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Biomedical subjects

F Naftolin

Publications and source records attributed to F Naftolin.

At least 217 records · Page 12Linked to original sources
PubMed1986

Effect of antihypertensive drugs on catechol-O-methyltransferase and monoamine oxidase activity in human term placental explants.

The effects of therapeutic concentrations of antihypertensive drugs on catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) activities in term placental explants were studied. The enzyme activities were measured in tissue fractions using radioenzymatic techniques. At 6 h the incubation COMT activity increased significantly following exposure to verapamil and hydralazine, while exposure to alpha methyldopa caused a significant suppression of the enzyme. At 24 h exposure to hydralazine significantly suppressed the COMT activity. By 6 h the MAO activity was significantly suppressed by verapamil. MgSO4 and propranolol had no effect on the activities of COMT and MAO at 6 and 24 h. These results suggest that COMT and MAO activities in the placenta can be modulated by antihypertensive drugs and, therefore, these drugs might affect local catechol metabolism.

Antihypertensive Agents↗
PubMed1986

Angiotensin II-like immunoreactivity in human ovarian follicular fluid.

Human ovarian follicular fluid (hFF) has angiogenic activity, although the causative factors are unknown. We recently found that hFF contains renin activity which converts renin substrate to angiotensin I (AI). Since the enzymatic cleavage product of AI, angiotensin II (AII), is a potent stimulator of new vessel formation, we have examined Sephadex G-25 column fractions of hFF and extracted hFF and plasma from individual patients for AII-like immunoreactivity (AII-IR). Eluent fractions from Sephadex G-25 column chromatography of hFF had significant AII-IR which eluted in the same fractions as synthetic AII. Individual, extracted FF samples contained approximately 10 times higher levels of AII-IR than extracts of plasma from the same patients. Serial dilutions of the Sephadex column fractions and extracted FF and plasma inhibited binding of 125I-AII to rabbit anti-AII serum in a manner parallel to the inhibition caused by synthetic AII, indicating that the detected immunoreactivity was not due to non-specific assay interference. In summary, the results indicate the presence of significant AII-like immunoreactivity in hFF. AII may now be considered as a potential mediator of the angiogenic activity present in hFF and may play an important paracrine and/or autocrine role in physiologic events in the ovary.

Angiotensin II↗
PubMed1986

Are catechol oestrogens obligatory mediators of oestrogen action in the central nervous system? I. Characterization of pharmacological probes with different receptor binding affinities and catechol oestrogen formation rates.

In an attempt to define pharmacological probes with which to test the role of catechol oestrogen formation in the central nervous system, five oestrogens (oestradiol-17 beta, oestradiol-17 alpha, 4-fluoro-oestradiol, 2-fluoro-oestradiol and moxestrol (11 beta-methoxy-17 alpha-ethynyloestradiol) were studied for binding to oestrogen receptors and conversion to catechol metabolites. Binding to cytosol oestrogen receptors was measured in the hypothalamus-preoptic area-amygdala (HPA), pituitary gland and uterus of ovariectomized rats. Conversion to catechol oestrogens was tested in microsomes from the HPA, pituitary gland and liver, using a catechol-O-methyltransferase-coupled radioenzymatic assay. Oestradiol-17 alpha was the only weak oestrogen receptor ligand. Binding affinities of the other compounds tested were much higher and comparable to those of oestradiol-17 beta. In contrast, oestradiol-17 alpha was rapidly converted to catechol metabolites, while moxestrol was a relatively poor substrate for catechol oestrogen formation. 4-Fluoro-oestradiol could be 2-hydroxylated but not 4-hydroxylated. 2-Fluoro-oestradiol exhibited impaired 2-hydroxylation but normal 4-hydroxylation.

Animals↗
PubMed1986

Are catechol oestrogens obligatory mediators of oestrogen action in the central nervous system? II. Potencies of natural and synthetic oestrogens for induction of gonadotrophin release and female sexual behaviour in the rat.

The role of catechol oestrogen formation in the mechanism by which circulating oestrogens facilitate gonadotrophin release and female sexual behaviour was explored in adult female rats. The effects of oestradiol-17 beta were compared with those of a group of oestrogens with either a reduced affinity for oestrogen receptors (oestradiol-17 alpha) or a reduced ability to act as substrates for catechol oestrogen formation (2-fluoro-oestradiol, 4-fluoro-oestradiol and moxestrol (11 beta-methoxy-17 alpha-ethynyloestradiol]. Rats were ovariectomized on the evening of dioestrus day 1 of the 4-day oestrous cycle and implanted s.c. 12 h later with infusion pumps containing either one of the test oestrogens or vehicle alone. Infusion rates for oestradiol-17 beta, moxestrol, 2-fluoro-oestradiol and 4-fluoro-oestradiol were adjusted to give concentrations of nuclear oestrogen receptors in the brain and pituitary gland within the range of those found in intact female rats during pro-oestrus. Oestradiol-17 alpha was infused at the same and at a tenfold higher rate than that of oestradiol-17 beta; neither of these treatments with oestradiol-17 alpha significantly increased brain or pituitary gland nuclear oestrogen receptor levels. On the day after the pump was implanted, samples of tail vein blood were withdrawn at 12.00, 14.00, 16.00 and 18.00 h for LH assay. All animals were then injected s.c. with 1 mg progesterone in propylene glycol, and tested for feminine sexual behaviour 5 h later. Oestradiol-17 beta, moxestrol, 2-fluoro-oestradiol and 4-fluoro-oestradiol all elicited pronounced LH surges and facilitated progesterone-triggered proceptive and lordosis behaviours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Semen evaluation following preparation for in vitro fertilization of human oocytes.

Semen preparation is an important step of in vitro fertilization (IVF) and can affect the success of this procedure. Prior to oocyte insemination, spermatozoa are washed to remove seminal plasma which is believed to contain decapacitation factors. This study was undertaken to evaluate the effect of preparation on semen quality and subsequent successful IVF. Oocytes were recovered from 12 hMG/hCG-stimulated women by laparoscopy, and 6 h later semen specimens were obtained from the male partners. After liquefaction, 1 ml of semen was centrifuged twice in Ham's F10 medium supplemented with 10% of homologous serum, and the final suspension was used to inseminate the preovulatory eggs. In the initial and washed-sperm suspensions, motility was evaluated by the MEP method, and the occurrence of acrosome reaction and sperm viability were evaluated by the triple-stain technique. Fertilization was documented by the formation of two pronuclei. Washing caused a significant decrease in the percentage of motile sperm from 68% to 59% but significantly increased mean sperm velocity from 26 to 29 micron/sec (p less than 0.01). The mean fertilization rate was 65%, and no correlation was found with any of the parameters of semen quality before or after washing. Semen preparation for IVF is associated with a decrease in the percentage of motile sperm that does not seem to affect the fertilizing ability of normal spermatozoa but may be of importance in patients with abnormal semen.

Cell Survival↗
PubMed1985

Intrinsic tyrosine hydroxylase (TH) immunoreactive axons synapse with TH immunopositive neurons in the rat arcuate nucleus.

Synaptic connections were demonstrated between tyrosine hydroxylase (TH) immunoreactive axons and dendrites in the arcuate nucleus of the rat, by electron microscopic immunocytochemistry. These connections were primarily found in the lateral part of the nucleus. The results of two types of medial-dorsal-lateral surgical de-afferentation suggest that the TH-TH contacts represent intrinsic connections.

Animals↗
PubMed1985

Estrogen responsive cells in the arcuate nucleus of the rat contain glutamic acid decarboxylase (GAD): an electron microscopic immunocytochemical study.

Twenty-one days after ovariectomy (OVX) an increased frequency of lamellar cytoplasmic organelles, termed 'whorl' bodies (WB), was observed in neurons of the rat arcuate nucleus (AN). When estradiol valerate (2 mg s.c.) was injected either at the time of OVX or one week later, the frequency of WB at 21 days was reduced. The estrogen treatment resulted in a concomitant rise in the frequency of 'nematosomes' (NS), filamentous electron-dense cytoplasmic structures. In the medial part of the AN glutamic acid decarboxylase (GAD) immunopositive symmetric (Gray II) synapses were observed in contact with WB- and NS-containing cells. After colchicine treatment, GAD immunoreactivity was observed in the WB- and NS-containing perikarya in the medial AN. Some of the NS-containing cells in the lateral AN of the colchicine-pretreated animals remained immunonegative for GAD.

Animals↗
PubMed1985

Gap junctions and myometrial steroid hormone receptors in pregnant and postpartum rats: a possible cellular basis for the progesterone withdrawal hypothesis.

Myometrial gap junctions, levels of cytosol and nuclear estradiol and progesterone receptors, and serum estradiol and progesterone levels were determined simultaneously in pregnant and postpartum rats. Between days 15 to 20 after conception, levels of progesterone nuclear receptors decreased (776.8 +/- 88.5 versus 241.1 +/- 56.5 fmol/mg of DNA, p less than 0.05). The mean serum progesterone also fell by about 50% during this period, but variation in individual levels between days 15 to 20 did not allow for this group to achieve statistical significance until day 21. As the progesterone nuclear receptors decreased, estradiol remained stable, but estradiol nuclear receptors increased (day 21 versus 22: 1710.6 +/- 61.1 versus 3254.8 +/- 203.8 fmol/mg of DNA, p less than 0.05), preceding the increase in gap junctions observed at parturition (day 21 versus 22: 2.0 +/- 0.2 versus 8.0 +/- 3.2 [per 1000 micron plasma membrane], p less than 0.05). Gap junctions fell to prepartum levels by 12 hours, when progesterone nuclear receptors were markedly increasing (6 versus 12 hours post partum: 637.7 +/- 324.8 versus 1509.6 +/- 283.2 fmol/mg of DNA, p less than 0.05). Relationships between gap junctions and cellular estradiol and progesterone nuclear receptors are clearer than could be forecast by circulating hormone measurements alone, and may offer a cellular basis for the role of progesterone in controlling labor.

Animals↗
PubMed1985

Neurons with whorl bodies have increased numbers of synapses.

The endoplasmic reticulum in some neurons of the rat hypothalamic arcuate nucleus forms concentric sheets of smooth cisternae which are known as whorl bodies. It has been reported that the number and size of these structures change under varying endocrine conditions. For example, the number of rat arcuate nucleus neurons containing whorl bodies increases after gonadectomy. In studying their relationship to other components of the cell, we found that neuron profiles which contain whorl bodies receive a significantly increased number of axosomatic presynaptic terminals (P less than 0.001). Whorl bodies may mark a subpopulation of endocrine sensitive cells which are characterized by a different pattern of connections and whose response to stimuli includes changes in endoplasmic reticulum organization.

Animals↗
PubMed1985

Ultrastructural analysis of malformations of the embryonic neural axis induced by in vitro hyperglycemic conditions.

Neural tube defects are the most common malformations associated with diabetic pregnancies. Although the teratogenic effects of excess glucose have been investigated in in vivo and in vivo studies, a cellular basis for neural tube defects has not been elucidated. We used rat embryo culture to study the organogenesis period of development, with excess d-glucose added to the serum medium to induce neural tube anomalies. Light and electron microscopic examination of control 12-day-old embryos grown 48 hours in culture revealed blastlike cells with few organelles or cellular processes. Twelve-day-old embryos cultured in excess d-glucose had advanced cellular maturation with differentiation, including the presence of free polysomes and copious cell processes, regardless of whether they had an open neural tube. Cytoarchitectural changes such as decreased numbers of mitotic figures with mitotic cells in the mantle layer were focally distributed throughout the neural epithelium but with predominance at the site of failed closure. In vivo studies failed to demonstrate neural processes in day 12 normal embryos. Fourteen-day-old embryos grown in utero also had foci of cell processes in the neural tube but to a much lesser degree than that observed in the in vitro day 12 glucose-exposed embryos. The cellular aberrations in the excess d-glucose-treated embryos are characteristic of a premature maturational change. Since they are present in excess d-glucose-exposed embryos with or without failure of neural tube closure, these maturational and cytoarchitectural changes may contribute to the cellular basis for neural tube defects.

Animals↗
PubMed1985

Application of avidin-ferritin and peroxidase as contrasting electron-dense markers for simultaneous electron microscopic immunocytochemical labelling of glutamic acid decarboxylase and tyrosine hydroxylase in the rat arcuate nucleus.

A pre-embedding immunostaining procedure was developed using ferritin and peroxidase to enable simultaneous electron microscopic localization of two antigens in the same tissue section. This method was used to study the anatomic relationship between glutamic acid decarboxylase (GAD) immunoreactive axons and tyrosine hydroxylase (TH) - containing neurons of the rat arcuate nucleus. The findings provide ultrastructural evidence that GAD-immunoreactive terminals establish symmetric (Gray II) synapses on TH-reactive neurons.

Animals↗
PubMed1985

The day of initiation of human menopausal gonadotropin stimulation affects follicular growth in in vitro fertilization cycles.

The attainment of synchronous follicular development in human menopausal gonadotropin/human chorionic gonadotropin-stimulated cycles for in vitro fertilization (IVF) continues to be a perplexing problem. Two regimens of follicle stimulation for IVF cycles were, therefore, compared. Twenty-nine patients commenced human menopausal gonadotropin (hMG) therapy on day 1 of the menstrual cycle (Group I), while 30 women received hMG from the third day of the cycle (Group II). The hMG therapy was tailored to the individual patients's response, based on ultrasonographic measurements of follicular size and serum estradiol (E2) levels. Both groups of patients received a mean of 19.6 +/- 1.4 ampules of hMG over a mean of 6.1 +/- 0.2 days. The pattern of serum E2 and progesterone levels in the periovulatory and luteal phase was not affected by the day of initiation of hMG therapy, although Group I patients demonstrated lower (P less than 0.05) E2 levels on the 2 days prior to human chorionic gonadotropin (hCG) administration. In terms of follicle growth, Group II follicles consistently demonstrated a significantly (P less than 0.01, chi 2 test) larger proportion of medium- and large-sized follicles compared to Group I follicles on almost all of the days when ultrasonographic measurements were taken. In addition, Group II follicles demonstrated an earlier shift (day-1) to the larger follicles than Group I follicles (day 0). Significantly (P less than 0.001) more oocytes were recovered per aspirated follicle in Group II patients, but the fertilization rate per oocyte was greater (P less than 0.003) for Group I oocytes. Nevertheless, pregnancy rates did not differ between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗
PubMed1985

LRFD6a has a dose-related stimulatory or inhibitory effect on the ovary in normal luteal phase women.

A dose response curve for LRFD6a-a potent LRF agonist-was established in normal midluteal phase women. At low doses (3-10 micrograms) an acute stimulatory effect on gonadotropins and ovarian steroidogenesis of estradiol and progesterone was observed. Despite large increases in circulating gonadotropins following the highest dose (30 micrograms LRFD6a), no acute changes in plasma steroids were noted. A sharp drop in progesterone was present after 3 days, with significant shortening of the cycle in 3 of 4 subjects in the group. While the stimulatory effect may be due to gonadotropin release and local action, the luteolytic effect observed is suggested to be a consequence of the direct inhibitory effect of the analog on ovarian function.

Adult↗
PubMed1985

Sex differences and maturational changes in arcuate nucleus neuronal plasma membrane organization.

Intramembrane particles (IMP) are believed to represent protein-containing structures in the membrane. Hypothalamic arcuate nucleus neuronal plasma membranes from male and female rats studied from birth to adulthood were quantitatively assessed for IMP number and size using freeze-fracture techniques. We found that newborn female rats have a significantly greater number of IMP than newborn males. There is also a progressive increase in the number of IMP during the first 20 days of postnatal life in both sexes. The rate of protein particle insertion favors females, maintaining the unequal protein particle content into adulthood with female rats having more IMP than males of the same age. The differences in IMP concentration are mainly due to greater numbers of small (less than 10 nm) particles in neuronal membranes from female rats. These data extend previous reports of sexual dimorphism in the arcuate nucleus to the level of plasma membrane organization.

Animals↗
PubMed1985

Estrogen replacement and tardive dyskinesia.

A double-blind randomized clinical trial was conducted among 10 post-menopausal women with tardive dyskinesia (TD) to test the effect of estrogen replacement of the severity of abnormal movements and other outcome variables. After 3 weeks of treatment, the mean Abnormal Involuntary Movement Scale (AIMS) score decreased by 38% in the estrogen group and by 9% in the placebo group; the difference between groups was marginally significant (p less than 0.10). However, the small sample size and the imbalance between groups in baseline AIMS scores do not allow us to rule out the confounding effects of other prognostic factors. There were no significant differences between treatment groups for parkinsonian and psychological symptoms at any visit or for changes in these variables between visits. The findings of this preliminary trial are consistent with the results of other human and animal investigations, and they support the need for future research to understand the role of estrogens in the neuropathology and treatment of TD.

Aged↗
PubMed1985

Estrogen formation in the developing rat brain: sex differences in aromatase activity during early post-natal life.

Aromatase activity in the brain of the rat was measured during perinatal development and in adulthood. In pooled hypothalamus, preoptic area, septum and amygdala (HPAS), estrogen formation per gram protein increased between embryonic days 15 and 19 and then declined. Results for males and females were indistinguishable, except for post-natal days 1 and 2 and 3 and 4 when estrogen formation was significantly higher in the male. Aromatization was not convincingly demonstrated in cerebral cortical tissue at any time studied. Regional dissection of the HPAS in 2-3 day post-natal animals revealed significant sex differences in aromatase activity in the corticomedial amygdala and the hypothalamus, but not in the preoptic-septal region or the remainder of the amygdala. These results are consistent with the idea that perinatal androgen secretion in the male rat may stimulate estrogen formation in the brain.

Age Factors↗
PubMed1985

A simple technique of ovarian suspension in preparation for in vitro fertilization.

Because laparoscopic ovum harvest for IVF is becoming more common, efforts must be made at the time of prior infertility surgery to render the ovaries accessible for ovum recovery. In this report, a simple technique of ovarian suspension in preparation for eventual IVF is described. Seventeen infertile patients undergoing lysis of adhesions underwent ovarian suspension by plication of the suspensory ligament of the ovary with a running suture of 3-0 Prolene, thus apposing the proximal pole of the ovary to the anterior-lateral surface of the uterus. Because the fallopian tube is independent of the sutured structures, the tubal anatomy was undisturbed. Fourteen of these 17 patients have since undergone laparoscopy during IVF. In 12 cases, despite the recurrence of adhesions, the ovaries were accessible for ovum recovery from all aspects. Two patients conceived normally after the lysis of adhesions. This simplified ovarian suspension represents an effective technique for facilitating ovum recovery for IVF which may not disturb fallopian tube ovum pickup or transport mechanisms.

Fallopian Tubes↗