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T Rabe

Publications and source records attributed to T Rabe.

At least 19 recordsLinked to original sources
PubMed2006

[Malaria in the central highlands of Madagascar: control strategies].

The purpose of this article is to present data on malaria in the central highland plateaux of Madagascar and strategies to improve the national malaria control program. Use of rapid diagnosis strips, early home-based fever management with pre-packaged chloroquine treatment kits and proposed new therapeutic combination based on artemisinine are discussed for management of patients with high suspicion of malaria attack. Preventive measures including alternated targeted and full-house indoor spraying for vector control, use of insecticide-impregnated bednets, implementation of intermittent preventive treatment in risk groups, optimization of the epidemic early detection and warning system using the Lot Quality Assurance Sampling method for epidemiological investigation if the alert threshold is exceeded, and provision of rapid diagnosis strips are presented.

Humans↗
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

Synthetic estrogen-mediated activation of ERK 2 intracellular signaling molecule.

Ovarian steroids are important modulators of normal cell growth and differentiation as well as of carcinogenesis. External stimuli trigger cell surface receptors, resulting in activation of central signal transduction pathways, that are mediated by members of the mitogen-activated protein kinase (MAPK) family. These in turn, indirectly regulate cellular functions such as cell proliferation, cell cycle, and maintenance of malignant phenotype. In our in vitro study, we have investigated the effects of two synthetic estrogens on ERK 2 activation. Estrogen receptor positive cells were incubated with the synthetic estrogens, ethinylestradiol (10(-9) mol/l) and 17 beta-estradiol valerate (10(-9) mol/l), epidermal growth factor (EGF) (10 ng/ml) and the natural estrogen 17 beta-estradiol (10(-9) mol/l), for 5 min. The same experiments were repeated prior to preincubation with the antiestrogen ICI 182780. ERK 2 or the active form alone were detected by immunoblotting. A cell proliferation assay was used to study the response of cells to various treatments. Time kinetics were performed to study duration of kinase activated state. Cell incubation with EGF as well as with either natural or synthetic estrogen stimulated proliferation. ICI 182780 inhibited this effect, but only in the case of estrogen. Synthetic estrogens activated MAP kinase in a time-dependent fashion, similar to 17 beta-estradiol. The estrogen receptor antagonist ICI 182780 blocked this effect. EGF induced a more pronounced and prolonged activation, even in the presence of the antiestrogen. Ethinylestradiol as used in oral contraceptives, and 17 beta-estradiol and 17 beta-estradiol valerate as used in hormone replacement therapy, are able to activate MAP kinase. This activation was blocked by an antiestrogen.

Blotting, Western↗
PubMed2002

Isolation and identification of antibacterial compounds from Vernonia colorata leaves.

Vernonia colorata (Compositae) is used throughout Africa for a variety of ailments. This prompted the screening of this plant for biological activity. Previous experiments carried out in our laboratory revealed that the leaves possessed high antibacterial activity. Through conventional chromatographic techniques and bioassay-guided fractionation, the following sesquiterpene lactones were isolated and identified by spectroscopic data; vernolide (1), 11beta, 13-dihydrovernolide (2) and vernodalin (3). Only 2 is a novel compound, although its antibacterial activity is low compared to compounds 1 and 3 which had minimum inhibitory concentrations of 0.1-0.5 mg/ml against Gram-positive bacteria.

Africa↗
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

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↗
PubMed2001

An investigation on the biological activity of Combretum species.

Leaf extracts of 20 Combretum species, many of which are used in southern African traditional medicine, were screened for anti-inflammatory, anthelmintic, anti-bilharzia (antischistosomal) and DNA-damaging activity. Significant activity in more than one bioassay was exhibited by Combretum apiculatum, Combretum hereroense, Combretum molle and Combretum mossambicense. Ethyl acetate extracts were generally most active, followed by acetone and then water extracts.

Animals↗
PubMed2001

Preclinical profiles of progestins used in formulations of oral contraceptives and hormone replacement therapy.

Progestins used in oral contraceptive formulations available in the United States include norgestimate, desogestrel, norethindrone, norethindrone acetate, and levonorgestrel. Progestins used in the United States in continuous and intermittent formulations of hormone replacement therapy are norgestimate, medroxyprogesterone acetate, and norethindrone acetate. The chemical structure of a progestin determines its relative binding affinity for the progesterone and androgen receptors, as well as the sex hormone binding globulin in human serum, and determines its clinical profile. Overall, the properties of levonorgestrel or norethindrone acetate in this regard differ from norgestimate and are more conducive to androgenic stimulation. Estrogen replacement offers cardioprotective effects in postmenopausal women. Progestins are added to hormone replacement therapy to counteract the well-known increased risk of endometrial hyperplasia associated with the use of unopposed estrogen. Animal models show that for some parameters, including improvement of lipid profiles, progestins can diminish the cardioprotective effect of estrogen. Initial animal studies of norgestimate combined with estrogen do not show an attenuation of estrogenic effects.

Animals↗
PubMed2001

Synthetic estrogens-mediated activation of JNK intracellular signaling molecule.

Signal transduction pathways regulate the transmission of specific signals to the cells from the surface to the nucleus. Activation of protein kinases such as JNKs (c-jun amino-terminal kinase), a subgroup of the mitogen activated protein kinase (MAPK) family, results in regulation of important cellular functions like cell growth and differentiation. The involvement of estrogens in stimulation of growth of already transformed breast cancer cells in vivo and in vitro accompanied with activation of JNKs prompted us to investigate the role of synthetic estrogens in the regulation of JNK expression. T 47D breast cancer cells were incubated with the synthetic estrogens, ethinylestradiol (10(-9)M) and 17 beta-estradiol valerate (10(-9)M), epidermal growth factor (EGF) (10 ng/ml) and the natural estrogen, 17 beta-estradiol (10(-9)M), for 5 minutes. The same experiments were repeated after pretreatment of the cells with ICI 182780 for 24 hours. EGF as well as natural and synthetic estrogens stimulated proliferation. This effect was reversed by the estrogen receptor blocker ICI 182780, but only in the case of both natural and synthetic estrogen. Like 17 beta-estradiol, synthetic estrogens induced a rapid and transient activation of JNK kinase. ICI 182780 blocked this effect, but not that mediated by EGF. Ethinylestradiol used in oral contraceptives, and 17 beta-estradiol and 17 beta-estradiol valerate for hormone replacement therapy, are able to activate JNK. The estrogen receptor is necessary for JNK activation upon estrogen stimulation.

Blotting, Western↗
PubMed2000

Plant part substitution--a way to conserve endangered medicinal plants?

Population growth, urbanization and the unrestricted collection of medicinal plants from the wild is resulting in an over-exploitation of natural resources in southern Africa. Therefore, the management of traditional medicinal plant resources has become a matter of urgency. In southern Africa the most frequently used medicinal plants are slow-growing forest trees, bulbous and tuberous plants, with bark and underground parts being the parts mainly utilized. A strategy which would satisfy the requirements of sustainable harvesting, yet simultaneously provide for primary health care needs, would be the substitution of bark or underground parts with leaves of the same plant. This paper outlines the concept of plant substitution, using preliminary results of our recent investigations into four of the most important and most threatened South African medicinal plants - Eucomis autumnalis (bulb), Siphonochilus aethiopicus (rhizome), Ocotea bullata (bark), and Warburgia salutaris (bark) - as a demonstration of the kind of research necessary. Extracts of various plant parts were compared chemically using TLC-analysis, and pharmacologically in terms of antibacterial activity and cyclooxygenase-1 inhibition in vitro. The importance of the concept of plant part substitution as a strategy for the conservation of medicinal plants in southern Africa is discussed in terms of the results obtained.

Africa, Southern↗
PubMed2000

Isolation of an antibacterial sesquiterpenoid from Warburgia salutaris.

The bark of Warburgia salutaris is used in traditional medicine as an expectorant and smoked for coughs and colds, including a topical application for sores and inflammation. A previous screening of South African medicinal plants showed that this plant had promising antibacterial activity. Subsequently, this endangered tree species was selected for bioassay-guided fractionation in order to identify the active principles. Fractionation of the ethyl acetate extract of the stem bark by chromatographic techniques yielded a sesquiterpenoid which exhibited antimicrobial activity against Gram-positive bacteria. The compound, muzigadial, has previously been reported in two other Warburgia species, this being the first time it has been reported from W. salutaris. Muzigadial had minimum inhibitory concentration values ranging from 12.5 to 100 microg ml(-1).

Africa↗
PubMed2000

Induction of estrogen receptor-alpha and -beta activities by synthetic progestins.

The cellular action of steroid hormones is mediated by specific receptors. Recently, two different estrogen receptors (ER), alpha and beta, have been cloned with a specific tissue distribution. Active estrogen as well as active progestin are compounds of oral hormonal contraceptives and hormone replacement therapy. To examine the regulation of ER-alpha and -beta activities after treatment with synthetic progestins and synthetic and natural estrogens, COS 7 cells were transfected with the vector expressing ER-alpha and -beta in combination with a luciferase reporter vector. ER-alpha activity was upregulated in the presence of synthetic progestins in a dose-dependent manner. Norethisterone, norethynodrel and desogestrel proved to be the most potent stimulatory agents of ER-alpha expression. On the other hand, not all progestins exhibited a stimulatory action on ER-beta activity. Only norgestrel, levonorgestrel, norethynodrel and norethisterone induced ER-beta-activating functions in a dose-dependent manner. Luciferase activity due to estrogen stimulation served as a positive control. Our results indicate that progestins have different effects on the activities of ER-alpha and -beta.

Animals↗
PubMed2000

Inhibition of skin 5 alpha-reductase by oral contraceptive progestins in vitro.

Androgenic disorders of female skin such as hirsutism, acne and alopecia are etiologically caused by androgen excess. Skin 5 alpha-reductase activity is a major factor influencing the manifestation of endogenous androgen excess in women. Oral contraceptives have proven useful for the treatment of androgen disorders of the skin. The mechanisms of action by which oral contraceptives correct skin androgen levels may include inhibition of 5 alpha-reductase and androgen receptor activity. We investigated the inhibitory effect of oral contraceptive progestins and ethinyl estradiol on skin 5 alpha-reductase and their influence on androgen receptor activity and affinity, using three different in vitro assay systems. It was shown that norgestimate blocked 5 alpha-reductase activity with an IC50 value of 10 microM, followed by levonorgestrel (IC50 52 microM), dienogest (IC50 55 microM), cyproterone acetate (IC50 87 microM) and gestodene (IC50 98 microM). To determine the full androgenic potential of the progestins, androgen receptor binding affinities and activation potentials were determined. The progestins norgestimate and dienogest in particular combined 5 alpha-reductase inhibition with minimal androgenic potential. These data demonstrate that the progestins norgestimate and dienogest might help in the treatment of clinical hyperandrogeny in women.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2000

[German Cohort Study of Women's Health--benefits of oral contraceptives. Study protocol].

This publication is about the study protocol of the German Cohort Study on Women's Health. The main objective is to investigate medical benefits of a long-term oral contraceptive use. The design is an analytical cohort study based on inquiries. Additional cases will be recruited to analyse rare events in separate case-control studies. Voluntary participants who signed to participate in a long-term study are included. An annual drop-out rate of 15% is expected. Study variables encompass personal characteristics, lifetime history of diseases, but also disturbances of the state of health, and quality of life. It is anticipated to achieve 400,000 women-years of observation by 2001 (historic and concurrent follow-up). The study started April 1, 1998 and the current financial phase finishes December 31, 2001. 6000 participants were recruited until December 1998 equivalent to about 190,000 observation-years. Until the end of 1999, an additional 70,000 women-years should be included. There have been many suggestions from participants' to include additional issues of women's health into the study.

Adult↗
PubMed2000

[Non-contraceptive benefits of the pill--an often neglected fact].

While rare cardiovascular risks of oral contraceptives (OCs) caused a lot of concern among OC-using women in the recent past, little attention has been paid in the public to the non-contraceptive benefits of OCs. Short, medium and long term non-contraceptive benefits have to be considered. The early Anglo-American cohort and case-control studies demonstrated a reduction of menstrual complaints, iron-deficiency anaemia, ectopic pregnancies, and a partly drastic reduction of some benign and malignant tumours such as endometrial and ovarian cancer. A risk reduction of rheumatoid arthritis is discussed controversially. The present paper gives an overview of the state of knowledge. For newer OCs with different composition, comparable studies are lacking. Therefore, a cohort study was initiated in Germany in April 1998 to investigate these associations as well for newer OCs, which is presented. The described non-contraceptive benefits should be considered in the benefit-risk assessment when prescribing OCs.

Arthritis, Rheumatoid↗
PubMed1998

Aneuploidy in human granulosa lutein cells obtained from gonadotrophin-stimulated follicles and its relation to intrafollicular hormone concentrations.

Proliferation of granulosa cells is inversely related to differentiation and hormone production. The purpose of this study was to evaluate the intrafollicular and serum steroid concentrations and to compare these results to granulosa cell proliferation as measured by DNA flow cytometry. Human granulosa lutein cells in follicular fluid of in-vitro fertilization (IVF) patients were investigated with regard to ploidy, percentage of S-phase cells and proliferation index (PI: percentage of cells in the S- and G2/M-phase). The study was originally designed to indicate an additional marker for the outcome of IVF treatment by DNA flow cytometric measurements of granulosa lutein cells. Follicular fluids of 160 follicles (45 patients) were evaluated; 45.6% (n = 73) of the follicles showed aneuploid granulosa lutein cells and 5.6% (n = 9) of the follicles contained multiploid granulosa cells, defined as at least two aneuploid populations of cells with different DNA indices. A total of 48.8% (n = 78) of the follicles had only diploid cells. Thus >50 % of the investigated follicles showed aneuploidy. In all, 73% (33 of 45) of patients had at least one follicle containing aneuploid granulosa lutein cells. The PI of the aneuploid cell populations significantly exceeded that of the diploid cell populations (median: aneuploid: 15.5; diploid: 7.4; P < 0.0001). The intrafollicular concentrations of testosterone, progesterone and dehydroepiandrosterone sulphate (DHEA-S) were significantly lower in follicles with aneuploid granulosa cell populations. Luteinizing hormone concentration was significantly higher in follicles with aneuploid granulosa cells. Intrafollicular concentrations of oestradiol, follicle stimulating hormone and the serum concentrations of all steroid hormones did not show any significant correlation to ploidy. Although aneuploidy has been reported for oocytes (in approximately 17% of the oocytes), no study, to our knowledge, has observed such a high incidence of aneuploidy in granulosa lutein cells after gonadotrophin stimulation. Except for aneuploidy found in tissues with some characteristics of neoplastic growth (colon adenoma, borderline tumours, endometriosis with atypic cells, etc.), it is unique for non-malignant human cells. The correlation with intrafollicular steroid concentrations points to a possible pathophysiological or physiological relevance of these findings. However, it was impossible to correlate the outcome of IVF with DNA flow cytometry results.

Adult↗