Biomedical subjects

Klaus Diedrich

Publications and source records attributed to Klaus Diedrich.

At least 19 recordsLinked to original sources

PubMed2006

Effects of testosterone on hormonal content and calcium-dependent basal secretion in female rat pituitary cells.

In vivo and in vitro effects of elevated androgens on agonist-induced gonadotropin secretion have been addressed previously. Here we investigated the effects of testosterone on hormonal content and basal (in the absence of agonists) hormone release in pituitary lactotrophs, somatotrophs and gonadotrophs from female rats. Furthermore we tested the hypothesis that testosterone action is dependent on the pattern of spontaneous and Bay K 8644 (a L-type calcium channel agonist) -induced calcium signalling. Mixed anterior pituitary cells were cultured in steroid containing or depleted media, and testosterone (1pM to 10nM) was added for 48h. Cells were studied for their spontaneous and Bay K 8644-induced calcium signalling pattern and total hormone levels (release and hormonal content). In lactotrophs, somatotrophs and gonadotrophs testosterone did not affect the pattern of spontaneous calcium signalling. Bay K 8644-induced calcium signalling and hormone release were not affected by testosterone. In both steroid-depleted and -containing medium, testosterone inhibited prolactin (PRL), luteinizing hormone (LH) and growth hormone (GH) cellular content and release in a dose-dependent manner, with IC(50)s in a sub-nanomolar concentration range. These results indicate that testosterone inhibits basal hormone release from lactotrophs, somatotrophs and gonadotrophs without affecting intracellular calcium signalling. This action of testosterone is not dependent on the presence of other steroid hormones.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2006

Distribution of persistent organochlorine contaminants in infertile patients from Tanzania and Germany.

PURPOSE: To test whether environmental pollutants could affect fertility in humans. METHODS: 31 women and 16 men from Tanzania and 21 couples from Germany were included (n = 89). Pesticides and polychlorinated biphenyls were measured in serum, follicular fluid or seminal plasma by gaschromatography and related to sperm quality and pregnancy rates. RESULTS: Higher concentrations of DDT+DDE and dieldrin in Tanzania and higher concentrations of PCBs in Germany and in men were detected. All compounds showed higher concentrations in serum and lowest concentrations in seminal plasma. A lower pregnancy rate in German women with high serum concentrations of DDT+DDE was observed. The toxins had no impact on sperm quality. CONCLUSIONS: The distribution of toxins between agricultural and industrial countries is different. Seminal plasma seems to be inert against chemicals. In patients with high serum concentrations of DDT and DDE pregnancy rates were impaired.

DDT↗

PubMed2006

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↗

PubMed2006

Epidural anaesthesia for labour: does it influence the mode of delivery?

BACKGROUND: Epidural anaesthesia (EDA) is an effective method to lower labour pain. EDA might have an impact on instrumental delivery rates and on caesarean section rates. The present study compares the mode of delivery in women who were either receiving EDA or not. The indication for EDA was pain relief only in order to switch off a selection bias. METHODS: During a 1-year duration, we included a total of 1,452 cases. Exclusion criteria were factors that could influence the mode of delivery, independent from EDA, as well as obstetrical indications for administering EDA. 530 women remained in the analysis. The primary outcome variable was the mode of delivery. RESULTS: We detected in both nullipara and multipara a statistically significant accumulatin in patients with EDA and caesarean section combined. Most importantly, the majority of the women without EDA (57% of nullipara and 60% of multipara) delivered within the median timeframe from admission until administration of EDA. CONCLUSIONS: It seems to be obvious to conclude that EDA as performed in our study results in a higher rate of caesarean sections. It is important though to take into consideration that between the period from admission to the delivery ward and administration of EDA most of the parturients without EDA had already delivered. Our results make evident, that the administration of EDA exclusively used for reducing labour pain is a result of a complex collaboration of temporal conditions of labour as well as psychological conditions and also of the mother's wish.

Adult↗

PubMed2006

Presurgical short term treatment of uterine fibroids with different doses of cetrorelix acetate: a double-blind, placebo-controlled multicenter study.

OBJECTIVE: To assess the efficacy and safety of different dosing schedules of cetrorelix acetate as a short term treatment for 4 weeks prior to surgery in patients with uterine fibroids. STUDY DESIGN: Randomized, double-blind, placebo-controlled study. Patients were 109 premenopausal women, with at least one uterine fibroid, more than 4 cm in diameter. Groups 1-3 received placebo, 5 and 10 mg of cetrorelix on days 1, 8, 15 and 22, respectively group 4 received 10mg of cetrorelix on days 1 and 15. MRI scan was performed at screening and on day 29. The main outcome measure was the reduction of uterine volume on day 29 and response, defined as >30% size reduction. RESULTS: Mean (+/-S.D.) reduction of uterine volume on day 29 (MRI scan) was 5.1+/-32.1% with placebo, 15.6+/-20.2% with 4 x 5 mg, 15.4+/-34.6% with 4 x 10 mg and 0.6+/-30.6% with 2 x 10 mg cetrorelix. Significant response versus placebo (p<0.05) occurred in the 4 x 10 mg group (42.3% versus 11.1%) CONCLUSIONS: Best objective response after 4 weeks of treatment was achieved after therapy with 4 x 10 mg of cetrorelix acetate. Short term presurgical treatment with the LHRH-antagonist cetrorelix is a flexible treatment protocol without any major side effects.

Adult↗

PubMed2006

Gonadotropin-releasing hormone antagonists do not influence the secretion of steroid hormones but affect the secretion of vascular endothelial growth factor from human granulosa luteinized cell cultures.

OBJECTIVE: To evaluate the secretion of E(2), P, and vascular endothelial growth factor (VEGF) in human granulosa luteinized cell cultures with the presence of a gonadotropin-releasing hormone (GnRH) agonist or antagonist. DESIGN: In vitro cell culture study. SETTING: Research laboratory of a university hospital. PATIENTS: Granulosa luteinized cells were obtained from 24 patients undergoing ovarian stimulation for IVF treatment. INTERVENTIONS: Granulosa cells were cultured for 48 hours with 1 nM of cetrorelix or leuprorelide. For a further 48 hours, granulosa cells were cultured with or without the combination of cetrorelix plus leuprorelide. MAIN OUTCOMES: At the end of each culturing period, the concentrations of E(2), P, and VEGF were measured in culture supernatants by immunoassays. RESULTS: Estradiol and P concentrations were similar between the culture supernatants from controls and treatment groups. The VEGF concentrations in supernatants from cultures with cetrorelix (2,315.1 +/- 1,565.5 pg/mL) were moderately, but significantly, lower than in controls (2,604.3 +/- 1,907.1 pg/mL) or cultures with leuprorelide (2,558.8 +/- 1,403.1 pg/mL). CONCLUSIONS: The GnRH analogues do not affect steroidogenesis in human granulosa luteinized cell cultures. The GnRH antagonists moderately affect the secretion of VEGF from human granulosa luteinized cells.

Adult↗

PubMed2006

Actions of gonadotropin-releasing hormone analogues in pituitary gonadotrophs and their modulation by ovarian steroids.

Recently, GnRH antagonists (GnRHant) like cetrorelix and ganirelix have been introduced in protocols of controlled ovarian hyperstimulation for assisted reproductive techniques to prevent premature luteinizing hormone (LH) surges. Here we tested, whether the actions of cetrorelix and the GnRH agonist (GnRHag) triptorelin in gonadotrophs are dependent on the steroid milieu. Furthermore, we characterized the actions of cetrorelix and triptorelin on LH secretion and the total LH pool. Female rat pituitary cells were treated either with 0.1 nM triptorelin for 1, 2, 4 and 6 days or for 1, 3, 5 and 6 h or with 1, 10 or 100 nM cetrorelix for 1, 2, 3 and 5 h or for 10 min. Cells were stimulated for 3h with different concentrations of GnRH (10 pM-1 microM). For analysis of the total LH pool, which is composed of stored and released LH, cells were lysed with 0.1% Triton X-100 at -80 degrees C overnight. To test, whether the steroid milieu affects the actions of cetrorelix and triptorelin, cells were incubated for 52 h with 1 nM estradiol (E) alone or with combinations of 100 nM progesterone (P) for 4 or 52 h, respectively. Cells were then treated with 0.1 nM triptorelin for 9 h or 1 nM cetrorelix for 3 h and stimulated for 3 h with different concentrations of GnRH (10 pM-1 microM). The suppressive effect of triptorelin on LH secretion was fully accomplished after 3 h of treatment, for cetrorelix only 10 min were sufficient. The concentration of cetrorelix must be at least equimolar to GnRH to block LH secretion. Cetrorelix shifted the EC50s of the GnRH dose-response curve to the right. Triptorelin suppressed total LH significantly (from 137 to 36 ng/ml) after 1 h in a time-dependent manner. In contrast, only high concentrations of cetrorelix increased total LH. In steroid treated cells the suppressive effects of triptorelin were more distinct. One nanomolar cetrorelix suppressed GnRH-stimulated LH secretion of cells not treated with steroids from 10.1 to 3.5 ng/ml. In cells, additionally treated with estradiol alone or estradiol and short-term progesterone, LH levels were higher (from 3.5 to 5.4 or 4.5 ng/ml, respectively). In cells co-treated with estradiol and progesterone for 52 h LH secretion was only suppressed from 10.1 to 9.5 ng/ml. Steroid treatments diminished the suppressive effect of cetrorelix on LH secretion. In conclusion, the depletion of the total LH pool contributes to the desensitizing effect of triptorelin. The actions of cetrorelix and triptorelin are dependent on the steroid milieu.

Animals↗

PubMed2006

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↗

PubMed2006

Vascular endothelial growth factor response to exogenous chorionic gonadotropic hormone in the luteal phase of women with a history of severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication of ovarian stimulation. No reliable test exists to predict the syndrome. The objective of the present prospective observational study was to examine vascular endothelial growth factor (VEGF) secretion after human chorionic gonadotropin (hCG) administration in the luteal phase of a spontaneous cycle of women with a history of severe OHSS. Five women with a history of severe OHSS were administered 250 mug recombinant hCG intravenously on day 21 of a spontaneous menstrual cycle. Plasma samples were collected at regular intervals from 15 min before hCG to 6 h thereafter and the free VEGF plasma concentrations were determined. Plasma levels of free VEGF remained at the lower detection limit of the assay throughout the observational period. Women with previous severe OHSS do not show a significant short-time response of VEGF secretion upon hCG administration. No evidence was found to support the notion that women inclined to develop a severe form of the syndrome after ovarian stimulation could possibly be identified by the VEGF short-time secretory response to exogenous hCG in the luteal phase of a spontaneous cycle.

Adult↗

PubMed2006

Fluorescence staining of human ovarian cancer tissue following application of 5-aminolevulinic acid: fluorescence microscopy studies.

BACKGROUND AND OBJECTIVES: Application of 5-aminolevulinic acid (ALA) for fluorescence-guided second-look laparoscopy has been shown to be a promising new procedure in the early diagnosis of ovarian carcinoma metastases. However, for assessing the reliability of this method, information on the microscopic distribution of protoporphyrin IX (PP IX) in the tissue is needed. Additionally, the selectivity of PP IX uptake is essential for a potential photodynamic therapy (PDT) of ovarian cancer metastases. STUDY DESIGN/MATERIALS AND METHODS: Thirty-six patients with epithelial ovarian cancer and two patients suffering from fallopian tube carcinoma underwent a laparoscopic second-look procedure 5 hours after the application of ALA. In 17 patients 36 fluorescence-guided biopsies were taken from fluorescing and non-fluorescing tissues for further evaluation. Fluorescence microscopy and digital image processing were utilized to determine the presence of PP IX fluorescence. RESULTS: A specificity of 88% and a sensitivity of 100% with a negative predictive value of 100% and a positive predictive value of 91% were calculated for PP IX fluorescence on a microscopic level as marker for ovarian cancer metastases. CONCLUSIONS: On a microscopic scale, ALA-induced PP IX fluorescence is confined to ovarian cancer tumor tissue sparing stromal tissues.

Aminolevulinic Acid↗

PubMed2006

Assessment of luteinizing hormone level in the gonadotropin-releasing hormone antagonist protocol.

In the GnRH-antagonist multiple-dose protocol, the LH level retrieved from a single measurement during ovarian stimulation and concomitant GnRH-antagonist administration can vary according to [1] the time point of sampling with respect to the GnRH-antagonist injection and [2] episodic changes in circulating LH concentration due to the pulsatile release of LH from the pituitary gland. To exemplify the size of pharmacodynamic effect of a single 0.25-mg cetrorelix administration on LH concentration profile and pulsatility, we measured endogenous LH levels every 15 minutes from 8 hours before the first cetrorelix administration until 24 hours thereafter on ovarian stimulation day 6 and 7 in a single patient.

Adult↗

PubMed2006

First pregnancy and life after preimplantation genetic diagnosis by polar body analysis for mucopolysaccharidosis type I.

Preimplantation genetic diagnosis (PGD) may help couples at risk to avoid pregnancies with known genetic diseases. In Germany, the only option to perform PGD is the analysis of polar bodies (PB). Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder. Q70X is one of the frequent diseases causing mutations of alpha-L-iduronidase (IDUA), leading to a severe phenotype with mental retardation and various somatic abnormalities, and making a request for PGD is understandable. Using five polymorphic DNA markers from the vicinity of IDUA, PGD on first PB was performed for a consanguineous couple, both heterozygotes of the Q70X mutation of IDUA. Sixteen first PB were obtained by laser assisted hatching of the zona pellucida. Genotyping led to the conclusion that 3/16 oocytes carried wild-type IDUA alleles. Only one of these oocytes showed pronucleus formation after intracytoplasmic sperm injection and was transferred on day 2 after oocyte retrieval. A singleton pregnancy was established. Prenatal diagnosis showed a fetus heterozygous for Q70X. For MPS I, PB analysis is a feasible way to perform PGD and it may be an acceptable alternative for couples with moral objections to embryo selection, or for countries in which genetic testing of the embryo is prohibited.

Base Sequence↗

PubMed2006

Role of LH in ovarian stimulation: considerations.

The role of LH in ovarian stimulation continues to be controversial. Most observational studies on both gonadotrophin-releasing hormone (GnRH) agonist and GnRH antagonist protocols failed to show an effect on ongoing pregnancy likelihood of punctually measured 'low' or 'high' endogenous LH concentrations during ovarian stimulation. As yet, it is still unknown whether individual patients with strongly suppressed levels of immunoreactive LH would actually benefit from additional LH administration. This can only be explored by means of interventional trials. Most trials on LH supplementation in general populations in both GnRH agonist and GnRH antagonist protocols have not found a benefit of LH supplementation, although it has been indicated that some subgroups, such as older age patients, or patients with a low ovarian response might benefit from LH. These concepts need to be explored further before recommendations can be given as to in who, in what protocol, at what time point and in what doses LH should be supplemented.

Female↗

PubMed2006

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↗

PubMed2006

Early fetal echocardiography: heart biometry and visualization of cardiac structures between 10 and 15 weeks' gestation.

OBJECTIVE: The purpose of this prospective cross-sectional study was to compile normative data about biometry of the fetal heart and great vessels between 10 and 15 weeks in 123 normal singleton pregnancies. Additionally, we investigated the different methods and the optimal examination time of early fetal echocardiography. METHODS: The interrogated parameters included total heart diameter; heart area and circumference; right and left ventricular diameter; diameter, circumference, and area of the thorax; and diameter of the aorta and pulmonary trunk. Visualization of the 4-chamber view, 3-vessel view, origin and crossover of the great arteries, aortic arch, ductus arteriosus, superior and inferior venae cavae, and pulmonary veins was analyzed, and the success rates by transvaginal sonography (TVS) and transabdominal sonography (TAS) were calculated. RESULTS: Complete evaluation of the fetal heart was impossible at 10 weeks; the total success rate increased from 45% at 11 weeks to 90% between 12 and 14 weeks and 100% at 15 weeks. Between 10 and 13 weeks, TVS was superior to TAS. At 14 weeks, both methods were similar to each other, and at 15 weeks, TAS allowed adequate visualization of all structures. Linear regression analysis showed a significant correlation between the interrogated parameters and gestational age, crown-rump length, and biparietal diameter (P < .05). The ratio of right and left ventricular diameters and the ratio of pulmonary trunk and aortic diameters were constant. CONCLUSIONS: Early fetal heart evaluation by TVS or TAS or both is reasonable and feasible. Our normative data could be helpful for understanding the normal development of the fetal heart and great arteries and for detection of cardiac defects in early pregnancy.

Adult↗

PubMed2006

Detection rate of early fetal echocardiography and in utero development of congenital heart defects.

OBJECTIVE: The purpose of this study was to evaluate the detection rate of early fetal echocardiography and the in utero development of congenital heart defects (CHD). METHODS: Cases were selected from all singleton pregnancies between 1997 and 2003 in which detailed fetal 2-dimensional and color-coded Doppler echocardiography was performed in our prenatal unit between 11 weeks' and 13 weeks 6 days' gestation; 2165 cases with complete outcome parameters were analyzed. RESULTS: During this study period, CHD were diagnosed in 46 fetuses. Between 11 and 13 weeks' gestation, 29 CHD were diagnosed (11 weeks, 9 cases; 12 weeks, 8 cases; and 13 weeks, 12 cases); 9 CHD were found in the second trimester and 2 in the third trimester. The in utero detection rate of fetal echocardiography was 86.96% (n = 40). Six additional CHD (13.04%) were detected postnatally. The spectrum of detected CHD changed with advancing gestational age and was different from the postnatal detected heart defects. CONCLUSIONS: Early fetal echocardiography is feasible and allows the detection of most CHD. Congenital heart defects vary in appearance at different stages of pregnancy and may evolve in utero with advancing gestational age. Therefore, early fetal echocardiography should always be followed by echocardiography at mid gestation.

Adolescent↗

PubMed2006

Cell-specific enhancement of liposomal transfection by steroids in steroid receptor expressing cells.

The DNA transfer efficiency in liposomal versus viral transfection is very low, mainly due to an insufficient nuclear transport of the delivered DNA after its endocytotic uptake to the cell. Ligand activation of intracellular steroid receptors and their subsequent mobilization to the nucleus could result in a co-transport of DNA to the nucleus. The augmentation of nuclear transport of DNA after steroid addition might cause enhanced transfection efficiency. We used cell lines from gynecologic malignoma expressing steroid receptors, such as T47D and Mcf-7 breast cancer cell lines, as well as receptor-negative cell lines, such as Hec1A from endometrium carcinoma or the breast cancer cell line MDA-MB-231. The cells were transfected by the liposomal transfection agent Dotap with the gene for firefly-luciferase as a reporter gene and transfection efficiencies were determined in the luciferase assay. We compared the effect of the addition of cholesterol and steroids in different cell lines on the transfection efficiency. The addition of cholesterol to transfection agents led to an enhancement of the luciferase activity in all cell lines. Steroids enhanced the transfection efficiency only in receptor-positive cell lines. The transfection efficiencies of HEC-1A or MDA-MB-231 cells were not enhanced by steroids. A progesterone preincubation of receptor-positive T47D cells resulted in a decrease of progesterone receptors and afterwards the progesterone enhanced transfection was dramatically diminished. We presume that the transfection enhancement by steroids is dependent on increased nuclear import of the delivered DNA only in the presence of steroid receptors. Steroid enhancement of transfection is different from the benefit of cholesterol for transfection that acts on general cellular properties or the transfection complex as such. Liposomal transfection in combination with steroids might be useful for a cell-specific enhancement of gene transfer for example in gynecological malignoma where subgroups are expressing high levels of steroid receptors.

Blotting, Western↗

PubMed2005

Follicular fluid high density lipoprotein-associated sphingosine 1-phosphate is a novel mediator of ovarian angiogenesis.

Angiogenesis plays an important role in the development of the ovarian follicle and its subsequent transition into the corpus luteum. Accordingly, follicular fluid is a rich source of mitogenic and angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor secreted by granulosa cells. In the present study, we show that follicular fluid deprived of basic fibroblast growth factor or vascular endothelial growth factor by means of thermal denaturation or antibody neutralization retains its capacity to stimulate endothelial proliferation and angiogenesis. Mass spectrometric analysis of chromatographic fractions stimulating endothelial growth obtained from follicular fluid revealed that the heat-stable mitogenic activity is identical with the subfraction alpha of high density lipoproteins purified from follicular fluid (FF-HDL). Further investigations demonstrated that sphingosine 1-phosphate (S1P), one of the lysophospholipids associated with HDL, accounts for the capacity of this lipoprotein to stimulate endothelial growth and the formation of new vessels. Activation of mitogen-activated protein kinase (p42/44(ERK1/2)), protein kinase C, and protein kinase Akt represent signaling pathways utilized by FF-HDL and S1P to induce endothelial proliferation and angiogenesis. We conclude that FF-HDL represents a novel mitogenic and angiogenic factor present in follicular fluid and that S1P is one of the FF-HDL lipid components accounting for this activity.

Antibodies↗