Expression of scavenger receptor class B1 in endometrium and endometriosis.

Endometriosis is characterized by the presence of endometrial glands and stroma within the peritoneum and other extrauterine sites. The presence of aromatase, a key enzyme in the biosynthesis of estradiol, has been demonstrated in eutopic endometrial samples of women with moderate to severe endometriosis, but not in those of disease-free women. Animal studies have shown that high density lipoprotein provides precursor cholesterol pool for steroidogenesis. Scavenger receptor class B1, a 82-kDa cell surface protein, is involved in the binding of high density lipoprotein to target cells and promotes cholesteryl ester uptake. In this study we detected the presence of scavenger receptor class B1 in eutopic and ectopic endometrium. There was more scavenger receptor class B1 protein associated with endometriosis compared with matched endometrium. Two bands (82 and 45 kDa) were detected in the endometrium and endometriosis samples. Glycanase treatment indicated that the 45-kDa protein might be a nonglycosylated form of scavenger receptor class B1. Immunostaining of fixed tissues detected scavenger receptor class B1 in glandular epithelium of both tissues. Scavenger receptor class B1 and aromatase mRNA were increased in endometriosis tissues. Scavenger receptor class B1 expression in the endometrium and endometriosis supports a role for this receptor in the uptake of high density lipoprotein cholesterol, possibly supporting in situ estrogen production, which is detrimental in the progression of endometriosis.

RU486-induced growth inhibition of human endometrial cells.

OBJECTIVE: To determine the direct action of RU486 on endometrial cell proliferation and to differentiate whether the antioxidant or the antiprogesterone property of RU486 is predominately responsible for its effect on cell growth. DESIGN: In vitro study comparing the effects of RU486 (antiprogesterone and antioxidant), reduced RU486 (antioxidant), ZK112,993 (antiprogesterone), and lazaroid U74,500A (antioxidant) on endometrial cell growth. The human endometrial cell line EM42 was used in transient transfection assays to confirm the relative antiprogesterone potency of the various compounds. SETTING: Academic medical center PATIENT(S): Women presenting with pelvic pain or infertility and diagnosed with endometriosis at time of surgery or women desiring tubal ligation with a normal pelvis (controls). INTERVENTION(S): Endometrial cell cultures were treated with RU486, reduced RU486, lazaroid U74,500A, and ZK112,993. MAIN OUTCOME MEASURE(S): Tritiated thymidine incorporation was used to assess cell growth. Inhibition of progesterone induction of transiently transfected reporter plasmids was used to measure antiprogesterone activity of compounds studied. RESULT(S): RU486 reduced cell growth in a dose-dependent fashion of the endometrial cell lines EM42 and RL95-2 and of endometrial and endometriosis cells from primary culture. After being reduced, RU486 lost most of its antiprogesterone activity but retained its antiproliferative properties. ZK112,993 was similar in potency to RU486 as a progesterone antagonist but did not significantly modify endometrial cell growth. Lazaroid U74,500A was devoid of antiprogesterone activity but was shown to be a potent antiproliferative agent. CONCLUSION(S): RU486 has a direct inhibitory effect on human endometrial cell growth. This activity appears to be at least partly mediated through its antioxidant property.

Endocrinopathies associated with recurrent pregnancy loss.

Repeated pregnancy wastage is defined as the loss of three consecutive pregnancies at less than 20 weeks of gestation andfetal weight less than 500 g. This article provides guidelines to evaluate endocrinopathies associated with recurrent abortions. Thyroid disorder, although usually obvious, has a high frequency in the female population and should be evaluated and treated, if revealed. Recent studies indicate that thyroid antibodies, even in the absence of abnormal thyroid function tests, may be related to pregnancy loss. Diabetes mellitus should be controlled. Luteal phase defects should be sought and, when consistently documented, treated with clomiphene citrate or progesterone supplementation. Bromocriptine may be added to the treatment of a patient with hyperprolactinemia prior to testing for luteal phase defect. An understanding of the stress and anxiety in these couples should always be considered and included in the treatment style of the physician.

Autoantibodies to markers of oxidative stress are elevated in women with endometriosis.

OBJECTIVE: To measure autoantibodies that recognize oxidatively modified proteins in the sera of women with surgically proven endometriosis. DESIGN: Prospective study. SETTING: Tertiary care academic medical center. PATIENT(S): Women undergoing surgery for endometriosis or tubal ligation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum and peritoneal fluid autoantibody titers to malondialdehyde-modified low-density lipoprotein, oxidized low-density lipoprotein, and lipid peroxide-modified rabbit serum albumin determined by ELISA. Correlation of autoantibody titers with revised American Fertility Society staging classification, symptoms, and morphologic type of endometriosis. RESULT(S): Mean (+/-SEM) serum autoantibody titers (in optical density units) to the three antigens were as follows: [1] lipid peroxide-modified rabbit serum albumin, 0.49 +/- 0.12 units in the patients with endometriosis and 0.2 +/- 0.02 units in the controls; [2] oxidized low-density lipoprotein, 0.22 +/- 0.005 units in the patients with endometriosis and 0.18 +/- 0.006 units in the controls; and [3] malondialdehyde-modified low-density lipoprotein, 0.21 +/- 0.005 units in the patients with endometriosis and 0.16 +/- 0.003 units in the controls. There was no correlation between autoantibody titers and revised American Fertility Society stage, symptoms, or morphologic type of endometriosis. Peritoneal fluid did not contain autoantibodies to any of the three antigens. CONCLUSION(S): Autoantibodies to markers of oxidative stress were significantly increased in women with endometriosis. These findings strongly support our data demonstrating that women with endometriosis have enhanced oxidative stress.

Endoscopic treatment for endometriosis.

Endometriosis is best regarded as a chronic disease that can vary in symptomatology over time. Endoscopic therapy for relief of pelvic pain as well as infertility is a therapeutic option. The formation of a rational treatment plan before surgery will ensure a minimum number of reproductive surgeries over the patient's lifetime.

Estradiol as an antioxidant: incompatible with its physiological concentrations and function.

Estradiol has been documented to inhibit the oxidation of low density lipoprotein (LDL). We show that physiological concentrations of estradiol do not inhibit the oxidation of LDL by copper. LDL samples isolated from a) premenopausal and postmenopausal women and from b) women at different time periods during their menstrual cycle, who differ vastly in plasma estradiol levels, were also oxidized at the same rates by copper. In contrast, LDL samples isolated from c) women who were hyperstimulated during in vitro fertilization (IVF), with estradiol concentrations above 2000 pg/ml, were resistant to oxidation by copper. However, these LDL samples were also oxidized at a higher rate by peroxidases. More importantly, subjects with high estradiol levels also showed an increase in myeloperoxidase (MPO) protein in the plasma. Based on these results, we conclude that at physiologic concentrations, it is unlikely that estradiol could act as an antioxidant. In fact, the ability of estradiol to induce MPO and become a prooxidant might instead suggest that MPO-mediated oxidative clearance of LDL from plasma by liver might favorably influence the outcome of atherosclerosis.

Regulation of monocyte to macrophage differentiation by antiglucocorticoids and antioxidants.

OBJECTIVE: Our purpose was to examine RU 486 and related compounds on monocyte to macrophage differentiation through scavenger receptors and cellular adhesion. STUDY DESIGN: Human monocytes were isolated, cultured, and treated with dexamethasone, levonorgestrel, RU 486, and other structurally related compounds alone or in combination. Macrophage scavenger receptor activity, inhibited by glucocorticoids and associated in the current literature with macrophage cellular adhesion, was determined in this study by counting the number of adherent cells after treatment. In addition, fluorescent-labeled acetyl-low-density lipoprotein uptake was determined as a function of scavenger receptor biologic activity. RESULTS: Dexamethasone, levonorgestrel (antiglucocorticoid only) and RU 486 (antiglucocorticoid and antioxidant) all significantly decreased adherent macrophages (4%, 52%, and 74% of control). Levonorgestrel, however, demonstrated a marked uptake of fluorescent-labeled scavenger receptor ligand. RU 486 and dexamethasone were antagonistic when combined (P < .001); levonorgestrel was less antagonistic but, however, still significant (P < .05). Reduced RU 486 (antioxidant but loses antiglucocortioid activity) decreased cellular adhesion, yet scavenger receptor function was enhanced. Both probucol (extracellular mechanism of action) and probucol analog (intracellular action) markedly up-regulated scavenger function, but once again a separation of adhesion from scavenger activity was noted. Vitamin E (antioxidant) and onapristone (antioxidant and antiglucocorticoid) had virtually little to no effect on adhesion and scavenger receptor activity. Finally, pyrrolidine dithiocarbamate, a potent oxygen-free radical quencher, was toxic to all cells examined. CONCLUSIONS: RU 486 is a known antiglucocorticoid with novel antioxidant properties first demonstrated by our laboratories. Levonorgestrel has antiglucocorticoid but no antioxidant activity. RU 486 antagonized the inhibitory effect of dexamethasone on scavenger receptor development, whereas levonorgestrel was stimulatory. A separation of scavenger receptor-induced cellular adhesion and scavenger receptor internalized ligand was demonstrated by (1) reduced RU 486, which loses its antiglucocorticoid activity but retains its antioxidant activity, and (2) probucol analog, which is chemically altered to allow intracellular entry. Glucocorticoids decrease the development of scavenger receptors, whereas antioxidants regulate inflammatory cytokines by intracellular mechanisms. It is therapeutically important to up-regulate scavenger receptor activity by antiglucocorticoids in the peritoneal cavity of women with endometriosis. However, because these mechanisms also induce inflammatory cytokines, a balance of antioxidants and antiglucocorticoids such as those demonstrated in the above study may prove beneficial.

Preliminary report on the treatment of endometriosis with low-dose mifepristone (RU 486).

OBJECTIVE: We have previously shown that treatment with mifepristone, 50 to 100 mg daily, results in amenorrhea, anovulation, and symptomatic improvement in women with endometriosis. In this study we lowered the dose to 5 mg daily to determine whether clinical efficacy is altered without other adverse actions. STUDY DESIGN: After a baseline cycle, seven women with endometriosis were given mifepristone, 5 mg daily, for 6 months. Daily symptom inventories were recorded. Laparoscopy was performed during the sixth month of therapy. RESULTS: Pelvic pain improved in six of seven patients. Cyclic bleeding ceased in all patients, but four of the seven patients complained of irregular bleeding. Surgical staging at the conclusion of the study (five of seven patients) did not detect a change in endometriosis. CONCLUSIONS: Mifepristone, 5 mg daily, resulted in symptomatic improvement, but did not stabilize the endometrium. From our experience with three doses of mifepristone, we would recommend a dose of 50 mg be used for continued investigations.

PIP: The authors' previous research has demonstrated that treatment with 50-100 mg/day of mifepristone produces symptomatic improvement of endometriosis. The present study assessed the efficacy of a substantially reduced antiprogesterone dose. After a baseline cycle, 7 US women with pelvic pain caused by endometriosis were administered 5 mg of mifepristone daily for 6 months. Clinical responsiveness was evaluated in daily symptom inventories completed by study participants. Pelvic pain improved significantly within 1 month of treatment initiation in 6 of 7 patients. Cyclic bleeding ceased in all 7 patients, but 4 women complained of irregular bleeding that begin 3-5 months into treatment. Menstrual cyclicity returned 23-37 days after study completion. 2 women did not complete the study--1 because of continued pelvic pain and 1 because of heavy bleeding during the fifth cycle. Surgical staging through laparoscopy in the 5 remaining women failed to document a significant change in endometriosis. 1 woman had a slight increase in endometriosis score compared to baseline, 1 had no change, and the remaining 3 women showed decreases from 32-45%. Given the failure of the 5 mg dose to stabilize the endometrium and the high rate of uterine bleeding, a dose of 50 mg of mifepristone is recommended for future investigations.

Macrophage scavenger receptor(s) and oxidatively modified proteins in endometriosis.

OBJECTIVE: To determine whether cultured human peritoneal macrophages have functional scavenger receptor(s) and whether activation of macrophages in endometriosis may involve an increase in scavenger receptor activity. DESIGN: A controlled clinical study comparing peritoneal fluid (PF) macrophages of women with endometriosis and controls without endometriosis. SETTING: Women undergoing laparoscopic evaluation and treatment in a tertiary medical center. PATIENT(S): Twenty-one women undergoing evaluation for pelvic pain or infertility and 10 women undergoing elective laparoscopic tubal ligation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Evidence for functional macrophage scavenger receptor and evidence of ligands for the scavenger receptor in PF. RESULT(S): Peritoneal macrophages of women with endometriosis degrade significantly more endothelial cell-low density lipoprotein (EC-LDL) and copper-oxidized LDL (Cu-LDL) than native LDL. Macrophages of women with endometriosis also incorporate more labeled oleic acid into cholesteryl ester in the presence of oxidized LDL (Ox-LDL) than in the presence of native LDL. Western blot analysis demonstrates the presence of adducts between lipid peroxidation products and proteins in PF of patients with and without endometriosis. The PF of women with endometriosis competes with labeled Ox-LDL for uptake by mouse peritoneal macrophages in a dose-dependent manner. CONCLUSION(S): We demonstrate for the first time that human macrophages have functional scavenger receptor(s) and that activation of macrophages in endometriosis involves an increase in scavenger receptor activity. Two lines of evidence indicate the presence of ligands for the scavenger receptor in PF.

Evidence for oxidatively modified lipid-protein complexes in endometrium and endometriosis.

OBJECTIVE: To evaluate for the presence of oxidatively modified lipid-protein complexes in endometriosis and endometrium of women with endometriosis and controls. DESIGN: Controlled clinical study. SETTING: Academic tertiary care center. PATIENT(S): Women undergoing surgery for pelvic pain, infertility, endometriosis, or tubal ligation controls. INTERVENTION(S): Biopsy of endometrium and endometriosis. MAIN OUTCOME MEASURE(S): Staining with antibodies to oxidatively modified lipid proteins (HNE-7, MDA2), macrophages (HAM-56), and muscle cell actin (HHF-35). RESULT(S): Both endometrium and endometriosis tissues contain stromal cells that immunostain with HAM-56 and show immunostaining (both intracellular and extracellular) with HNE-7 and MDA2. Some endometriotic implants show patchy staining with HHF-35. Endometrium was devoid of staining with HHF-35. Control staining with nonimmune sera in both tissues was also devoid of staining. CONCLUSION(S): These data strongly implicate the occurrence of oxidative stress in endometriosis tissue. These data also suggest that oxidative modification is a normal physiological process in endometrium.

Lysophosphatidyl choline, a chemotactic factor for monocytes/T-lymphocytes is elevated in endometriosis.

Inflammatory processes have been hypothesized to mediate some of the clinical sequelae associated with endometriosis. The peritoneal fluid (PF) of women with endometriosis is known to contain more inflammatory cells and their associated cytokines, chemokines, and growth factors. This work provides strong evidence for oxidative stress in the PF of women with endometriosis. 1) The low density lipoprotein (LDL) isolated from the PF of subjects with endometriosis shows a small but detectable increase in electrophoretic mobility compatible with mildly oxidized LDL compared with LDL isolated from the plasma of the same subjects and PF of controls. 2) Isolated PF-LDL of endometriosis subjects is more readily oxidized in vitro than PF-LDL of controls, or LDL isolated from plasma. 3) Vitamin E content is significantly lower in endometriosis PF compared with controls, and compared with plasma of women with endometriosis and controls. No difference is seen between plasma and PF of control subjects. 4) The ratio of phosphatidylcholine/lyso phosphatidylcholine (Ptd/lyso PtdCho) in the PF of endometriosis subjects is significantly lower compared with PF of controls. Taken together, these data provide strong evidence for a pro-oxidant environment in the peritoneal cavity of women with endometriosis. Lyso PtdCho, a product derived from phospholipase A2 action on peroxidized phosphatidylcholine and a potent chemotactic factor for monocytes and T-lymphocytes, is elevated in endometriosis. We hypothesize that the increased presence of lipid peroxidation products in the PF of endometriosis subjects may, at least partly, account for the recruitment of leukocytes, the increase in macrophage activation, the secretion of monocyte--macrophage-derived cytokines, and the endometrial growth-promoting activity associated with endometriosis.

Generation and characterization of a polyclonal antipeptide antibody to human glycodelin.

OBJECTIVE: To develop and characterize an antiglycodelin antibody using a 15-amino acid synthetic peptide as antigen, derived from the sequence of human glycodelin. DESIGN: We have developed a chicken antiglycodelin-derived peptide antibody and have characterized the antibody with the use of endometrial and ovarian cell lines. The antibody was also tested for its ability to detect glycodelin by ELISA assay, immunocytochemistry, and by Western blot. SETTING: Various cell lines, cell culture medium, and amniotic fluid were used in the experiments. PATIENT(S): Amniotic fluid was collected from pregnant patients in their first trimester of pregnancy. INTERVENTION(S): No intervention. MAIN OUTCOME MEASURE(S): Detection of glycodelin. RESULT(S): The cell lines RL95-2 (human endometrial carcinoma cells), OVCAR-3 (human ovarian adenocarcinoma cells), HeLa (human cervical epitheloid carcinoma cells), and EM42-D (human endometrial epithelial cells) reacted with the antibody, indicating the presence of glycodelin. A specific 45-kd protein representing glycodelin was detected by Western blot in the amniotic fluid. CONCLUSION(S): Antipeptide antibodies can be successfully used to detect and quantify the presence of glycodelin in cells and fluids.

Endometriosis: a disease of oxidative stress?

Our central hypothesis proposes that oxidatively damaged red blood cells (RBCs), apoptotic endometrial cells or undigested endometrial tissue may signal the recruitment and activation of mononuclear phagocytes. Women with endometriosis are prone to respond to this stimulus with an inadequate macrophage scavenger receptor response although the secretory response is not impaired. Activated macrophages in the peritoneal cavity generate an oxidative stress, which consists of lipid peroxides, their degradation products, and products formed from their interaction with low-density lipoprotein (LDL) apoprotein and other proteins. The lipoproteins of the peritoneal fluid (interstitial fluid) have been shown to have lower vitamin E levels and to be more readily oxidized than plasma, so peritoneal fluid may actually contribute to the disease process actively rather than as a passive carrier of mediators of inflammation and growth. As a result of such a stress, a sterile, inflammatory reaction with secretion of growth factors, cytokines, and chemokines is generated, which is deleterious especially to successful reproduction. We propose that such a pro-oxidant environment (peritoneal fluid as well as activated macrophages) promotes growth of ectopic endometrium. The data presented in this review are just the beginning of exploring the role of oxidative stress in mediating the pathophysiology of endometriosis. Only by understanding the mechanisms involved in the pathogenesis of endometriosis can we develop the basis for new diagnostic and therapeutic approaches.

Fresh mouse peritoneal macrophages have low scavenger receptor activity.

Peritoneal macrophages are easily isolated by lavage, suggesting that they are either nonadherent or weakly adherent in situ. Cultured macrophages express class A scavenger receptors (SCR), which mediate Ca2+-independent adhesion in vitro. We examined fresh peritoneal macrophages from mice and from women with endometriosis to determine whether the adherence of these cells was associated with increased expression of class A SCR. Fresh human macrophages were not immunoreactive to SCR antibodies; however, SCR immunoreactivity increased with time in culture. Fresh mouse and human macrophages took up minimal amounts of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI)-acetyl-low density lipoproteins (Ac-LDL), a class A SCR ligand. Murine macrophages in culture for 24-72 h internalized four times more Ac-LDL than fresh cells. Cells cultured for 2 days incorporated 3.2 times more [14C] oleate than freshly isolated cells (55.7 +/- 7.9 versus 17.6 +/- 3.0 nmol/mg cell protein). In contrast to SCR activity, mouse macrophage SCR mRNA expression was similar in freshly isolated macrophages and those cultured for 3 days. These results suggest that peritoneal macrophages express only low levels of SCR activity in situ and that posttranscriptional regulation after isolation leads to an increase in SCR activity that correlates with adherence of the macrophages in vitro.

Surgical approaches to ovulation induction.

This article provides a review of published data on surgical methods of ovulation induction for polycystic ovary syndrome (PCOS). Areas that were discussed include the historical background of these procedures, their outcome as reported in the literature and potential adverse effects.

Interaction of Interceed oxidized regenerated cellulose with macrophages: a potential mechanism by which Interceed may prevent adhesions.

OBJECTIVE: The objective of the study was to determine whether Interceed oxidized regenerated cellulose (Johnson & Johnson Medical, Arlington, Tex.), because of its polyanionic nature, may compete for the macrophage scavenger receptor. STUDY DESIGN: RAW macrophages were incubated with Interceed oxidized regenerated cellulose and known scavenger receptor ligands. The production of interleukin-1beta by mouse peritoneal macrophages was measured in the presence of Interceed cellulose. RESULTS: When macrophages were incubated with Interceed cellulose, increasing concentrations inhibited the uptake of fluorescent acetyl low-density lipoprotein. In the presence of Interceed cellulose there was a decrease in the production of interleukin-1beta by mouse macrophages. CONCLUSION: These results suggest that the interaction of Interceed oxidized regenerated cellulose with macrophages with scavenger receptors may result in a decreased secretion of matrix components, inflammatory mediators, and cellular growth factors. Thus Interceed cellulose may function as a biologic barrier in preventing adhesions.

Charge-based interactions of mammalian sperm with oocytes: inhibition of fertilization of mouse oocytes by ligands of macrophage scavenger receptor(s).

OBJECTIVE: To determine whether anionic ligands for the macrophage scavenger receptor inhibit the fertilization of mouse oocytes by mouse spermatozoa. DESIGN: In vitro study of sperm binding and two-cell embryo formation in the presence of scavenger receptor ligands. Sperm-oocyte interaction may be mediated by sulfated sugars. In this study, we tested other nonsulfated anionic ligands for the scavenger receptor for their ability to affect fertilization. The only common feature of these ligands is their anionic nature. SETTING: Oocytes and sperm from mice were used. MAIN OUTCOME MEASURE(S): Binding of sperm to oocytes and subsequent formation of two-cell embryos were determined. RESULT(S): Fucoidin, polyinosinic acid, oxidized low-density lipoprotein, acetyl low-density lipoprotein, and malondialdehyde-modified LDL inhibited the binding and fertilization of mouse sperm to mouse oocytes. Addition of fresh sperm to oocytes previously treated with sperm in the presence of these agents restored the binding and fertilization. CONCLUSION(S): These results show that charge-based interactions analogous to the interactions of the scavenger receptor with its ligands may play an important role in mammalian fertilization.

The effect of RU 486 and related compounds on cultured macrophage differentiation and function.

OBJECTIVE: Our purpose was to examine RU 486 and related compounds on macrophage scavenger receptors and cellular adhesion. STUDY DESIGN: THP-1 cells were activated with phorbol myristate acetate and treated with dexamethasone, levonorgestrel, and RU 486 alone or in combination. Scavenger receptor activity was determined by counting adhered cells. In addition, fluorescently labeled acetyl low density lipoprotein uptake was determined. RESULTS: Both dexamethasone and RU 486 significantly decreased activated macrophages (81% and 26% of control). Levonorgestrel stimulated adherent cells in activated monocytes (130% of control). RU 486 and dexamethasone were antagonistic when combined (p < 0.001). In contrast, dexamethasone could not overcome the stimulatory effect of levonorgestrel (p < 0.001). Fluorescent studies yielded similar results. CONCLUSIONS: RU 486 is a known antiglucocorticoid with novel antioxidant properties. Levonorgestrel has antiglucocorticoid but no antioxidant activity. Glucocorticoids decrease scavenger receptors and antioxidants regulate inflammatory cytokines. RU 486 antagonized the inhibitory effect of dexamethasone on scavenger receptors, whereas levonorgestrel was stimulatory. It is therapeutically important to up-regulate scavenger receptor activity by antiglucocorticoids in the peritoneal cavity of women with endometriosis. However, because these mechanisms also induce inflammatory cytokines, a balance of antioxidants and antiglucocorticoids may prove beneficial.

Inhibition of oxidative modification of proteins by RU486.

OBJECTIVES: To elucidate further the antioxidant properties of RU486. We determined whether it can protect biologic molecules such as proteins (albumin, low-density lipoprotein [LDL] and oxidized LDL) from damage by pre-existing lipid peroxides. DESIGN: In vitro study. INTERVENTIONS: We tested the effects of RU486 on the formation of fluorescent oxidatively modified proteins by pre-existing lipid peroxides. We used two model systems, the incubation of oxidized linoleic acid with serum albumin and the incubation of human LDL with copper. MAIN OUTCOME MEASURES: The formation of modified protein was established by determining fluorescence at excitation wavelength of 330 nm and emission wavelength between 390 and 500 nm. Modified protein has a characteristic emission between 425 and 430 nm. RESULTS: The addition of increasing amounts of RU486 inhibited the formation of fluorescent oxidatively modified protein products in both model systems. CONCLUSION: These results provide evidence that RU486 not only can prevent the formation of lipid peroxide, but also can block the formation of fluorescent protein adducts in the presence of pre-existing lipid peroxides.

Mifepristone: clinical application in general gynecology.

PIP: RU-486, the first clinically available antiprogestin, has numerous gynecologic applications beyond first-trimester pregnancy termination. Long-term administration of 2 mg/day of RU-486 suppresses ovulation while maintaining serum estrogen levels and ovarian follicular activity. In the endometrium, long-term RU-486 administration results in significant endometrial dysynchrony and stromal compaction. RU-486 has been demonstrated to relieve pain in women with symptomatic endometriosis and decrease the size of uterine leiomyomata by about 50%. There are preliminary findings indicating that RU-486 is effective in the treatment of premenstrual syndrome, ectopic pregnancy, and anovulatory uterine bleeding. In need of further investigation is the RU-486 dosage that can treat pathophysiologic states while minimizing the endometrial effects.^ieng