Biomedical subjects

George Falkay

Publications and source records attributed to George Falkay.

22 records · Page 2Linked to original sources

PubMed2002

Synthesis and receptor-binding examination of 16-hydroxymethyl-3,17-estradiol stereoisomers.

The four 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers were synthesized and tested in a radioligand-binding assay. The estrogen receptor recognizes these compounds, but their relative binding affinities are lower than 2.0% relative to that of the reference molecule estra-1,3,5(10)-triene-3,17beta-diol. The affinities of the tested compounds for the androgen and progesterone receptors are very low (K(i)> 100 microm and 1 microM, respectively). The prepared 16-hydroxymethylestra-1,3,5(10)-triene-3,17-diol isomers are therefore estrogen receptor-selective molecules.

Animals↗

PubMed2002

In vitro and in vivo study in rats of rectal suppositories containing furosemide.

The aim of our experimental work was to formulate furosemide-containing rectal suppositories, to study drug release with in vitro membrane diffusion examinations and to increase drug liberation with the use of non-ionic surfactants (Solutol HS 15, Cremophor RH 60, Montanox 60 DF), which were incorporated in the suppository base in various concentrations. Suppocire AS2X proved to be the best suppository base (diffused drug: 69.78%). The use of 1% Cremophor RH 60 additive with the Witepsol H 15 base increased the quantity of the diffused drug from 62 to 75%. The membrane diffusion examinations were followed by studying the influence of suppository bases and additives exerted on the actual diuretic effect in Sprague-Dawley male rats. Once again the Suppocire AS2X suppository base gave the best results compared to the control; the quantity of the animals' urine showed a fourfold increase. Used with the Witepsol H 15 base, even 1% of all the three additives resulted in a considerable increase of diuretic effect, so their use proved to be advantageous. The comparison of the membrane diffusion examinations with the in vivo diuretic effect reveals that in vitro drug release and the pharmacological effect usually showed the same tendency, that is a greater extent of in vitro furosemide release was associated with a greater quantity of rat urine.

Administration, Rectal↗

PubMed2002

Functional and histochemical characterization of a uterine adrenergic denervation process in pregnant rats.

The time course of pregnancy-induced changes in the contractile responses of isolated uterine rings and sympathetic innervation pattern were studied using electric field stimulation and histofluorescence techniques, respectively, in intact and 6-hydroxydopamine-treated rats. Neurally mediated contractions elicited by field stimulation (0.6 msec, 1-70 Hz, 40 V) were measured in uterine preparations obtained from nonpregnant, 6-hydroxydopamine-treated and 5-, 10-, 15-, 18-, and 22-day (term) pregnant rats. At all frequencies, the amplitudes of contractions were highest in nonpregnant uteri. Stimulation at 1-2.5 Hz evoked contractions in 10-day pregnant uteri but failed to cause contractions on Day 5 and from Day 15 onward. In uterine preparations obtained from term and from 6-hydroxydopamine-treated rats, contractions could not be evoked by stimulation at 1-20 Hz. Fluorescence histochemistry of uterine adrenergic nerves revealed rich perivascular and myometrial innervation in nonpregnant and in pregnant rats through Day 10. Degeneration and loss of adrenergic nerve fibers was apparent by Day 15, and fluorescent myometrial and perivascular nerves were practically absent by Day 22. These findings demonstrate a progressive, frequency-related reduction of nerve-mediated uterine contractions beginning in midterm pregnancy, in parallel with a gradual loss of adrenergic nerve fibers. Pregnancy-induced nerve degeneration may promote the development of nonsynaptic alpha-adrenergic uterine contractile activity towards term. The reduced responsiveness of uterine smooth muscle to electric field stimulation in early pregnancy appears to be unrelated to alterations in uterine innervation but may be related to changes associated with implantation.

Animals↗

PubMedDate not supplied

Effect of alpha-adrenoceptor subtype-selective inverse agonists on non-pregnant and late-pregnant cervical resistance in vitro in the rat.

1. The aim of the present study was to compare and elucidate the effects of alpha(1)-adrenoceptor (alpha(1)-AR) subtype-selective inverse agonists on non-pregnant and late-pregnant rat cervical tone. 2. Cervical resistance was investigated in in vitro stretching tests in the absence or presence of alpha(1)-AR subtype-selective inverse agonists (WB 4101, AH 11110A and BMY 7378; all at 10(-6) mol/L), whereas the mRNA levels and density of the alpha(1)-AR subtypes and the G-protein-activating effects of the inverse agonists were determined by reverse transcription-polymerase chain reaction, western blot and [(35)S]-GTPgammaS binding techniques, respectively. 3. The inverse agonists did not cause any change in resistance in non-pregnant and 18-day-pregnant samples. WB 4101 increased cervical resistance from Day 20, whereas AH 11110A had no effect and BMY 7378 exhibited such an action only on Day 21. Phenylephrine (10(-4) mol/L) had no effect on cervical resistance on Day 22. The mRNA levels and density of all alpha(1)-AR subtypes were increased on Day 18, but no further changes were observed after that. The [(35)S]-GTPgammaS binding studies revealed increased G-protein activation of alpha(1A)-AR and a moderate G-protein activation of alpha(1B)- and alpha(1D)-AR. The effect of WB 4101 to increase [(35)S]-GTPgammaS binding was blocked by pertussis toxin (50 ng/mL). Phenylephrine caused a slight and significant decrease in the amount of activated G-protein on Day 22. 4. The effects of inverse agonists on the alpha(1A)-AR can enhance cervical resistance in the late-pregnant rat in vitro. This action is mediated, at least in part, by a pertussis toxin-sensitive G(i)-protein. This effect of the alpha(1A)-AR inverse agonist WB 4101 may offer a new therapeutic target in the prevention of premature labour.

Adrenergic alpha-Agonists↗