Norethisterone concentration in breast milk and infant and maternal plasma during ethynodiol diacetate administration

Twelve women with established lactation of 4–8 weeks duration were given a low-dose progestogen-only contraceptive, ethynodiol diacetate 0.5 mg (Femulen) daily. On the seventh and eighth day of the study, prior to the mother's taking the pill, a blood sample was taken from her and from the infant. Further blood samples were collected from the mother 4 and 12 hours later. Breast milk samples were collected at every feed on day 7 and day 8.

Ethynodiol diacetate is rapidly metabolised in humans, changing into the metabolite norethisterone which is found in both blood and milk. Hence, norethisterone concentrations were estimated.

On day 7 and day 8, four hours after ingestion of the pill, the median norethisterone maternal plasma concentration was 1.60 ng/ml and it fell to a median level of 0.30 ng/ml prior to the next dose of the pill. At this time the median infant concentration was 0.10 ng/ml but the maximum observed level was 0.50 ng/ml.

In the breast milk the norethisterone concentration appears to peak at around 4–8 hours following the ingestion of the pill. The maximum observed concentration in breast milk was 0.84 ng/ml. The amount of norethisterone ingested by the infant averaged 0.02% (6.65 μg) of the dose of ethynodiol diacetate ingested by the mother. The maximum observed on any one day was 0.07% (27.52 μg).

The above results indicate that the amount of progestogen ingested by the infant from its mother's milk is small and is unlikely to pose a risk to the infant.     

Plasma levels of d-norgestrel after oral administration

Peripheral plasma levels of d-norgestrel were determined by radioimmunoassay in five women after oral administration of 30, 250 and 1000 μg d-norgestrel. Peak levels of d-norgestrel in plasma were mostly seen within 2 hours after intake of the pills. The peak concentrations found were 0.9–2.0 ng/ml, 3.3–5.1 ng/ml and 14.0–23 ng/ml, respectively, for the three doses administered. The plasma concentrations of d-norgestrel 24 hours after ingestion of the pills were 0.05–0.14 ng/ml, 0.3–0.7 ng/ml and 1.8–5.2 ng/ml, respectively.The plasma half-life of d-norgestrel for the period 8–24 hours following the tablet intake was around 13 hours but varied considerably among the participants. For the period 24–72 hours the corresponding half-life was around 21 hours.During 3 weeks treatment with combined oral contraceptives containing d-norgestrel and ethinyl estradiol, increasing d-norgestrel levels in plasma were found in most of the subjects. Patients on low dose gestagen pills (30 μg d-norgestrel) showed constant plasma levels of d-norgestrel throughout a treatment period of 3 weeks.The results obtained in this study suggest that the gradual increase of the d-norgestrel levels found in plasma when d-norgestrel is given in combination with ethinyl estradiol might be due to increased levels of sex hormone binding globulin, the carrier protein for d-norgestrel, rather than to accumulation caused by a long biological half-life.     

Bio-availability and pharmacokinetics of cyproterone acetate-14C and ethinyloestradiol-3H after oral administration as a coated tablet (SH B 209 AB)

Eight young women were each given 2 mg cyproterone acetate-methyle-ne-¹⁴C and 50 μg ethinyloestradiol-6,7-³H, ingredients of the contraceptive SH B 209 AB, orally in coated tablet form. The ¹⁴C and ³H activity in plasma, urine and faeces was determined up to 7 or 10 days post-administration.Cyproterone acetate was absorbed completely. The maximum plasma level was reached between 30 minutes and 3 hours after administration. At this time 2.2 ± 0.6 % of the dose was found in total plasma, which corresponds to 24 ± 6 ng cyproterone acetate equivalents/ml. At first the plasma level decreased with a half-life of 7.9 ± 1.3 hr (distribution and elimination) and later with a half-life of 2.5±0.6 d (elimination).Elimination via urine was 37 ± 5%. Up to the 10th day after administration 91±2 % of the dose had been found in urine and faeces.Ethinyloestradiol was absorbed very rapidly and almost completely. The maximum plasma level was reached only 60 ± 30 minutes after administration. At this time 10 ± 2% of the dose could be found in the plasma, which corresponds to 2.1 ± 0.5 ng ethinyloestradiol equivalents/ml. Due to processes of distribution and elimination, the plasma level dropped up to about 8 hr post-administration with a half-life of 5.1±1.5 hr, later with a half-life of 27 ± 8 hr, corresponding to the rate of elimination. Ethinyloestradiol was eliminated in urine and faeces in the ratio 4: 6. 91 ± 9 % of the dose could be recovered in this investigation.     

Depression of plasma testosterone levels in men with norethindrone

This preliminary study demonstrates the ability of norethindrone (NET) to depress plasma levels of testosterone (T) in men. A single oral dose of 25 mg of NET had no effect on the T levels despite peak plasma levels of NET of about 80 ng/ml. A daily dose of 25 mg of NET given orally for three weeks resulted in plasma levels of NET of 10–20 ng/ml when measured about 12 hours after the intake of the tablet. After four to five days of this treatment the plasma levels of T had decreased to 1–2 ng/ml, but were not further depressed below this level. After discontinuing the NET treatment, normal plasma levels of T were reached within four to five days. The daily treatment with 25 mg of NET for three weeks followed by 25 mg once a week decreased the total sperm count and increased the percentage of abnormal spermatozoa. The treatment had no effect on libido or potency.     

Hypovitaminosis D: Which oral supplement therapy?

Objectives

the possible therapeutic role of vitamin D in different kind of diseases explains the growing interest in this vitamin due to its pleiotropic effects. This short report shows preliminary results of prevalence of hypovitaminosis D in a group of patients and proposes a oral supplement therapy effective in correcting hypovitaminosis in a short time, without side effects.

Methods

243 patients (aged 26–93; 67 males) were enrolled at this study. We evaluated plasma levels of 25-hydroxyvitamin D [25(OH)D] with the following cut-off values: < 10ng/ml or <0–25 nmol/L (deficient), 10–30 ng/ml or 25–75nmol/L 30–50 (insufficient) and > 30 ng/ml or > 50 nmol/L (normal). The first 73 patients with hypovitaminosis D received at baseline 25,000 IU (Cholecalciferol) per os twice a month (Tp.A). The next patients (Tp.B) at baseline received a loading dose of 50,000 IU once a week for 8 weeks, followed by a maintenance dose of 25,000 IU twice a month.

Results

hypovitaminosis D is a widespread condition (i.e. 82.3%) not only in elderly (75.6% of 75 patients aged <65 yrs and 86.5% of 168 subjects aged >65 yrs). Preliminary results at 6 months show that Tp.B is more effective in correcting hypovitaminosis D (baseline 14.4 ± 5.3 ng/ml; 24 wk 43.3 ± 14.7 ng/ml; p<0.0001).

Conclusion

hypovitaminosis D is an important public health problem. We believe it is important to quickly achieve normal Vit. D plasma values in order to produce pleiotropic effects.     

Pharmacokinetics of cyproterone acetate and ethinylestradiol in 15 women who received a combination oral contraceptive during three treatment cycles

The pharmacokinetics of cyproterone acetate (CPA) and ethinylestradiol (EE₂) were determined in 15 healthy women (age 19 to 34 years), following single dose administration of a combination oral contraceptive, containing 2.0 mg CPA together with 0.035 mg EE₂ (Dia-ne-35^R). After a wash-out period of one week, the same preparation was administered during a treatment period of three months. After single dose administration, maximum concentrations of CPA in the serum were 15.2 ± 6.6 ng/ml. Post maximum drug levels declined biphasically with half-lives of 0.8 ± 0.4 h and 54.0 ± 26.0 h, respectively. The apparent clearance was calculated to be 3.6 ± 0.9 ml × min⁻¹ × kg⁻¹ and the volume of distribution (V_z) was 986 ± 437 1. The free fraction of CPA was 3.5 ± 1.9% and the fractions bound to heat labile proteins and albumin were 4.6 ± 2.2 % and 92.0 ± 3.5%, respectively. Trough levels of CPA in the serum increased during a treatment cycle, reaching a steady-state around day 16. An about two-fold accumulation of CPA was observed, which was less than expected theoretically. SHBG concentrations in the serum increased by a factor of three during a cycle, without having any effect on the protein binding of CPA. At the end of treatment cycle three, the terminal half-life of CPA had increased to a mean value of 78.6 ± 16.0 h and the volume of distribution to a value of 1304 ± 427 1. The apparent clearance showed a small, although significant decrease to a value of 3.0 ± 0.4 ml × min⁻¹ × kg⁻¹. The observed changes V_z and t_1/2 during the treatment period were attributed to the distribution of CPA into a deep compartment and the slow release of the drug from this compartment. The AUC(0–4h) values of EE₂ following single dose administration of the combination oral contraceptive were found to be 187.5 ± 79.7 pg × ml⁻¹ × h. On the last day of cycles one and three, the AUC(0–4h) values were 311.2 ± 109.3 and 304.8 ± 121.5 pg × ml⁻¹ × h, respectively, which corresponds to an about 60% increase as compared to single dose administration. Total and free testosterone concentrations decreased during treatment cycles one and three by about 39 % and 62%, respectively, compared with the corresponding values measured prior to treatment.     

The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy

In a group of 5 women on long-term anticonvulsant and oral contraceptive therapy, the plasma ethynylestradiol (EE) concentration on 50 μg EE daily was 11.1 ± 4.5 pg/ml. These values were at the lower end of the range found in normal women in this laboratory taking 30 μg EE daily (6–190 pg/ml). Four women have been studied prospectively for 3 months, over 1 cycle before and 2 cycles during phenobarbital 30 mg b.i.d. therapy. Significant falls in the plasma EE concentration were seen in two women (from 104.8 ± 13.4 to 37.7 ± 2.0 pg/ml and from 125.6 ± 23.8 to 34.8 ± 6.7 pg/ml p < 0.01) and breakthrough bleeding was seen in both women. No changes in plasma concentrations of follicle stimulating hormone, progesterone, norethindrone or norgestrel were seen. There was a significant increase in the sex hormone binding globulin capacity from 100.7 ± 5.8 to 133.3 ± 1.2 nmoles/1 (p < 0.05). These changes are consistent with the known microsomal enzyme inducing effect of phenobarbital.     

Treatment of postpartum rhesus monkeys with progestogen: Appearance in milk and effects on lactation

R-2323 (13-ethyl-17-ethinyl-17-hydroxy-gona-4,9,11-trien-3-one) was administered to four lactating rhesus monkeys (Macaca mulatta) by subdermal Silastic® capsules for 3 months beginning 48 hours after parturition. During this experiment the dosage of R-2323 obtained from the implants was approximately 150 μg/24 hr per animal. A control group of four monkeys were implanted with capsules containing magnesium silicate. Blood and milk samples were collected from the mothers of both groups at weekly intervals for 12 weeks. Blood samples were obtained from the infants of both groups at 4, 8, 12 and 16 weeks of age. Serum and milk levels of R-2323, measured by radioimmunoassay, were 0.88 ± 0.30 and 0.83 ± 0.45 ng/ml (mean ± S.E.), respectively, two days after insertion of the implants. The serum and milk levels then declined to 0.65 ± 0.19 and 0.28 ± 0.12 ng/ml, respectively, at the 13th week postpartum. R-2323 was barely detectable in the infants' serum. R-2323 treatment, in this dose and mode, had no effect on milk yield, proteins, fats and lactose or on the infants' growth. The drug did not raise serum glutamic pyruvic transaminase (GPT) and glutamic oxalacetic transaminase (GOT) concentrations of mothers, nor was there any effect on serum sodium and potassium concentrations of the mothers and infants.     

Plasma ochratoxin A levels, food consumption, and risk biomarkers of a representative sample of men and women from the Molise region in Italy

Background

Ochratoxin A (OTA) is a mycotoxin present in food that can be found in human blood, due to its long half-life. Plasma OTA detection represents a good parameter for evaluating the exposure at the population level.

Purpose

The relation between plasma OTA levels, dietary habits, and specific disease risk biomarkers (body mass index (BMI), C-reactive protein (CRP), and cardiovascular risk score) was investigated.

Methods

The study involved 327 subjects (150 men and 177 women) aged between 38 and 48?years. Food consumption was evaluated by means of the EPIC questionnaire; plasma OTA was measured by HPLC; CRP was determined in fresh serum samples by a latex particle-enhanced immunoturbidimetric assay.

Results

OTA was detected in 99.1% of plasma samples (LOD 25?ng/L); the mean?±?SD value was 0.229?±?0.238?ng/mL. However, only 5.2% of samples exceeded 500?ng/L, considered the threshold for a possible pathogenic activity. The estimated mean daily dietary intake of OTA resulted 0.452?±?0.468?ng/kg body weight (bw)/day, markedly lower than the tolerable daily intake set by EFSA (17.1?ng/kg bw/day). Processed and mutton/lamb meat were found to contribute most to plasma OTA variance. Nevertheless, cereals, wine, beer, and jam/honey consumption correlated positively with OTA levels. Plasma OTA showed a significant positive association with CRP and cardiovascular risk score (β?=?0.20?±?0.08; P?=?0.015 and β?=?0.25?±?0.08; P?=?0.001, respectively); however, the association was present in men but not in women.

Conclusions

Even if the hypothesis of a possible hepatic toxicity of OTA in humans is yet to be verified, the positive association between plasma OTA and CRP may indicate a possible role of OTA in inflammation status and consequently in the genesis of cardiovascular diseases and cancer.     

Therapeutic abortion of early human gestation with intramuscular 15-methyl prostaglandin F2 alpha.

Plasma levels of medroxyprogesterone acetate (MPA) were determined by radioimmunoassay in five women after oral administration of 10 mg of MPA and during treatment with intravaginal rings homogenously impregnated with 100 mg of MPA. Peak plasma levels of MPA of 1.15–5.15 ng/ml were reached within two hours after oral administration. The levels thereafter rapidly declined being 0.09–0.35 ng/ml at twelve hours. During IVR treatment rather stable plasma levels between 0.37 and 0.63 ng/ml were reached. Vaginal absorption of MPA was found to be very rapid with plasma levels between 0.29 and 0.47 ng/ml already three hours after insertion of the IVR. The plasma levels found are lower than previously reported probably due to methodological differences. The plasma levels of MPA are much lower than the d-norgestrel levels found after administration of smaller amounts of d-norgestrel. This is probably explained by differences in compartmentalization of the drugs. The elimination halflife of MPA was found to be about 30 hours which is longer than for d-norgestrel (20 hours).     

The enzyme inducing effect of rifampicin in the rhesus monkey and its lack of interaction with oral contraceptive steroids

Four female rhesus monkeys have been studied before and after two weeks of administration of rifampicin (150mg daily by mouth) to study the interaction between rifampicin and oral contraceptive steroids. Norethindrone (N) (1mg) and ethynylestradiol (EE) (100μg) were given intravenously on both occasions and plasma samples collected over 24 hours. The same doses of N and EE were also given on a separate occasion by mouth to the same monkeys. Blood samples were taken from 0–60 minutes from the hepatic portal vein and from a peripheral arm vein. Rifampicin caused microsomal enzyme induction as shown by a significant increase in antipyrine plasma clearance (from 11.5 ± 4.5 (mean ± S.E.) ml/min to 25.3 ± 0.7 ml/min p < 0.05) and in the urinary excretion of 6β-hydroxycortisol (from 24.4 ± 4.6 μg/day to 142.1 ± 28.4 μg/mlp < 0.05).However, rifampicin caused no significant change in the pharmacokinetics of N and EE given intravenously. There was a trend in favour of an increased clearance of intravenously administered norethindrone after rifampicin but this failed to achieve statistical significance because of the small numbers of monkeys studied. After oral administration of N and EE,the area under the plasma norethindrone versus time curve in the hepatic portal vein was significantly increased by rifampicin from 8.19 ± 2.5 ng/ml × h to 14.39 ± 2.3 ng/ml × h perhaps due to inhibition of the gut wall metabolism of N. Both N and EE appeared to undergo considerably more first pass removal through both the liver and the gastrointestinal wall of the rhesus monkey than in humans. We conclude that the rhesus monkey is not a suitable model for the study of the effect of rifampicin on oral contraceptive steroids.     

The effect of rifampicin oh the pharmacokinetics of ethynylestradiol in women

A single dose of Minovlar^R (50 μg ethynylestradiol (EE) and 1 mg norethindrone acetate) was given to seven women during treatment with rifampicin (450–600 mg/day) and again one month after stopping rifampicin. Blood samples were taken at intervals over a 24-hour period. The area under the plasma EE versus time curve increased significantly on stopping rifampicin from 1014 ± 317 pg/ml × h (mean ± SE) to 1747 ± 218 pg/ml × h (p < 0.01). The terminal plasma half-life increased from 2.9 ± 0.8 h to 6.3 ± 1.4 h (p < 0.005). The sex hormone binding globulin (S.H.B.G.) capacity was also reduced from 213.4 ± 11.5 nmoles to 129.0 ± 7.7 nmoles/1 after stopping rifampicin. In one patient starting rifampicin who was taking Minovlar as a long-term oral contraceptive, a fall in the plasma EE concentration was associated with a rise in the plasma follicle stimulating hormone concentration. These effects of rifampicin on EE pharmacokinetics are consistent with induction of the microsomal enzymes that metabolise EE.     

不同分娩方式产妇产后血清催乳素水平、自评泌乳量及初乳中生长因子浓度

目的:比较自然分娩与剖宫产产妇产后2～5天自评泌乳量、产后6～24h血清中催乳素(PRL)以及初乳中胰岛素样生长因子-1(IGF-1)、表皮生长因子(EGF)浓度的差异。方法:在医院产科对招募的志愿者收集产后6～24h的血清及产后2～5天的初乳。采用化学发光免疫分析法测定自然分娩组与剖宫产组PRL的含量,采用生物素-亲和素酶联免疫吸附试验测定两组初乳中IGF-1和EGF的浓度。结果:自然分娩组产后血清PRL浓度为(361.67±80.74)ng/ml,剖宫产组为(221.94±90.82)ng/ml,两组之间差异有统计学意义(P0.05)。产后2～3天,剖宫产组初乳中IGF-1浓度高于自然分娩组(P0.05),而自评泌乳量低于自然分娩组(P0.05)。产后4～5天,两组IGF-1浓度及自评泌乳量差异无统计学意义(P0.05)。产后2～5天,剖宫产组EGF浓度略高于自然分娩组,但两组差异无统计学意义(P0.05)。结论:剖宫产组产妇早期初乳中较高的IGF-1以及血清中较低的PRL水平与泌乳延迟和泌乳量相关,建议剖宫产后产妇仍应坚持早接触、早吸吮,提倡早期母乳喂养。     

Levonorgestrel in milk and plasma of breast-feeding women with a levonorgestrel-releasing IUD

A levonorgestrel-releasing intrauterine contraceptive device was used by 10 breast-feeding women beginning 6 weeks after delivery. Two models of IUD were used. One released 10 microgram (5 patients), the other 30 microgram (5 patients) of levonorgestrel per day. Plasma and milk samples were collected 8 times over a 3-month period and the concentrations of levonorgestrel determined by radioimmunoassay. An improved and sensitive method for the determination of levonorgestrel in milk was developed. A column chromatographic purification of a milk extract before radioimmunoassay made possible the use of large milk samples in order to improve the sensitivity. The plasma concentrations during the follow-up period were 207 +/- 64 pg/ml (mean + SD) in the 10 microgram and 235 +/- 87 pg/ml in the 30 microgram/day releasing IUD groups. The milk levonorgestrel concentrations were 56 +/- 35 and 57 +/- 34 pg/ml, respectively. The plasma to milk ratio of levonorgestrel was initially 100:15 and at the end of the 3-month follow-up period 100:25. There were no significant differences in the milk and plasma concentrations between the study groups. The total amount of levonorgestrel excreted per day in 600 ml breast milk is approximately 0.1 per cent of a daily dose of 30 microgram.     

13C]linoleic acid oxidation and transfer into milk in stunted lactating women with contrasting body mass indexes.

BACKGROUND: The fat concentration of human milk is associated with maternal adiposity, but there is no clear understanding of the mechanisms controlling milk fat concentration. OBJECTIVE: We evaluated the effect of postpartum body mass index (BMI; in kg/m(2)) on the metabolic distribution of an oral dose of [13C]linoleic acid in lactating women. DESIGN: Ten lactating women stratified by BMI (either <22.5 or >23.5) at 5 mo postpartum received orally 2.5 mg [13C]linoleic acid/kg body wt. Exhaled air, milk, and plasma samples were collected in relation to tracer administration. Linoleic acid was determined by gas chromatography. Dietary intake, serum, milk composition, [13C]linoleic acid enrichment in milk and plasma, and exhaled 13CO2 (by isotope ratio mass spectrometry) were assessed. RESULTS: Women with a higher BMI exhaled more 13CO2 than did women with a lower BMI (22.8 +/- 9.4% compared with 8.6 +/- 3.5% of dose, P < 0.03). Cumulated 72-h transfer of [13C]linoleic acid to milk was not significantly different between groups (14.8 +/- 6.5% compared with 17.7 +/- 6.7% of dose). Within the first 9 h after dose administration, 51.6 +/- 4.9% of the total isotope transfer into milk had passed in women with a higher BMI, but only 24.0 +/- 15.3% had passed in those with a lower BMI (P = 0.02). CONCLUSIONS: Women with a lower BMI, who were reputed as having less body fat, oxidized and secreted into milk less dietary linoleic acid within 12 h after tracer administration than did women with a higher BMI. In both groups, a large proportion of [13C]linoleic was retained in the maternal compartment, most likely fat tissue, in a slow turnover pool, and released slowly in later hours.     

Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure

Objective

Daily adult human exposure to bisphenol A (BPA) has been estimated at < 1 μg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration of BPA and compared findings in mice and monkeys with prior published data in women.

Methods

Eleven adult female rhesus macaques were fed 400 μg/kg deuterated BPA (dBPA) daily for 7 days. Levels of serum dBPA were analyzed by isotope-dilution liquid chromatography–mass spectrometry (0.2 ng/mL limit of quantitation) over 24 hr on day 1 and on day 7. The same dose of BPA was fed to adult female CD-1 mice; other female mice were administered ³H-BPA at doses ranging from 2 to 100,000 μg/kg.

Results

In monkeys, the maximum unconjugated serum dBPA concentration of 4 ng/mL was reached 1 hr after feeding and declined to low levels by 24 hr, with no significant bioaccumulation after seven daily doses. Mice and monkeys cleared unconjugated serum BPA at virtually identical rates. We observed a linear (proportional) relationship between administered dose and serum BPA in mice.

Conclusions

BPA pharmacokinetics in women, female monkeys, and mice is very similar. By comparison with approximately 2 ng/mL unconjugated serum BPA reported in multiple human studies, the average 24-hr unconjugated serum BPA concentration of 0.5 ng/mL in both monkeys and mice after a 400 μg/kg oral dose suggests that total daily human exposure is via multiple routes and is much higher than previously assumed.     

Chlorproguanil and chlorcycloguanil concentrations in human plasma and urine after Lapudrine administration

Chlorproguanil and chlorcycloguanil concentrations in human plasma and urine were measured using a high performance liquid chromatographic method. The detection limit in plasma and urine was 5 ng/ml for chlorproguanil and 10 ng/ml for chlorcycloguanil. The elimination half-life of chlorproguanil (Lapudrine) in 2 healthy volunteers, after a single oral dose of the drug, was 14.7 and 16.1 h. No chlorcycloguanil could be detected in plasma over 32 h after dosing.     

血管细胞粘附分子-1与妊娠期高血压疾病的相关性

目的:探讨血管细胞粘附分子-1(VCAM-1)在妊娠期高血压疾病中的病理生理作用及二者的相关性。方法:用酶联免疫吸附法(ELISA)对29例妊娠期高血压疾病患者(分妊娠期高血压组7例,子痫前期组22例),15例正常妊娠孕妇(正常孕妇组),分3个孕期即16～21周、25～28周、33～42周,14例非孕健康育龄妇女(正常对照组),所有对象均抽取清晨空腹肘静脉血测定血浆VCAM-1值。结果:子痫前期组VCAM-1值(1471.95±423.12)ng/ml与妊娠期高血压组VCAM-1值(880.49±256.63)ng/ml相比明显升高,有显著性差异(P(0.01),妊娠期高血压组的VCAM-1值与正常孕晚期组(936.31±217.53)ng/ml相比,无显著性差异(P>0.05),正常孕晚期组VCAM-1值与正常对照组(614.91±412.99)ng/ml比较,有显著性差异(P(0.02),正常孕妇组不同孕龄的VCAM-1值比较,无显著性差异(P>0.05)。结论:外周血中VCAM-1水平变化与妊娠期高血压疾病密切相关,随着病情加重VCAM-1值明显升高,VCAM-1对预测子痫前期的发生、发展及终止妊娠时机的选择有重要作用;VCAM-1值在正常妊娠中不随孕龄的增长而升高。     

Ethinyl estradiol in human milk and plasma after oral administration

In order to estimate the concentration of ethinyl estradiol in milk, four fully lactating women were given an oral contraceptive containing 50 μg ethinyl estradiol + 4 mg megestrol acetate, starting two months after delivery, and four women who wanted to stop nursing after a lactation period of 6–18 months were given one tablet of 500 μg ethinyl estradiol. Milk and blood samples were taken simultaneously after 3, 7, 11 and 23 hours. The concentration of ethinyl estradiol in plasma and milk were estimated by radioimmunoassay. The method for the assay of ethinyl estradiol in milk is evaluated in this paper.The concentration of ethinyl estradiol in milk from the women taking the oral contraceptive was below the detection limit of the assay. In the women taking 500 μg of ethinyl estradiol, the plasma:milk ratio of ethinyl estradiol was found to be about 100:25. The relative dose of ethinyl estradiol ingested by a fully nursed baby, when its mother takes an oral contraceptive containing 50 μg of ethinyl estradiol, has been calculated to be about 10 ng per day, which is 0.02 per cent of the dose given to the mother.