Tryptophan and its metabolite concentrations in human plasma and breast milk during the perinatal period.

Concentrations of tryptophan (free and protein bound) and its metabolites in plasma of maternal vein at delivery, umbilical vein, umbilical artery, neonatal vein and breast milk were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in umbilical vein and artery were significantly higher than those in maternal vein. The concentration of total tryptophan in plasma of neonatal vein showed marked decrease at 24 h after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in plasma of neonatal vein. The colostrum contained a high level of total tryptophan. There were high ratios of free to total tryptophan in colostrum, transitional and mature milk. In the blood, ratios of free to total of tryptophan and kynurenine were kept at constant level throughout the perinatal period.</p

Polyamine levels in gynecologic malignancies.

Polyamines are closely related to many aspects of cell growth. Since increased amounts of polyamines in the urine of human cancer patients were reported in 1971, polyamines have been studied from the standpoint of tumor markers. In this study, polyamines in erythrocytes, plasma and urine were determined in 42 controls and 105 patients with gynecologic malignant tumors. The changes in polyamine levels were investigated before and after treatment. With advances in the stage of uterine cervical cancer, the frequency of abnormal levels of polyamines (concentrations greater than two standard deviations above the mean control level) became greater, and reached nearly 80% in recurrent and ovarian cancer. In the early stage of cancer, the diagnostic value was low. Comparison with carcinoembryonic antigen (CEA) was also performed. The polyamines lack specificity for malignant diseases, but they can be used to some extent as a tumor marker in the gynecologic field.</p

Changes in plasma human atrial natriuretic peptide (hANP) level in normal pregnancy and pregnancy induced hypertension.

We determined plasma human atrial natriuretic peptide (hANP) levels in normal pregnancy and pregnancy induced hypertension (PIH). The plasma hANP levels slightly decreased in the first trimester of normal pregnancy and tended to recover as pregnancy advanced, although these changes were slight. However, the plasma hANP level in puerperium was higher than that in the third trimester of normal pregnancy. The plasma hANP level in mild PIH was not significantly higher than that in the third trimester of normal pregnancy. In contrast, the plasma hANP level in three cases of severe PIH was approximately 200% higher than those in the normal third trimester and mild PIH.</p

Alterations in Polyamine Levels in Amniotic Fluid, Plasma and Urine During Normal Pregnancy

Polyamines have a close relationship with rapid cell proliferation. We measured polyamine levels in amniotic fluid, maternal plasma and urine during normal pregnancy. Plasma putrescine, spermidine and spermine gradually increased in the third trimester and reached the highest concentration at the end of pregnancy. There was a significant correlation between the level of these polyamines and the level of plasma estradiol and progesterone. In urine, putrescine and spermine increased with the progress of gestation and reached the highest level during the 8th to 10th months of gestation. In amniotic fluid, putrescine and spermidine concentrations were significantly high in the first trimester and decreased in the other trimesters, whereas spermine showed no significant change. Polyamine concentrations in maternal plasma and urine appear to reflect not only fetal metabolic changes but also the metabolic changes of the pregnant women, and to be influenced by several hormones which increase during pregnancy. Polyamines in amniotic fluid mainly reflect activated fetal metabolism and may be useful as biochemical indicators of fetal growth.</p

Concentrations of polyamines in umbilical blood.

Red blood cell and plasma polyamines in umbilical and maternal blood at delivery were measured using high performance liquid chromatography. The concentration of each polyamine in red blood cells and plasma of umbilical blood was significantly higher than in maternal blood. Spermidine and spermine concentrations in fetal red blood cells decreased markedly with the progress of pregnancy. In addition, younger red blood cells contained more polyamines than older cells. Red blood cell polyamines are closely associated with the cell membrane. Plasma polyamine in umbilical blood reflect active fetal metabolism, whereas red blood cell polyamines mainly reflect alterations in erythropoiesis in bone marrow and may indicate the proliferation of the bone marrow.</p

Rat liver epidermal growth factor receptors in intrauterine growth retarded and heavy-for-date fetuses.

We recently reported that epidermal growth factor (EGF) levels in the first urine to be voided by intrauterine growth retardation (IUGR) and heavy-for-dates (HFD) infants were lower than control infants (8). In this study, we analyzed EGF receptors to reveal the mechanisms controlling EGF levels. EGF binding to fetal rat liver increased markedly from day 19-21 of gestation. Fetal rats were divided into IUGR, control and HFD groups. EGF binding to the liver in each group was as follows, IUGR; 380 +/- 57 fmol/mg protein, control; 258 +/- 47, and HFD; 545 +/- 112. The binding to IUGR and HFD rat liver was significantly greater than in the control group (p &#60; 0.05). These data suggest that IUGR rats compensate for a lack of EGF by increased receptor expression and that HFD rats consume more EGF and have decreased urinary EGF excretion. These data also suggest that EGF is closely related to fetal growth and may play some important roles in fetal growth.</p

Hormonal regulation of ornithine decarboxylase and polyamines in primary cultured rat hepatocytes--differences in hormonal response between adult and fetal hepatocytes.

Polyamines are polycationic substances which are widely distributed in living organisms and have a close relation to rapid growth phenomena. We examined ornithine decarboxylase (ODC), which is the rate limiting enzyme of polyamine biosynthesis, and polyamine induction in primary cultured rat hepatocytes by various hormones which increase during pregnancy, and revealed differences in hormonal responses between adult and fetal rat hepatocytes. Thirteen hormones, including estrone, estradiol, progesterone, testosterone, human chorionic gonadotropin (HCG), cortisol, dexamethasone, insulin, glucagon, epinephrine and epidermal growth factor (EGF), were tested. Among these hormones, only insulin, dexamethasone and EGF induced ODC activity and polyamine biosynthesis, especially that of putrescine, in both adult and fetal hepatocytes. The effects of EGF were the most significant. The combined effect of insulin and dexamethasone was additive, while that of insulin and EGF was synergistic. The rate of ODC induction was higher in adult hepatocytes than in fetal hepatocytes, however, the reaction was earlier in fetal hepatocytes. These observations suggest that ODC and polyamines in the fetal stage of development are regulated by a mechanism different from that in the adult liver.</p

Effects of Epidermal Growth Factor on Neonatal Growth of Rat Intestines

The effects of epidermal growth factor (EGF) on neonatal intestines were examined in the rat. In 5-day-old rats, sucrase, trehalase, alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) activities in the small intestines were significantly increased after subcutaneous injection of EGF for 3 days (1 microgram/rat/day). gamma-GTP activity was also accelerated after oral EGF administration (2 micrograms/rat/day). Small intestines of 12-day-old rats injected with EGF for 10 days (1 microgram/rat/day) were significantly heavier than those of controls. These results suggest that EGF influences neonatal growth improving enlargement and functional development of their intestines.</p

Changes in erythrocyte deformability in normal pregnancy and pregnancy-induced hypertension, as revealed by electron spin resonance.

To study changes in hemorheologic properties during pregnancy, erythrocyte deformability was measured by an electron spin resonance (ESR) method. The results obtained by this method showed that erythrocyte deformability in normal pregnancy decreased significantly in the first trimester compared with nonpregnant controls, and continued to decrease slightly as pregnancy progressed. On the other hand, erythrocyte deformability in severe pregnancy-induced hypertension (PIH) was significantly lower than that in the third trimester of normal pregnancy. Additionally, we found that the hematocrit level needed for erythrocytes to exhibit high deformability is lower during pregnancy. These results suggest that hemodilution in normal pregnancy, so-called hydremia, compensates for the decrease in erythrocyte deformability. Conversely, since erythrocytes become less deformable in a hemoconcentration condition in severe PIH, microcirculatory disturbance of various organs, including the uteroplacental unit, may occur. The lowered erythrocyte deformability may be one of the important pathologic features in PIH.</p

Localization and developmental change of indoleamine 2,3-dioxygenase activity in the human placenta.

Previously, we pointed out the importance of the kynurenine metabolism in fetuses and neonates. We examined localization and developmental change of indoleamine 2,3-dioxygenase activity in human placenta. The indoleamine 2,3-dioxygenase was found localized in syncytiotrophoblast in the placenta. The indoleamine 2,3-dioxygenase activity was not detected in placenta in the early stage of gestation. It was first detected at around 14 weeks of gestation, increased rapidly thereafter and was maintained at high levels till near term. The indoleamine 2,3-dioxygenase activity was significantly lower in placenta with retarded intrauterine development. These results suggest the importance of placental indoleamine 2,3-dioxygenase during fetal development.&#60;/P&#62;</p