Ketoconazole Impairs Early Pregnancy and the Decidual Cell Response via Alterations in Ovarian Function

Ketoconazole (KCZ) is an imidazole antifungal agent that alsoaffects P450 enzymes of the mammalian steroidogenic system.Several steps in the ovarian steroidogenesis pathway are knownto be inhibited by KCZ, but previous work has failed to addressthe ramifications of such inhibition with respect to early pregnancy.In initial studies, Holtzman rats (8–10/group) were administered10–100 mg/kg KCZ during days 1–8 of pregnancy. Onday 9, evaluations revealed a reduction at both 75 and 100 mgKCZ/kg in the number of implantation sites and serum progesteronelevels as well as an increase in ovarian weight The decidualcell response (DCR) was blocked by KCZ in parallel with decreasedserum progesterone and increased ovarian weight, indicatingdirect interference with uterine function. KCZ had no effectwhen given to long-term-ovariectomized rats that were hormonesupplemented to permit the DCR, indicating that the ovary wasat least one site of KCZ action on early pregnancy. Measurementof ovarian progesterone production in vitro from ovaries removedfrom rats treated in vivo with KCZ indicated a decline in progesteroneproduction, suggesting a direct effect of KCZ on ovarian steroidogenesis.These data demonstrate that KCZ can compromise early pregnancyand appears to do so by inhibiting progesterone synthesis inthe ovary.     

Two-step carcinogenesis induced by neonatal exposure to 5-bromo-2'- deoxyuridine and subsequent administration of urethan in BALB/c mice.

Male and female BALB/c mice were exposed to subcutaneous injections of 1 mg 5-bromo-2'-deoxyuridine (BrdUrd) at the 1st, 3rd and 7th days after their birth and/or starting from 3 months of age, and every third day were given 5 intraperitoneal injections of 0.1 ml of 5% solution of urethan. Treatment with BrdUrd alone followed by delay in mice development, reduction of the body and liver weight did not significantly increase the incidence of tumor development at 9 months of age. Exposure to both BrdUrd and urethan lead to summation or potentiation of their effects, manifested in increased lung adenoma incidence and their number per tumor-bearing mouse. In males, which received BrdUrd and urethan a significant increase in lung adenocarcinomas and haemoblastosis was observed in comparison to other groups. It was suggested that genome instability induced by exposure to BrdUrd facilitate the realization of the carcinogenic effect of urethan.     

Chromosomal imbalances in clear cell ependymomas.

Clear cell ependymoma is a rare and diagnostically challenging subtype of ependymoma, whose genetic features are essentially unknown. We studied 13 clear cell ependymomas (five cases WHO grade II, eight cases WHO grade III) by comparative genomic hybridization (CGH). Chromosomal imbalances were found in 12/13 cases. The most common aberrations overall were +1q (38%), -9 (77%), -3 (31%), and -22q (23%). Clear cell ependymomas of WHO grade II were characterized by -9 (40%), whereas WHO grade III cases mainly showed +1q (63%), and +13q (25%), as well as -9 (100%), -3 (38%), and -22q (25%). In contrast to other ependymal tumors, clear cell ependymomas of WHO grade II showed fewer imbalances than WHO grade III samples (1.4 vs 3.5 per case). Although some of the implicated chromosomes have previously been shown to be involved in other ependymoma variants, the striking frequency of +1q, -9, and -3 suggests that aberrations differ between clear cell and other types of ependymomas, in particular, for loss of chromosome 9 which can be regarded as the molecular hallmark of clear cell ependymomas.     

Study of the molecular structure of ethylene-propylene copolymers obtained with catalysts of different composition

The monomer composition and sequence distribution in ethylene-propylene copolymers (EPCs) obtained with supported titanium/magnesium (TMC) and vanadium/magnesium (VMC) catalysts as well as with titanium trichloride was studied by means of ¹³C NMR spectroscopy. Based on these data ethylene-propylene reactivity ratios were determined. The EPCs obtained on these catalysts are inhomogeneous in composition; the soluble fractions contain larger amounts of propylene. The microstructures of copolymers obtained on TMCs and TiCl₃ are similar. For EPCs obtained on VMCs, propylene “head-to-head” or “tail-to-tail” inversions and a more homogeneous distribution of propylene are observed.     

Microwave Spectroscopy of Myocardial Ischemia and Infarction. 2. Biophysical Reconstruction

The proposed dielectrical relaxation model of the myocardium in the microwave spectrum has been verified both on test solutions and on normal canine myocardium. Furthermore, the model was utilized to reconstruct the changes in tissue properties (including myocardial bulk resistance and water content) following myocardial acute ischemia and chronic infarction. It was shown that the reconstructed myocardial resistance and water content correlate dynamically with the process of the development of acute myocardial ischemic injury. In chronic cases the reconstructed resistance and water content of infarcted myocardium are significantly different from that of normal myocardium: the resistance is lower and water content is higher than in normal myocardium. © 2000 Biomedical Engineering Society. PAC00: 8764-t, 8719Xx