Effect of oestrogen receptor status and time on the intra-tumoural accumulation of tamoxifen and N-desmethyltamoxifen following short-term therapy in human primary breast cancer

Chronic in utero methamphetamine treatment, throughout gestation in rats, resulted in alterations in both behavior and brain monoamine function in the adult offspring. The higher dose of methamphetamine (10 mg/kg/b.i.d.) caused a significant decrease in square crossing and rearing in an open field, as well as a regional increase of serotonin and dopamine uptake sites. In contrast, the lower dose of in utero methamphetamine (2 mg/kg/b.i.d.) resulted in a significant decrease in regional densities of serotonin and dopamine uptake sites, and only decreased rearing behavior. Across treatment groups, there were significant correlations between open-field square crossing activity and the number of uptake sites in specific brain areas. Other measured behaviors, such as the neonate righting reflex and the adult Morris water maze performance, were unaffected by either in utero drug regimen. These results are discussed in terms of the known neurotoxicity of amphetamines and the ability of the immature nervous system to compensate for fetal exposure to methamphetamine.     

Pharmacological characterization of endomorphin-1 and endomorphin-2 in mouse brain

The recently isolated peptides endomorphin-1 and endomorphin-2 have been suggested to be the endogenous ligands for the mu receptor. In traditional opioid receptor binding assays in mouse brain homogenates, both endomorphin-1 and endomorphin-2 competed both mu1 and mu2 receptor sites quite potently. Neither compound had appreciable affinity for either delta or kappa1 receptors, confirming an earlier report. However, the two endomorphins displayed reasonable affinities for kappa3 binding sites, with Ki values between 20 and 30 nM. Both endomorphins competed 3H-[D-Ala2, MePhe4,Gly(ol)5] enkephalin binding to MOR-1 receptors expressed in CHO cells with high affinity. In mouse brain homogenates 125I-endomorphin-1 and 125I-endomorphin-2 binding was selectively competed by mu ligands. 125I-Endomorphin-1 and 125I-endomorphin-2 also labeled MOR-1 receptors expressed in CHO cells with high affinity. Autoradiography of the two 125I-labeled endomorphins demonstrated regional patterns in the brain similar to those previously observed for mu drugs. Pharmacologically, the endomorphins were potent analgesics. Although they were equipotent supraspinally, endomorphin-1 was more potent spinally. Endomorphin analgesia was effectively blocked by naloxone, as well as the mu-selective antagonists beta-funaltrexamine and naloxonazine. In CXBK mice, which are insensitive to supraspinal morphine, neither endomorphin was active, consistent with a mu mechanism of action. Finally, the endomorphins inhibited gastrointestinal transit. In conclusion, these results support the mu selectivity of these agents.     

The formation of electrical excitability in cultured frog embryonic myocytes

Quantitative changes of sodium and potassium ionic currents were studied in the frog embryonic skeletal myocytes cultures under conditions preventing cell fusion and division. During 7 days of culturing the mean values of the sodium and potassium currents densities were 7- and 1.8-fold increased, resp. In currents clamp records the APs were observed only after 5 days of culturing, and in cells with proportion of sodium and potassium conductances above the critical level.     

Survival, developmental and morphogenic deficiencies of Parasarcophaga argyrostoma (Diptera: Sarcophagidae) induced by the biosynthesis inhibitor, chlorfluazuron (IKI-7899)

To evaluate the activity of benzoylphenyl urea chitin biosynthesis inhibitor chlorfluazuron (IKI-7899) against Parasarcophaga argyrostoma, seven doses were topically applied (once) onto early third (last) instar larvae, puparia, or newly formed pupa: 150, 100, 50, 10, 1.0, 0.5, and 0.25 microgram/insect. After topical treatment of last instar larvae, the highest mortality was caused by both higher doses and the lowest mortality was caused by the lowest dose. The lethal activity of IKI-7899 as pronouncedly decreased as the treatment was lately carried out (at the puparial time). IKI-7899 failed to cause cumulative mortality because no pupal or adult mortalities were observed, irrespective of the time of treatment. Treated larvae suffered the action of IKI-7899 because they had decreased weight gain. Except the lowest dose, the weight gain of larvae inversely correlated with the dose-levels. IKI-7899 prolonged not only the larval duration but also the pupal duration after topical treatment of last instar larvae with doses 50-0.25 micrograms/larva. With no exception, all doses topically applied onto puparia or newly formed pupae enhanced pupae to live longer. Topical application onto last instar larvae resulted in different degrees of reduction of pupation rate, but IKI-7899 could not affect the pupal morphogenesis after larval treatment except by its highest dose which led to 8.33% pupal deformities and 7.69% larval-pupal intermediates. The dose 100 micrograms/larva topically applied onto last instar larvae detained 7.69% of what known as "permanent larvae" which suffered the action of the compound along 16 days and eventually perished without any external feature of puparium formation. A metamorphic effect of IKI-7899 pronouncedly appeared in the adult stage. Three higher doses completely arrested the adult flies. Topical application of the compound onto prepupae did not greatly reduce the pupation rate especially at the doses 50, 10 and 1.0 micrograms/puparium. The dose 50 micrograms/puparium was only the dose halting the pupal moulting program because 7.14% of permanent prepupae remained about 12 days and then died. In respect to adult emergence, the highest dose led to zero rate and the lowest dose allowed to all pupae to emerge without malformation.