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Biomedical subjects

B Runnebaum

Publications and source records attributed to B Runnebaum.

At least 145 records · Page 8Linked to original sources
PubMed1988

[Gonadotropin-releasing hormone receptors in human breast cancer tissue].

Analogues of gonadotropin-releasing hormone (GnRH) are presently being investigated for the treatment of metastatic breast cancer. Although their effects are thought to be mediated via the suppression of gonadotropins and gonadal steroids, they could possibly also act directly on the tumour. The binding of a GnRH-agonist to membrane fractions of 97 primary human breast carcinomas was investigated. In 43 cases (44%) the presence of specific GnRH receptor binding sites (above 3 fmol/mg membrane protein) was shown. GnRH receptor content was 6.2 fmol/mg membrane protein in estradiol receptor (ER) positive tissues and in ER negative tissues 2.0 fmol/mg membrane protein (p less than 0.05). Progesterone receptor (PR) positive contained 5.2 fmol/mg protein and PR negative carcinoma contained 2.0 fmol/mg membrane protein. In postmenopausal women GnRH receptor concentration was 5.4 and 2.9 fmol/mg membrane protein, respectively, in ER positive and negative tissues (p less than 0.05) whereas 4.4 and 5.2 fmol/mg membrane protein, respectively, in PR positive and negative samples. Binding of GnRH was positive (above 3 fmol/mg protein) in 33% premenopausal and in 54% of postmenopausal cases. Further clinical studies with GnRH analogues will clarify the therapeutic value of GnRH receptor determination in breast cancer.

Binding, Competitive↗
PubMed1988

Pulsatile gonadotrophin releasing hormone therapy in patients with hyperandrogenaemia or hypothalamic amenorrhoea.

From 1984 to 1985, 18 patients with infertility and oligomenorrhoea were treated with pulsatile GnRH administration (Zyklomat). According to the hormone levels and the ultrasonographic observation of the ovaries, they could be divided into two categories, group A (n = 11), patients with hyperandrogenaemia, and group B (n = 7), patients with hypothalamic amenorrhoea. As in hyperandrogenaemic patients a pathological LH-secretion pattern was suspected, assessment of LH-pulsing (5 ml blood samples at 10 min intervals over 6 h) was performed in this group of patients followed by an oestrogen-gestagen (E-Ge) suppression. One day before discontinuation of this medication, the GnRH pump was applied intravenously. Ovulation induction was more successful in group B than in group A. Hyperandrogenaemic women, in whom ovulation could be induced by the GnRH pump, exhibited higher basal concentrations of FSH, LH, LH/FSH ratio, oestradiol- 17 beta and testosterone (T) than the women not responding to pulsatile GnRH administration. The suppression of T and LH/FSH ratio with E-Ge treatment was more pronounced, while the non-responders had higher basal prolactin concentrations as well as after E-Ge therapy and a significantly greater body weight. The results indicate that GnRH therapy in hypothalamic amenorrhoea is more successful than in hyperandrogenaemia. Overweight hyperandrogenaemic patients appeared to be unsuitable for GnRH treatment, even after previous suppression of the hypothalamic pituitary ovarian axis with E-Ge.

Adult↗
PubMed1988

Effects of antimicrobial therapy on sperm-mucus interaction.

Sperm-mucus interaction under in-vitro or in-vivo conditions might be affected by microorganisms colonizing the reproductive tract. In order to study the influence of antimicrobial therapy, an extensive microbial screening was performed including Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae, a broad spectrum of potentially pathogenic aerobic and anaerobic bacteria, Trichomonas vaginalis, herpes simplex virus and yeasts. One-hundred-and-six couples with a mean duration of infertility of 5.5 years (range 1-12 years) and with isolation of potentially pathogenic microorganisms in semen samples and/or cervical swabs were submitted to a prospective pilot study. None of the patients displayed signs or symptoms of infection in the lower genital tract. Before and after specific therapy, based on antimicrobial susceptibility testing, sperm analyses and in-vitro sperm penetration meter tests (SPMT) (Kremer) were performed. SPMT was evaluated with cervical mucus of patients' wives, collected after a standardized oral treatment with oestrogens and, additionally, in a crossed manner with cervical mucus and spermatozoa of fertile donors. The success of antimicrobial therapy was controlled by repeating the same microbial screening and was 96%. However, there was a marked change in the microbial pattern. A comparison of the results of sperm analyses before and after treatment revealed neither significant differences for sperm volume, sperm count, propulsive motility, morphology, vitality, pH, fructose concentration or number of round cells, nor was there a significant influence on the cervical index and the number of leukocytes in cervical mucus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Parenteral contraceptive drugs: depot progestins].

Depot progestins as injectables, implantables or vaginal rings are suitable for contraception in those female patients, in which risk factors (e.g. cardiovascular risk) exclude the use of estrogen-progestin mixtures. In this paper the mode of action, indications, contraindications, advantages and disadvantages of the various methods using depot-progestins are discussed. Injectables contain either medroxyprogesterone acetate or norethistronenantate; both steroids are released slowly within a limited time interval (2 to 4 months) out of a depot. The major effect is a change of the cervical mucus. Side-effects are disturbances of the menstrual cycle (e.g. breakthrough bleedings) as well as an amenorrhea after frequent use (up to 50% of all cases). The subdermal implantables (Norplant 2 or 5) release levonorgestrel out of a depot over a time period of at least 5 years. Steroid plasma levels are lower than in those patients using a progestin-only pill. Side-effects of implantables are disturbances of the menstrual cycle (e.g. breakthrough bleeding); in patients who desire to conceive a child or suffer from undesirable side-effects the implantables can be removed at every time. The progestin releasing vaginal rings are in a stage of controlled clinical trials. The advantages depend on ethe easy mode of administration (implantation or removal). Side-effects are also breakthrough bleedings.

Administration, Intravaginal↗
PubMed1987

[Risk-benefit analysis of contraception with steroids].

Oral hormonal contraception is a low risk and safe form of contraception for women between 15 and 35 years of age without risk factors in the history (smoking, obesity, diabetes mellitus, hypertension, hypercholesterinemia). Women over 35 years should take the pill only when risk factors have been excluded previously. In general, low dose pills with less than 50 micrograms ethinylestradiol should be used, because they have the lowest impact on the metabolism. There should be an additional indication even after exclusion of risk factors, if women over 40 years take the pill. Besides that it could be shown that using the pill has many positive effects on health, as for example benign mamma tumors more seldomly occur, in most of the cases the dysmenorrhoea improves, anaemia and inflammatory adnex diseases are significantly more seldom, and it could be shown that there is a clearly protective effect concerning the morbidity of endometrium and ovarian cancer.

Contraceptives, Oral, Hormonal↗
PubMed1987

Effect of inositol 1,4,5-trisphosphate and GTP on calcium release from pituitary microsomes.

Microsomal vesicles from bovine anterior pituitary accumulate Ca2+ and maintain a steady-state ambient Ca2+ level of 200 nM. IP3 and GTP both induce calcium release from the microsomal vesicles. The effect of IP3 is inhibited by polyethylene glycol (PEG), and the effect of GTP is absolutely dependent on PEG. Half-maximal effect of IP3 (without PEG) is 0.26 micron, the maximal calcium release attaining 7% of the A23187-releasable pool. The same values for GTP (in the presence of PEG) are 80 microM and 10%, respectively. GTP potentiates the effect of IP3. This potentiation is not mediated by protein phosphorylation.

Animals↗
PubMed1987

Binding of inositol phosphates and induction of Ca2+ release from pituitary microsomal fractions.

Bovine anterior-pituitary microsomal fractions exhibit high-affinity, saturable and reversible binding of inositol 1,4,5-[32P]trisphosphate; 50% of the labelled ligand is displaced by 3.5 nM-inositol 1,4,5-trisphosphate. 0.5 microM-inositol 1,4-bisphosphate and 10 microM-ATP. Inositol 1,4,5-trisphosphate induces the release of Ca2+ from the microsomal vesicles (half-maximal effect at 290 nM), and its action is potentiated by inositol tetrakisphosphate (half-maximal effect at 4 microM).

Animals↗
PubMed1987

Stimulation of gonadotropin release by arachidonic acid and its lipoxygenase metabolites in superfused pituitary cells.

Luteinizing hormone and follicle stimulating hormone secretion was stimulated by 4 min pulses of arachidonic acid (3 X 10(-5) to 10(-4)M) in superfused rat pituitary cells. The effect of its lipoxygenase metabolites, 5-hydroxy-6,8,11,14-eicosatetranoic acid (5-HETE) and 15-hydroxy-5,8,10,14-eicosatetranoic acid (15-HETE) was more potent on hormone release when added in the same dose. Using 3 X 10(-5)M 5-HETE, its releasing activity on gonadotropins was comparable to that of GnRH (10(-9)M). 15-HETE (3 X 10(-5)M) was even more potent on LH and FSH secretion than 5-HETE. The secretory profile induced by 5-HETE and 15-HETE was also similar to that shown for GnRH, resulting in a rapid increase and a more prolonged decline of the hormone release. The addition of these fatty acids to superfused pituitary cells did not alter the response of the cells to their physiological ligand. These findings give further support to the proposal that metabolites of arachidonic acid may be involved in receptor-mediated mechanisms of gonadotropin release in pituitary cells.

Animals↗
PubMed1987

Contraceptive progestins and gonadotropin secretion in vitro.

In an in vitro bioassay using rat pituitary cell cultures the effect of contraceptive progestins was tested on basal and gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in vitro. Progestins diminished gonadotropin release in pituitary cells stimulated with GnRH, but did not alter basal values. This inhibitory effect was dose dependent in a range of 10(-10)-10(-5) M tested and the inhibitory action of most of the progestins examined was more potent than that of progesterone. The maximal reduction of LH and FSH values was by 60% of GnRH-induced control levels. Progestins also caused a shift in sensitivity of cells to GnRh (10(-12)-10(-6) M). When time dependence was investigated, some progestins potentiated GnRH effect on gonadotropins in pituitary cell cultures pre-incubated for a short time (4 h) with steroids. More prolonged pre-incubations from 23 to 71 h resulted in a progressive suppression of LH and FSH response to GnRH (10(-7) M). In order to examine intracellular effects, cells were pretreated with progestins and inositol phosphate metabolism was investigated. The data obtained in pituitary cells give evidence that polyphosphoinositide breakdown is potentially an early step in the action of GnRH on gonadotropin secretion by providing diacylglycerol and inositol phosphates. Addition of gonadotropin-releasing hormone to myo-2[3H]inositol-prelabeled rat pituitary cells in primary culture evoked a dose-dependent increase of the accumulation of [3H]inositol phosphates with a rise of inositol triphosphate, inositol diphosphate and inositol monophosphate within 1 min. Using one contraceptive progestin, gestoden, inositol phosphate production was inhibited by 80% compared to controls of GnRH-treated cells without the addition of steroids. The data obtained in this study suggest that this in vitro bioassay using rat pituitary cells is a useful tool in testing progestational compounds regarding their potency on gonadotropin release. In addition, these results show that one possible site of interference of progestins with GnRH-induced gonadotropin secretion may involve polyphosphoinositide breakdown.

Animals↗
PubMed1987

Weight percentile at birth. I. Clinical data of pregnancy and relevance for early childhood development.

The influence of the weight percentile at birth on childhood development was examined in a prospective study of 847 singleton pregnancies. In the first two years of life significant relationships between the birth weight percentiles and the infant's development could be proven, while at the age of four social factors were predominant. Though various clinical data in pregnancy and delivery were related to fetal growth, such as weight of the mother, previous abortions and diseases, additional biochemical and biophysical information is desirable for early recognition of intrauterine growth disorders.

Birth Weight↗
PubMed1987

Weight percentile at birth. II. Prediction by endocrinological and sonographic measurements.

In a prospective study of 847 singleton pregnancies, the importance of various endocrine methods (serum estriol, HPL, SP1, beta-HCG, estradiol-17 beta, urinary estrogen excretion) and of two sonographic measurements (biparietal and thoracic diameter) for the diagnosis of growth retardation in the third trimester was studied. HPL and estriol determinations were best suited for the diagnosis of growth retardation. The thoracic diameter correlated most closely with the birthweight of the newborns. Sensitivity in relationship to growth retardation was between 17 and 35% for the HPL and estriol determinations as well as for both sonographic methods. Specificity was around 90% for these methods. The validity for all methods improved as the time of birth approached. Through the simultaneous measurement of one of the hormones and the thoracic diameter, an antepartal diagnosis of up to 50% of the hypo- and hypertrophic growth disorders was achieved. In the first two years of life a relationship between development and the HPL and estriol concentrations could be observed which was independent of the weight percentile at birth.

Birth Weight↗
PubMed1987

Stimulation of luteinizing hormone release by melittin and phospholipase A2 in rat pituitary cells.

Gonadotropin release in rat pituitary monolayer cultures was stimulated by phospholipase A2, as well as by its activator melittin. A dose-dependent stimulation of luteinizing hormone secretion by melittin was observed in a dose range of 10(-8) to 10(-4) M. A higher dose (1 mM) melittin had a sub-optimal effect. The stimulatory action of melittin was calcium-dependent and blocked by phospholipase A2 inhibitors, chloroquine and quinacrine. Similar to melittin, phospholipase A2 enhanced the effect of LH release in a dose range of 0.1-100 units/ml. The effect of this enzyme was also calcium-dependent with optimal calcium concentrations at 1.5 mM, as obtained also for melittin. In superfusion experiments, the stimulatory action of melittin and phospholipase A2 was reproducible in their effects on LH release in gonadotrophs. In addition, melittin (10(-7) M) stimulated LH and 3H-arachidonic acid efflux in superfused pituicytes following prelabelling with radiolabelled arachidonate. These data suggest that phospholipase A2, which releases arachidonic acid from phospholipids, may participate in controlling gonadotropin secretion in gonadotrophs, since arachidonic acid and its metabolites have previously been found to enhance gonadotropin release.

Animals↗
PubMed1987

New progestogens in oral contraceptives.

The aim of using new synthetic progestogens (gestodene and norgestimate) in oral hormonal contraceptives is to find a combination that has a more beneficial effect on metabolism and endometrium than presently available formulations. Our studies with low-dose pills containing 30 micrograms ethinyl estradiol/150 micrograms levonorgestrel or 30 micrograms ethinyl estradiol/150 micrograms desogestrel compared with the new pills with 35 micrograms ethinyl estradiol/250 micrograms norgestimate or 30 micrograms ethinyl estradiol/75 micrograms gestodene revealed no significant alterations of serum glucose after glucose loading. With all four combination pills, insulin levels were slightly elevated when compared with controls. Studies of the lipid metabolism showed that depending on the type and estrogen combination, progestogens have different effects on lipid metabolism. The new progestogens seem to have a more pronounced effect on triglycerides, whereas total cholesterol and high-density lipoprotein cholesterol remain almost unchanged. In general, it could be shown that low-dose oral contraceptives have little impact on lipid metabolism. Studies with low-dose monophasic preparations, including the new formulations, reveal only a low effect on blood coagulation. According to our and other data on the new progestogens in oral contraceptives available so far, it can be expected that such low-dose monophasic and triphasic combination pills will be beneficial during longtime use with respect to side effects on the cardiovascular system and control of the menstrual cycle.

Contraceptives, Oral, Combined↗
PubMed1987

[Risk-benefit analysis of a hCG-500 kcal reducing diet (cura romana) in females].

The British physician A.T.W. Simeons described in 1954 a new method for dieting. He combined a reduction diet (500 kcal per day) with daily injections of the pregnancy hormone human chorionic gonadotropin (hCG) (125 IU i.m.). According to Simeons the patient should not lose more weight during a 4-to-6 weeks' diet than without hCG, but the injections should facilitate to maintain the diet and to lose body weight at specific parts of the body (e.g. hip, belly, thigh). After the first publication various studies conducted with male and female patients analysed the efficacy of the "Cura romana". 10 of these studies showed positive and another 10 studies negative results with regard to hCG-related weight reduction. Two of these studies with positive results were double-blind studies (hCG vs. placebo). Most of them were reports on therapeutical experiences and were not controlled studies. According to these reports the body proportions normalized and the feeling of hunger was tolerable. Four out of 10 studies with negative results were controlled studies (hCG vs. control without hCG), whereas 6 were double-blind studies. These studies showed a significant weight reduction during dieting, but no differences between treatment groups in respect of body weight, body proportions and feeling of hunger. One of them is the only German study conducted by Rabe et al. in 1981 in which 82 randomised premenopausal volunteers had been dieting either with hCG or without hCG injections. In recent publications describing mostly well-documented double-blind studies authors largely reject hCG administration in dieting. Supporters of the hCG diet must prove the efficacy of this method in controlled studies according to the German Drug Law. Until then the opinion of the German steroid toxicology panel is still valid, that hCG is ineffective in dieting and should not be used (Bolt 1982 a, 1982 b).

Appetite↗
PubMed1987

[Effect of the PGE1 methyl analog misoprostol on the pregnant uterus in the first trimester].

The effect of misoprostol, a PGE1 methyl analogue, on the pregnant human uterus was unknown at dosage levels normally used in the treatment of gastric and duodenal ulceration. Data from animal fertility and teratology studies suggested no activity at an anti-ulcer dosage level. In a double-blind placebo-controlled study, 300 patients (9.-12. week of gestation) were treated with two doses of misoprostol (study A: 2 X 400 micrograms; study B: 2 X 200 micrograms) or placebo during the evening before a legally permitted termination of first-trimester pregnancy. A partial or complete abortion occurred spontaneously in 11% of patients receiving misoprostol 2 X 400 micrograms, 9% of patients receiving misoprostol 2 X 200 micrograms and none of the patients receiving placebo. The incidence of vaginal bleedings (A: 45%, B: 34%), abdominal pain (A: 42%, B: 43%) and the softening of the cervix were all significantly increased by misoprostol treatment. These results show that the sensitivity of the human pregnant uterus to prostaglandin analogues cannot be reliably predicted from animal studies. Furthermore, misoprostol should not be used in human first-trimester pregnancy. The effect of misoprostol on second and third-trimester pregnancy (e.g. labour induction) is still unknown.

Abortifacient Agents↗
PubMed1987

Arachidonic acid and its lipoxygenase metabolites stimulate prolactin release in superfused pituitary cells.

The direct effect of leukotrienes and other lipoxygenase products on prolactin release has been assessed. Arachidonic acid and its lipoxygenase metabolites 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) and 15-hydroxy-5,8,10,14-eicosatetranoic acid (15-HETE) stimulated the release of prolactin in superfused rat pituitary cells in a dose-dependent manner. Leukotrienes (LT) A4, B4, C4 and E4 provoked a very marked biphasic and dose-dependent secretion of prolactin from superfused cells. Maximal effects were achieved with leukotrienes at a concentration of 3 X 10(-11) to 3 X 10(-10) M but LTD4 did not affect peptide release under these conditions. The metabolites were more potent than arachidonic acid in affecting hormone secretion. Pulses of 4 minutes duration of these fatty acids may even elicit a more pronounced response than thyrotrophin-releasing hormone (TRH). Nordihydroguaiaretic acid (NDGA 10(-6) M), a lipoxygenase inhibitor, prevented the effect of arachidonic acid on peptide secretion. Repeated TRH (10(-7) M) administration to pituitary cells led to a reduction in cell response, which may also be observed in cells pre-treated with pulsatile 5-HETE or 15-HETE. These data support previous findings that arachidonic acid and its lipoxygenase metabolites may play a role in the secretory mechanism of prolactin release in pituitary cells.

Animals↗
PubMed1987

Influence of microbial colonization on sperm-mucus interaction in vivo and in vitro.

Two-hundred-and-thirty-three asymptomatic couples with a mean duration of infertility of 5 years were submitted to postcoital testing (PT) and to sperm penetration meter test (SPMT) and simultaneous microbial screening. Cervical swabs and semen specimens were collected for culture of Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis, Neisseria gonorrhoeae, other potentially pathogenic and commensal aerobic and anaerobic bacteria, herpes simplex virus, vaginal swabs for Trichomonas vaginalis and yeasts. Results of microbial screening were analysed with regard to sperm penetration ability into wives' cervical mucus in vivo and in vitro, but no marked influence was revealed for most microorganisms. Samples of only one of the 233 couples proved to be completely sterile. The findings suggest that in asymptomatic patients microbial colonization is of minor importance for sperm-mucus interaction.

Adult↗