Low-dose antiprogestin administration has been proposed as a new contraceptive modality to interference with endometrial receptivity without disturbing ovarian function. The effects of 1 mg/day mifepristone for 150 days on the menstrual cycle were assessed in 21 surgically sterilized women. The aim was to study each woman for one control cycle and during months 1, 3 and 5 of treatment. Ovulation, endometrial thickness, serum oestradiol and progesterone, urinary luteinizing hormone, endometrial morphology and cervical mucus were assessed. Luteal phase progesterone concentrations were observed in 36 of the 60 treated months assessed and less frequently as treatment progressed. The bleeding pattern was regular in most biphasic cycles, while prolonged interbleeding intervals or no bleeding were associated with monophasic cycles. Altered endometrial morphology was found in all cases irrespective of the occurrence of luteal activity. Increased endometrial thickness and dilated glands were observed in 25 and 34% respectively of the monophasic cycles. Mifepristone, 1 mg/day, interferes with endometrial development while allowing the occurrence of biphasic ovarian cycles and regular bleeding. However, it also prevents ovarian cyclicity in a high proportion of treated months, and this is associated with increased endometrial growth in some women, which may be of concern.
Significant ofloxacin reservoir capacity of a single human amniotic layer could be demonstrated in vitro. AM acted as an ofloxacin slow release device for upto 7 h in vitro, depending on the duration of pretreatment of AM. Individual pretreatment of AM could increase beneficial effects of AM transplantation, especially in infectious keratitis.
The use of beta2-Adrenergic Receptor (AR) agonists and the potential use of alpha1-AR blockers as tocolytics raise the question of how they influence placental circulation. The receptor profile was characterized via the amounts of the mRNA of alpha1-AR subtypes and beta2-ARs. The mRNAs were detected by reverse transcription-polymerase chain reaction. Electric field stimulation (EFS) was applied to test the pharmacological reactivity of the placental vessels. Expressions of beta2- and all subtypes of alpha1-AR mRNA were demonstrated in human placental vessels, and were significantly higher in the arteries. A significant difference was not found between the veins and the arteries as concerns the amount of alpha1D-AR mRNA. There was a preponderance of alpha1A- and alpha1B-AR mRNA as compared to alpha1D-AR mRNA both in the arteries and in the veins. beta2-AR agonists and alpha1-AR antagonists antagonized the EFS-induced contractions of the placental arteries in a dose-dependent manner. These effects were significantly less marked on veins at all applied doses. Urapidil antagonized the EFS-induced contractions of both the placental arterial and vein rings in a dose-dependent manner. The beta2-, alpha1A-, and alpha1B-AR are the important subtypes involved in the regulation of the contractility of the human term placental vessels. The possible increase in placental blood flow mediated by these ARs can even be beneficial during pregnancy. Accordingly, the use of beta2-AR agonists and the potential use of alpha1-blockers as tocolytics seem safe on the basis of in vitro examinations as concerns the placental circulation.
The in vitro model of the Franz-diffusion cell system was found to be applicable for drug permeability studies of human amniotic membranes to water-based solutions. The filter membrane and AM were permeable to a water-based solution of ofloxacin. Significant barrier function of the AM could be measured in ofloxacin permeability. Cryopreservation did not influence the permeability of the AM.
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