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Biomedical subjects

T Strowitzki

Publications and source records attributed to T Strowitzki.

At least 19 recordsLinked to original sources
PubMed2006

Contribution of linseed intake to urine and serum enterolignan levels in German females: a randomised controlled intervention trial.

Linseeds are a rich source of lignans, secondary plant substances which are suggested to possess chemopreventive effects inter alia with regard to breast cancer. In a randomised controlled trial 40 German women were informed about "5-a-day" and encouraged to increase their dietary intake of fruit and vegetables. Moreover 19 participants were randomly assigned to an intervention group supplemented with ground linseeds (20 g/d) over a 2-month period. Before and after intervention, urine and blood samples were collected after an overnight fast. Analysis was by intention-to-treat and the outcome parameters of interest were enterolignan concentrations. After linseed supplementation, enterolignan concentrations (mean) measured as their glucuronides by a newly developed high performance liquid chromatography electrospray mass spectrometry (HPLC-ESI-MS) in serum (122 nmol/l) as well as in urine (72 micromol/l) showed a significant increase (P<0.01) compared to pre-intervention values (47 nmol/l and 29 micromol/l). In the control group enterolignan levels were raised slightly but did not reach significance. Serum and urinary enterolignans of the whole collective showed a good pairwise correlation.

Adult↗
PubMed2006

Analysis of enterolignan glucuronides in serum and urine by HPLC-ESI-MS.

A method involving the coupling of high-performance liquid chromatography with electrospray ionisation mass spectrometry (HPLC-ESI-MS) for the quantitative determination of the mammalian lignans enterolactone and enterodiol in human blood and urine has been developed. In contrast to techniques previously published, the method allows direct measurement of free enterolignans as well as their monoglucuronide conjugates in human biofluids with minimal sample preparation. Thereby the method is suitable for large-scale intervention, case-control and epidemiologic studies. Comprehensive, high-precision (1)H and (13)C nuclear magnetic resonance data (CD3OD as solvent) obtained at 11.7 T in combination with polarimetric data show that the major form of lignan precursor in the linseeds used is (-)-secoisolariciresinol diglucoside ((2R,3R)-2,3-bis(4'-hydroxy-3'-methoxy-benzyl)-1,4-butanediyl-bis-beta-d-glucopyranoside) which is transformed by human intestinal bacteria into (+)-enterodiol and (+)-enterolactone. However, these metabolites are mono-glucuronidated after absorption and are detected as (-)-enterodiol 3'-beta-d-glucuronide=(2R,3R)-2-(3'-O-(beta-d-glucopyranosyluronic acid)benzyl)-3-(3''-hydroxybenzyl)-butane-1,4,diol and (-)-enterolactone 3'-beta-d-glucuronide=(2R,3R)-2-(3'-O-(beta-d-glucopyranosyluronic acid)benzyl)-3-(3''-hydroxybenzyl)-beta-butyrolactone in blood and urine.

Chromatography, High Pressure Liquid↗
PubMed2006

Premature ovarian failure (POF) syndrome: towards the molecular clinical analysis of its genetic complexity.

The Premature Ovarian Failure (POF) syndrome is a very heterogeneous clinical disorder due probably to the complex genetic networks controlling human folliculogenesis. Clinical subgroups of POF patients whose aetiology of ovarian failure is based on the same genetic factors are therefore difficult to establish. Some experimental evidence suggests that these genes might be clustered on the female sex chromosome in the POF1 and POF2 loci. This review is aimed to present an overview of the actual structural changes of the X chromosome causing POF, and to present a number of X and autosomal female fertility genes which are probably key genes in human folliculogenesis and are therefore prominent POF candidate genes. Towards the molecular analysis of their functional contribution to the genetic aetiology of POF in the clinic, an interdisciplinary scheme for their diagnostic analysis is presented in a pilot study focussed on chromosome analyses and the expression analysis of some major POF candidate genes (DAZL, DBX, FOXL2, INHalpha, GDF9, USP9X) in the leukocytes of 101 POF patients. It starts with a comprehensive and significantly improved clinical diagnostic program for this large and heterogeneous patient group.

Animals↗
PubMed2005

Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial.

CONTEXT: Metformin is successfully used in the treatment of cycle disorders and anovulation in women with polycystic ovary syndrome (PCOS). No data of the exact point and the impact of insulin resistance (IR) on metformin's efficacy exist. OBJECTIVE: The objective of the study was to evaluate the early potential effects of metformin treatment, their time of onset, and the role of IR on metformin's efficacy. DESIGN: This was a prospective randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted at the University of Heidelberg, Heidelberg, Germany. PATIENTS: The patient population was 45 oligo-/anovulatory PCOS women with typical ovaries. INTERVENTIONS: Women were stratified for IR (32 of 13) and then randomly allocated to receive either metformin (n = 22) or placebo (n = 23) and were assessed before and every 4 wk within a treatment period of 12 wk. MAIN OUTCOME MEASURES: Menstrual disturbance and markers of insulin metabolism were measured. RESULTS: The main outcome criterion menstrual disturbance was successfully improved in the metformin-treated group, depending on IR (12 of 15 vs. three of 17), whereas women without IR (four of seven vs. four of six) had no significant amelioration of their menstrual irregularities (P < 0.05). Estradiol levels increased continuously only in the treatment group (P < 0.005), indicating an improvement of ovulatory function. Sixty-seven percent of metformin-treated women had at least one ovulation, compared with only 45% in the placebo group, shown by biphasic body temperature curves. Insulin sensitivity improved within 4 wk after beginning of metformin as shown by an increased area under the curve glucose to insulin ratio, compared with baseline (P < 0.005). CONCLUSIONS: IR is a baseline predictor of clinical efficacy in metformin treatment in PCOS women measured by improved menstrual cyclicity and ovulatory function.

Adult↗
PubMed2005

Galectin fingerprinting in human endometrium and decidua during the menstrual cycle and in early gestation.

The emerging functionality of the sugar code via cell surface glycans and endogenous lectins ascribes pertinent roles in cell physiology to the carbohydrate signals of cellular glycoconjugates. To initiate monitoring of endogenous lectins in human endometrium, we focused on a family of growth/adhesion-regulatory lectins, i.e. galectins. Comprehensive fingerprinting was performed on samples throughout the menstrual cycle and in decidua. The endometrium (n = 30) and decidua (n = 7) were collected from patients undergoing hysterectomy for benign reasons and from induced abortions. Measurements by RT-PCR and then by multiprobe RNase protection assay with total endometrial and decidual tissue and with epithelial cells, stromal cells and CD45-positive cell fractions (n = 16), isolated by the use of antibody-coated magnetic beads, revealed a predominant expression of galectins-1 and -3. Protein analysis was performed by immunocytochemistry with monoclonal and polyclonal antibodies (n = 40). Galectin-1 was localized mainly in stromal cells, whereas galectin-3 was predominantly found in epithelial cells. Expression of galectin-1 increased significantly in the late secretory phase endometrium and in the decidual tissue. Expression of galectin-3 increased significantly during the secretory phase of the menstrual cycle. Cycle-dependent expression of galectin-1 in stromal cells and galectin-3 in epithelial cells suggest these lectins to be involved in the regulation of different endometrial cellular functions.

Adult↗
PubMed2005

[Infertility treatment and endometriosis -- risk and benefit of assisted reproductive techniques].

Infertility is a common clinical finding in patients with endometriosis. Surgical procedures have shown some benefit, whereas endocrine treatment alone does not improve fertility. Although assisted reproduction is superior to observation only, the pregnancy rate after IVF is lower than in patients with tubal or idiopatic infertility. The grade of endometriosis correlates to the pregnancy rate. The role of endometriomas in assisted reproduction is still a matter of debate. Ultralong stimulation protocols have no advantage to standard long luteal phase regimens. In particular in multifactor infertility IVF seems to be the treatment option of choice.

Endometriosis↗
PubMed2005

Determination of the fertile window: reproductive competence of women--European cycle databases.

OBJECTIVES: The objective of the present paper is to review the main results of recent European cycle databases on ovulation detection and determination of the fertile window performed by the women themselves. METHODS: The ongoing German Long-term Cycle Database currently comprises 32788 prospectively collected cycle charts of 1551 women, the I European Cycle Database (10 countries) 1328 women/19048 cycles, the II European Cycle Database (six countries) 782 women/6724 cycles, and the World Health Organization Database (one European country) 234 women/2808 cycles. The women record cycle parameters (cervical mucus changes, temperature rise, etc.), family planning intention and sexual behavior. RESULTS: With the symptothermal method of natural family planning it has become possible to determine the fertile window in order to avoid pregnancy with a method effectiveness of 0.3%. According to a small sub-study, the ovulation time observed by the women themselves correlates closely with ovulation detected by ultrasound and measurement of luteinizing hormone (correlation within 1 day in 89% of the 62 cycles). Fertility awareness methods can be integrated into the management of sub-fertility. They seem to shorten the time to pregnancy. CONCLUSIONS: Self-observation of the fertile window puts women into a position to develop a high level of reproductive competence that could be used much more in different areas than is currently the case.

Adult↗
PubMed2004

[Pregnancy after treatment of breast cancer].

The number of patients asking for pregnancy after being treated for breast cancer is steadily increasing. Chemotherapy, in particular alkylants, might impair fertility. The prognosis of breast cancer is not negatively affected by a consecutive pregnancy as shown in retrospective studies. The relative risk concerning survival is reduced to 0.2-0.8 by pregnancy. However, a short interval of less than 6 months after breast cancer treatment could have a negative effect. The nodal status is without significance. Study results could be severely biased by a so-called "healthy mother" effect. There is no sufficient data to allow any conclusions on the effect of hormonal stimulation for infertility treatment in breast cancer patients.

Breast Neoplasms↗
PubMed2004

Matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression is not regulated by norgestimate or norelgestromin.

Steroid hormones regulate endometrial expression of matrix metalloproteinases (MMPs) and their inhibitors. Synthetic progestins are widely used in oral contraceptives and for hormone replacement therapy. To assess whether the synthetic progestins norgestimate and its derivative norelgestromin (17-deacetylnorgestimate) modulate the expression of MMPs, Ishikawa endometrial cancer cells were separately treated with 17 beta-estradiol, 17 alpha-hydroxyprogesterone, norgestimate and norelgestromin. Culture supernatants were assayed for MMPs 2, 3 and 9, and for tissue inhibitors of MMPs (TIMP-1 and TIMP-2) by enzyme-linked immunosorbent assays (ELISAs). No marked modulation of MMP-2 and TIMP-2 expression was observed upon incubation of the cells with the synthetic progestins. By ELISA, neither MMP-3 or MMP-9 nor TIMP-1 immunoreactivity was detected. Interestingly, TIMP-2 expression was down-regulated by 17 beta-estradiol and 17 alpha-hydroxyprogesterone.

17-alpha-Hydroxyprogesterone↗
PubMed2004

Induction of androgen receptor activity by norgestimate and norelgestromin in MDA-MB 231 breast cancer cells.

The function and clinical significance of the androgen receptor (AR) in human breast cancer are still not clear. The synthetic progestins, norgestimate and norelgestromin, were designed to minimize the adverse effects such as acne, hirsuitism and metabolic changes observed with older oral contraceptives while maintaining contraceptive effectiveness and cycle control. AR-mediated effects of these synthetic progestins were studied in an in vitro transactivation assay, employing DNA co-transfection of an AR expression vector and luciferase reporter gene construct in the MDA-MB 231 human breast cancer cell line. Testosterone acetate and 5alpha-dihydrotestosterone induced the reporter gene transcription, whereas incubation of the transfected cells with the natural progestin 17alpha-hydroxyprogesterone did not markedly induce luciferase activity. The progestins norgestimate and norelgestromin exerted a very low androgenic activity. Our data suggest that norgestimate and its metabolite norelgestromin possess weak androgen-like properties. The use of these compounds for clinical application may be of great advantage in the treatment of breast cancer as well as hyperandrogenism in women.

17-alpha-Hydroxyprogesterone↗
PubMed2003

Seminal plasma induces mRNA expression of IL-1beta, IL-6 and LIF in endometrial epithelial cells in vitro.

The influence of seminal plasma on the mRNA expression of cytokines in human endometrial epithelial and stromal cells and the cytokine production of spermatozoa were investigated in vitro. Seminal plasma and spermatozoa were collected from healthy volunteers and were screened by enzyme-linked immunosorbent assay for cytokines. Epithelial and stromal cells from fertile women were cultured on matrigel or polystyrol and incubated with pooled seminal plasma or with transforming growth factor beta1 (TGF-beta1), interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF), which were found to be significantly concentrated in seminal plasma. Endometrial cytokine expression was analysed by RNase protection assay and supported by RT-PCR. Supernatants of highly purified spermatozoa did not contain detectable levels of IL-1beta, IL-6 and VEGF. Screening of seminal plasma revealed concentrations >10-fold above the serum level for TGF-beta1, IL-8 and VEGF. Incubation of epithelial cells with 0.1, 1 and 10% seminal plasma resulted in concentration-dependant stimulation of IL-1beta, IL-6 and LIF mRNA expression. Maximum stimulation was found in epithelial cells from tissue samples taken in the mid secretory phase. Epithelial mRNA expression of IL-1beta, IL-6 and LIF increased by stimulation with TGF-beta1 and IL-8, but not with VEGF. In conclusion, seminal plasma stimulates expression of pro-inflammatory cytokines in endometrial epithelial cells in vitro. This effect might at least in part be exerted by TGF-beta1 and IL-8, abundantly present in seminal plasma. The in-vivo physiological relevance of these in-vitro studies remains to be determined.

Cells, Cultured↗
PubMed2002

Endometrial interleukin-6 in vitro is not regulated directly by female steroid hormones, but by pro-inflammatory cytokines and hypoxia.

Endometrial interleukin-6 (IL-6) mRNA has been reported to be suppressed in the mid-secretory phase in patients with recurrent early spontaneous abortions. This prompted our study concerning the regulation of endometrial IL-6 in cell culture models of endometrial epithelial and stromal cells. Steroid-dependent secretion of IL-6 was analysed by 17beta-estradiol (10(-8) mol/l) or progesterone (10(-6) mol/l) treatment and withdrawal (n = 8). Regulation by pro-inflammatory cytokines was studied in co-cultures of endometrial cells with human blood peripheral mononuclear cells (PBMC; n = 5) and by stimulation with IL-1beta, IL-6 and tumour necrosis factor alpha (TNFalpha), secreted by PBMCs at high concentrations. Regulation by hypoxia was assessed by culture of endometrial cells in 2% oxygen for 6 and 24 h (n = 5). IL-6 mRNA and protein levels were analysed by RT-PCR and enzyme-linked immunosorbent assays respectively. Endometrial IL-6 was not directly affected by 17beta-estradiol and/or progesterone. Co-culturing endometrial cells with PBMCs led to an increase of stromal but not epithelial IL-6 mRNA levels. In stromal cells, IL-6 secretion increased 2-10-fold if stimulated with 10 ng/ml recombinant IL-1beta or TNFalpha (P < 0.05). Hypoxia stimulated IL-6 secretion in epithelial cells up to 2-fold and in stromal cells up to 48-fold (P < 0.05). In conclusion, IL-6 expression in stromal and epithelial cells in vitro is regulated differently by pro-inflammatory cytokines and hypoxia. These results suggest a tight and specific network of control for this important cytokine within different endometrial compartments.

Cell Culture Techniques↗
PubMed2002

Body fat distribution, insulin sensitivity, ovarian dysfunction and serum lipoproteins in patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by various endocrine and metabolic abnormalities, whose mutual associations and symptoms are still not clear. In the present study, fifteen PCOS patients and fifteen controls, matched for age and body weight, were investigated. Endocrine profiles were evaluated by the nafarelin and the adrenocorticotropin (ACTH) test. Insulin sensitivity was determined by an intravenous insulin tolerance test. Patients showed a significant predominance of abdominal adiposity [waist-to-hip ratio (WHR), 0.86 +/- 0.05 vs. 0.79 +/- 0.04] with markedly higher fasting insulin levels (+75%) and reduced insulin sensitivity (-37%). Fasting insulin, testosterone and free androgen index were positively correlated with the body mass index (BMI). In contrast, insulin sensitivity and BMI were inversely correlated in patients only. In the nafarelin test increases of 17-OH-progesterone and androstenedione were higher in patients and positively correlated with fasting insulin levels. Lipoprotein profiles showed trends towards higher triglycerides, lower HDL-cholesterol and a preponderance of small, dense LDL in patients. In PCOS higher triglycerides and lower HDL cholesterol were correlated with insulin sensitivity. It is concluded that PCOS patients show metabolic abnormalities combined with a more adroid type of adiposity when compared to cyclic controls of similar BMI.

17-alpha-Hydroxyprogesterone↗
PubMed2002

Testosterone and 5 alpha-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines.

Androgens are of biological and clinical importance for the growth and development of breast cancer in women, and the androgen receptor (AR) has been shown to be a predictor of tumor differentiation. In the present study, we investigated the relationship between AR status and testosterone and 5 alpha-dihydrotestosterone (DHT)-dependent proliferation of the human breast carcinoma cell lines MCF-7, T47-D, MDA-MB 435S and BT-20. AR status was studied by means of immunocytochemistry and Western blot analysis. All four cell lines stained positively for AR. Western blot analysis revealed a strong expression of AR in MCF-7, in contrast to BT-20 cells. According to proliferation kinetics, we observed a significant (p < or = 0.05) dose-dependent inhibition of cell growth by testosterone and DHT treatment in all four cell lines. In the estrogen receptor (ER)-negative cell lines BT-20 and MDA-MB 435S, testosterone was a more potent inhibitor of cell proliferation than DHT (p < or = 0.05), in contrast to the ER-positive cells lines MCF-7 and T47-D, in which a stronger inhibition of proliferation was achieved by DHT. A partial transformation of testosterone to estrogen in ER-positive cells might be an explanation for this effect. Our data favor a possible role of androgens in growth regulation of breast cancer. Clinical studies are needed to analyze the importance of AR as a possible predictor in response to endocrine therapy of breast cancer.

Blotting, Western↗
PubMed2002

Endometrial expression and secretion of interleukin-6 throughout the menstrual cycle.

Previous findings revealing reduced endometrial interleukin-6 (IL-6) mRNA expression in patients with recurrent early abortions gave rise to the analysis of IL-6 synthesis in the human endometrium, and how it relates to concentrations in uterine secretions. Endometrial tissues and uterine secretions were collected from patients undergoing hysterectomy. Expression of IL-6 receptor and gp130 mRNA (n = 28) in total endometrium, of IL-6 mRNA in endometrial epithelial and stromal cells, and CD45-positive leukocytes were investigated by RNAase protection assay throughout the cycle. IL-6 protein was assessed in endometrial tissue by immunohistochemistry (n = 32) and in uterine secretions by enzyme-linked immunosorbent assay (ELISA) (n = 33). IL-6 mRNA was expressed at low levels in the proliferative phase, and expression increased progressively in the secretory phase. The increase was attributed to epithelial and stromal cells and leukocytes. Concentrations of IL-6 protein in endometrial glands and in uterine secretions were low in the proliferative phase, and increased 5-10-fold in the mid- to late secretory phase. mRNA expression of IL-6 receptor and gp130 remained constant in total endometrium throughout the menstrual cycle. High concentrations of IL-6 in the mid-secretory phase, the putative implantation window, and a further increase in the late secretory phase, the premenstrual period, support a role of IL-6 in the regulation of endometrial functions.

Antigens, CD↗
PubMed2002

Impact of obesity and leptin levels on the secretion of estradiol, inhibin A and inhibin B during ovarian stimulation with gonadotropins.

We examined the impact of high leptin levels on the secretion of estradiol, inhibin A and inhibin B in obese and lean women during ovarian stimulation. Patients undergoing long-term pituitary suppression, ovarian stimulation and in vitro fertilization for non-endocrine reasons were included in this case-control study. Obese women (body mass index (BMI) > 28 kg/m(2); n = 17) were individually matched with lean women (BMI 20-25 kg/m(2); n = 17) for age and baseline follicle stimulating hormone and luteinizing hormone concentrations. Blood samples were collected in a previous menstrual cycle and 1-3 days apart throughout ovarian stimulation. Serum levels of estradiol, leptin, inhibin A and inhibin B were measured. Obese and lean women had similar serum concentrations of estradiol, inhibin A and inhibin B in the follicular and luteal phases of the spontaneous menstrual cycle, and throughout ovarian stimulation. Serum levels of leptin were higher in obese than in lean women, and increased during stimulation in both groups. In the obese group, area-under-the-curve (AUC) leptin levels correlated with AUC inhibin A levels. In the lean group, there was no correlation between AUC leptin levels and AUC levels of ovarian hormones. The results suggest that high leptin concentrations in vivo are not associated with impaired secretion of estradiol and dimeric inhibins during ovarian stimulation.

Body Mass Index↗