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Biomedical subjects

G Falkay

Publications and source records attributed to G Falkay.

At least 37 records · Page 2Linked to original sources
PubMed1998

Morphologic, endocrine and thermographic measurements of testicles in comparison with semen characteristics in mature Holstein-Friesian breeding bulls.

Twenty Holstein-Friesian breeding bulls (62-79 months of age) were examined 3 times, at 30-day intervals. Scrotal thermograms for assessment of scrotal surface temperature (SST) and blood samples for plasma testosterone concentrations were taken just before and then 45 and 90 min, respectively, after treatment with GnRH (50 micrograms, Gonavet, i.m. per bull). Following GnRH treatment, there generally were significant increases in mean values of both top SST (range, -0.1 to 1.4 degrees C) and bottom SST (range, 0.3 to 1.8 degrees C). Scrotal circumference was highly repeatable but SST and video-measurements of scrotal dimensions were less repeatable, because apparently they were affected by ambient temperature. Plasma testosterone concentrations before GnRH treatment were more repeatable than those after GnRH treatment. Correlations between examinations of 0.67 to 0.81 and -0.14 to 0.47, respectively, but the converse was true for SST measurements. Semen was collected with an artificial vagina 3 times per week for 12 weeks starting 2 weeks before the first examination. The total number of spermatozoa per ejaculate was highly repeatable and the percentage of motile and live spermatozoa were relatively consistent. Separate regressions for each variable and for each examination were conducted for these 3 semen characteristics as dependent variables. For the number of spermatozoa per ejaculate and for the percentage of motile spermatozoa, significant independent variables were plasma testosterone concentrations and difference between top and bottom SST, respectively. The slopes of these equations were nearly all negative and the R2 was from 0.15 to 0.42. For prediction of the percentage of live spermatozoa, both SST gradient and plasma testosterone concentrations were significant independent variables. For these regressions, the slopes were negative and the regression coefficients were generally lower than for the other 2 dependent variables (range, 0.16 to 0.25). Treatment with GnRH and assessment of SST and plasma testosterone concentrations have some correlation with the semen production in the mature bull.

Animals↗
PubMed1998

Evidence of non-synaptic regulation of postpartum uterine contractility in the rat.

Myometrial tissue rings from postpartum rats (24 h after delivery) were studied in vitro by electric field stimulation, and the alpha1/beta2-adrenoceptor ratio was determined by a radioligand binding technique. Pregnancy-denervated uterine rings were stimulated by long-duration pulses (100 ms). The contractions were inhibited by beta2-agonists (terbutaline and fenoterol) and alpha-antagonists (phentolamine, urapidil and yohimbine) in a concentration-dependent manner. Their effects were not altered by the adrenergic neuron-blocking agent bretylium. The alpha-antagonists (except phentolamine) elicited the same maximal inhibition as the beta2-agonists. Receptor assays revealed that the alpha1/beta2 ratio was about 2 in the measured uteri. It was concluded that the inhibitory effects of alpha-antagonists and beta2-agonists are mediated via non-synaptic adrenoceptors of the denervated postpartum rat uterus. The same inhibitory activity could be explained by the greater amount of alpha-receptors. It is believed that this is the first functional proof of the existence of non-synaptic alpha1-adrenoceptors in smooth muscle.

Adrenergic beta-Agonists↗
PubMed1998

Do alpha 2-adrenoceptors and imidazoline binding sites coexist in the human term placenta? Evidence from direct binding studies.

Alpha2-Adrenergic receptors and non-adrenergic imidazoline binding sites (IBS) in human placental membranes were investigated by means of the radioligands [3H]-RX 821002 and [3H]-RX 781094 (idazoxan) respectively. Human term placentae (38-40 weeks) were obtained immediately after vaginal delivery. The specific binding of the alpha2-subtype-selective [3H]-RX 821002 confirms the presence of alpha2-adrenoceptors in the human placenta, while [3H]-idazoxan binds to non-adrenergic IBS. The sites were characterized by displacement analyses with various imidazoline and non-imidazoline drugs. The presence of an endogenous ligand for IBS has not yet been demonstrated. Clonidine displacing substance (CDS) was recently identified as agmatine; it recognizes both alpha2 and imidazoline receptors. This phenomenon was studied in crude placental membranes. The studies revealed that: (i) alpha2-adrenoceptors coexist with non-adrenergic IBS in human placental membranes; (ii) there is a strong probability that alpha2-adrenoceptors and IBS are pharmacologically distinct; and (iii) agmatine binds to placental alpha2 and imidazoline receptors with different affinities.

Binding, Competitive↗
PubMed1998

Correlation between alpha1/beta-adrenoceptor ratio and spontaneous uterine motor activity in the post-partum rat.

The spontaneous uterine motor activity of the post-partum rat was investigated in parallel with the in-vitro determination of the density of the alpha1 and beta-adrenergic receptors of the myometrium. The in-vivo experiments were performed by an improved method, using a Millar catheter fitted with a latex microballoon. The spontaneous contractility of the post-partum rat uterus was found to be highest 24 h after delivery, indicating that this time is the most suitable for pharmacological examinations of tocolytic agents. A very close correlation was found between the results of the in-vivo experiments and the alpha1/beta-adrenergic receptor ratio assessed by an in-vitro receptor assay, thus indicating that the state of the adrenergic receptor system fundamentally determines the contractility of the uterus. This conclusion is supported by the fact that the pharmacological sensitivity of the rat uterus to prazosin and fenoterol changed as a function of the post-partum time in accordance with the alpha1/beta-adrenoceptor ratio. These results and the relevant data available reveal a crucially important role of an alpha1-adrenoceptor-mediated process, implicating alpha1-blockers as theoretically potent agents for inhibition of premature uterine contractions.

Adrenergic alpha-Antagonists↗
PubMed1997

Are alpha-adrenergic antagonists potent tocolytics? In vivo experiments on postpartum rats.

The aim of this study was to investigate the effects of alpha-adrenergic antagonists on the motor activity of the postpartum uterus of the rat in vivo. Intrauterine pressure was assessed by means of a Millar catheter fitted with a latex microballoon. Some of the tested compounds (urapidil, yohimbine, phentolamine, benoxathian and prazosin) decreased the uterine activity to a significant extent (57.4-67.4%). However, none of the investigated alpha receptor blockers exerted the same effect as beta-adrenergic agonists. Our results suggest that alpha-adrenergic antagonists could possibly be used as an alternative to beta-adrenergic agonists in clinical tocolysis after an appropriate clinical evaluation.

Adrenergic alpha-Antagonists↗
PubMed1996

Determination of RU486 (mifepristone) in blood by radioreceptorassay; a pharmacokinetic study.

A human progesterone receptor assay has been developed for the measurement of the biologically active molecular fraction of RU486 (RU486 binding equivalent) for studying its pharmacokinetic properties. Thirty-nine healthy pregnant volunteers with amenorrhoea of 49 days or less receiving a single oral dose of 200 mg, 400 mg or 600 mg RU486 orally in a single dose were involved in this study. Blood samples were collected within 48 hours for the analysis. It was found that the pharmacokinetics of the RU486 binding equivalent followed an open two-compartment model. The dose was rapidly absorbed and peak serum concentrations were measured within 1-2 hours after ingestion of the drug. The distribution was also rapid, but the elimination was slow, the elimination half-life ranging between 83 and 90 hours. Significant differences were found between the peak plasma values for the 200 mg and 600 mg doses (p < 0.05) and between the AUCs for the 200 mg and 600 mg doses (p < 0.01) and the 400 mg and 600 mg doses (p < 0.05). It can be concluded that this newly developed radioreceptor assay satisfies the requirements of radioligand binding techniques and can be used to determine the serum levels of RU486 and its metabolites, which are able to bind to human myometrial progesterone receptors. The pharmacokinetics for the RU486 binding equivalent is similar to that for RU486, with the exception of very slow elimination, which may originate from the measurement of the biologically active metabolites together with the parent compound.

Biological Availability↗
PubMed1994

Expression of two alpha 2-adrenergic receptor subtypes in human placenta: evidence from direct binding studies.

Adrenergic receptors may play an important role for mediating a variety of metabolic and haemodynamic effects of catecholamines including placental blood flow. The alpha-adrenergic receptors of the human placenta were characterized in vitro by the use of [3H]rauwolscine and [3H]prazosin as radioligands. Saturation experiments would suggest that the alpha-adrenoceptors in the human placenta are alpha 2. Comparative binding studies were performed, using recently synthesized compounds (Beecham Pharmaceuticals, UK) selective for alpha 2A (BRL-44408) and alpha 2B (BRL-41992) subtypes. The results indicate that human placenta contains at least two pharmacologically distinct alpha 2-adrenoceptor subtypes with approximately 60 per cent alpha 2A and 40 per cent alpha 2B receptors. In contrast with the pattern of increasing beta-adrenoceptor density, the concentration of alpha 2-adrenoceptors in term placentae is significantly lower than in placentae from the first trimester.

Adult↗
PubMed1994

Correlation between beta- and alpha-adrenergic receptor concentrations in human placenta.

alpha 2- and beta-adrenergic receptors in human placental membranes have been investigated using the radioligands [3H]-RX 821002 and [3H]-dihydroalprenolol, respectively. The specific binding of the alpha 2-adrenoceptor antagonist RX 821002 confirms the presence of an alpha 2-adrenoceptor in the human placenta, which has been characterized previously with [3H]-rauwolscine. The major finding presented here is a correlation between the alpha 2- and beta-adrenergic receptor concentrations (r = 0.765) in the human placenta at term. It is suggested that the alpha 2/beta adrenoceptor balance may play an important role in regulation of the vascular bed of the placenta. Determination of the alpha 2/beta ratio may help towards an understanding of the contractility of the placental vascular muscles.

Dihydroalprenolol↗
PubMed1994

[Pharmacokinetics of RU 486 and its active metabolites in humans].

The pharmacokinetics of RU 486 and its active metabolites were studied in 31 women who received a single oral dose of 200 mg (n = 9), 400 mg (n = 10) or 600 mg (n = 12) of RU 486 for termination of an early unwanted pregnancy. The serum levels were measured within 48 hours after the intake by radioligand binding assay using human myometrial cytosolic progesterone receptor as binding protein. The assay is based on the competitive replacement of 3H-ORG-2058 by the active molecular fraction of RU 486 present in the serum. The results were expressed as RU 486 equivalent. It was found that pharmacokinetics of the RU 486 equivalent followed two-compartment open model. The pharmacokinetic parameters were calculated by MEDUSA computer programme. Rapid absorption and distribution was followed by relatively slow elimination. The elimination half-life ranged between 80-90 hours. No significant difference was found between the parameters of the absorption distribution and elimination processes of three different doses. Thus, the RU 486 equivalent followed first-order kinetic. Peak serum concentrations were reached within 1-2 hours after the ingestion of the drug. Significant differences were found between 200 and 600 mg doses in the peak plasma values (p < 0.05) and in the areas under the curve (p < 0.01). However, these differences were not directly proportional to the increase of the dose.

Female↗
PubMed1993

Changes in adrenergic receptors in the pregnant human uterine cervix following mifepristone or placebo treatment in the first trimester.

There is increasing evidence that the antiprogesterone mifepristone (RU-486) can dilate the cervix of pregnant women. The uterine and cervical smooth muscle contractile response to adrenergic agonists is regulated by the steroidal environment. This study was undertaken to assess the effects of treatment with RU-486 on the concentrations of alpha- and beta-adrenoceptors in cervical crude membranes from pregnant women using a radioligand binding assay. A special needle biopsy technique was used for human cervical specimens. The probable relative oestrogen dominance due to the antiprogesterone treatment selectively decreased the alpha-2 adrenoceptor in human cervix at an early stage of gestation. This finding was similar to that reported earlier in pregnant rabbits. The existence of a functionally distinct alpha-2 adrenergic receptor subtype will have important implications for our understanding of the contractile activity of the cervix.

Adolescent↗
PubMed1992

[Radioreceptor assay for determination of the anti-progestogen, RU-486 and its active metabolites in the blood].

RU-486 is an antiprogesterone 19-norsteroid with high binding affinity for the progesterone receptor. It can be used with success for termination of early human pregnancy. Since the metabolites of RU-486 are often biologically active, their concentrations in blood can also have clinical significance. We have developed a rapid sensitive radio receptor assay for determination of RU-486 and its active metabolites. Human myometrium progesterone receptor was used as binding protein. The assay is based on the competitive replacement of 3H-ORG-2058 by the active molecular fraction of RU-486 present in the serum. The analytical parameters of this assay are the followings: intraassay percent of coefficient of variation (CV%) is ranged between 7.6 and 10.4%. The interassay CV% was from 7.1 to 16.3. The sensitivity of the receptor assay was 8.7 pmol/tube and the acceptable range was between 10 and 120 pmol/tube. The recovery ranged between 95 and 122% (r = 0.983). These parameters are suitable for the requirement of radioligand binding techniques based on the immunoassays.

Adult↗
PubMed1990

[Therapeutic use of a gonadotropin releasing hormone analogue in breast cancer].

Superagonistic analogues of Gn-RH given chronically produce a paradoxic inhibition of pituitary gonadotropin secretion and consequently decrease the peripheric hormones estradiol and progesterone to a postmenopausal level. For curative purposes buserelin (SuprefactR, Hoechst) treatment has been performed by the authors in two cases of breast cancer. The patients--one with NED (no evidence of disease) and the other with pulmonary and osseal metastases--in addition to low hormonal levels developed amenorrhoea. A group of climacteric complaints were observed without any toxic side effects, however. The treatment of premenopausal women suffering from breast cancer with chronic administration of Gn-RH analogues may constitute a valuable alternative to surgical oophorectomy.

Breast Neoplasms↗
PubMed1990

Adrenergic receptors in human fetal liver membranes.

The adrenergic receptor binding capacities in human fetal and adult livers were measured to investigate the mechanism of the reduced alpha-1 adrenoreceptor response of the liver associated with a reciprocal increase in beta-adrenoreceptor activity in a number of conditions. Alpha-1 and beta-adrenoreceptor density were determined using 3H-prazosin and 3H-dihydroalprenolol, respectively, as radioligand. Heterogenous populations of beta-adrenoreceptors were found in fetal liver contrast to adult. Decreased alpha-1 and increased beta-receptor density were found which may relate to a decreased level in cellular differentiation. These findings may be important for the investigation of perinatal hypoglycaemia of newborns after treatment of premature labour with beta-mimetics. This is the first demonstration of differences in the ratio of alpha-1 and beta-adrenoceptors in human fetal liver.

Adult↗
PubMed1990

Effects of antiprogestogen (RU-486) treatment on myometrial and cervical alpha and beta-adrenoceptors in pregnant rabbits.

Oestrogen and progesterone influence myometrial and cervical responses at different levels of the mechanisms regulating uterine contractility. One of these mechanisms could involve alterations in the adrenoceptor concentrations. This study was undertaken to assess the effects of treatment with the antiprogestogen RU-486 on the concentrations of alpha- and beta-adrenoceptors in pregnant rabbit myometrial and cervical membranes by means of a radioligand binding technique. The probable relative oestrogen dominance due to the antiprogestogen treatment selectively decreased the alpha 2-adrenoceptor subtype in the cervix, where an alpha-adrenoceptor dominance was found on day 27 of pregnancy. The results indicate a heterologous regulation of alpha-adrenoceptors by sex steroids, i.e. suppression of the alpha 2-adrenoceptor concentration by antiprogestogen treatment.

Animals↗
PubMed1990

Physiological values of cysteine and metalloproteinase activities in chorionic villi.

Lysosomal cysteine proteinases (cathepsin H, B + L) and metalloproteinase (MMP7-ase) activities were measured from early gestational period (6-12 weeks) in frozen, non-cultivated chorionic villi. The mean activity of cathepsin H was 50.99 mU/mg protein, of cathepsin B + L, 71.16 mU/mg protein, and of MMP7-ase, 16.16 mU/mg protein. The MMP7-ase enzyme activities showed a correlation with gestational age. There was a significant correlation between the activities of cathepsin H and MMP7-ase.

Cathepsins↗
PubMed1989

Modulation of uterine GABAA receptors during gestation and by tetrahydroprogesterone.

Binding of a GABAA receptor agonist, [3H]muscimol, was studied in rat uterine membranes of non-pregnant rats and those at days 15 and 19 of pregnancy. Also, an interaction of the uterine GABAA receptors with tetrahydroprogesterone was examined. At day 15 of gestation [3H]muscimol binding was twice as high as in non-pregnant rats, but at day 19 it was reduced. These changes resulted from an increase of the receptor affinity and decrease of the receptor density, at days 15 and 19, respectively. Since tetrahydroprogesterone, in vitro, also increased [3H]muscimol binding, we propose that this steroid may participate in regulation of uterine function during pregnancy.

Animals↗
PubMed1989

Pregnancy-induced alterations of GABAA receptor sensitivity in maternal brain: an antecedent of post-partum 'blues'?

Pregnancy increases affinity of [3H]muscimol binding to GABAA receptors in the rat forebrain. Post-partum, the receptor affinity is further increased concomitantly with a reduction of the receptor density. These changes may result from an action of endogenous placental and adrenal steroids, tetrahydroprogesterone and tetrahydrodeoxycorticosterone, which in vitro behave as allosteric agonists of GABAA receptors. The alterations may contribute to the psychological phenomena associated with pregnancy and the puerperium.

Animals↗