The influence of concentration of simvastatin (SIM) on free radicals in A‐2058 human melanoma malignum cells was studied. The proliferation assay for melanoma A‐2058 cells with SIM in concentration ...range from 0.1 to 20 µM was performed. SIM in the concentrations of 0.1, 0.3, and 1 μM only slightly changed the growth of A‐2058 cells, but the growth of the cells considerably decreased for higher concentrations of SIM. Free radicals in the cells were examined by an X‐band (9.3 GHz) electron paramagnetic resonance (EPR) spectroscopy. o‐Semiquinone free radicals with g‐factors in the range of 2.0060 to 2.0065 were found in A‐2058 cells. The asymmetric broad EPR spectra with linewidths (ΔBpp) from 0.87 to 1.25 mT were measured. The fast spin‐lattice relaxation processes characterized all the tested cells. The free radical concentrations in the all A‐2058 cells cultured with SIM were lower than in the control cells. The quenching of free radicals in A‐2058 cells depended on concentration of SIM. This effect was the weakest for concentration of SIM of 3 μM. The strongest decrease of free radical concentration caused SIM in concentration of 1 μM.
The spectroscopic studies were the useful techniques to determined the influence of simvastatin (SIM) on A‐2058 human melanoma malignum cells. The exposure of A‐2058 cells to higher concentrations of SIM resulted in a decrease in the degree of cell proliferation. SIM decreased free radical concentrations in melanoma A‐2058 cells dependent on concentration of this substance in the cell culture.
Tibolone (Org OD14) is a synthetic steroid used for post-menopausal hormone replacement therapy (HRT). Since HRT might increase breast cancer risk, it is important to determine the possible effects ...of tibolone on breast tissues. Tibolone and its metabolites Org 4094, Org 30126 and Org OM38 have been reported to inhibit estrone sulfatase activity in MCF-7 and T47D breast cancer cell lines, which suggest beneficial effects on hormone dependent breast cancer by reducing local production of free estrogens. Breast adipose stromal cells (ASCs) contain aromatase activity—an obligatory step in the biosynthesis of estrogens—and possibly contain sulfatase activity. We investigated the effects of tibolone, its metabolites and the pure progestin Org 2058 on PGE
2-stimulated aromatase activity and on sulfatase activity in human ASC primary cultures and on sulfatase activity in MCF-7 and T47D cell lines. In MCF-7, tibolone and metabolites, but not Org 2058, were found to inhibit sulfatase activity. In T47D, tibolone inhibited sulfatase only at 10
−6
M, although weakly. ASC had high sulfatase activity, which was inhibited by 10
−6
M of tibolone, Org 4094 and Org 30126, but not by Org OM38 or Org 2058. Surprisingly, aromatase activity in ASC was increased by both tibolone and Org 2058 at 10
−6
M. As ligand binding assay results and immunohistochemistry indicated the absence of progesterone and estrogen receptors in ASC, these effects on aromatase and sulfatase activity in ASC likely take place by other routes. Because tibolone and its metabolites inhibit sulfatase activity, and because tibolone only increases aromatase activity at a high concentration, we conclude that effects of tibolone on the breast are probably safe.
16 alpha-Ethyl-21-hydroxy-19-norpregn-4-ene-3,20-dione (ORG 2058) is a ligand widely used in progesterone receptor assays. An improved synthesis of the compound is reported, starting from ...norethisterone acetate. The preparation of the tritiated radioligand 3HORG 2058 is also described.
Five putative iodinated progesterone receptor (PR) binding ligands were synthesized and evaluated as potential imaging agents for PR-positive human breast tumours. Two compounds (
E- and
...Z-17-hydroxy-21-iodo-19-nor-17α-pregna-4,20-dien-3-one;
E- and
Z-IPG1) were previously described, but are re-evaluated. The other three were novel compounds: two nortestosterone analogues derived from ORG 3236 (
E- and
Z-13-ethyl-17-hydroxy-21-iodo-11-methylene-18,19-dinor-17α-pregna-4,20-diene-3-one;
E- and
Z-IPG2) and one norprogesterone analogue derived from ORG 2058 (21-4-iodophenoxy-16α-ethyl-19-norpregn-4-ene-3,20-dione; IPG3). The
E-iodovinyl nortestosterone compounds were obtained by a new route of synthesis. Competitive binding studies were performed to determine their binding affinities for the PR in three types of tissue (human MCF-7 breast tumour cells and rat uterine and mammary tumour tissue) and for the androgen receptor (AR) in human MCF-7 breast tumour cells, as well as for the sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) in human plasma. All four 17α-iodovinyl nortestosterone derivatives displayed high binding affinity for the human PR, that of
Z-IPG1 and
E- and
Z-IPG2 being even higher than that of ORG2058. Their affinities for the rat PR were somewhat lower, especially those of both E-isomers. The affinity of IPG3 was lower for both the human and rat PR. The nortestosterone derivatives also showed AR binding, the relative binding affinities ranging from 4.3 to 17.0% as compared with 5αDHT. Additionally, neither of these steroids displayed any significant binding to either SHBG or CBG in human plasma. We conclude that the
in vitro binding properties of all four 17α-iodovinyl nortestosterone derivatives warrant evaluation of the distribution characteristics of their
123I-labelled analogues to determine their usefulness as PR imaging agents.
India
Shiva Rathom Shiby Ravana
Shiva (white) and Parvati (green) sit in carriage (ratha) with Ravana (red) as the choir vein. The sun god Surya and the moon god Soma or Chandra serve as wheels.
...Iconographic details: Shiva, Parvati and Ravana wear a golden, jewel-obsessed crown (kirita-mukuta) on their heads. (Niklas, 2000)
India
1883.05.0068
Shiva Rathom driving by Ravana
Shiva (vit) och Parvati (grön) sitter i vagn (ratha) med Ravana (röd) som körsven. Solguden Surya och månguden Soma eller Chandra tjänar som hjul.
Ikonografiska detaljer: Shiva, Parvati och Ravana bär en gyllene, juvelbesatt krona (kirita-mukuta) på sina huvuden. (Niklas , 2000)
1883.05.0068
Gudarnas Indien
India
T.D. 9468
United States. Internal Revenue Bulletin,
11/2009
2009-44
Trade Publication Article
T.D. 9468, under Section 2053, relates to the amount deductible from a decedent's gross estate for claims against the estate. In addition, the regulations update the provisions relating to the ...deduction for certain state death taxes to reflect the statutory amendments made in 2001 to Sections 2053(d) and 2058.
We assessed the hypothesis that due to variations in the conformation of the progesterone receptor induced by the antiprogestin RU38486 compared to the progestin ORG 2058, differences may result in ...the asociation of the receptor with some of the chromatin components. The physical properties of the receptor-bound chromatin fragments released by micrococcal nuclease digestion were characterized by sucrose gradient sedimentation and by gel filtration on Agarose A-1.5m or Agarose A-5m columns. The nuclear fraction was isolated from T47D cells previously exposed to 0.1 μM
3HRU38486 or 0.1 μM
3HORG 2058. Micrococcal nuclease digestion solubilized two receptor forms sedimenting at 4.4 S and 6.3 S for the antiprogestin bound receptor and only one receptor at 4.4 S for the progestin ligated receptor. High-salt buffer dissociated either the antiprogestin or the progestin-bound receptor to smaller receptor forms sedimenting at 3.5 S. Chemical cross-linking with the cross-linker 2-iminothiolane of the micrococcal nuclease solubilized receptor forms resulted in 6.7-S and 4.4-S forms sedimenting on 0.4 M KCl gradients for the antiprogestin and progestin ligated receptors, respectively. Stokes radii of 7.3 nm and 6.4 nm were determined by gel filtration in 0.4 M KCl for the 6.7-S and the 4.4-S receptor forms, respectively. Using the sedimentation coefficient and the Stokes radius, molecular weights of 202000 and 116000 were calculated for the antiprogestin and progestin ligated receptors. We conclude that the micrococcal nuclease solubilized antiprogestin ligated receptor is associated with additional or different chromatin components compared to the progestin bound receptor.
The susceptibility of the progesterone receptor, liganded either by the antiprogestin RU 486 or by the progestin ORG 2058, to chymotrypsin and trypsin degradation was investigated. The nuclear ...fraction was isolated from T47D cells previously exposed either to 0.1 microM 3HRU 486 or to 0.1 microM 3HORG 2058. The proteolytic digestion was performed on the micrococcal nuclease hydrolysate. The molecular weights of the receptor fragments were calculated, in high salt buffer, from the sedimentation coefficients determined on a sucrose gradient and from the Stokes radii estimated by gel filtration on an Agarose A-0.5 m column. Micrococcal nuclease solubilized receptor forms with molecular weights of 80,000 and 75,000 for the antiprogestin- or progestin-liganded receptor, respectively. Chymotrypsin degraded these receptor forms to fragments with molecular weights of 23,000 either for the antiprogestin- or progestin-liganded receptor. Similar molecular weights of 23,000 were calculated for the progesterone receptor liganded either by the antiprogestin RU 436 or the progestin ORG 2058 following trypsin cleavage. We conclude that the degradation pattern of the progesterone receptor liganded either by the antiprogestin RU 486 or the progestin ORG 2058 following chymotrypsin or trypsin digestion seems to be similar.
