Impaired spreading of surfactant phospholipids in the lungs of newborn rats with pulmonary hypoplasia as a model of congenital diaphragmatic hernia induced by nitrofen.
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In order to clarify the pathological outcome of congenital diaphragmatic hernia (CDH), we devised an animal model of CDH by administration of 2,4-dichlorophenyl-p-nitrophenyl ether (nitrofen) to pregnant rats, and determined the level and distribution of lung surfactant using the monoclonal antibody toward sphingomyelin and disaturated phosphatidylcholine (disat-PC). In control rats, the concentration of disat-PC was found to increase greatly from 16 to 18 days of gestation. Intragastric administration of nitrofen to pregnant rats at day 9 of gestation resulted in CDH in 42.7% of fetuses delivered after 20 days of gestation. In nitrofen-treated fetuses, the concentration of disat-PC in the lungs was lower than those in control fetuses, and surfactant apoprotein SP-A was similarly reduced in nitrofen-treated fetuses. However, the concentration of disat-PC in nitrofen-treated fetuses was higher than that in control fetuses at 18 days of gestation, indicating a synthetic potential of surfactant in nitrofen-treated fetuses comparable to that at the late stage of normal gestation. Immunohistochemical study with the antibody revealed that surfactant phospholipid was mainly in the form of intracellular granules in nitrofen-treated fetuses, probably causing the hypoplastic lungs and then CDH, in contrast to the uniform distribution on the pulmonary alveolar surface in control fetuses. (+info)
Endothelium-derived nitric oxide synthase protein expression in ovine placental arteries.
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During the third trimester, fetoplacental and uterine blood flows increase dramatically to meet the high metabolic demands of the growing fetus. We hypothesized that the expression of endothelial nitric oxide synthase (eNOS) in fetoplacental artery endothelium and the concentrations of nitric oxide (NO) and cyclic GMP (cGMP) in amniotic fluid (AF) are increased during the third trimester of ovine gestation. Placental arteries and AF were collected from ewes at 110, 120, 130, and 142 days of gestation (n = 24; mean +/- SEM term = 145 +/- 3 days). Expression of eNOS protein was measured in intact and denuded placental arteries and in endothelium-derived protein by Western analysis and confirmed by immunohistochemistry. Concentrations of NO (nitrates plus nitrites) and cGMP were determined in AF. Placental artery eNOS protein expression was localized to the endothelium, where it was markedly greater than in vascular smooth muscle. Placental artery endothelium-derived eNOS expression and AF cGMP concentrations were similar at 110 and 120 days of gestation; however, both peaked at 130 days at levels two- to threefold above baseline (P < 0.05) before returning to baseline at 142 days of pregnancy. The AF NO (nitrates plus nitrites) levels, however, increased progressively between 120 days of gestation and term (P < 0.05). We concluded that endothelium-derived placental artery eNOS levels, AF NO (nitrates plus nitrites), and AF cGMP were markedly increased during the third trimester, thus supporting a role for NO-mediated elevations in cGMP in the control of fetoplacental blood flow. (+info)
Placental protein 14 induces apoptosis in T cells but not in monocytes.
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Substantial evidence exists in literature to suggest that placental protein 14 (PP14) (recently renamed glycodelin A), exhibits immunosuppressive properties and is an indispensable macromolecule in the maternal system for the establishment, maintenance, and progression of pregnancy. Though there are several reports substantiating the above, the mechanism of its action at the molecular level has not been elucidated as yet. In this paper we provide data that suggest that amniotic fluid PP14 and recombinant PP14 expressed in Pichia pastoris induce apoptosis in human peripheral blood lymphocytes upon activation, independent of monocytes. That PP14 has a direct apoptotic action on T cells but not on monocytes was also demonstrated by utilizing human cell lines. PP14 was shown to induce apoptosis in the human T cell lines, Jurkat and MOLT-4 cells, but not in the human monocytic cell line, U937. (+info)
Early life events in allergic sensitisation.
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The timing of events leading to allergic sensitisation has become a very important area in the attempt to halt the dramatic increase in the prevalence of diseases such as asthma, eczema and hay fever. Recent research has demonstrated that events taking place during the gestational period may well play a role in determining whether or not a genetic susceptibility becomes translated into disease processes. Maternal atopy seems to have an important effect on the developing immune response of the infant and increases the chances of the child developing allergy in later life. Maternal IgE, IgG and amniotic fluid cytokines, combined with the presence of allergen in the feto-maternal environment are all possible factors involved in the ultimate outcome in terms of infant Th-1/Th-2 responses to common environmental antigens. Immune modulation at this stage of development may, in the future, be a way forward in the prevention of allergy. (+info)
Mitogenic activity of high molecular weight forms of insulin-like growth factor-II in amniotic fluid.
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Amniotic fluid (AF) collected from ewes and goats at mid gestation displayed mitogenic activity in mouse fibroblasts. Upon fractionation of this material by size exclusion chromatography, the mitogenic activity was resolved into two peaks, whose activity was inhibited by an anti-IGF type 1 receptor blocking antibody. One of the peaks contained IGF-I and IGF-II (mature form), whereas the other contained high M(r) precursor forms of IGF-II. The presence in this latter fraction of IGF-binding proteins (IGFBP) suggests that the AF IGFBPs do not efficiently inhibit the mitogenic activity of the high M(r) forms of IGF-II. In agreement with this conclusion, exogenous IGFBP-1 failed to affect this activity. Analysis of IGF-II in sheep AF showed that the AF concentrations of both forms of IGF-II increased dramatically from mid pregnancy until 106-120 days of gestation, and fell thereafter. The amniotic IGFBPs followed a similar evolution. High M(r) forms of IGF-II were also found in human AF, with a pattern of electrophoretic migration different from that of sheep. We suggest that the precursor forms of IGF-II may play an important role in foetal development. (+info)
Deoxycytidylate deaminase in pregnancy.
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Deoxycytidylate (DCMP) deaminase was assayed at various times during and after normal and abnormal pregnancies. The level in amniotic fluid was assessed at induction and at caesarean section, and cord blood levels were estimated after normal delivery and at caesarean section. A rise occurred during labour and after hysterectomy and caesarean section--returning to normal after 2-3, and 12 days respectively. Levels above 4.8 X 10-minus 4 ml-minus 1 were found in cases of preeclamptic toxaemia and early intrauterine death and in twin pregnancies over 36 weeks' gestation. It is suggested that because of its low incidence of false-negative and false-positive results this test is far superior to other enzyme tests in pregnancy, and a further trial is in progress to assess its role. (+info)
Maternal and transplacental kinetics of trimethoprim and sulfamethoxazole, separately and in combination.
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The fate of trimethoprim and sulfamethoxazole and the combination of both these agents was studied in a group of healthy pregnant women who were undergoing therapeutic abortion. Assays were performed on samples of blood, urine, amniotic fluid and fetal tissues, using a standardized protocol for the selection of patients, dose administration, sample collection and assay techniques. A comparative evaluation of kinetics to assess the maternal handling and the distribution of trimethoprim throughout the fetoplacental unit disclosed no significant difference in the concentration within fetal fluids and tissue compartments. On the other hand, the concentration of sulfamethoxazole was lower in fetal tissues than in fetal fluids when relative ratios to trimethoprim were compared. The implications of the difference in behaviour of pharmacokinetic and clinical points of view. (+info)
Sonographic assessment of amniotic fluid volume between 11 and 24 weeks of gestation: construction of reference intervals related to gestational age.
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OBJECTIVE: At present, most of the methods for sonographic assessment of amniotic fluid volume are unreliable in the second trimester of pregnancy, or else they do not present nomograms related to gestational age. DESIGN: The aim of this prospective cross-sectional study was to construct normal reference ranges of four ultrasound parameters for the evaluation of amniotic fluid volume which could be applied in the second trimester. For these parameters we calculated normal curve limits suitable for use in clinical practice. SUBJECTS: From a population of normal pregnant women between the 12th and the 24th weeks of gestation undergoing a routine ultrasound examination during 1997 at our institute, 273 were found to be suitable for the study, after the exclusion of all cases which presented any feto-maternal pathology or complications up to the 24th week. METHODS: The largest 'amniotic pocket' in a vertical direction, free of small fetal parts and umbilical cord, was measured: the maximum vertical and transverse diameters were measured on the same scan; the mean diameter and the product of the two diameters were calculated. The 'mean amniotic fluid diameter', the 'two-diameter pocket', the 'largest vertical pocket' and the 'largest transverse pocket' were the four sonographic parameters considered. RESULTS: The four parameters correlated well with gestational week and with the biparietal diameter; the normal reference intervals and normal curve were then calculated. All these parameters were found to have good intra- and interoperative reproducibility. CONCLUSIONS: We conclude that the use of an ultrasound semiquantitative method based on the measurement of a single amniotic fluid pocket and involving normal reference intervals according to gestational age could improve the early diagnosis of amniotic fluid variations during the second trimester, although this has yet to be confirmed by extensive clinical trials. (+info)