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T Rabe

Publications and source records attributed to T Rabe.

At least 37 records · Page 2Linked to original sources

Influence of 5-lipoxygenase on in vitro growth of human mammary carcinoma cell line MCF-7.

The aim of this study was to investigate the direct effect of 5-lipoxygenase (5-LO) on the growth of human mammary cancer cells MCF-7 in vitro. Cell growth was measured according to the level of 3H-thymidine incorporation. 5-LO was shown to inhibit 3H-thymidine incorporation. The inhibitory effect was 19, 42 and 78% when administered at concentrations of 0.1, 0.2 or 0.5 U/ml, respectively. Its effect was time- and dose-dependent and was statistically significant at concentrations of 0.2 and 0.5 U/ml. We have also shown that the specific 5-LO inhibitor MK-886 (1 microM) lifts the inhibitory effect of 5-LO (0.2 U/ml). Moreover, when treated with an activator of 5-lipoxygenase calcium ionophore A23187 (10 microM) MCF-7 cells synthesize LTB4. The results of this study are evidence of the role of 5-lipoxygenase in the regulation of human mammary cancer cells growth in vitro.

Arachidonate 5-Lipoxygenase↗

Influence of leukotrienes on in vitro growth of human mammary carcinoma cell line MCF-7.

OBJECTIVES: The aim of this work was to study the action of leukotrienes on the growth of human mammary cancer cells MCF-7. STUDY DESIGN: The growth of the cells was measured by incorporation of 3H-thymidine. The action of leukotriene (LT)B4, LTD4, LTC4, LTE4 or arachidonate (AA) was tested in human mammary cancer cells MCF-7 in vitro. RESULTS: LTB4 or LTD4 but not LTC4 or LTE4 reduced significant incorporation of 3H-thymidine in MCF-7 cells up to 52% or 56% respectively, when administered in concentrations 0.1-1000 pM. Agents in concentrations of 0.01 pM or 10000 pM did not effect 3H-thymidine incorporation. We have shown, that MCF-7 cells synthesise LTB4 when treated with calcium ionophor A23187 (10 microM). Leukotriene-antagonist LY171883 (10 microM) lifts inhibitory effects of LTB4 or LTD4. Arachidonic acid (10 microM) inhibits 3H-thymidine incorporation up to 72%. 5-lipoxygenase inhibitor MK-886 (100 nM) lifts the inhibitory effect of arachidonate. CONCLUSIONS: LTB4 or LTD4 inhibits MCF-7 breast cancer cell growth. LT-receptors mediate the growth-inhibitory effect of LTB4 or LTD4.

Acetophenones↗

Endometrial integrin expression is independent of estrogen or progestin treatment in vitro.

OBJECTIVE: To examine the regulation of endometrial integrin expression by estrogens and progestins in vitro. DESIGN: Immunocytochemical study. SETTING: Academic research unit. PATIENT(S): Twenty-five regularly cycling women without endometrial pathology, of whom seven had endometriosis. INTERVENTION(S): Endometrial cells obtained by aspiration curettage were treated with diethylstilbestrol, promegestone, and antiprogestin. Immunocytochemistry was performed with antibodies directed against integrins alpha 1 beta 1, alpha 2 beta 1, alpha 4 beta 1, alpha 5 beta 1, alpha v beta 3, and beta 3 integrin subunit. MAIN OUTCOME MEASURE(S): Semiquantitative staining score. RESULT(S): Endometrial cells express several integrins in vitro in a consistent and cell specific pattern. Neither differences between treated and untreated cells nor an effect of treatment duration or dosage were observed. Cells from patients with and without endometriosis showed similar patterns. CONCLUSION(S): The cellular distribution of integrin expression was similar to that described in vivo. In contrast, a steroid regulated expression could not be detected in vitro. Rather, a derepression by a factor not included in our model could be responsible for the cyclic appearance of some integrins. In endometriosis, no fundamental difference of integrin expression was detected.

Cells, Cultured↗

Antibacterial activity of South African plants used for medicinal purposes.

Crude extracts from 21 South African medicinal plants, traditionally used for ailments of an infectious or septic nature, were screened for in vitro antibacterial activity using the agar diffusion and dilution methods. Almost all the activity exhibited was against Gram-positive bacteria, with 12 of the 21 plant species tested showing some activity against Bacillus subtilis. Only the Warburgia salutaris methanol extract inhibited the growth of Escherichia coli. None of the extracts had any activity against Klebsiella pneumoniae. The highest activity was found in the methanol extracts from Bidens pilosa, Psidium guajava, Artemisia afra and Warburgia salutaris. The majority of the antibacterial activity was present in the methanolic, rather than the aqueous extracts.

Anti-Bacterial Agents↗

The effects of monophasic and triphasic oral contraceptives on ovarian function and endometrial thickness.

OBJECTIVE: To analyze and compare the effects of seven low-dose oral contraceptives (OCs) on ovarian function and endometrial thickness. METHODS: Cross-sectional study of users of one of five monophasic OCs, one of two triphasic OCs and a control group of non-users. Ovarian function, endometrial thickness and serum hormone levels were monitored during days 10-12 and 16-18 of the cycle. RESULTS: Serum estradiol was suppressed in OC users to a greater degree during days 16-18 than during days 10-12, whereas serum progesterone during 16-18 was in the anovulatory range with each preparation. Ovarian activity as measured by follicular size was lowest with desogestrel-containing OCs, whereas greater activity was seen with triphasic levonorgestrel/ethinylestradiol and triphasic norgestimate/ethinylestradiol. Endometrial thickness in OC users was significantly smaller than in controls. CONCLUSIONS: All preparations demonstrated profound suppression of ovarian activity and effectively prevented ovulation. Ovarian suppression with desogestrel/ethinylestradiol 150/20 did not differ from that of other OCs despite its lower ethinylestradiol content. The use of both triphasic OCs, having a relatively low progestogenic activity, was associated with a higher ovarian activity than that of the monophasic OCs.

Adolescent↗

Inhibitory effect of leukotrienes on luteinizing hormone release.

The aim of this work was to study the effect of high concentrations of leukotrienes on luteinizing hormone (LH) secretion in rat anterior pituitary cells. We also investigated the effect of leukotrienes in parallel with gonadotropin-releasing hormone (GnRH) action. Experiments were on cells gained from trypsinized pituitaries of female rats. Tests were performed by superfusion of the cells attached to cytodex-1 carrier beads. The LH content in samples of perfusate was estimated by radioimmunoassay. This work reports 48% inhibition of basic LH release by action of leukotriene C4 in superfused cells when applied continuously at a concentration of 100 nmol/l. Moreover, we have shown that leukotrienes suppressed GnRH-induced LH secretion in rat pituitary cells when applied in parallel to GnRH (1 nmol/l) as a 4-min pulse at a concentration of 0.1 nmol/l. GnRH-induced LH release was reduced to 66% of its value by leukotriene (LT) B4 (0.1 nmol/l) action; also to 54% by LTC4, 66% by LTD4 and 74% by LTE4 action. In contrast, arachidonic acid (50 pmol/l) and its other 5-lipoxygenase metabolites: 5-hydroperoxyeicosatetraenoic acid (5-HPETE) (50 pmol/l), or 5-hydroxyeicosatetraenoic acid (5-HETE) (50 pmol/l), had no inhibitory effect on GnRH-induced LH release. Arachidonic acid and 5-HETE potentiated GnRH-induced LH release up to 249% and 429%, respectively, when applied in parallel with GnRH (1 nmol/l) as a 4-min pulse at a concentration of 10 pmol/l. In our earlier work we have shown that several leukotrienes are potent stimulants of LH release. The present report documents the finding that the 5-lipoxygenase pathway is also involved in the inhibitory regulation of hormone release in anterior pituitary cells.

Animals↗

Spacing-out of progestin--efficacy, tolerability and compliance of two regimens for hormonal replacement in the late postmenopause.

Estrogen replacement therapy with sequential progestin at greater than monthly intervals has been frequently used in practice to reduce progestational side-effects and bleeding episodes, but clinical trials are still lacking. Two new regimens were tested. The main objective was to evaluate efficacy, predominantly in urogenital complaints, tolerability, and patient acceptance. Transdermal estradiol (0.05 mg/day) and norethisterone acetate orally (2.5 mg/day) were administered for 12 days every 2 or 3 months (group A, n = 83, group B, n = 89) to patients whose menopause had begun at least 4 years earlier. Study duration was three long cycles in each group within 7-10 months. Efficacy was good [group A/B = 94/92%], as was systemic tolerability [95/97%]; major skin reactions occurred in 7 and 4%, respectively. Patients' acceptance for continuation of spaced-out treatment was 88 and 87%, respectively. Progestin-associated withdrawal bleedings occurred in 66 (61%) of patients; mean duration 4.3 +/- 1.9/4.8 +/- 1.6 days, with no significant changes during therapy; intensity decreased during therapy. Breakthrough bleeding which required sonographic or histological work-up occurred in 8 and 13%, respectively. Despite the low dosage, transdermal estradiol proved to be efficacious in urogenital complaints. The high acceptance and the reduction of the overall progestin dose to avoid side-effects are of particular prognostic importance with regard to the prevention of cardiovascular diseases. Transdermal estradiol combined with 2- or 3-monthly progestin may be a valid regimen in the late post-menopause, but further studies using spacing-out regimens are urgently needed.

Administration, Cutaneous↗

A study of the influence of a gestodene-containing triphasic oral contraceptive on endometrial morphology.

The objective of the study was to investigate histological changes in the endometrium in 20 volunteers treated with a low-dose, gestodene-containing triphasic oral contraceptive. Endometrial biopsy specimens were taken before, during a 6-month period of oral contraceptive use and in a post-treatment period. These specimens were evaluated using light microscopy, scanning and transmission electron microscopy. In addition, ultrasound examinations of the uterus, endometrial thickness and ovaries were performed. The low-dose, gestodene-containing triphasic oral contraceptive had no adverse effects on the endometrium (e.g. no proliferation, no polyps, no inflammatory processes), was well tolerated and showed a low side-effect profile. The inhibition of endometrial transformation was demonstrated both by endometrial morphology as well as by endometrial thickness, as measured by transvaginal ultrasound examination.

Adolescent↗

Aneuploidy of human granulosa cells in follicular fluids from in vitro fertilization patients.

OBJECTIVES: To study the proliferative behavior of granulosa cells found in follicular fluids from patients after hormone stimulation in the framework of in vitro fertilization (IVF) with gonadotropins. STUDY DESIGN: The deoxyribonucleic acid ploidy and the proliferation indices of granulosa cells in fresh and unfixed follicles (n = 119) from gonadotropin-stimulated patients (n = 32) were analyzed by flow cytometry. RESULTS: Aneuploid cells were found in a large number of follicles (65/119) as well as patients (25/32). A small number of follicles (8/119) and patients (7/32) contained multiploid cells. There was no correlation between proliferation indices and ploidy. Granulosa cells were the predominant cells in follicular fluids. No malignant cells were found in any case. CONCLUSION: This is the first report concerning the high incidence rate of aneuploidy in ovarian granulosa cells in IVF patients. The clinical relevance of the phenomenon is not clear. There should be further study to determine whether there is any link to a previously discussed possible relation between gonadotropin stimulation in women attempting to become pregnant and the occurrence of ovarian cancer or granulosa cell tumors. Of further interest might be a possible relation between ploidy and proliferation indices of stimulated granulosa cells as well as side effects of gonadotropin therapy and biologic parameters, like maturity, fertilizability of oocytes and rates of pregnancy.

Adult↗

Effect of central and ovarian endocrine disturbances on the female genital tract--clinical signs and symptoms.

Disorders of the female genital tract caused by endocrine disturbances commonly lead to two presenting complaints: dysfunctional uterine bleeding and infertility. In oestrogen deficiency, sequelae of vaginal atrophy may also be present. The common pathogenic "turntable" of these clinical signs is an impaired ovarian function, for which primary (i.e. intraovarian) and secondary (i.e. resulting from dysfunctions of other endocrine systems) causes are known. Primary ovarian failure can be the result of gonadal dysgenesis or premature menopause. Secondary ovarian dysfunction may be caused by hypothalamic-pituitary dysregulation, hyperprolactinaemia, thyroid disorders, and hyperandrogenaemia, which often also has an intraovarian component. For clinical considerations, several severities of ovarian dysfunction can be distinguished, ranging from corpus luteum insufficiency which is only relevant for the selection of infertility treatment to the complete absence of ovarian steroidogenesis leading to severe long term sequelae of the skeletal, cardiovascular and probably central nervous systems. Diagnosis and differential diagnosis are made by clinical examination, vaginal ultrasound, hormone assays, curettage and laparoscopy. Rarely, additional techniques like magnetic resonance imaging of the pituitary or the adrenals, or sequential catheterization of the inferior vena cava are needed.

Adult↗

Action of recombinant follicle stimulating hormone in superfused human granulosa cells in vitro.

The aim of this work was to compare the action of recombinant follicle stimulating hormone (rFSH) and urinary FSH (uFSH). Moreover we aimed to compare the secretory efficiency of continuous versus pulsatile stimulation by rFSH in superfused human luteal cells. Progesterone concentration was measured in culture medium by radioimmunoassay. Action of rFSH and uFSH was compared in static cultures of human granulosa cells at doses of 0.001-10 IU/ml. The secretory efficiency of both rFSH and uFSH was found to be similar in a defined range of concentrations (0.001-0.3 IU/ml). At concentrations of 1 and 10 IU/ml, the action of uFSH was significantly more potent than rFSH, up to 139% (P < 0.01) and 133% (P < 0.01) respectively. A concentration of 0.3 IU/ml of rFSH was most potent in static cultures, and evoked progesterone release up to 80 mg/ml. For a stimulation period of up to 4 h, the action of rFSH and uFSH in human granulosa cells was time-dependent and differences between them were not significant. Irregularities were observed at > 4 h stimulation time. In another experiment, in superfused human granulosa cells, we showed that the stimulatory effectiveness of pulsatile rFSH administration (time interval 60 min, application time 10 min) was greater for progesterone release (3973 ng of progesterone/1 IU rFSH) than was continuous administration (848 ng of progesterone/1 IU rFSH). In conclusion, the secretory action of rFSH is similar to that of uFSH for defined times and doses. Moreover, pulsatile rFSH administration is more efficient at stimulating the release of progesterone than continuous administration.

Cells, Cultured↗

[Change in the spectrum of uterus-preserving myoma operations including endoscopy and dual myoma therapy].

OBJECTIVE: On the basis of the evaluation of 300 patients who underwent myoma surgery with the desire for uterus preservation at the Department of Obstetrics and Gynaecology of Heidelberg University, a management scheme including endoscopic techniques was developed. METHOD: Despite the patients' wish for organ preservation, in 12 cases (family planning complete, therapy-resistant sterility, no desire for a child) with an extremely large uterus (20th-24th week of gestation) or a degenerated, intramural myoma (a sarcoma not being excluded), a primary hysterectomy had to be performed. Overall, 37.9% of patients underwent conventional, 42% laparoscopic and 20.1% hysteroscopic surgery. Additionally, to objectify the role of a pretreatment with GnRH analogues (GnRHa), the following control parameters were examined in 128 patients with and 160 patients without pretreatment: rate of primary laparotomies, conversion, secondary hysterectomy, intraoperative bleedings, amount of distension medium and percentage of repeat interventions. RESULTS: No significant differences in the study parameters between study and control groups could be found in the patients treated by laparoscopy. In the hysteroscopy group, conversion rate (13.3 vs. 7%), operation time (35 vs. 21.9 min), rate of severe intraoperative bleeding (33.3 vs. 9.3%), amount of distension medium necessary (difference 2.1 litres) and rate of repeat interventions (40.4 vs. 16.3%) differed significantly between study and control groups. CONCLUSION: In the operative management, the key question is when to perform an invasive procedure. The second question should be which access route is the most convenient. The decision whether to give GnRHa pretreatment is also an individual one, especially in cases of a conventional or laparoscopic operative procedure. A preoperative GnRHa therapy is mandatory before hysteroscopy for submucous myoma.

Adult↗

Cyproterone acetate: is it hepato- or genotoxic?

The preclinical safety assessment of cyproterone acetate (CPA) with regard to liver tumorigenesis was based on tumorigenicity studies, which revealed no mutagenic potential. Recently, in vitro studies on the formation of adducts and the enhancement of DNA repair synthesis with CPA have been published. These results are not unique to CPA, and the role of adducts and increased DNA synthesis in mutagenesis is still not clear. Dose-related hepatic toxicity has been reported with the prolonged use of CPA. An active surveillance study of patients taking long term CPA treatment has shown no correlation between the duration of CPA treatment and the prevalence of liver enzyme elevations. In a multicentre surveillance study of long term CPA use in 2506 patients included so far, not a single case of hepatocellular carcinoma has been observed. These findings do not support the theory of an elevated risk of hepatocellular carcinoma as a result of CPA treatment. In conclusion, there have been no observations which could point to an increased risk of proliferative liver change as a result of CPA treatment.

Androgen Antagonists↗

Action of vasopressin in superfused human granulosa cells in vitro.

Arginine-vasopressin as well as luteinizing hormone (LH)/follicle-stimulating hormone (FSH) stimulate progesterone release in superfused human granulosa cells. Extracellular administration of inositol triphosphate (10(-6) mol/l) or calcium ions (10(-4) mol/l) mimics the action of both arginine-vasopressin and LH/FSH and evokes progesterone secretion in superfused granulosa cells.

Arginine Vasopressin↗

Role of leukotriene C4 in follicle-stimulating hormone (FSH) secretion in female rat pituitary.

Leukotriene C4, at doses of 0.01 and 0.1 nmol/l added to superfused cells in pulse of 4-min duration, evoked follicle-stimulating hormone (FSH) release up to 12- to 26-fold of basal secretion. Higher and lower concentrations of leukotriene C4 were not able to induce FSH secretion. Gonadotropin-releasing hormone (GnRH)-induced FSH release was reduced by 38-57% by the leukotriene receptor antagonist FPL 55712 (10 mumol/l). Moreover, we have shown that FSH release occurs parallel to leukotriene C4 synthesis in rat anterior pituitary cells. Mellitin (100 nmol/l), an activator of phospholipase A2, induced FSH and radioactivity secretion in rat anterior pituitary cells previously preincubated for 24 h with [3H]arachidonic acid (AA).

Animals↗

[The value of laparoscopic and laser-assisted techniques in reconstruction of distal fallopian tube pathology].

In an overall study population (3 different study designs) of n = 285 patients the role of laparoscopic resp. laser-assisted techniques was evaluated on the basis of the results of distal tubal reconstruction. An interventional comparison of a laparoscopic (n = 150) with a retrospective microsurgical (n = 135) group of patients with distal tubal pathology showed a significantly higher baby-take-home rate in the laparoscopically treated patients (38% vs. 22.2%, p < 0.05), but detailed critical analysis of indication revealed a certain selection effect in the laparoscopic group. A prospective study on laser (n = 100) and non-laser techniques for salpingostomy showed in no significant differences between the two groups, as results were concerned (delivery 35% in the laser, 44% in the non-laser cohort). In a prospective randomized subgroup laparoscopic fimbrial eversion with the laser was compared to suture eversion (n = 20). In both groups the reocclusion rate was of 20%. On may thus conclude, that the most important surgical approaches for treatment of a tuboperitoneal sterility: micro-surgery and endoscopy, resp. the various surgical techniques: laser and non-laser, should not be regarded as competing procedures, but as components of a multimodal strategy. The indication, however, must be critically viewed in every particular case. Of major importance being strict scientific evaluation criteria to prevent misinterpretations, e.g. based on indication-specific selection.

Adult↗