Pharmacokinetics of progesterone in postmenopausal women: 2. Pharmacokinetics following percutaneous administration.

Progesterone was administered percutaneously to postmenopausal women in topical applications on the breast and chest areas in a hydrophilic (gel), lipophilic and an emulsion type base. Venous blood samples were taken 2, 4, 6, 24, 48 and 72 h following administration. The plasma levels were evaluated by radioimmunoassay. Time of maximum concentration (tmax) was, in all cases, in the neighborhood of 4 h. Mean peak plasma concentrations were: 1 ng/ml for the lipophilic, 1.24 ng/ml for the hydrophilic and 2.26 ng/ml for the emulsion type base. The areas under the curves (AUCs) were practically equivalent for the first two methods, but higher values were obtained for administration in the emulsion type base. The elimination was slow, with a half-time varying in the range of 3040 h for all three types of base, a value that was much higher than those obtained after administration of progesterone via vaginal suppositories. The AUCs were parallel with the peak plasma concentrations: almost 2-fold higher for emulsion than for the gel and lipophilic base. Fit for plasma levels using mono-, bi- and tricompartmental models furnished acceptable results only in the case of monocompartmental model, which raises a number of physiological and physico-chemical considerations. A 'pseudomonocompartmental' model was constructed to explain this 'anomaly'.

Pharmacokinetics of progesterone in postmenopausal women: 1. Pharmacokinetics following intravaginal administration.

Progesterone was administered to postmenopausal women in a form of vaginal suppositories containing 100 and 200 mg active substance in Butyrum cacao (BC) and Massa estarinum (ME), a base with emulsifying properties. In the case of single doses, blood samples were taken at 2, 4, 6, 24, 48 and 72 h. Another group of patients received vaginal suppositories (100 mg progesterone) once a day for a 6 day period, with blood samples taken 12 h after each administration. The plasma levels of progesterone were evaluated by radioimmunoassay. The time of maximum concentration (tmax) was 4 h in most cases, and 6 h in the others. The plasma levels were not dose-proportional. Peak plasma concentrations were in the range of 10-15 ng/ml with a mean of 10.5 ng/ml for the 100 mg and 12 ng/ml for the 200 mg doses. The ratio of the mean area under the curve (AUC) for 200 mg and the mean AUC for the 100 mg dose was found to be 1.37. Replacing BC with ME resulted in the lowering of cmax and AUC, and an increase in tmax following a reducing in the rate and extent of adsorption. In the case of ME suppositories, the variability in AUC, cmax and tmax was greater compared to that observed with the BC suppositories. Elimination half-time was in the range of 9-10 h for BC and 14 h for ME suppositories. In vitro assessment of the release kinetics from a hydrophobic and an emulsion type base confirmed previous findings: the latter base assured better pharmaceutical availability. The repeated doses did not seem to produce an accumulation of progesterone in the plasma. On the contrary, a small decrease in plasma levels over time appeared during the 6 day period. Numerical analysis revealed an excellent goodness of fit for the in vivo experimental data via biexponential curves, i.e. a pseudomonocompartmental model.

[A nutrient medium for culturing fungi based on a flores chamomillae infusion. II. The evaluation of the biological properties of fungi cultured on a medium with a flores chamomillae infusion]. / Mediu nutritiv pentru cultivarea fungilor preparat pe baza de infuzie de flores chamomillae. II. Evaluarea unor propietati biologice ale fungilor cultivati pe mediul cu infuzie de flores chamomillae.

The paper reports on the biological properties of Candida albicans (strain I.C. - 130) cultivated on a medium with infusion of Flores chamomillae (I.F.C.) in parallel to the same strain cultivated on the medium Sabouraud (control). The results obtained showed an identical phenotypical profile for the biological properties investigated (fermentation capacity of glucides, reduction of TTC, formation of chlamydospores on the PCB special medium, antigenic structure, sensibility to antifungal substances, virulence). The qualities of the I.F.C. medium for the optimum insurance of the metabolic requirements of the fungi, for their recovery from clinical samples with a high rate of positivity, for ensuring the maintenance of the main biological properties of the fungi, to which the economical advantages are added (low price, easy availability of the raw material simple and rapid preparation methodology) recommend its use in the clinical laboratory, instead of the classical Sabouraud medium to which it corresponds qualitatively.

[A nutrient medium for culturing fungi based on a flores chamomillae infusion. I. The nutrient capacity and capacities for selecting and recovering fungi from clinical samples of a medium with a flores chamomillae infusion]. / Mediu nutritiv pentru cultivarea fungilor preparat pe baza de infuzie de Flores chamomillae. I. Capacitatile nutritive, selective si de recuperare a fungilor din probe clinice ale mediului cu infuzie de Flores chamomillae.

The study suggests a new culture medium, of the Sabouraud type. The medium was tested for its nutritive and recovery properties of the fungi in clinical samples, in parallel to the classical medium Sabouraud with chloramphenicol (Sab. + C). The results obtained showed the following: the I.F.C. + C medium ensures optimum cultivation conditions of some fungi species, potentially pathogenic for man, has a high selectivity and the ability of making evident the fungi in different clinical samples at very near-related parameters practically identical with the parameters of the classical Sabouraud medium. These qualities, completed by the economical advantages and the availability of the raw material necessary for the preparation of the basic vegetal extract, recommend the use of the I.F.C. + C medium as a nutrient medium for isolation and cultivation of fungi.

Experimental investigations in hamsters and rabbits with DNA extracted from human uterine tumors.

Experimental inoculation of a DNA preparation extracted from a fragment of non-irradiated human uterine cervix carcinoma was followed by the appearance of neoplasia in four hamsters and of lymphosarcoma in one rabbit. Similar DNA preparations obtained from three cases of irradiated human uterine cervix carcinoma and from a human uterine fibroma proved to have no biological activity.