Membrane-bound estrogen receptor alpha initiated signaling is dynamin dependent in breast cancer cells.

Background: Although membrane-associated estrogen receptors (mERs) have been known to play important role in steroid-induced signal transmission, we still know little about their function in the estrogen-induced proliferation of breast cancer cells.

Methods: In our current work we tried to separate membrane-initiated estrogen receptor signaling from the overall estrogenic effect in MCF-7 breast carcinoma cells. Re-analyzing expression data from multiple microarray experiments, we selected a set of key regulatory genes involved in proliferation regulation and estrogen signaling to monitor estrogen-induced transcription changes.

17-β-estradiol Decreases Neutrophil Superoxide Production through Rac1.

Neutrophil granulocytes form the biggest free radical producing system of the human body. The importance of this system in atherosclerotic plaque formation and other free radical mediated disorders is confirmed by both in vivo and in vitro studies. Estrogen's effect on free radical production involves multiple estrogen receptors and occurs both on transcriptional and on protein phosphorylational level.

Antioxidant effect of the active metabolites of tibolone.

Certain steroidal compounds have an antioxidant effect in humans. Our aim was to test whether the synthetic steroid tibolone and its metabolites are also able to display such a property. For this, granulocytes from healthy men and women were incubated for two hours with different concentrations (10(-7), 10(-8), 10(-9 )M) of either estradiol, tibolone, 3α-hydroxytibolone, 3β-hydroxytibolone, Δ(4)-tibolone, 3α-sulfated-tibolone, 3α-17β-disulfated-tibolone, 3β-sulfated-tibolone or 3β-17β-disulfated-tibolone.

The effect of indomethacin, myeloperoxidase, and certain steroid hormones on bactericidal activity: an ex vivo and in vivo experimental study.

Background: The role of myeloperoxidase (MPO) is essential in the killing of phagocytosed bacteria. Certain steroid hormones increase MPO plasma concentration. Our aim was to test the effect of MPO, its inhibitor indomethacin, and certain steroid hormones on bactericidal activity.

Endothelial relaxation mechanisms and nitrative stress are partly restored by Vitamin D3 therapy in a rat model of polycystic ovary syndrome.

Aims: In polycystic ovary syndrome (PCOS), metabolic and cardiovascular dysfunction is related to hyperandrogenic status and insulin resistance, however, Vitamin D3 has a beneficial effect partly due to its anti-oxidant capacity. Nitrative stress is a major factor in the development of cardiovascular dysfunction and insulin resistance in various diseases. Our aim was to determine the effects of vitamin D3 in a rat model of PCOS, particularly the pathogenic role of nitrative stress.

Increased total scavenger capacity in rats fed corticosterone and cortisol on lipid-rich diet.

Background: In our earlier studies both corticosterone and cortisol had antioxidant effect in vitro.

Objectives: Our aim was to clarify whether corticosterone and cortisol oral administration results in beneficial antioxidant changes in Sprague-Dawley adult male rats in vivo.

Methods: Experimental animals were fed a lipid rich diet and treated with corticosterone or cortisol in the drinking fluid.

The effect of certain steroid hormones on the expression of genes involved in the metabolism of free radicals.

Steroid hormones influence the antioxidant processes of cells. However, the molecular mechanism of this effect is not fully clear. Our aim was to examine how steroid hormones affect the expression of certain genes that play a role in antioxidant processes.

The effect of selegiline on total scavenger capacity and liver fat content: a preliminary study in an animal model.

Selegiline is a selective irreversible inhibitor of the B-type of monoamine oxidase (MAO-B). The spectrum of its pharmacological activity is wide, possesses antioxidant, antiapoptotic and neuroprotective properties and, additionally, we found it is effective on the total scavenger capacity (TSC), and the regulation of fat content in rat liver kept on lipid-rich diet. Our aim was to clarify whether the oral treatment with selegiline is protective on oxidative damage of Sprague-Dawley adult rats in vivo.

Increased total scavenger capacity and decreased liver fat content in rats fed dehydroepiandrosterone and its sulphate on a high-fat diet.

Background: Weak androgens have an antioxidant effect in vitro which is represented as a beneficial change in the antioxidant status.

Objective: Our aim was to clarify whether dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) oral administration results in beneficial antioxidant changes in Sprague-Dawley adult male rats in vivo.

Methods: Groups of experimental animals were fed a high-fat or a normal-fat diet and treated with DHEA or DHEAS in the drinking fluid.

Biomechanics and vasoreactivity of female intramural coronaries in angiotensin II induced hypertension.

Hypertension causes small vessel remodeling, vasomotor alterations. We investigated diameter, tone and mechanics of intramural small coronaries of female rats that received chronic angiotensin treatment to induce hypertension.Angiotensin II infusion (AII, 100 ng/bwkg/min, sc.

DNA flow cytometry of human spermatozoa: consistent stoichiometric staining of sperm DNA using a novel decondensation protocol.

Rapid flow cytometric measurement of the frequency of aneuploid human sperms is in increasing demand but development of an exploitable method is hindered by difficulties of stoichiometric staining of sperm DNA. An aggressive decondensation protocol is needed after which cell integrity still remains intact. We used flow cytometry to examine the effect of lithium diiodosalicylate (LIS, chaotropic agent) on fluorescence intensity of propidium iodide-treated human spermatozoa from 10 normozoospermic men.

The effect of estrogens on superoxide anion generation by human neutrophil granulocytes: possible consequences of the antioxidant defense.

The present study aimed to test whether, beyond the known antioxidant effect of estradiol, such a property is also possessed by estrone and estriol. For this purpose, an in vitro investigation of the effect of estrone and estriol on superoxide anion production by human neutrophil granulocytes was carried out. Blood samples were obtained from healthy volunteers and neutrophil granulocytes were separated for measurement of superoxide anion generation after incubation with estrone, estriol (10(-7), 10(-6) and 10(-5) M) and 17beta-estradiol (10(-7) M).

Effect of inhibitors of myeloperoxidase on the development of aortic atherosclerosis in an animal model.

Our earlier studies have shown that some steroids increase myeloperoxidase enzyme (MPO) release from human granulocytes, and that MPO plasma levels are significantly lower in postclimacteric people. Moreover, we have proven that MPO inhibits production of atherogenic free radical superoxide anion and MPO-inhibitors increase superoxide release. The aim of the present study was to investigate the effect of MPO-inhibitors on the early phase of aortic atherosclerosis, namely the extent of intimal plaques and the thickening of the medial layer.

Inhibition of human hepatocellular carcinoma by L-proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13) in vitro and in vivo.

A new anticancer tripeptide, L-proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13), was investigated for its activity and mechanism in human hepatocellular carcinoma (HCC) cell lines. MF13 showed antiproliferative activities in the panel of 7 human HCC cell lines with IC50 in the range of 0.08-2.

Systematic investigation of different steroid precursors with respect to their effect on superoxide anion production by human neutrophil granulocytes.

Free radicals are involved in several pathological processes in living organisms, for example in athero- and oncogenesis. Some steroids are known to be effective antioxidants, while others do not play any such role. The aim of our study was to examine the antioxidant capability of different metabolites in the synthesis of steroid hormones.

Inhibition of microtubule polymerization by 3-bromopropionylamino benzoylurea (JIMB01), a new cancericidal tubulin ligand.

3-Bromopropionylamino benzoylurea (JIMB01) is a small molecular weight compound (MW 313) that has been synthesized in our laboratory. This compound showed antiproliferative activities in a panel of thirteen human tumor cell lines with IC(50) values in the range of 0.25 to 0.

Double blockade of cell cycle at g(1)-s transition and m phase by 3-iodoacetamido benzoyl ethyl ester, a new type of tubulin ligand.

3-Iodoacetamido benzoyl ethyl ester (3-IAABE) is a new compound synthesized in our laboratory. The primary action of 3-IAABE is to inhibit microtubule assembly by interacting with -SH groups on tubulin. In contrast to other known microtubule disrupters, 3-IAABE caused a double blockade in the cell cycle at G(1)-S transition and in M phase.

Plasma concentration of myeloperoxidase enzyme in pre- and post-climacterial people: related superoxide anion generation.

Neutrophil granulocytes are involved in the pathogenesis of atherosclerosis also through their free radical generation. The aim of the study was to test how extracellular levels of myeloperoxidase (MPO; a granulocyte enzyme playing role in free radical production) change by age and what effect this change has on the production of the free radical superoxide anion by neutrophils. We also wanted to examine whether the antioxidant effect of different steroid hormones is realized through the MPO.

High anticancer efficacy of L-proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13) in vivo.

The anticancer efficacy of the new anticancer tripeptide, L-proline-m-bis (2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride (MF13), was investigated in mice. MF13 showed a therapeutic effect in liquid tumors and induced complete remission even in late stage malignancies. MF13 also inhibited human colon cancer growth in nude mice by more than 85% (volume, p<0.

Antibody responses to HIV-1 antigens are higher in HIV-1(+) intravenous drug users than in HIV-1(+) homosexuals.

Immune responses to HIV-1 infection of 42 HIV-1-positive asymptomatic intravenous drug users (IVDUs) were compared with those of 135 HIV-1-infected asymptomatic homosexual men in the present study. Twenty-five HIV-1(-) individuals served as normal controls. The comparison included antibody responses to five computer-predicted epitopes of HIV-1 p17, and viral proteins gp120 and p24 as well as p17.

Induced myeloperoxidase activity and related superoxide inhibition during hormone replacement therapy.

Objective: To test whether the menopause entails any changes in the myeloperoxidase activity of neutrophil granulocytes. The effects of hormone replacement therapy on myeloperoxidase activity and related changes in free radical production were also investigated.

Design: Laboratory investigation of the effect of oestrogen on intracellular myeloperoxidase activity and release from human neutrophil granulocytes.

In vitro effects of different steroid hormones on superoxide anion production of human neutrophil granulocytes.

Neutrophil granulocytes play an important role in atherogenesis also through their free radical generation. According to recent studies, a point of action by which estrogens can provide protection against atherosclerosis is their inhibiting effect on superoxide anion production. The aim of our study was to test whether this means a common effect of steroids on superoxide production, or whether various steroid hormones have different action on superoxide generation of human granulocytes.

Recombinant human granulocyte colony-stimulating factor after kidney transplantation: a retrospective analysis to evaluate the benefit or risk of immunostimulation.

Background: Leukopenia due to immunosuppressive drugs represents a well-known complication in graft recipients, which might put patients at an increased risk for infections. In this study, recombinant human granulocyte colony-stimulating factor (rhG-CSF), a hematopoietic growth factor that selectively stimulates neutrophil colony formation and neutrophil cell differentiation, was tested for safety and efficacy.

Methods: We evaluated 30 episodes of leukopenia (<2000/mm3) in 19 kidney graft recipients treated with rhG-CSF.

Low frequency of the ccr5delta32 HIV-resistance allele in mainland China: identification of the first case of ccr5delta32 mutation in the Chinese population.

A 32-bp deletion on the CCR5 gene (ccr5delta32) confers resistance to HIV-1 infection. This deletion is common in Caucasians, but rare in Asians. Since the frequency of the ccr5delta32 allele of Chinese in mainland China has been unknown we investigated the ccr5delta32 mutation in a cohort of 407 Chinese people in this area.

[Changes in the myeloperoxidase activity of human neutrophilic granulocytes and the amount of enzyme deriving from them under the effect of estrogen].

Free radicals which are produced constantly in the human body have a significant role in the development of atherosclerosis. The responsibility of leukocytes for vascular disease has been proved in several ways. Hormonally active women are protected much more against myocardial infarction than men, which fact can be explained partly by endocrinological reasons, too.