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Biomedical subjects

F Z Stanczyk

Publications and source records attributed to F Z Stanczyk.

At least 127 records · Page 7Linked to original sources
PubMed1988

A randomized comparison of nonoral estradiol delivery in postmenopausal women.

We compared the transdermal and subdermal routes of estrogen administration with respect to the constancy of estrogen delivery and metabolic effects. Twenty postmenopausal women were randomized to receive either two 25 mg estradiol pellets subdermally (n = 10) or a 0.1 mg estradiol transdermal patch twice weekly (n = 10). Blood was sampled at 0, 2, 4, 6, 8, 12, 24, and 72 hours and 1, 2, 4, 8, 12, 16, 20, and 24 weeks (fasting samples at 0, 12, and 24 weeks), and a fasting urine was obtained after diuresis at 0, 12, and 24 weeks. In a 72-hour profile, serum estradiol levels (mean +/- SE) were highest at 24 hours (179 +/- 20 pg/ml) and fell to 139 +/- 16 pg/ml at 72 hours in the pellet group. In the patch group, estradiol levels rose rapidly to 152 +/- 33 pg/ml at 4 hours, remained relatively constant over 8 hours, and fell to 46 +/- 10 pg/ml at 72 hours. At 1 week, estradiol levels in the pellet group were 113 +/- 12 pg/ml and remained relatively constant for 24 weeks. In contrast, estradiol levels in the patch group were 52 +/- 11 pg/ml at 1 week and then varied widely until 24 weeks, when the levels were 89 +/- 26 pg/ml. The mean estradiol/estrone ratio ranged between 1 and 2.5 in both groups but fluctuated widely in the patch group. Follicle-stimulating hormone was suppressed in both groups; however, the decrement in the pellet group was greater (p less than 0.002). There was a significant increase in high-density lipoprotein cholesterol and a decrease in total cholesterol/high-density lipoprotein cholesterol at 12 weeks with the pellet but only at 24 weeks with the patch. The urinary calcium/creatinine ratio was reduced more consistently with the pellet than with the patch. Hot flushes were eliminated in all subjects.

Administration, Cutaneous↗
PubMed1987

Plasma concentrations of prostaglandin F2 alpha and prostaglandin E2 metabolites after transabdominal and transvaginal cervical cerclage.

Circulating prostaglandin metabolites 13,14-dihydro-15-keto-prostaglandin F2 alpha and the bicyclo derivative of prostaglandin E2 were measured in maternal plasma by radioimmunoassay after transabdominal cervicoisthmic cerclage and after transvaginal cerclage (Shirodkar and McDonald procedures) performed in the first and second trimesters. Statistically significant elevations in prostaglandin E2 metabolite or 13,14-dihydro-15-keto-prostaglandin F2 alpha occurred after transabdominal cervicoisthmic and transvaginal cerclage; they returned to control levels within 6 to 24 hours after surgery and were associated with good fetal outcome. Increases in 13,14-dihydro-15-keto-prostaglandin F2 alpha were proportionately greater than in prostaglandin E2 metabolite. Mean basal levels and the rise in prostaglandin metabolites were not related to cerclage type, trimester of pregnancy, or cervical status (dilatation less than or equal to 3 cm; effacement less than or equal to 60%). Highest basal and postcerclage 13,14-dihydro-15-keto-prostaglandin F2 alpha and prostaglandin E2 metabolite levels were associated with advanced cervical changes, uterine irritability, membrane prolapse or rupture, and premature delivery. Routine administration of prostaglandin synthetase inhibitors is not indicated for transvaginal cerclage or transabdominal cervicoisthmic cerclage; plasma prostaglandin metabolite levels may identify patients not suitable for cerclage.

Adult↗
PubMed1987

Temporal changes in uterine activity and prostaglandin response to RU486 in rhesus macaques in late gestation.

Progesterone withdrawal as a mechanism of parturition in primates is controversial because maternal, fetal, and amniotic fluid progesterone concentrations do not decrease before parturition. We therefore studied the effects of RU486 on uterine activity and amniotic fluid prostaglandins in four rhesus macaques implanted with amniotic fluid and maternal vascular catheters and with fetal electrocardiogram and uterine electromyogram electrodes at 119 to 124 days' gestation (term = 168 days). Uterine electromyogram, intra-amniotic pressure (hourly contraction area, mm Hg.sec/hr), and fetal electrocardiogram were monitored continuously. After a stabilization period (6 to 9 days) RU486 was administered orally (20 mg/kg/day) at 1000 hours for 3 days. Uterine activity increased from basal levels (less than 4000 mm Hg.sec/hr) 8 hours after the first dose of RU486, reaching levels of 12,000 mm Hg.sec/hr. A sustained increase in uterine activity (13,000 to 30,000 mm Hg.sec/hr) was observed for 48 hours before cesarean section with little or no cervical effacement or dilatation. Increases in amniotic fluid prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha, and 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 epsilon-cycloprostaglandin E2 occurred 40 hours after the onset of increased uterine activity. In contrast, amniotic fluid prostaglandins in the control animals delivering at term (n = 4) increased 24 to 48 hours before significant increases in uterine activity occurred. Control animals but not those given RU486 demonstrated a progressive nocturnal peak in uterine activity before delivery. Progesterone receptor blockade stimulates intense preterm uterine activity but not the orderly sequence of changes in prostaglandins and cervical status observed during normal parturition.

Amniotic Fluid↗
PubMed1986

Maternal estradiol response to alterations in uteroplacental blood flow.

Low levels of maternal estrogens are commonly regarded as indicators of fetal stress. We continuously monitored distal aortic blood flow by flowmeter, fetal heart rate, and amniotic fluid pressure in seven pregnant baboons near term. Four of the animals received a constant intravenous infusion of [7-3H]dehydroepiandrosterone and [4-14C]estradiol for 270 minutes. A 50% reduction in mean distal aortic blood flow was imposed after 60 minutes by means of partial occlusion of the aorta with a snare device and released at 180 minutes. Blood was collected at 10-minute intervals from 30 to 60 minutes, 120 to 180 minutes, and 240 to 270 minutes. Concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, estradiol, and cortisol in maternal plasma were determined by radioimmunoassay. Metabolic clearance rates of dehydroepiandrosterone and estradiol were calculated from plasma concentrations of [3H]dehydroepiandrosterone and [14C]estradiol. There was no significant change in maternal levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, or cortisol with alterations in distal aortic blood flow. Three animals exhibited no fetal heart rate evidence of fetal stress; estradiol levels declined during occlusion and returned toward control after release of the snare. Four animals exhibited repetitive late decelerations under conditions of reduced flow; estradiol was unchanged or rose slightly during occlusion but increased three- to 10-fold after release whereas the metabolic clearance rate of both dehydroepiandrosterone and estradiol remained stable. We conclude that placental hypoperfusion without fetal stress results in decreased conversion of aromatizable substrate and elevated maternal estradiol levels during acute hypoxemic fetal stress probably represent increased production of fetal androgen.

Animals↗
PubMed1986

Alterations in sex steroid-binding protein (SBP), corticosteroid-binding globulin (CBG), and steroid hormone concentrations during pregnancy in rhesus macaques.

Temporal relationships between concentrations of sex steroid-binding protein (SBP), corticosteroid-binding globulin (CBG), total and free estradiol, total and free testosterone, cortisol, and progesterone were studied in plasma obtained at 1- to 3-day intervals throughout gestation in six rhesus macaques. Concentrations of SBP and CBG were measured by diethylaminoethyl cellulose filter assays. Total and free steroids were estimated by radioimmunoassay and ultrafiltration dialysis, respectively. We found that SBP was elevated between days 30 and 50 and CBG between days 60 and 140; both then declined until term (167 days). Estradiol increased gradually throughout gestation. Testosterone was elevated between days 10 and 40, then declined, and rose slightly in late gestation until approximately 15 days before delivery, when it increased markedly. Free estradiol and testosterone increased dramatically before parturition. Progesterone was elevated between days 25 and 45 and declined to relatively constant levels thereafter. Cortisol was essentially unchanged throughout gestation. Our data show that in the pregnant rhesus, levels of SBP and CBG vary independently of one another, but both decline before term; concentrations of both total and free estradiol and testosterone increase markedly before parturition; in late gestation, elevated estrogen is not associated with increased levels of SBP or CBG (as it is in human females).

Animals↗
PubMed1985

Relationship of uteroplacental blood flow to placental clearance of maternal plasma C-19 steroids: evaluation of mathematical models.

The concept that the placental clearance of maternal plasma dehydroepiandrosterone sulfate through estradiol formation is a function of uteroplacental blood flow in women has been disputed. We obtained data on the clearance of maternal plasma dehydroepiandrosterone through placental estradiol formation in the baboon and used these data to evaluate some mathematical models of placental clearance. Our evaluation shows that the placental clearance of dehydroepiandrosterone is proportional to uteroplacental blood flow in the baboon.

Animals↗
PubMed1985

Effect of dexamethasone treatment on sex steroid-binding protein, corticosteroid-binding globulin, and steroid hormones in cycling rhesus macaques.

We tested the hypothesis that dexamethasone lowers sex steroid-binding protein levels and observed the effect of dexamethasone on corticosteroid-binding globulin and specific steroid hormones in plasma. Four cycling rhesus macaques were studied during three consecutive menstrual cycles (first and third cycles served as controls). In the second cycle, each animal received 0.5 mg of dexamethasone intramuscularly at 8:00 AM and 8:00 PM daily for 21 consecutive days. Blood samples were taken at 1- to 3-day intervals during each cycle. Concentrations of sex steroid-binding protein, corticosteroid-binding globulin, cortisol, testosterone, progesterone, and estradiol were measured in plasma. The percentage and plasma concentration of free testosterone were also determined. Within 2 days of treatment, dexamethasone suppressed cortisol to 5% of baseline values, which returned in the third cycle. All cycles were ovulatory. Dexamethasone significantly lowered plasma levels of all the compounds except progesterone: sex steroid-binding protein, -30%; corticosteroid-binding globulin, -14%; testosterone, -36%; and estradiol, -45%. The percentage of free testosterone was significantly elevated, but free testosterone concentrations were unchanged. Although our data conclusively show that dexamethasone suppresses plasma sex steroid-binding protein levels in the rhesus macaque, it remains to be established whether this suppressive effect leads to an increase in the metabolic clearance rate of testosterone.

Animals↗
PubMed1985

Direct effect of sex steroid-binding protein (SBP) of plasma on the metabolic clearance rate of testosterone in the rhesus macaque.

We report direct evidence for the effect of the sex steroid-binding protein (SBP) on the metabolic clearance rate of testosterone (MCRT). Pure rhesus SBP or human SBP was infused intravenously into three different cycling female rhesus monkeys. MCRT was measured before and after SBP had reached 150-300% of basal levels. A decrease in MCRT was observed in all cases. The effect of SBP on MCRT was tested further in four additional cycling females by infusing immunoaffinity-purified monospecific human SBP antibodies known to cross-react with rhesus SBP. SBP dropped to 54, 40, 4 and 2% of basal levels with a concomitant increase of 118, 190, 320 and 640% of basal MCRT. In one of these animals, pure rabbit SBP was administered after the anti-human SBP infusion resulting in a decrease in MCRT. The magnitude of the SBP effect on MCRT is related to the distribution of testosterone (T) bound to SBP and albumin in the plasma. Calculations show that as long as the percent of T bound to SBP is equal or higher than the percent of T bound to albumin, the influence on MCRT is small. However, if SBP is reduced to the extent that T is bound mostly to albumin, the redistribution of T is associated with a dramatic increase in MCRT. We conclude that under normal conditions each animal has an optimum concentration of plasma SBP which binds a maximum amount of T. If SBP increases above this level, little effect on MCRT will result. However, a drop below the optimum level, as is the case in certain physiological or clinical conditions, will produce a large increase in the clearance of T.

Animals↗
PubMed1985

Maternal and fetal production rates of progesterone in rhesus macaques: placental transfer and conversion to cortisol.

Maternal and fetal progesterone (P4) metabolism and placental transfer were examined in vivo. Via a femoral vein, 3.2 microCi[14C]P4 were infused at a constant rate for 2 h into five rhesus macaques on days 131-137 of gestation. Simultaneously, 12 microCi[3H]P4 were infused into the fetuses via a placental bridging vein. Measurement of steady state concentrations of [14C]- and [3H]P4 in the maternal and fetal circulations permitted calculation of the MCRs, production rates (PRs), and transfer rates (Vs) of P4. The maternal MCR (533 liters/day) was higher than the fetal MCR (93 liters/day), whereas the maternal PR did not differ significantly from the fetal PR (2.3 and 1.0 mg/day, respectively). Placental transfer of P4 from the fetal to maternal circulation (VFM) was greater than that from the maternal to fetal circulation (VMF). Values were 0.23 and 0.07 mg/day, respectively. The utilization of circulating P4 as a substrate for fetal cortisol (F) production was examined in three additional monkeys for whom the amount of isotopically labeled P4 infusate was increased 5-fold. By determining the ratio of specific activities of [3H]F and [3H]P4 in the fetal circulation, we found the maximum contribution of circulating fetal P4 as a precursor of fetal F to be less than 1%. Our results indicate that: 1) higher fetal than maternal plasma P4 concentrations (11.3 and 4.3 ng/ml, respectively) are most likely the result of 5-fold lower fetal MCR, since the PRs are similar in the fetal and maternal compartments, and the VFM is greater than the VMF; and 2) fetal F production using circulating P4 as a substrate is minimal.

Animals↗
PubMed1985

Relationship of uteroplacental blood flow to the placental clearance of maternal dehydroepiandrosterone through estradiol formation in the pregnant baboon.

The theory that maternal intervillous blood flow is a major determinant of the rate at which the placenta clears androgenic steroid precursors through estrogen formation has never been tested by direct experimentation. We studied the effects of graded reductions in maternal distal aortic blood flow (Qda) on the placental clearance (PC) of dehydroepiandrosterone (D) through estradiol (E2) formation in pregnant baboons near term. A continuous iv infusion of [7-3H]D and [4-14C]E2 was administered to four pregnant baboons (Papio anubis) at 155-165 days gestation (term, 184 days) for 270 min (t0-t270). Maternal Qda was continuously recorded by electromagnetic flow transducer at the aortic bifurcation and altered with an aortic snare device. A 50% reduction in Qda was imposed at t60 and released at t180. Blood samples were collected at 10-min intervals from t30-t60 (control interval), t120-t180 (occlusion interval), and t240-t270 (release interval). All four animals were later studied after pregnancy with an identical infusion for 90 min, with blood samples obtained at 10-min intervals from t30-t90. Equilibrium concentrations of [3H]D, [3H]E2, and [14C]E2 in plasma were determined and the MCR of D (MCR-D), the transfer constant of conversion of D to E2 (rho DE2), and the PC of D through E2 formation (PCDE2) were calculated for each of the three levels of Qda corresponding to the control, occlusion, and release intervals in pregnant animals and under conditions of existing Qda in the nonpregnant state. Control MCR-D during pregnancy (mean +/- SE, 740 +/- 74 liters/day) exceeded MCR-D after pregnancy (500 +/- 40 liters/day). MCR-D fell significantly during occlusion (P less than 0.05). Both rho DE2 and PCDE2 decreased uniformly when Qda was reduced by 50% and returned toward the control level with release of the aortic constriction. The mean rho DE2 in pregnant animals was 0.068 +/- 0.0073 (+/- SE), 0.039 +/- 0.0020, and 0.059 +/- 0.0063 during control, occlusion, and release intervals, respectively, all exceeding rho DE2 in the nonpregnant state (0.013 +/- 0.0004). Control mean PCDE2 was 46.3 +/- 8.24 (+/- SE) ml/min; it decreased to 18.9 +/- 2.68 with 50% reduction in Qda and was 35.6 +/- 5.43 when Qda was restored to 75% of the control value. PCDE2 was directly proportional to Qda (r2 = 0.98; P less than 0.01; n = 12) and remained a constant fraction (0.13 +/- 0.002) thereof in all four animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Daily hormonal changes in the maternal, fetal, and amniotic fluid compartments before parturition in a primate species.

The daily hormonal fluctuations that occur simultaneously in the fetus, mother, and amniotic fluid during late gestation and before preterm parturition were studied in long term catheterized rhesus macaques. Blood and amniotic fluid samples were collected twice daily and analyzed by RIA for estrone, estradiol, dehydroepiandrosterone sulfate (DHEAS), progesterone, cortisol, and prostaglandin F2 alpha metabolite (PGFM). Vaginal delivery in monkeys with live fetuses was preceded by rising concentrations of DHEAS in fetal, but not maternal, blood. Parallel increases in fetal plasma estrone, maternal plasma estrone and estradiol, and amniotic fluid estrone preceded the rise in amniotic fluid PGFM (P less than 0.005, by analysis of variance). Cortisol levels remained stable in maternal blood and amniotic fluid, but increased before delivery in fetal blood. Nocturnal progesterone peaks in both fetal and maternal blood increased progressively in magnitude in fetuses before parturition. Rising concentrations of fetal DHEAS, estrone, and progesterone indicated an increase in adrenal activity before parturition in the rhesus fetus. PG production, reflected in amniotic fluid PGFM concentrations, was temporally related to increasing amniotic fluid concentrations of estrone. Although progesterone withdrawal may occur at a local tissue level, parturition occurred without an apparent decrease in circulating maternal, circulating fetal, or amniotic fluid progesterone concentrations.

Amniotic Fluid↗
PubMed1984

Quantitation of delta 4-reduced metabolite of norethindrone in human plasma by HPLC-RIA.

An HPLC-RIA method for the measurement of the delta 4-reduced metabolite of norethindrone is described. The sensitivity of the method was such as to permit the quantitation of pg amounts (30 pg with an inter-assay CV of less than 7%). Nineteen volunteers received a single oral dose of 1 mg of norethindrone and, blood samples withdrawn at timed intervals, were pooled for each time period and assayed. The plasma concentrations of the dihydro metabolite ranged from 460 pg/ml at 30 min to 20 pg/ml at 24h.

Biotransformation↗
PubMed1983

Plasma levels and pharmacokinetics of norethindrone and ethinylestradiol administered in solution and as tablets to women.

Twenty-four normal adult female volunteers were dosed orally with a solution and tablet formulation containing the contraceptive combination of norethindrone (NET, 1.0 mg) and ethinylestradiol (EE2, 0.12 mg) in a crossover bioequivalence study. Blood was sampled sequentially following single oral doses and the plasma separated for analysis of NET and EE2 by specific radioimmunoassays. Comparisons of both drugs following a dose in solution and tablets were made with respect to the following parameters: (a) plasma concentrations at each sample time; (b) maximum plasma concentration (Cpmax); (c) time to maximum plasma concentration (Tmax); (d) total area under the plasma concentration vs. time curve (AUC), and (e) plasma half-life (t1/2). It was found that the tablet and solution doses were bioequivalent with respect to EE2 absorption. However, absorption of NET from solution and tablet doses exhibited significant differences with respect to plasma levels at certain time points as well as AUC (which were higher following the tablet dose), but Cpmax, Tmax and t1/2 were not significantly different. Pharmacokinetic analysis of both drugs following the tablet dose was carried out using a two-compartment open model. The absorption rate constant (ka) and peripheral to central compartment transfer rate constant (k21) were similar for NET and EE2, but statistically significant differences were observed with respect to the distribution rate constant (alpha), the central to peripheral transfer rate constant (k12), the overall elimination rate constant (ke1), and volume of distribution (V1/F). The elimination rate constant (beta) for both drugs showed a difference of borderline statistical significance.

Adolescent↗
PubMed1983

Current status of the molecular structure and function of the plasma sex steroid-binding protein (SBP).

Purification and characterization of the sex steroid-binding protein (SBP) from human, macaque, baboon, and rabbit sera indicate that the protein is composed of two polypeptide chains which associate noncovalently to yield a native structure having molecular weight distributions of about 88,000 for primate SBPs, and 80,000 for rabbit SBP. The subunit molecular weight distributions are 44,000 for human SBP, 47,000 for macaque and baboon SBP's, and 40,000 for rabbit SBP. Isoelectric focusing show extensive microheterogeneity for all four SBPs. The patterns appear to be unique for each species and reveal the presence of at least twelve bands of different colour intensity reflecting a specific spectrum of active SBP molecules. The existence of the large number of dimeric forms of SBP arises through the combination of many variants of the same two subunits containing different amounts and types of carbohydrate sidechains. Physiological studies on the intravenous infusion of pure rhesus SBP, human SBP, and purified monospecific SBP-antibodies into the rhesus reveal an inverse relationship between SBP and the metabolic clearance rate of testosterone. The effect is complex and depends on the concentration of SBP, albumin, and testosterone which in turn influences the distribution of testosterone between albumin and SBP.

Animals↗
PubMed1983

Male pseudohermaphroditism due to 17,20-desmolase deficiency.

In a 5-yr-old 46,XY male pseudohermaphrodite with microphallus, perineal hypospadias, chordee and cryptorchidism, serum C19 steroid levels were abnormally low in the basal state and after adrenal and testicular stimulation. Serum C21 steroid levels were elevated in the basal state and increased further after adrenal, but not after gonadal, stimulation. Urinary excretion of pregnanetriolone, a metabolite of 17-hydroxypregnenolone and 17-hydroxyprogesterone not normally present in the urine, was increased in the basal and stimulated states. Cortisol production was normal, and all steroid hormone levels were suppressed by dexamethasone. Testicular biopsy was consistent with prepubertal cryptorchid testes. Incubation of testicular tissue with labeled 17-hydroxyprogesterone revealed failure of conversion of precursor to androstenedione and testosterone. A significant increase in phallic length occurred after treatment with exogenous androgen. These findings are consistent with 17,20-desmolase deficiency in both gonads and adrenal glands.

Adolescent↗
PubMed1981

Urinary estradiol-17-beta-glucuronide assay for gonadotropin therapy.

To investigate the possibility of using urinary estradiol-17 beta-glucuronide (E2-17G) measured by direct radioimmunoassay to monitor ovulation induction with human menopausal gonadotropin (hMG), serum estrogen and urinary E2-17G levels were determined daily by 21 women treated with hMG for a total of 32 treatment cycles. Urinary E2-17G was measured in 24-hour and overnight specimens. A significant correlation was found between serum estrogens (primarily estradiol) measured by radioimmunoassay without preceding chromatography and urinary E2-17G excretion measured at 24 hours and overnight. The correlation was not significantly improved by correcting the 24-hour and overnight urinary E2-17G excretion levels with creatinine measurements. Although there was significant correlation between serum estrogens and urinary E2-17G measured by direct radioimmunoassay, the urinary E2-17G concentrations observed when serum estrogens levels indicated preovulatory follicle maturation (ie, at serum estrogens levels between 500 and 1000 pg/ml) varied so much that a clinical decision to trigger or not to trigger ovulation with human chorionic gonadotropin could not be reached in each case. These data indicate that significant correlation is not the only prerequisite for a new method to replace a proved procedure. Further studies are required to determine the reliability of monitoring hMG therapy with direct E2-17G radioimmunoassays in overnight urine collections.

Adult↗