Biological research in pregnancy and perinatology最新文献

We studied 125I-insulin binding to monocytes and plasma levels of two trophoblastic proteins from 38 pregnant patients with varying degrees of carbohydrate intolerance, including 10 pregnant controls (PC), 17 Class A diabetics (A), 6 Class B diabetics - prior to insulin therapy (B-noRx) and 5 different Class B diabetics studied 1-6 weeks following initiation of insulin therapy (B-Rx). All studies were performed in the second half of pregnancy. In comparison to six age- and weight-matched nonpregnant controls (NPC), insulin binding to monocytes was somewhat higher in both PC and A. B.noRx patients had significantly lower tracer binding than did PC (0.71 +/- 0.3 vs 2.6 +/- 0.6%/10(7) cells, p less than 0.01). Insulin treatment of Class B patients restored insulin tracer binding levels to above normal. Levels of human placental lactogen (HPL) were significantly elevated in B-noRx patients compared to PC and A and were lowered to levels comparable to normal in insulin-treated B patients. A highly significant inverse relationship existed between HPL levels and the tracer binding of insulin for all patients studied (r = -0.52, p less than 0.005). Elevations of pregnancy-specific beta 1 glycoprotein were observed in patients with mild carbohydrate intolerance (A) as well as Bno-Rx, but were comparable to normal in those B-patients receiving insulin therapy. There were no significant differences of insulin binding or receptor number in the patient groups in the postpartum state. This further supports the hypothesis that placental factors may be responsible for the insulin binding defects seen in gestational diabetes.

The concentrations of catecholamines in cord venous plasma were measured by trihydroxyindole fluorimetric assay in four fetuses with normal fetal heart rate (FHR) and three distressed fetuses with late deceleration of pathologic FHR. The concentrations (nmol/l) of norepinephrine and epinephrine in normal fetuses were 40.3 +/- 7.9 (mean +/- SD) and 5.4 +/- 1.5, respectively, whereas those in distressed fetuses were 156.8 +/- 48.0 and 12.1 +/- 4.5, respectively. In normal fetuses about 88% of total catecholamines consisted of norepinephrine, the remaining 12%, epinephrine. The ratio of norepinephrine to epinephrine in distressed fetuses (12.9) was thus higher than the ratio in normal fetuses (7.5). Higher levels of total catecholamine concentrations were associated with the presence of late deceleration of pathologic FHR pattern, low one-minute Apgar score, low umbilical arterial pH value (pH less than 7.20), and fetal hypertriglyceridemia (greater than 48 mg/100 ml). The relationship between fetal hypertriglyceridemia and elevated concentration of cord plasma total catecholamines is elucidated and the physiologic significance of increased secretion of catecholamines in distressed fetuses is discussed.

As part of our series of fundamental studies on the application of piperacillin (PIPC) in the gynecologic field, we studied the transfer of PIPC to the uterine tissues. During our pharmacokinetic study of PIPC, a two-compartment model was used for blood levels: C1 = Ae-beta t + Be-alpha t. A three-compartment model was applied for the levels in the various uterine tissues and the retroperitoneum; C3 = A'e-beta t + B'e-alpha t + Ce-K31t. PIPC showed rapid transfer to the various uterine tissues and its disappearance rate developed parallel to decreases in blood concentrations. Although its transfer to the retroperitoneum was relatively rapid, since there was a clear delay in time required for the drug concentration to reach its peak (C max), the existence of a third compartment was conjectured. From the correlation between the MIC80 and the drug concentrations in the various uterine tissues and the retroperitoneum, it was found that effective doses were maintained in the uterine tissues for 3-5 h and in the retroperitoneum for 8-19 h. Thus, adequate clinical efficacy could be anticipated during administration of PIPC.

The maternal peripheral serum level of estradiol-17 beta (E2), which reaches a peak a few weeks before delivery, may play a role in initiating delivery. In this study, the steroidal activity regulated by both the production and conjugation was estimated by measuring estradiol-17-glucosiduronate (E2-17-G), E2, estriol-16-glucosiduronate (E3-16-G), and estriol (E3) before and at delivery. At delivery, levels of E2 and E2-17-G were higher in the maternal peripheral vein (MP) than in the umbilical vein (UV) and umbilical artery (UA), but those of E3 and E3-16-G were higher in UV and UA than in MP. These results suggested that the production and conjugation of E2 were mainly regulated on the maternal side, but those of E3 were regulated mainly in the feto-placental unit. The ratios of E2/E2-17-G in MP were or became high a few weeks before delivery but decreased remarkably as pregnancy progressed to delivery. The activity of E2 seems to be regulated at least in part by conjugation in late pregnancy and at delivery.

In view of still unsolved problems concerning disturbances in early pregnancy, the efficacy of various substances with regard to endocrine systems in the first trimester of pregnancy has been investigated. Seventy-five women, who had been referred to our hospital for an authorized termination of pregnancy during weeks 7-9 of gestation, and 6 women between weeks 10 and 16 of gestation volunteered to take part in the study. After single administration of the test substances, blood was drawn from an indwelling catheter with one group of patients at hourly intervals over an 8-hour period, while with all other patients this was done at 3-hourly intervals over a 24-hour period. In all samples beta-HCG, progesterone (P), estradiol-17 beta (E2), and 17 alpha-hydroxyprogesterone (17-OHP) were determined. The following substances were studied in detail: HCG, allylestrenol, 17-hydroxyprogesterone caproate, tamoxifene, R 5020, betamethasone, and dehydroepiandrosterone sulfate (DHAS). Two hundred and seventy-one women with imminent abortion were either treated with allylestrenol (n = 130) or simple clinotherapy and no medication (n = 141). One hundred and two women had a miscarriage, while 168 carried to term. The serum concentrations of beta-HCG, P, E2 and estriol (E3) were determined serially. Twelve women with a history of repeated miscarriages were treated with vaginal progesterone suppositories. Five of them experienced another miscarriage. The serum concentrations of beta-HCG and P were determined serially. It could be shown that diagnostics in early pregnancy have been complemented by assessment of the E2-increase after DHAS loading. Maternal serum concentrations were not affected by administration of HCG and various progestational agents including allylestrenol. Only in the case of parenteral or vaginal application of progesterone could increased serum concentrations of this hormone be demonstrated. Progesterone substitution in early pregnancy may, therefore, be chosen under special conditions as possible therapeutic procedure.

Alterations in cyclic AMP levels before and after trypsin treatment as compared with cyclic AMP levels of normal individuals are found in peripheral blood lymphocytes (PBL) of patients in which a defect in cell mediated immunity is suspected. Such conditions include pregnancy. It is concluded that low cyclic AMP levels in lymphocytes of pregnant women correlate with their clinical and immunological state and might partially explain the exception of pregnancy to the rule of allograft rejection.

The effect of human pregnancy plasma on phytohemagglutinin-(PHA-)induced blastogenesis of lymphocytes from unrelated donors was studied in relation to the sialic acid (N-acetyl-neuraminic acid) content of the plasma. The total sialic acid levels in plasma were found to be elevated during pregnancy as compared with plasma from non-pregnant, normally menstruating control groups (p less than 0.001) and to increase with advancing gestation, reaching peak values in the post-partum period (1-14 days). On the other hand, pregnancy plasma at a concentration of 15% caused a significant suppression of lymphocyte proliferation (p less than 0.05 to p less than 0.001, depending on the stage of gestation). The maximum effect was observed with plasma obtained during the third trimester of pregnancy. The immunosuppressive activity was not detectable after parturition. It was further observed that desialation of both pregnancy and control plasma with neuraminidase diminished lymphocyte response to PHA (p less than 0.05). Addition of free sialic acid (0.1-1.0 mumol/ml) or treatment of the cells with neuraminidase (0.06-1.0 IU/ml) had no effect on lymphocyte transformation under assay conditions. These findings support the hypothesis that an immunosuppressive environment provided by pregnancy plasma could be one of the mechanisms protecting the antigenically alien fetus from maternal immunologic attack. The sialic acid content of maternal plasma did not appear to play a role in the immunosuppressive property of maternal plasma. On the contrary, the presence of plasma-bound sialic acid in the culture medium was found to be necessary for normal lymphocyte reactivity.

In vivo, a single dose of 1000 mg danazol was given orally to pregnant volunteers (n = 8) prior to a therapeutic abortion (8th-12th week of gestation). Changes in serum progesterone and estradiol were evaluated both by analysis of percentage values related to initial concentrations or statistically by a Kruskal-Wallis test comparing absolute steroid concentrations. Following treatment (n = 8), a significant decrease in mean plasma progesterone of about 20% was observed within 2-4 hours; progesterone levels varied between 80-120% during 24 hours in controls (n = 10); individual serum estradiol decreased up to 30% of control values 2 hours after danazol application. Changes in estradiol in controls versus tests were not statistically significant (p less than 0.05) when absolute estradiol concentrations were compared. Only a slight (10-20%) decrease in mean serum DHAS was found between 2 to 6 hours following danazol treatment. This study demonstrates the inhibitory activity of danazol on the human maternal and fetal steroidogenesis in vivo. The possible sites of action of danazol are discussed.

Spontaneous activity and BaCl2 responsiveness of portal veins from non-pregnant and from 1-, 2-, and 3-week pregnant rats were compared. Isometric tension was recorded from vessels suspended in oxygenated, 37 degrees C Krebs solution. After 60-90 min equilibration, peak isometric tension, contraction frequency, and duration were measured. Then responses to cumulative additions of BaCl2 were determined. Initial isometric tension development of veins from pregnant rats was not significantly different from that of the non-pregnant rats. However, the frequency of contractions was reduced at all three stages of pregnancy and the duration of major contractions was increased. Barium caused dose-related increases in tension and reduced contraction frequencies of all vessels. Maximum increases in tension of veins from all pregnant rats were significantly less, however, than those of veins from non-pregnant rats, while barium-induced decreases in contraction frequencies were significantly greater only at 3-weeks gestation. Thus, pregnancy decreases the frequency of the spontaneous contractions of the rat portal vein throughout pregnancy, and inhibits the barium-induced increases in tension development. These changes in venous smooth muscle activity are similar to pregnancy-induced changes that have been reported to occur in arterial, uterine, and gastrointestinal smooth muscle, and may be dependent on a general smooth muscle inhibitory effect of elevated progesterone during pregnancy.

The metabolic effects of a widely used betamimetic agent (ritodrine) were studied in two groups of pregnant patients with abnormal glucose tolerance. No significance modification of various metabolic parameters was detected when the drug was orally administered in standard doses for at least 1 week. The possible reasons for this finding are discussed. Following the absence of any diabetogenic effect, a prolonged use of betamimetics to achieve tocolysis seems to be safe even in patients with metabolic disorders.