Biomedical subjects

Elof D B Johansson

Publications and source records attributed to Elof D B Johansson.

4 recordsLinked to original sources

PubMed2006

Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells.

BACKGROUND: This study was conducted to evaluate the effects of graded concentrations (10(-8), 10(-7) and 10(-6) M) of progesterone receptor (PR) modulator CDB-2914 on the protein contents of PR, of vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and their receptors in cultured human uterine leiomyoma and matching myometrial cells. METHODS: PR-A, PR-B, VEGF-A, VEGF-B, VEGF receptor (VEGFR)-1, VEGFR-2, ADM and ADM receptor (ADMR) contents were assessed by Western blot analysis. RESULTS: Treatment with 100 ng/ml progesterone increased VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells and normal myometrial cells. The concomitant treatment with 10(-6) M CDB-2914 significantly decreased the progesterone-induced VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment alone decreased VEGFR-1, VEGFR-2 and ADMR contents in cultured leiomyoma cells but not in normal myometrial cells. CDB-2914 treatment increased PR-A and decreased PR-B contents in cultured leiomyoma cells in a dose-dependent manner compared with untreated cultures, whereas no significant changes in PR isoform contents were observed in normal myometrial cells. CONCLUSIONS: These results suggest that CDB-2914 down-regulates VEGF, ADM and their receptor contents and modulates PR isoform contents in cultured leiomyoma cells in a cell-type-specific manner.

Adrenomedullin↗

PubMed2004

Progesterone receptor modulator CDB-2914 down-regulates proliferative cell nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and poly(adenosine 5'-diphosphate-ribose) polymerase expression in cultured human uterine leiomyoma cells.

The present study was conducted to evaluate the effects of the progesterone receptor modulator CDB-2914 on proliferative activity and apoptosis in cultured human uterine leiomyoma cells. Isolated leiomyoma cells were subcultured in phenol red-free DMEM supplemented with 10% fetal bovine serum for 120 h and then stepped down to serum-free conditions for 12, 24, 48, and 96 h in the absence or presence of graded concentrations of CDB-2914 (10(-9), 10(-8), 10(-7), and 10(-6) M). The number of viable cultured leiomyoma cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazodium bromide assay. Proliferating cell nuclear antigen (PCNA) expression was evaluated by immunocytochemistry and Western blot analysis. Apoptosis was examined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay. Caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), and Bcl-2 expression were assessed by Western blot analysis. Compared with untreated control cultures, treatment with CDB-2914 decreased the number of viable cultured leiomyoma cells and the PCNA-positive rate in those cells and increased the TUNEL-positive rate in cultured leiomyoma cells in a dose-dependent manner. Western blot analysis revealed that treatment with CDB-2914 significantly decreased the expression of PCNA and Bcl-2 protein and increased the expression of cleaved caspase-3 and cleaved PARP in a dose-dependent manner compared with untreated control cultures. These results suggest that CDB-2914 inhibits the proliferation of cultured leiomyoma cells by down-regulating PCNA expression and induces apoptosis by up-regulating cleaved caspase-3 and PARP expression and down-regulating Bcl-2 protein expression in those cells.

Apoptosis↗

PubMed2004

New delivery systems in contraception: vaginal rings.

Vaginal rings, made of soft flexible silicone rubber, for delivery of contraceptive hormones are currently gaining clinical acceptance. This method provides extended release of hormones, which are implanted in the core of the ring and slowly disseminate into vaginal tissue. Although formulations and sizes vary, most rings are approximately 58 mm in diameter with a cross-section of 8.4 mm. Depending on the type of ring used, prolonged hormone release may occur from 3 weeks to 1 year. Advantages of the vaginal ring method are that it is user controlled, does not interfere with intercourse, does not require daily intake of a pill, and allows continuous delivery of a low dose of steroids. The Population Council has developed a progesterone-releasing ring, which is currently on the market in Chile and Peru for contraception in breastfeeding women. This ring may be effective for progesterone therapy during in vitro fertilization as well. A contraceptive ring releasing very low doses of the potent progestin Nestorone (Population Council, New York, NY) for 6 to 12 months is also under investigation. The optimal ring formulations, however, contain hormone combinations that provide excellent contraceptive efficacy with few side effects and good control of menstrual bleeding. The Food and Drug Administration has recently approved Organon's monthly ring releasing etonogestrel and ethinyl estradiol. The Population Council is developing a 1-year contraceptive ring releasing low doses of Nestorone and ethinyl estradiol. Combination rings are associated with very low pregnancy rates and side effects consistent with those of oral contraceptives.

Contraceptive Devices, Female↗

PubMed2004

Future developments in hormonal contraception.

The range of contraception options has recently increased to include long-term, reversible, and highly effective methods. Several new oral contraceptive (OC) formulations are now available in the United States, where OCs are the most popular reversible method. Long-term contraceptive systems that deliver hormones via subdermal implants, vaginal ring, intrauterine system, and transdermal patch afford convenient and effective alternatives to OCs. Contraceptives using hormone combinations appear to be especially effective with safety profiles comparable to OCs. All recently approved in the United States, the transdermal contraceptive patch offers once-weekly dosing with an improved compliance profile, the monthly vaginal ring has the convenient advantage of being user-controlled; a monthly combination injectable provides good pregnancy protection and improved bleeding control compared with the progestin-only formulatin; and the 5-year the levonorgestrel-releasing intrauterine system significantly diminishes menstrual blood loss. A single subdermal implant has been approved for use in Europe. With 60% of all unintended pregnancies occurring in women using birth control, it is anticipated that this increasing range of options will enhance compliance and provide more effective contraception suitable for the individual user.

Contraceptive Agents, Female↗