Effect of prolactin and dopaminergic drugs on uterine response to chronic estrogen exposure.

The aim of this work was to examine the role of prolactin and dopaminergic drugs, which affect prolactin secretion, on proliferative and morphogenetic reactions in the uterus under continuous estrogen treatment. Ovariectomized mice received injections of estradiol dipropionate (2 microg per 100 g, weekly) or vehicle and daily injections of prolactin (0.25 mg/100 g) or saline (0.05 ml) for 30 days. Other groups of mice received injections of estradiol or vehicle and injections of saline, and were allowed to drink bromocriptine (25 mg/l), metoclopramide (25 mg/l), or only tap water for 30 days. Prolactin administration results in a decrease in the incidence of abnormal glands with abnormal epithelium, the incidence of atypical hyperplasia, uterine weight, proliferation (the number of mitotic and bromodeoxyuridine-labeled cells) and the levels of estrogen receptor-alpha, but causes an increase in the level of beta-catenin in uterine tissues of estrogen-treated mice. The effect of metoclopramide, which increases prolactin secretion, is principally similar to prolactin, but much less expressed. Bromocriptine, which reduces prolactin levels, increases uterine weight, proliferation, the levels of estrogen receptor-alpha, the incidence of abnormal glands with abnormal epithelium, the incidence of complex and atypical hyperplasia, and decreases the level of beta-catenin in uterine structures of estrogen-treated mice. In the absence of estradiol, none of the treatments used had any effect on the parameters tested. Thus, prolactin or metoclopramide produce antiestrogenic effects in the uterus of mice and prevent the formation of atypical hyperplasia which has an unfavorable prognosis, but bromocriptine has the opposite effect. Estrogen receptor-alpha and beta-catenin were associated with the actions of prolactin, metoclopramide and bromocriptine on estrogen-dependent processes in the uterus.     

Effect of hydrocortisone on sodium and potassium distribution in the sections of the cerebral cortex of rats after their electric stimulation]

Sections of the rat brain cortex were incubated in various physiological media using container-electrodes, similar to the McIlwain's type. The shifts of sodium and potassium distribution between the extra- and intracellular spaces of the slices after different stimulation parameters and the subsequent restoration were measured. The administration of hydrocortisone (for 7 days, 5 mg/100 g daily) usually increased the response of the slices to the stimulation in incubation in the glutamate devoid medium. When 0.2--0.5 mM of glutamate was added to the media the effect of hydrocortisone disappeared. Possible physiological significance of the mentioned results is discussed.     

Multiplex photoacoustic molecular imaging using targeted silica-coated gold nanorods

The establishment of multiplex photoacoustic molecular imaging to characterize heterogeneous tissues requires the use of a tunable, thermally stable contrast agent targeted to specific cell types. We have developed a multiplex photoacoustic imaging technique which uses targeted silica-coated gold nanorods to distinguish cell inclusions in vitro. This paper describes the use of tunable targeted silica-coated gold nanorods (SiO(2)-AuNRs) as contrast agents for photoacoustic molecular imaging. SiO(2)-AuNRs with peak absorption wavelengths of 780 nm and 830 nm were targeted to cells expressing different cell receptors. Cells were incubated with the targeted SiO(2)-AuNRs, incorporated in a tissue phantom, and imaged using multiwavelength photoacoustic imaging. We used photoacoustic imaging and statistical correlation analysis to distinguish between the unique cell inclusions within the tissue phantom.     

Dexmedetomidine hemodynamics in children after cardiac surgery

Background: Dexmedetomidine has opposing effects on the cardiovascular system. Action in the central nervous system produces sympatholysis and a reduction in blood pressure, while peripherally it causes vasoconstriction leading to an increase in blood pressure. The purpose of our study is to define the concentration–response profile for these hemodynamic effects in children after cardiac surgery. Methods: A simultaneous pharmacokinetic–pharmacodynamic analysis of data from 29 children given a single bolus of dexmedetomidine 1–4 mcg·kg^?1 following cardiac surgery was undertaken using mixed effects modeling. There were four dexmedetomidine concentrations available from each patient, and mean arterial blood pressure (MAP) was recorded electronically every 5 min for 5 h after drug administration. A composite Emax model was used to relate mean arterial pressure changes to plasma dexmedetomidine concentration. Results: Children had a mean age of 2.67 years (range 4 days–14 years) and a mean weight of 12.34 (range 3.4–48.4) kg. The peripheral vasopressor effect was directly related to plasma concentration with an Emax_pos of 50.3 (CV 44.50%) mmHg, EC_50pos 1.1 (48.27%) μg·l^?1 and a Hill_pos coefficient of 1.65. The delayed central sympatholytic response was described with an Emax_neg of ?12.30 (CV 37.01%) mmHg, EC_50neg 0.10 (104.40%) μg·l^?1 and a Hill_neg coefficient of 2.35. The equilibration half‐time (T_1/2keo) was 9.66 (165.23%) min. Conclusions: Dexmedetomidine administered as a single bolus dose following cardiac surgery produces a biphasic effect on MAP. A plasma dexmedetomidine concentration of above 1.0 μg·l^?1 was associated with a 20% increase in MAP in this specific cohort. A dosage regimen involving a small bolus dose (0.5 μg·kg^?1) followed by a continuous infusion should be used to avoid initial increases in MAP.     

Expression of estrogen receptor-alpha,glucocorticoid receptor,beta-catenin and glycogen synthase kinase-3beta in the uterus of mice following long-term treatment with estrogen and glucocorticoid hormones

BACKGROUND: It has been shown that long-term glucocporticoid administration to chronically estradiol-treated mice decreases uterine weight, proliferation in all uterine tissues, the number of perpendicularly oriented mitoses in uterine epithelia and the incidence of atypical endometrial hyperplasia. However, mechanisms of chronic glucocorticoid action on estrogen-dependent processes in the uterus are unclear. METHODS AND RESULTS: Results of present research showed that adding of glucocorticoid dexamethasone (in drinking water, 2mg/l) to estradiol-treated mice led to a decrease in the level of glucocorticoid receptor, to an increase in levels of estrogen receptor-alpha, beta-catenin and glycogen synthase kinase-3beta in uterine tissues of ovariectomized mice at 30, 60 and 90 days of the treatment. When vehicle was used instead estradiol, dexamethasone did not produce detectable changes in all parameters tested at all periods of observation. CONCLUSION: Results allow to conclude that estrogen and glucocorticoid receptors, beta-catenin and glycogen synthase kinase-3beta are involved in estrogen-dependent changes in uterine morphology and hyperplasia formation.