Results 1 - 10 of 1436
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[en] Estramustine phosphate (EMP), a nor-nitrogen mustard carbamate derivative of estradiol-17β-phosphate, causes G2/M phase arrest in treated cells through its specific binding to microtubule associated proteins. Since cells in the G2/M phase are the most radiosensitize, cell culture experiments were performed to determine whether EMP would enhance the radiosensitivity of related human tumor cells. A Phase II prospective study of concomitant radiotherapy (RT) and EMP plus Velban for locally advanced carcinoma of the prostate was carried out. Three established human tumor cells, DU-145 cells (prostate), MCF-7 cells (breast), and U-251 cells (malignant glioma), were used to determine cell survival curves with and without the drug. Flow cytometry was used to obtain the cell cycle distribution of cells that were exposed to the drug for periods of 1 day to 1 week. Patients with locally advanced prostate cancer were entered into the Phase II study. All patients received a total tumor dose of 65-70 Gy over 7 weeks. Oral EMP was administered daily and Velban was administered weekly, concomitantly during the course of RT. Radiosensitization was dependent on the exposure time and the drug concentration prior to radiation. No radiosensitization was obtained when cells were exposed to the drug after irradiation. The enhancement ratios varied from 1.3-1.6 at the 10% survival level. All patients who received the combined RT and EMP plus Velban achieved complete response. The rate of PSA (prostate specific antigen) reduction was very prompt compared to that of the RT alone group. There were no disproportionately enhanced side effects for the combined regimen. EMP enhances radiation induced cytotoxicity in several human tumor cells in culture. The effect is most significant after prolonged exposure to the drug before irradiation. Documented G2/M phase cell cycle block by EMP is the likely mechanism of radiosensitization. 9 refs., 2 figs., 1 tab
[en] Bisphenol-A (BPA) is known to be a potent endocrine disrupter. Evidence is emerging that estrogen exerts a rapid influence on hippocampal synaptic plasticity and the dendritic spine density, which requires activation of NMDA receptors. In the present study, we investigated the effects of BPA (ranging from 1 to 1000 nM), focusing on the rapid dynamic changes in dendritic filopodia and the expressions of estrogen receptor (ER) β and NMDA receptor, as well as the phosphorylation of NMDA receptor subunit NR2B in the cultured hippocampal neurons. A specific ER antagonist ICI 182,780 was used to examine the potential involvement of ERs. The results demonstrated that exposure to BPA (ranging from 10 to 1000 nM) for 30 min rapidly enhanced the motility and the density of dendritic filopodia in the cultured hippocampal neurons, as well as the phosphorylation of NR2B (pNR2B), though the expressions of NMDA receptor subunits NR1, NR2B, and ERβ were not changed. The antagonist of ERs completely inhibited the BPA-induced increases in the filopodial motility and the number of filopodia extending from dendrites. The increased pNR2B induced by BPA (100 nM) was also completely eliminated. Furthermore, BPA attenuated the effects of 17β-estradiol (17β-E2) on the dendritic filopodia outgrowth and the expression of pNR2B when BPA was co-treated with 17β-E2. The present results suggest that BPA, like 17β-E2, rapidly results in the enhanced motility and density of dendritic filopodia in the cultured hippocampal neurons with the concomitant activation of NMDA receptor subunit NR2B via an ER-mediated signaling pathway. Meanwhile, BPA suppressed the enhancement effects of 17β-E2 when it coexists with 17β-E2. These results provided important evidence suggesting the neurotoxicity of the low levels of BPA during the early postnatal development of the brain.
[en] We investigated the behavioral effects of exposure to waterborne phytoestrogens in male fighting fish, Betta splendens. Adult fish were exposed to a range of concentrations of genistein, equol, β-sitosterol, and the positive control 17β-estradiol. The following behaviors were measured: spontaneous swimming activity, latency to respond to a perceived intruder (mirror reflection), intensity of aggressive response toward a perceived intruder, probability of constructing a nest in the presence of a female, and the size of the nest constructed. We found few changes in spontaneous swimming activity, the latency to respond to the mirror, and nest size, and modest changes in the probability of constructing a nest. There were significant decreases, however, in the intensity of aggressive behavior toward the mirror following exposure to several concentrations, including environmentally relevant ones, of 17β-estradiol, genistein, and equol. This suggests that phytoestrogen contamination has the potential to significantly affect the behavior of free-living fishes. - Environmentally relevant concentrations of phytoestrogens reduce aggressive behavior in fish
[en] Highlights: • 17β-Estradiol can suppress limited serum-induced apoptosis and MMPs in rat NPCs. • 17β-Estradiol activated autopahgic flux in rat NPCs. • 17β-Estradiol can enhancing autophagy in NPCs under serum deprivation. • Promotion of autophagy attenuated serum deprivation-induced pathology in rat NPCs. Serum deprivation is a likely contributor to intervertebral disc (IVD) degeneration (IVDD).17β-estradiol (E2) have been noted to protect nucleus pulposus cells (NPCs) against apoptosis. Autophagy and apoptosis play a paramount role in maintaining the homeostasis of IVD. So far, little research has been published on whether autophagy plays a role for the E2 mediated protection of NPCs. The aim of this study is to understand whether autophagy is involved in the protective effect of E2 against serum deprivation-induced cell apoptosis and expression of matrix metalloproteinase (MMP)-3 and MMP-13. mCherry-GFP-LC3-adenovirus transfection is used to monitor autophagy detection. The expression levels of autophagy-related proteins were measured by Western blotting, Apoptosis and MMPs were detected by flow cytometry and Western blotting. Accordingly, Autophagy and apoptosis was detected in NP cells under serum deprivation conditions, the autophagy incidence began to reached a peak value at 48 h, the apoptosis and MMPs incidence began reached a minimum value treat with E2 (10−7 M). Whereas the combined use of E2 and 3-MA led to a dramatic decrease in autophagy, while aberrantly elevated expression levels of apoptotic and MMPs. These data suggest that serum deprivation-induced apoptosis and MMP-3, MMP-13, which was efficiently suppressed by the E2 through promoting autophagy in rat NPCs.
[en] Due to nutritional facts of milk in human life, the quality assessment of dairy products is of the utmost importance. The aim of the current study was to determine the 17β-estradiol level in commercial pasteurized and sterilized milk brands in Mashhad, Iran. In this regard, 160 samples including 80 pasteurized (40 high-fat and 40 low-fat) and 80 sterilized milk (40 high-fat and 40 low-fat) of widely used brands from different supermarkets were collected. The mean level of 17β-estradiol was 8.2 ± 0.59 pg/ml. The mean amount of estradiol was found to be 7.6 ± 0.47, 7.9 ± 0.45, 8.6 ± 0.63, and 8.9 ± 0.54 pg/ml for the low-fat pasteurized, low-fat sterilized, high-fat pasteurized and high-fat sterilized milk, respectively. There was no significant difference between the amount of estradiol in pasteurized and sterilized milk. As expected, the level of estradiol was statistically higher in high fat milks than that of low-fat milks. Considering the levels of 17β-estradiol measured here and the maximum permissible daily level of external estradiol entered to body through edible products recommended by EU and CAC (3.5 µg), at least in the short term, there will be no remarkable impact on the endocrine system. However, judging the long-term effects of using these products is not easy and simple at all, as cancers develop during a long period of time and has a multifactorial etiology.
[en] Pulmonary arterial hypertension (PAH) is more prevalent in females. Paradoxically, female patients have better right ventricular (RV) function and higher survival rates than males. However, the effects of 17β-estradiol (E2) on RV function in PAH has not been studied. Twenty-four male rats were exposed to monocrotaline (MCT) to induce experimental PAH, while treated with E2 or vehicle respectively. Together with eight control rats, thirty-two rats were examined by echocardiography 4 weeks after drug administration. Echocardiographic measurement of RV function included: tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), RV fractional area change (RVFAC) and tricuspid annular systolic velocity (s′). RV free wall longitudinal strain (RVLSFW) and RV longitudinal shortening fraction (RVLSF) were also used to quantify RV function. RV morphology was determined by echocardiographic and histological analysis. TAPSE, RVFAC and s′ were reduced, and RIMP was elevated in the MCT-treated group and vehicle-treated group, when compared with control group (P < 0.01). TAPSE, RVFAC and s′ in the E2 group were higher, while RIMP was lower than those in the MCT-treated group and vehicle-treated group (P < 0.01). Myocardial functional parameters (RVLSFW and RVLSF) were also higher in the E2 group. Enhanced serum E2 levels were closely correlated with the improvement in RV functional parameters and enhancement of serum BNP levels (P < 0.01 for all groups). RV function decreased significantly in male rats with MCT-induced PAH, while E2 exhibited a protective effect on RV function, suggesting that E2 is a critical modulator of sex differences in PAH.
[en] Serum samples from male buffaloes were radioimmunoassayed for steroid and thyroid hormones to investigate circadian rhythms, the effect of growth and season. An evaluation of RIA of serum testosterone with and without extraction yielded unacceptably low recoveries in unextracted serum samples. Studies on temporal variations during the day revealed three peaks for testosterone, four peaks for cortisol and one peak each for T4 and T3. In growing calves the testosterone levels were low (0.1 ng/mL) up to 15 months of age but exhibited peaks at puberty (0.4 ng/mL) and maturity (0.8 ng/mL). Cortisol, T4 and T3 also exhibited peaks at puberty and maturity. Progesterone and oestradiol remained at basal levels throughout growth and development. Breeding buffalo bulls exhibited significant seasonal variations in testosterone, progesterone and oestradiol but not in T4 and T3. Semen quality and sexual behaviour did not vary between seasons. (author)