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Biomedical subjects

Daniela Hornung

Publications and source records attributed to Daniela Hornung.

11 recordsLinked to original sources

Regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 in follicular fluid accumulate differentially in patients with and without endometriosis undergoing in vitro fertilization.

OBJECTIVE: To compare the amount of regulated upon activation, normal T cell expressed and secreted (RANTES) and monocyte chemotactic protein 1 (MCP-1) in follicular fluid (FF) of patients with and without endometriosis and to determine their oocyte fertilization and pregnancy rates. DESIGN: Case-control study. SETTING: Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Germany. PATIENT(S): Thirty-two women with endometriosis stages I-IV and 28 women without endometriosis, both groups surgically and histologically confirmed. INTERVENTION(S): Diagnostic laparoscopy, IVF-ET. MAIN OUTCOME MEASURE(S): RANTES and MCP-1 levels in follicular fluid, measured by ELISA, and oocyte fertilization and pregnancy rates. RESULT(S): Follicular response and days of gonadotropin stimulation were similar between the two groups. The levels of RANTES in FF from patients with endometriosis were significantly higher (460.4 +/- 90.3 pg/mL) compared with concentrations in patients with tubal infertility (243.8 +/- 70.9 pg/mL; P<.05). In contrast, MCP-1 concentrations in FF from women with endometriosis (330.0 +/- 29.2 pg/mL) were lower than in women with tubal infertility (420.5 +/- 46.6 pg/mL; P<.05). Oocyte fertilization rates in the endometriosis group (54%) were significantly lower than those of the tubal infertility group (73%; P<.05), as were the pregnancy rates (19% vs. 35%, respectively; P<.01). CONCLUSION(S): Women with endometriosis-associated infertility have a poor IVF outcome. Immune cell recruitment into the ovary might affect follicular function and lead to impaired oocyte quality.

Adult↗

Is endometriosis associated with systemic subclinical inflammation?

Endometriosis is a pelvic inflammatory process with altered function of immune-related cells and increased number of activated macrophages in the peritoneal environment that secrete various local products, such as growth factors and cytokines. The elevation of cytokines and other factors in the peritoneal fluid is accompanied by the elevation of similar factors, such as CRP, SAA, TNF-alpha, MCP-1, IL-6, IL-8 and CCR1, in the peripheral blood of patients with endometriosis. CD44+ and CD14+ monocytes are significantly increased, while CD3+ T lymphocytes and CD20+ B lymphocytes show modest, but significant decrease in peripheral blood of women with endometriosis. This indicates that endometriosis could be viewed as a local disease with systemic subclinical manifestations. This review provides an overview of data on the changes of various factors in peripheral blood and their potential use as diagnostic tools in patients with endometriosis.

Ascitic Fluid↗

Expression of human endogenous gammaretroviral sequences in endometriosis and ovarian cancer.

Endogenous retroviruses (ERVs) probably originate from ancient germ cell infections by exogenous retroviruses. A high expression of retroviruses in reproductive tissue increases the risk of viral transmission to germ line cells. We therefore investigated the expression of human ERVs (HERVs) in normal endometrium, endometriosis, normal ovaries, and ovarian cancer. Four real-time PCRs (QPCRs) for HERV-E, HERV-I/T, HERV-H, and HERV-W, respectively, and an expression control gene were used. HERV-E RNA expression was significantly higher in endometriotic tissue (average, SD) than in normal endometrium (average, SD), both measured as ratios versus control gene expression and as. HERV-E and HERV-W RNA were higher in normal ovarian tissue than in ovarian cancer. This illustrates that HERV expression is not automatically higher in malignant tissues. The other HERV PCRs did not show expression patterns as distinctive as HERVE and HERV-W in the two kinds of reproductive tissue. A small number of candidate HERV-E loci from which the transcription took place were identified by sequencing of amplimers. The role of HERV-E and HERV-W in endometriosis merits further investigation.

Base Sequence↗

Lethal outcome in xanthogranulomatous endometritis.

Xanthogranulomatous inflammation is rare, mainly involving the kidneys, while primary xanthogranulomatous endometritis (XE) is a very unusual finding, histologically characterized by partial or complete replacement of the mucosa by granulation tissue with an abundance of foamy histiocytes, siderophages and multinucleated giant cells. We present the case of a 69-year-old woman with a short history of abdominal pain and a palpable mass in the pouch of Douglas. Dilatation of the cervix drained a pyometra. Histological examination of the curettage rendered the diagnosis of XE. Microbiological studies revealed enterococcus spp. and Peptostreptococcus magnus. Despite antibiotic treatment the patient died of heart failure due to systemic inflammation. Autopsy confirmed the diagnosis of XE with transmural extension into the peritoneal cavity. Such a lethal course of XE is extraordinary. Proposed causes of XE include obstruction, infection and hemorrhage. Demonstration of enterococcus spp. and P. magnus supports the probable significance of bacteria in the development of XE. Because this condition may mimic malignant disease macroscopically and histologically, knowledge of XE is of major importance for both pathologists and gynecologists.

Aged↗

Cetrorelix in the treatment of female infertility and endometriosis.

The use of cetrorelix within ovarian-stimulation protocols demonstrates several advantages compared with gonadotropin-releasing hormone (GnRH) agonist-containing protocols, which include, for example, significantly less time for analogue treatment and a reduction in the amount of gonadotropins needed. Furthermore, fewer side effects can be expected. There is no difference regarding endometrium quality and hormone profiles, and the results of assisted reproduction cycles are comparable. Cetrorelix also seems to be useful in the treatment of endometriosis which, in most cases, is an estrogen-dependent disease. Furthermore, fewer side effects occur with this agent (e.g., postmenopausal symptoms) and no estradiol add-back is needed. In the future, new nonpeptic GnRH antagonists are expected to be available for oral administration. Although they are still under investigation, these agents have the potential to improve patients' comfort and compliance.

Adult↗

Sulindac suppresses nuclear factor-kappaB activation and RANTES gene and protein expression in endometrial stromal cells from women with endometriosis.

CONTEXT: The nuclear factor-kappaB (NF-kappaB) pathway is a critical mediator of RANTES (regulated on activation, normal T cell expressed and secreted) gene regulation and therefore represents a potential target for therapy of endometriosis-associated symptoms. OBJECTIVE: The objective of this study was to investigate the effects of the antiinflammatory drug sulindac on NF-kappaB activation, NF-kappaB-mediated gene expression, RANTES gene and protein expression in endometrial stromal cells isolated from women with endometriosis, and unaffected controls. DESIGN: This was a clinical experimental study. SETTING: The study was conducted at a university hospital. RESULTS: The inflammatory response in endometriosis is augmented by a 5-fold increased TNFalpha-induced RANTES secretion from ectopic endometriotic stromal cells, compared with normal endometrial stromal cells (P < 0.05). Western blot analysis revealed basal activation of NF-kappaB in endometriotic cells, which could be suppressed by sulindac. EMSAs showed that sulindac dramatically decreased NF-kappaB activation and diminished TNFalpha and IL-1beta-induced NF-kappaB DNA binding activity. Sulindac pretreatment resulted in a significant decrease in TNFalpha-induced luciferase activity of NF-kappaB response element and -477 bp RANTES promoter constructs in normal and endometriotic stromal cells. The addition of sulindac to IL-1beta- and TNFalpha-treated endometriotic stromal cells also resulted in a 4-fold inhibition of RANTES protein secretion (P < 0.05). CONCLUSIONS: We have demonstrated that sulindac exerts strong antiinflammatory effects by suppression of NF-kappaB translocation, inhibition of NF-kappaB-mediated gene transcription, RANTES gene expression, and protein secretion in normal and endometriotic stromal cells. These results suggest that drugs targeting the NF-kappaB pathway may be beneficial in the treatment of endometriosis-associated symptoms.

Adult↗

Expression and regulation of CCR1 in peritoneal macrophages from women with and without endometriosis.

CCR1 is a CC chemokine receptor with high affinity for RANTES (regulated upon activation, normal T cells expressed and secreted). CCR1 protein and mRNA concentrations in native peritoneal cells were twofold greater, in cultured peritoneal cells threefold greater, in patients with endometriosis compared to patients without endometriosis, as determined by Western blotting fluorescence activated cell sorting analysis, reverse transcription-polymerase chain reaction, and in situ hybridization.

Analysis of Variance↗

New developments in the use of peptide gonadotropin-releasing hormone antagonists versus agonists.

Gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH), and thus controls the hormonal and reproductive functions of the gonads. The blockade of the effects of GnRH may be sought for a variety of reasons; for example, to control premature LH surges and to reduce the cancellation rate with the aim of improving the pregnancy rate per treatment cycle or in the treatment of sex hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. GnRH analogues are indicated for clinical situations in which the suppression of endogenous gonadotropins (precocious puberty, contraception and controlled ovarian hyperstimulation) or sexual steroids (endometriosis, prostate hyperplasia, cancer and uterine fibroids) is desired. The immediate suppression of the pituitary that is achieved by GnRH antagonists without an initial stimulatory effect is the main advantage of these compounds over the agonists. GnRH antagonists have been developed for clinical use with acceptable pharmacokinetic, safety and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy, but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All of the current indications for GnRH agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence has been in assisted reproduction and prostate cancer.

Animals↗

Granulomatous mastitis.

INTRODUCTION: Granulomatous mastitis (GM) is a rare disease which predominantly occurs in premenopausal women shortly after their last childbirth. ETIOLOGY: Its etiology is unclear, however, the disease has been shown to be correlated with breast-feeding and the use of oral contraceptives. An autoimmune component has also been discussed. PRESENTATION: It presents with the clinical symptoms of galactorrhea, inflammation, breast mass, tumorous indurations and ulcerations of the skin. In mammography and sonography nodular opacities and hypoechoic nodules are found. Very often clinical and radiological findings mimic breast cancer. HISTOLOGICAL DIAGNOSIS: The diagnosis is made by histopathology. Histological features in GM include signs of a chronic granulomatous inflammation with giant cells, leucocytes, epitheloid cells and macrophages as well as abscesses. TREATMENT: Therapy of GM consists of complete surgical excision combined with oral steroid therapy, eventually in combination with anti-inflammatory drugs or colchicine. Use of methotrexate has also been successful. In case of formation of abscesses antibiotic therapy should be applied before steroid therapy. Immune-suppressive therapy should be performed until complete remission as rates of recurrence can be up to 50%.

Adrenal Cortex Hormones↗

Thiazolidinedione inhibition of peritoneal inflammation.

Chemoattraction of macrophages into the peritoneal cavity is one of the important characteristics in patients with endometriosis. An inflammatory response is postulated to be responsible for infertility and pelvic pain associated with this syndrome. The present in vivo studies were designed to test if thiazolidinediones (TZDs), activators of peroxisome proliferator activated receptor gamma, could inhibit monocyte chemotaxis in a murine model. TZDs were first used as orally bioavailable insulin-sensitizing agents. They are currently under investigation in the treatment of inflammatory diseases, including arthritis or colitis. Intraperitoneal injection of thioglycollate was used to elicit high numbers of activated peritoneal macrophages in female mice. Concomitant peritoneal injection of ciglitazone, a member of the TZD family, significantly reduced the number of macrophages. When cultured and stimulated by tumor necrosis factor alpha, these peritoneal macrophages also secreted less RANTES and less IL-1beta protein. This animal model suggests that treatment of endometriosis patients with TZDs may diminish symptoms associated with intraperitoneal inflammation.

Animals↗