. All the steps of this model were standardized; and after the experiments, the rats were euthanized for further examination of their tissues by scanning and transmission electron microscopy. Standardized features included the use of non-ovariectomized rats, sterile distilled water as the hormone vehicle, estradiol hexa-hydrobenzoate administered at 0.20 mg/week/rat fractionated three times/week, and a yeast suspension of 5 × 10(8) yeasts/ml in a single vaginal administration 1 week after hormone induction. In this way, 100% of the rats were in pseudo-estrus and developed and maintained the infection until the third week of the experiment. Electron microscopy observation of the vagina of the rats confirmed the presence of both pseudo-estrus and vaginal infection. The standardized experimental model proved inexpensive, reproducible, and easily feasible for the induction of vaginal infection with C. albicans and may help to clarify important aspects of the pathogenesis and treatment of VVC.
Assuntos
Candida albicans/patogenicidade , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/patologia , Modelos Animais de Doenças , Animais , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Feminino , Fatores Imunológicos/administração & dosagem , Microscopia Eletrônica , Ratos , Ratos Wistar , Vagina/patologiaRESUMO
The adhesion of Candida albicans to the genital epithelium has not been fully investigated in vivo. The objective of this study was to evaluate the ultrastructural aspects of C. albicans adhesion in the lower genital system of female Wistar rats through scanning and transmission electron microscopy. The genital infection persisted until the end of the experiment, and all rats showed the same adhesion aspects. Various associated yeast/hyphae were observed in the lumen and adhered both at the vaginal and endocervical levels where the fungal filamentation process occurred. In the vaginal epithelium, closely adhered yeasts were observed as stretched strands bridging between yeasts and the epithelium surface. Different stages of the adhesion, where yeasts internalized into the epithelial cell inside a cytoplasmic vacuole, resembling endocytosis, and a wide fibrillar-floccular, glycocalyx-like layer on the yeasts were observed. On the endocervix, the adhesion occurred between the cilia. In the uterine body, only a yeast-like form was observed with superficial contact. This study reached the initial goal of demonstrating an experimental model for in vivo studies. Continuation of this line of research is important for studies of vulvovaginal candidiasis.
Assuntos
Candida albicans/patogenicidade , Candida albicans/ultraestrutura , Adesão Celular , Epitélio/microbiologia , Epitélio/ultraestrutura , Animais , Feminino , Genitália Feminina , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Ratos , Ratos WistarRESUMO
OBJECTIVE: The purpose of this study was to develop an experimental model of diabetes in female rats and verify its influence on vulvovaginal candidiasis. STUDY DESIGN: The animals were divided into control and diabetic groups. Diabetes was induced with the use of an intravenous solution of alloxan (42 mg/kg bodyweight). One week after confirmation of hyperglycemia, the inoculation of Candida albicans yeast, previously standardized from a vaginal isolate, in concentrations of about 5 x 10(8), was performed. Infection control was made through vaginal culture, Papanicolaou cytology, and scanning electron microscopy (SCEM). RESULTS: The results pointed to different glycemias between the control (74.8 +/- 2.6) and experimental groups (543.1 +/- 12.1) and a significant bodyweight decrease (227.6 +/- 4.77 and 204 +/- 6.39, respectively). The positive infection was shown by culture, Papanicolaou test, and SCEM in the experimental group. CONCLUSION: Diabetes mellitus causes hyperglycemia, which was favorable to the vaginal colonization and infection by C albicans.
Assuntos
Candidíase Vulvovaginal/etiologia , Diabetes Mellitus Experimental/complicações , Animais , Feminino , Ratos , Ratos WistarRESUMO
A hipercolesterolemia é um dos principais fatores de risco para doenças cardiovasculares. Avaliamos os níveis de colesterol total em três cidades do Paraná Douradina, Cianorte e Guaíra. Douradina apresenta de um modo geral característica mais voltada para o cotidiano rural. Realidade diferente foi constatada em Cianorte, considerada hoje um pólo industrial. Guaíra é uma região preparada para o turismo e com grande atividade comercial. Foram analisadas amostras de 600 indivíduos, sendo 200 de cada localidade,distribuídos previamente em diferentes faixas etárias e gênero. Em Douradina observaram-se as menores taxas de colesterol (186,9 ± 2,9 mg/dl), seguido por Cianorte (203,1 ± 1,4 mg/dl) e Guaíra (219,7 ± 3,2 mg/dl). Concluiu-se que houve uma variação de colesteroltotal nas diferentes cidades, mostrando que hábitos regionais influenciam nos níveis de colesterol total sérico.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Colesterol/análise , Doenças Cardiovasculares/prevenção & controle , Hipercolesterolemia/diagnóstico , Estilo de Vida , Fatores de RiscoRESUMO
The antihypertensive effect of crude stevioside obtained from the leaves of Stevia rebaudiana (Bertoni) Bertoni (Compositae) on previously untreated mild hypertensive patients was examined. Patients with essential hypertension were submitted to a placebo phase for 4 weeks. The volunteers selected in this phase were randomly assigned to receive either capsules containing placebo during 24 weeks or crude stevioside 3.75 mg/kg/day (7 weeks), 7.5 mg/kg/day (11 weeks) and 15.0 mg/kg/day (6 weeks). All capsules were prescribed twice a daily (b.i.d.), i.e. before lunch and before dinner. After the placebo phase and after each dose of crude stevioside, body mass index, electrocardiogram and laboratory tests were performed. During the investigation blood pressure (BP) was measured biweekly and the remaining data were collected at the end of each stevioside dose step. All adverse events were prospectively recorded but no major adverse clinical effects were observed during the trial. Systolic and diastolic BP decreased (p < 0.05) during the treatment with crude stevioside, but a similar effect was observed in the placebo group. Therefore, crude stevioside up to 15.0 mg/kg/day did not show an antihypertensive effect. Moreover, the results suggest that oral crude stevioside is safe and supports the well-established tolerability during long term use as a sweetener in Brazil.