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Biomedical subjects

A Scommegna

Publications and source records attributed to A Scommegna.

At least 37 records · Page 2Linked to original sources
PubMed1987

The effect of peritoneal macrophage incubates on the spermatozoa assay.

PFM have been implicated as a possible cause of infertility in endometriosis. Previous work from our laboratory has indicated that medium incubated with PFM caused a significant decrease in sperm penetration when added to the sperm penetration assay (SPA). To further delineate this finding, medium incubated with killed macrophages, heat-inactivated medium, and various concentrations of macrophage media were added to the SPA. Analysis of the data implied that there is a 1.536% decrease in penetration for every 1% increase in the concentration of PFM medium. Heat-inactivated medium and medium incubated with dead PFM both produced penetrations statistically different from the control. We conclude that medium incubated with PFM is capable of decreasing sperm penetration as measured in the SPA in a dose-dependent fashion. Furthermore, the substance responsible for this decrease appears to be heat-stable and released from dead as well as live macrophages.

Animals↗
PubMed1986

Peritoneal fluid in patients with and without endometriosis: prostanoids and macrophages and their effect on the spermatozoa penetration assay.

Peritoneal fluid from 35 women with endometriosis and from 34 control women was aspirated at laparoscopy and analyzed. No differences in prostanoid levels were found. The peritoneal fluid volume, macrophage concentration, macrophage content, and content of activated macrophages as measured by acid phosphatase staining were all significantly elevated in the endometriosis patients. The macrophages were incubated and the medium was added to the zona-free hamster egg sperm penetration assay. This medium caused a significant decrease in the percentage of ova penetrated in this assay. It is postulated that one of the mechanisms of infertility in women with endometriosis may involve the increased number of activated macrophages and their ability to interfere with sperm-egg interaction.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

The effect of dehydroepiandrosterone sulfate on de novo and low-density lipoprotein-stimulated progesterone secretion by human choriocarcinoma JEG-3 cells.

It has been suggested that fetal adrenal steroids affect the secretion of progesterone by the human trophoblast and decrease the progesterone/estrogen secretory ratio at the time of parturition. In the present study, cultured human choriocarcinoma JEG-3 cells were used as an experimental model in order to examine the effect of dehydroepiandrosterone sulfate on both de novo and low-density lipoprotein-stimulated progesterone secretion. In serum-free and cholesterol-free Dulbecco's modified Eagle's medium, JEG-3 cell cultures demonstrated a significant secretion of both pregnenolone and progesterone. A 200% to 300% increase in pregnenolone and progesterone secretion was achieved by physiologic low-density lipoprotein concentrations added to Dulbecco's modified Eagle's medium while androgens and estrogens remained undetectable. Dehydroepiandrosterone sulfate added to Dulbecco's modified Eagle's medium was actively converted into C-19 and C-18 steroids but had no significant effect (up to 20 micrograms/ml) on basal (de novo) progesterone secretion. In contrast, the addition of dehydroepiandrosterone sulfate (1 to 5 micrograms/ml) to cultures grown in Dulbecco's modified Eagle's medium plus low-density lipoprotein induced a dose-related inhibition of progesterone and a return of that secretion to basal levels.

Cell Line↗
PubMed1986

Competitive studies with dehydroepiandrosterone sulfate and 16 alpha-hydroxydehydroepiandrosterone sulfate in cultured human choriocarcinoma JEG-3 cells: effect on estrone, 17 beta-estradiol, and estriol secretion.

The estradiol (E2) to estriol (E3) ratio during human pregnancy depends on fetal liver hydroxylation of fetal adrenal dehydroepiandrosterone sulfate (DHEAS) and conversion by the trophoblast of DHEAS and 16 alpha-hydroxy-DHEAS (16 OH-DHEAS) to estrone (E1), estradiol (E2), and estriol (E3), respectively. It is not known whether the conversion of DHEAS into E1 and E2 influence the conversion of 16OH-DHEAS into E3 and vice versa. To examine this question, we studied these interactions in human choriocarcinoma JEG-3 cells. In serum-free medium (Dulbecco's Modified Eagle's Medium), JEG-3 cells secreted hCG [27 +/- 3 (+/- SEM) ng/mg cellular protein X 24 h] and progesterone (22 +/- 2.5), but neither C-19 nor C-18 steroids. The addition of DHEAS resulted in secretion of E1 and E2; at a concentration of 500 ng DHEAS/ml, the secretion of E1 (1 +/- 0.16) and E2 (11 +/- 3.1) was maximal, while E3 remained undetectable. The addition of 1000 ng 16 OH-DHEAS/ml resulted in maximum E3 secretion (13 +/- 1.8), while E1 and E2 remained undetectable. The addition of increasing concentrations of DHEAS to cultures exposed to 1000 ng 16OH-DHEAS/ml caused a decrease in E3 secretion and increased secretion of E1 and E2. Conversely, addition of increasing concentrations of 16OH-DHEAS in cultures exposed to 500 ng DHEAS/ml resulted in inhibition of E1 and E2 secretion and increased E3 secretion. A concentration of 16OH-DHEAS that inhibited the conversion of DHEAS into E1 and E2 neither altered the intracellular to extracellular steroid ratios (approximately 0.1) nor reduced the secretion of DHEA, androstenedione, and testosterone. The inhibitory effect of 16OH-DHEAS was minimal at low DHEAS concentrations (favoring the secretion of E1 and E2) and was greatly enhanced at concentrations of DHEAS that induced maximum E1 and E2 secretions. The results indicate that in trophoblastic cells, the metabolism of DHEAS can modulate E3 secretion, and the metabolism of 16OH-DHEAS can modulate the secretion of E1 and E2; and this regulatory mechanism appears to take place at the level of the aromatase system.

Cells, Cultured↗
PubMed1985

The effect of medroxyprogesterone acetate on premature labor in the sheep.

The ability of medroxyprogesterone acetate to delay premature delivery was investigated in nine chronically catheterized pregnant sheep (125 to 130 days' gestation). Catheters were placed for measurement of intrauterine pressure and uterine vein concentrations of progesterone, 17 beta-estradiol, and 15-keto-13,14-dihydroxyprostaglandin F2a. Premature parturition was induced in all animals by infusion of dexamethasone (1 mg/24 hours) to the fetus. Three ewes served as controls, three ewes received oral medroxyprogesterone acetate (5 mg/kg/day) 48 hours prior to the start of and during dexamethasone (early medroxyprogesterone acetate), and the remaining three animals received oral medroxyprogesterone acetate 12 hours after the onset of dexamethasone infusion (late medroxyprogesterone acetate). The lengths of time from dexamethasone until the onset of labor and from dexamethasone until delivery were compared, and were significantly longer for each group compared to control times. Of all endocrine events analyzed, the fall in plasma progesterone was the most consistent in all groups, showing that animals with rapid falls in progesterone levels (control group) tended to deliver earlier. These results demonstrate that medroxyprogesterone acetate can delay premature parturition in the sheep. Also medroxyprogesterone acetate appears to delay the endocrinologic events that normally occur at this time.

Animals↗
PubMed1983

Ontogenesis and characteristics of epidermal growth factor receptors in human placenta.

Epidermal growth factor promotes growth in many cell types. The role of epidermal growth factor during gestation and fetal development is unknown. This study investigates the presence and binding characteristics of epidermal growth factor receptors in placentas throughout gestation. Cell membrane preparations were obtained from first-, second-, and third-trimester placentas and hydatidiform moles. Specific epidermal growth factor receptors were observed as early as 6 weeks of gestation. Throughout gestation, Scatchard analysis of epidermal growth factor binding was curvilinear, and dissociation studies were consistent with site-to-site interaction with negative cooperativity. Affinity constants at high (Ke = 9.9 +/- 0.79 X 10(9) L/mol) and low (Kf = 3.0 +/- 0.25 X 10(9) L/mol) receptor occupancy were unchanged throughout normal gestation. However, the number of receptors per milligram of protein significantly increased with advancing normal gestation (correlation coefficient, r = 0.81). In hydatidiform moles, the number of receptors was reduced when compared to that of normal tissue of similar gestational age. Our study provides a quantitative basis for further evaluation of epidermal growth factor as a possible factor in embryogenesis and fetal development.

Cell Membrane↗
PubMed1983

Frequency of androgen insensitivity in infertile phenotypically normal men.

In 1979 Aiman and associates reported on a group of phenotypically normal men with severe oligospermia or azoospermia and androgen receptor deficiency. They calculated an androgen insensitivity index (ng./ml. serum testosterone times mIU/ml. serum luteinizing hormone) to identify these men and found the mean to be 233. We calculated the androgen insensitivity index in 144 infertile male patients in our fertility clinic. Of these patients 86 had azoospermia or severe oligospermia (mean sperm concentration 3 million per ml.). In this group 11.6 per cent had an androgen insensitivity index of more than 200, suggesting androgen insensitivity. These patients were compared to a control group with known fertility (16 semen donors) and to 34 men with idiopathic infertility (mean sperm concentration 47 million per ml.) treated with clomiphene citrate. The androgen insensitivity index may help to identify a group of 10 per cent or more of azoospermic or oligospermic men who are not amenable to therapy.

Clomiphene↗
PubMed1982

Integrity of central dopaminergic system in women with postpartum hyperprolactinemia.

In order to elucidate the role of elevated prolactin (PRL) on the central dopaminergic systems, the suppressive effects on PRL were studied after the administration of L-dopa and L-dopa plus carbidopa on consecutive days to the following three groups: 10 normoprolactinemic subjects, six nonnursing normal puerperal women, and seven hyperprolactinemic women without any evidence of pituitary tumor. In the normoprolactinemic subjects (basal PRL 13 +/- 2 ng/nl mean +/- SE), the suppressive effects of L-dopa alone and L-dopa plus carbidopa were similar (48% +/- 4% and 58% +/- 6%, respectively). In puerperal hyperprolactinemic subjects, the basal PRL (116.8 +/- 16.4 ng/ml) was suppressed 77% +/- 2% after administration of L-dopa and 51% +/- 7% after L-dopa plus carbidopa, significantly different from that of L-dopa alone (p less than 0.005), but similar to that observed in normal subjects. In the patients with idiopathic hyperprolactinemia, the baseline PRL (131 +/- 38 ng/ml) decreased 56.3% after the administration of L-dopa. In the presence of peripheral dopa decarboxylase inhibition, the administration of L-dopa decreased plasma PRL values 30%, a drop significantly different from that of L-dopa alone (p less than 0.02). Women with idiopathic hyperprolactinemia exhibit reduced central dopaminergic inhibition of PRL secretion similar to that in patients with pituitary tumor; whereas the response to central dopaminergic inhibition in postpartum women with comparable baseline PRL levels is similar to that in normoprolactinemic subjects. This indicates that hyperprolactinemia per se is not associated with a state of reduced central dopaminergic inhibition. The increased pituitary sensitivity to L-dopa observed in puerperal women may be due to alterations in PRL receptors or vascularity.

Carbidopa↗
PubMed1982

Endocrine and clinical effects of estradiol and testosterone pellets used in long-term replacement therapy.

Ten women with estrogen deficiency symptoms because of premature menopause [3], gonadal dysgenesis [3], or surgical menopause [4] received subcutaneous implants consisting of 25--75 mg estradiol (E2) with or without 75 mg testosterone (T). All had elevated plasma FSH, and LH, and low E2 prior to treatment. Plasma levels of FSH, LH, E2, T and estrone (E1) were measured by specific radioimmunoassay techniques prior to treatment, three times a week for the first week and once a week for up to 76 weeks after implantation. Mean plasma E2 levels rose abruptly and reached a maximum of 190 +/- 35 pg/ml within 2 weeks. They fluctuated around 150 pg/ml for 46 weeks, then gradually declined, but remained above pretreatment values for more than 68 weeks. Plasma E1 increased to a lesser extent resulting in E2:E1 ratio between 1 and 5. Elevated FSH and LH titers became suppressed within 4--6 weeks. The lowest average E2 increased occurred after 25 mg implant and was associated with incomplete FSH and LH suppression. There were no differences in maximal E2 levels reached after 50 mg or 75 mg implant, however, after 75 mg implant, E2 levels appeared less variable and were sustained for a longer period of time, averaging 125 pg/ml for 70 weeks. Plasma FSH and LH concentrations were suppressed below pretreatment levels in all patients. The degree of suppression was related to the dose of E2 implanted and, therefore, to plasma E2 levels. The FSH and LH suppression appeared more complete in women with gonadal dysgenesis than in those with premature or natural menopause. Plasma T rose abruptly to a peak mean level of 2.5 +/- 1.6 ng/ml within 2 weeks of implantation. A precipitous and steady decline with return to preimplantation titers between 17th and 18th week were then observed. The E2:E1 ratio during the first 18 weeks after implantation was significantly higher in women who received E2 implant alone than in those who received E2 + T implant. Clinically, all patients had symptomatic improvement within 24--48 hours. Regular withdrawal bleeding followed administration of oral progestogen for up to 76 weeks after implantation in six patients with intact uterus.

Adult↗
PubMed1982

The effect of albumin gradients and human serum on the longevity and fertilizing capacity of human spermatozoa in the hamster ova penetration assay.

The motility and the capability to penetrate zona-free hamster eggs of Y-enriched or washed sperm were evaluated after protracted in vitro incubation with and without the addition of preheated human serum. The addition of 50% preheated serum decreased the motility loss over time for both the washed and Y-enriched sperm. Such motility loss was decreased by 25% and 27% at 20 hours, by 31% and 39% at 30 hours, and by 30% and 40% at 40 hours of incubation for the washed and Y-enriched sperm, respectively. The washed and Y-enriched sperm suspensions with and without addition of preheated human serum achieved 100% penetration rate after 2 hours of preincubation. However, when scored by the sperm per egg ratio, washed sperm achieved 1.2 +/- 0.2 (mean +/- standard error [SE]) sperm per egg, while the Y-enriched sperm achieved 3.0 +/- 0.4 sperm per egg. After 24 hours of incubation, penetration by washed sperm decreased to a mean of 62.8%. The Y-enriched sperm penetrated a mean of 18% of the ova. Addition of preheated serum increased the egg penetrating capacity of washed sperm at 24 hours but failed to improve the Y-enriched spermatozoa. This study suggests that for optimum conception rates, precise ovulation timing is crucial when Y-enriched fractions are used for insemination.

Animals↗
PubMed1982

Variable effects of danazol on endometriosis at 4 low-dose levels.

Danazol was administered in a daily dose of 100, 200, 400, or 600 mg for 6 months in a double-blind fashion to 27 women with pelvic endometriosis. Symptoms and pelvic findings were observed and recorded monthly. Laparoscopy and laparoscopic biopsies were performed before and on the last day of treatment to evaluate the extent of endometriosis and the effect of the drug. The findings were documented with drawings and photography. The degree of clinical improvement varied with the daily dose used, from just over 50% on a regimen of 100 mg/day to 83% on a regimen of 600 mg/day. Laparoscopic improvement in the extent of endometriosis was noted in all patients but residual disease was common. The degree of laparoscopic improvement appeared to be related to the dose of danazol and to the effect of the drug on the menstrual cycle. The highest, 81%, laparoscopic improvement was observed in patients who developed amenorrhea during the study. After the completion of treatment, 6 patients required operation for residual endometriosis or for its early recurrence. The recurrence of endometriosis during 24 months of follow-up was observed in 29% of patients. Six of 15 infertile patients conceived spontaneously within 6 months after treatment in spite of mild (5) or moderate (1) residual disease. There was no difference in the extent of endometriosis between infertile patients who did or did not conceive. There was, however, a statistically significant difference in the adhesion score between these 2 groups. The authors conclude that danazol may be less effective in doses lower than the standard 800 mg/day. However, downward adjustment of the individual dose may be attempted on the basis of the development of amenorrhea and clinical improvement.

Adolescent↗
PubMed1981

Lack of relationship between prolactin and adrenal steroidogenesis in the ovine fetus.

The role of fetal prolactin (PRL) as a fetal adrenotropic hormone was investigated in eight chronically catheterized fetal lambs. Catheters were placed for measurement of plasma prolactin (PRL), cortisol (F), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione (A). Daily (9 AM) samples were obtained until the onset of labor. In four animals 2-Br-alpha-ergocryptine (BC) was administered subcutaneously (1 mg/12 hours) for 11 to 21 days prior to delivery. Four animals served as controls. No difference between groups was noted in the duration of gestation. PRL increased in the control animals from 8.4 +/- 2.4 to 43.0 +/- 5.6 ng/ml (mean +/- SEM) at the time of delivery whereas in animals that received BC it decreased within 24 hour of administration and remained below 3 ng/ml throughout the study period. No differences were noted in the concentration of F, DHEA, DHEA-S, and A between groups. These results suggest that PRL does not play a role in adrenal steroidogenesis or in the initiation of parturition.

Adrenal Cortex Hormones↗
PubMed1981

Mechanism of luteolysis: effect of estradiol and prostaglandin F2 alpha on corpus luteum luteinizing hormone/human chorionic gonadotropin receptors and cyclic nucleotides in the rhesus monkey.

Recent studies from our laboratory suggest that estrogen-induced luteolysis in the primate may be mediated through synthesis of prostaglandin F2 alpha (PGF2 alpha). To elucidate further the mechanism of luteolysis, normally cycling rhesus monkeys received intra-corpus luteum (CL) injections of estradiol (100 microgram), PGF2 alpha (500 microgram), or the appropriate vehicles on the seventh day after the preovulatory estradiol surge. Peripheral vein blood was drawn, at 30-minute intervals for 6 hours for progesterone and luteinizing hormone (LH) assays. Five hours after intra-CL injection, the CL was excised and the LH/human chorionic gonadotropin (hCG) receptor-binding activity and cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) were measured. PGF2 alpha significantly (p < 0.05) lowered progesterone within 1 hour, while the time required for estradiol to lower progesterone significantly was 3.5 hours; there was no significant change in LH, Estradiol and PGF2 alpha significantly (p < 0.05) decreased the LH receptor-binding capacity at 5 hours, without any change in the binding affinity. Also PGF2 alpha significantly (p < 0.05) increased cGMP in the CL, while cAMP remained unchanged; estradiol treatment resulted in a significant (p < 0.05) increase in cAMP with no change in cGMP. This study suggests that estradiol and PGF alpha cause a decrease in progesterone secretion by a loss of the LH/hCG receptor and the PGF2 alpha may act further through the cGMP system.

Adenosine Monophosphate↗
PubMed1981

Abnormal follicle-stimulating hormone and luteinizing hormone patterns contrasting with normal estradiol and progesterone secretion in women with longstanding unexplained infertility.

Six women with unexplained longstanding infertility and regular menstrual cycles were studied. All had luteal structures identified at laparoscopy on normal appearing ovaries and normal plasma androgen levels. Daily or every other day determinations of FSH, LH, estradiol (E2), and progesterone (P) were performed in one cycle. The results were compared to similar data obtained in five apparently normal women. All six infertile women had normal patterns of E2 secretion, with a characteristic midcycle rise, followed by a normal sustained elevation of plasma P. Contrasting with the above were grossly abnormal secretory patterns of FSH and LH in five of six patients. Two types of alterations were observed. 1) Four women had plasma LH persistently higher than FSH, with absolute LH concentrations above control levels in three. Midcycle LH surges were identifiable in all four, while a FSH surge was present in only one. The LH to FSH ratio was consistently above 2. 2) One patient had plasma FSH and LH levels fluctuating between high normal and the menopausal range. At midcycle, there was a synchronized rise of both FSH and LH though not as high as on other occasions in the same cycle. This was preceded by an E2 rise and followed by P elevation. The latter type (no. 2) of endocrine changes have been previously observed in much older women, during menopausal transition. The study indicates that normal E2 and P secretion, suggestive of normal ovarian function, may occur in the absence of characteristic FSH and LH patterns. The abnormal gonadotropin patterns may well be causally related to the patient's infertility.

Adult↗
PubMed1981

Human chorionic gonadotrophin (HCG) and free alpha subunit secreted by cultured human choriocarcinoma (JEG-3) cells.

The cultured human choriocarcinoma JEG-3 cells secrete biologically active HCG and free HCG alpha-subunit. When compared with the alpha-subunit dissociated from HCG obtained either from pregnancy urine or JEG-3 cells, free alpha-subunit has a larger molecular weight, is more acidic and is non-functional, lacking the property to recombine with the HCG beta-subunit. The understanding of the biochemical differences observed between free alpha-subunit and alpha-subunit found in HCG is important and should help to unravel the biosynthesis of gonadotrophins. Two proteins which bind to the cell membrane, epidermal growth factor and concanavalin A, are capable of stimulating JEG-3 cell secretion. Epidermal growth factor stimulates the secretion of HCG while concanavalin A stimulates both HCG and HCG alpha-subunit secretion. Amphotericin B, an antifungal agent commonly used in tissue cultures, which also affects the cell membrane, was shown to stimulate HCG and HCG alpha-subunit secretions. The use of these agents should contribute to the understanding of membrane-related events which lead to the secretion of HCG and alpha-subunit.

Amphotericin B↗
PubMed1981

Comparison of maternal and fetal effects of vacuum extraction with forceps or cesarean deliveries.

Results of 90 vacuum extraction (VE) deliveries were compared with effects on the mother and fetus of forceps delivery or cesarean section. Forceps delivery increased the incidence of birth canal trauma threefold and the incidence of anemia sevenfold (18% for VE versus 48% for forceps delivery, and 4 versus 30%, respectively) (P less than or equal to .001). When cesarean section was the alternative operation, the incidence of blood loss was significantly increased (72%, versus 18% with VE), as was febrile morbidity (48%, versus 6% with VE) (P less than or equal to .001). Hospitalization time and costs in the present and future for cesarean section deliveries are markedly higher than for VE. Maternal requirements for anesthesia are markedly reduced with VE because of the gentleness of the operation. A failed trial of VE in 7 patients did not constitute any greater hazard to the mother than initial management by cesarean section. However, babies born by cesarean section after failed VE had a slightly lower Apgar score at 1 minute (P less than or equal to .05) but not at 5 minutes, as compared with babies born by cesarean section attempted initially. Otherwise, Apgar scores of infants born by VE did not differ from those of infants delivered by forceps or cesarean section. Infants delivered by VE had a higher incidence of transient cosmetic deformations, including "chignon" and cephalhematoma, whereas infants delivered by forceps had forceps marks and facial lacerations more frequently. Neither perinatal mortality nor serious traumatic complications were attributable to VE, due to its judicious use for a limited time of approximately 15 minutes.

Anesthesia, Obstetrical↗