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.

ABSTRACT

In contrast to the general view that IR is a pathological process associated with gestational diabetes, a certain degree of IR may represent an important physiological mechanism for blood glucose maintenance during fasting.

The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application.Uniterms: Felodipine/self-microemulsifying delivery. Felodipine/chronotherapeutic application. Selfmicroemulsifying drug delivery system/development. Drugs/controlled release. Ethyl cellulose/drugs coated. Hypertension/treatment. Chronotherapeutics/hypertension treatment.O objetivo desse trabalho de pesquisa foi planejar, desenvolver e otimizar sistema de liberação de fármaco auto-microemulsificante(SMEDDS) de felodipino (FL) em cápsulas de gelatina dura revestidas com polímero, a fim de obter liberação rápida após tempo desejado no manejo da hipertensão. A microemulsão é composta de FL, lauroglilcol FCC, Transcutol P e Cremophor EL. A proporção ótima de tensoativo e de co-tensoativo foi de 2:1. As microemulsões resultantes têm tamanho de partícula na faixa de 65-85 nm com potencial zeta de -13,71 mV. A liberação de FL foi ajustada adequadamente, utilizando-se polímero independente de pH, como etilcelulose com ftalato de dibutila como plastificante. A influência das variáveis da formulação, como viscosidade do polímero, tipo de plastificante e ganho percentual de peso do revestimento foi investigada para caracterizar o intervalo de tempo de liberação. A formulação de cápsulas de FL SMEDDS revestidas com etilcelulose mostrou intervalo de tempo de liberação de 5 a 7 horas, o que é desejável para uma aplicação cronoterapêutica.Uniterms: Felodipino/liberação de fármaco auto-emulsificante. Felodipino/aplicação cronoterapêutica. Sistema de liberação de fármaco auto-emulsificante/desenvolvimento. Fármacos/liberação controlada. Etilcelulose/revestimento de fármacos. Hipertensão/tratamento. Cronoterapia/tratamento da hipertensão.

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ABSTRACT

We previously demonstrated an increased liver gluconeogenesis (LG) during insulin-induced hypoglycaemia. Thus, an expected effect of sulphonylureas induced hypoglycaemia (SIH) could be the activation of LG. However, sulphonylureas infused directly in to the liver inhibits LG. Considering these opposite effects we investigated herein LG in rats submitted to SIH. For this purpose, 24 h fasted rats that received glibenclamide (10 mg kg(-1) ) were used (SIH group). Control group received oral saline. Glycaemia at 30, 60, 90, 120 and 150 min after oral administration of glibenclamide were evaluated. Since the lowest glycaemia was obtained 120 min after glibenclamide administration, this time was chosen to investigate LG in situ perfused livers. The gluconeogenesis from precursors that enters in this metabolic pathway before the mitochondrial step, i.e. L-alanine (5 mM), L-lactate (2 mM), pyruvate (5 mM) and L-glutamine were decreased (p < 0·05). However, the gluconeogenic activity using glycerol (2 mM), which enters in the gluconeogenesis after the mitochondrial step was maintained. Taken together, the results suggest that the inhibition of LG promoted by SIH overcome the activation of this metabolic pathway promoted by IIH and could be attributed, at least in part, to its effect on mitochondrial function.

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.