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At least 1,495 records · Page 83Linked to original sources
PubMed2005

Insulin resistance in human preeclamptic placenta is mediated by serine phosphorylation of insulin receptor substrate-1 and -2.

CONTEXT: Preeclampsia is a severe complication of human pregnancy often associated with maternal risk factors. Insulin resistance represents a major risk for developing preeclampsia during pregnancy. OBJECTIVE: A putative second messenger of insulin, inositol phosphoglycan P type (P-IPG), was previously shown to be highly increased during active preeclampsia. Its association with insulin resistance was investigated. DESIGN AND SETTING: A cross-sectional study was carried out in a referral center. PATIENTS: Nine preeclamptic (PE) and 18 healthy women were recruited and matched for maternal age, body mass index, parity, and ethnicity in a 1:2 ratio. Placental specimens were collected immediately after delivery. INTERVENTION: Placental tissue was incubated with insulin and P-IPG production assessed. Insulin signaling proteins were subsequently studied by immunoblotting. RESULTS: P-IPG extracted from human term placentas upon incubation with insulin was found to be far lower in those with preeclampsia than controls (P < 0.001). Immunoblotting studies revealed serine phosphorylation of insulin receptor substrate-1 and -2 in PE placentas (P < 0.001) with downstream impairment of insulin signaling. The activation of the p85 regulatory subunit of phosphatidylinositol 3- kinase was markedly decreased in PE samples (P < 0.001). CONCLUSIONS: These findings highlight the importance of P-IPG in active preeclampsia and demonstrate a substantially different response to the insulin stimulus of human PE placentas. Acquired alterations in activation of proteins involved in insulin signaling may play a role in the complex pathogenesis of preeclampsia, probably as a consequence of the immunological dysfunction that occurs in this syndrome. These results seem to confirm an insulin-resistant state in PE placenta and shed a different light on its role in the pathogenesis of this disease with potential therapeutic implications.

Adult↗
PubMed2026

Timing of carbetocin administration in vaginal deliveries: a double-blind, randomized controlled trial.

OBJECTIVES: This study aimed to compare the efficacy of administering carbetocin before vs. after placental delivery in preventing postpartum hemorrhage (PPH) in low-risk vaginal deliveries. METHODS: The randomized controlled trial was conducted at Kartal City Hospital, Istanbul, Turkey. A total of 160 primiparous women with uncomplicated pregnancies who underwent vaginal delivery were enrolled. Participants were randomly assigned to receive 100&#x202f;&#x3bc;g of carbetocin either before or after placental delivery. The primary outcome was the incidence of PPH. Secondary outcomes included the need for additional uterotonics, manual removal of the placenta with consequent antibiotic administration, blood transfusions, maternal adverse events, and changes in hemoglobin levels at baseline and 24&#x202f;h postpartum. RESULTS: The incidence of PPH was significantly lower in the carbetocin-before group than in the carbetocin-after group (p=0.015). The carbetocin-before group had a significantly lower mean hemoglobin drop compared to the carbetocin-after group (p<0.001). The need for additional uterotonics was significantly higher in the carbetocin-after group (p<0.001). Manual placenta removal and the need for antibiotics were more frequent in the carbetocin-before group (p=0.017). No significant differences in adverse maternal events were observed between the groups. CONCLUSIONS: Administering carbetocin before placental delivery significantly reduces the incidence of PPH, blood loss, and the need for additional uterotonics. However, the increased rate of manual placenta removal necessitates individualized risk-benefit assessment; pre-placental administration may be most advantageous in women at elevated risk for PPH, in whom the hemorrhagic benefit outweighs the risks associated with manual extraction.

Humans↗
PubMed1984

The effect of insulin on ovine fetal oxygen extraction.

Infusion of exogenous insulin (54 +/- 19 mU/kg/hr) to seven fetal lambs caused hyperinsulinism and arterial hypoxemia but not hypoglycemia. We measured the relationship between fetal oxygen delivery and oxygen use for a better understanding of the cause of the observed hypoxemia. Oxygen delivered to the fetus is the product of fetal umbilical venous oxygen content and umbilical blood flow. Both of these quantities decreased as fetal insulin concentration rose. The fall in umbilical blood flow was due to a change in the distribution of cardiac output. Cardiac output rose, but placental perfusion decreased while blood flow to the fetal carcass increased. Oxygen consumption by the ovine fetus increased as insulin concentration rose. Since the delivery of oxygen to the fetus did not increase when its use was rising, fetal extraction of available oxygen increased. Fetal arterial hypoxemia is the result of this increased extraction of available oxygen.

Animals↗
PubMed2001

Comparative genomic hybridization: a new tool for reproductive pathology.

OBJECTIVE: To demonstrate the effectiveness of comparative genomic hybridization (CGH) for analysis of reproductive pathology specimens in clinical cytogenetics laboratories. DESIGN: A total of 856 CGH analyses were performed on various placental and fetal tissues derived from 368 specimens of spontaneous abortions and on placentas from 219 pregnancies with live-born infants. The live-born infants were clinically evaluated as normally developed, with either a normal birth weight or with intrauterine growth restriction; some live-born infants had an abnormal prenatal triple screen with normal cytogenetic results on amniotic fluid cell cultures. RESULTS: Comparative genomic hybridization analysis was successfully performed on 856 samples from spontaneously aborted specimens and term placentas. Failure of analysis occurred in 1.6% of samples and was due to an insufficient amount of tissue for DNA extraction. Comparative genomic hybridization identified aneuploidy in 53% of spontaneous abortion samples and 3.1% of term placentas. CONCLUSIONS: Comparative genomic hybridization analysis is a useful clinical tool for detection of aneuploidy in placental and fetal tissues. It provides a genome-wide screen while eliminating tissue culture failures, culture artifacts, and maternal cell contamination. We present practical guidelines for interpreting CGH profiles derived from human reproductive specimens.

Abortion, Spontaneous↗
PubMed1989

Factors affecting gas transfer across the placenta and the oxygen supply to the fetus.

The factors that affect placental gas exchange are reviewed, with particular reference to recent measurements of the effect of changes in one or more of these factors on O2 delivery to the fetus and on fetal O2 uptake. Fetal or maternal placental blood flows and blood O2 capacities can be altered by 50% without any major change occurring in fetal O2 uptake: umbilical venous O2 content and fetal O2 delivery fall, but the O2 consumption of the fetus is maintained by increasing the fractional extraction of O2 from the blood. There is evidence that the fetus can also cope with a reduction in blood O2 affinity resulting from replacement of fetal with maternal blood. The critical level of O2 delivery is about 0.6 mmol.min-1.kg-1 in the fetal sheep. When O2 delivery is reduced below this level, by decreasing maternal placental blood flow, raising or lowering fetal haematocrit, decreasing maternal O2 capacity, or decreasing fetal O2 affinity, fetal O2 uptake tends to fall. The resultant tissue hypoxia and inability to maintain oxidative metabolism is reflected in a lowering of arterial blood pH and base excess. Whilst the results of short-term experiments suggest that there exists a large reserve for placental O2 transfer and fetal O2 supply, there is evidence that fetal O2 uptake is more tightly linked to O2 delivery when the latter is reduced for a period of days or weeks. In the long term, restriction of the supply of O2 and nutrients leads to a reduced rate of fetal growth and a reprogramming of tissue development.

Animals↗
PubMed1980

Determination of urinary placental estriol by reversed-phase liquid chromatography with fluorescence detection.

Ww describe a liquid-chromatographic procedure for determining urinary estriol concentrations. The urine sample, after enzymatic hydrolysis to free the conjugated estrogen, is extracted with ether, and an aliquot of the resulting extraction residue is injected into the liquid chromatograph. Sample components are separated with a reversed-phase C18 column and isocratic elution with an acetonitrile/water mobile phase. Using a far-ultraviolet excitation wavelength, we measure the natural fluorescence of the eluted estrogen with a fluorescence detector. The procedure provides excellent sensitivity for determing near-term pregnancy concentrations of urinary estriol. The selectivity of the method limits the effect of potentially interfering compounds.

Chromatography, Gas↗
PubMed1988

Detection of histamine in human placental perfusate and the effect of histamine releasers.

Studies on full-term human placentas were conducted to determine whether the vasogenic actions of certain agents on perfused placental vasculature are due to histamine release. Compound 48/80 and morphine were selected because they liberate the autacoid via different mechanisms. Initially, a control effluent was collected prior to each drug challenge and again collected throughout the rise and fall in perfusion pressure. The drugs were given alone and in the presence of a 50 mcg dose of histamine free base (HFB) to assess the release of stored histamine and also to serve as a control. Following extraction in n-butanol and recovery in 0.1 N HCl, all effluents were fluoresced with o-phthalaldehyde and assayed for histamine content via spectrophotofluorometry. A baseline histamine level was discovered in the majority of placental effluents collected prior to the administration of any agent. No significant increases above this initial level occurred following treatment with compound 48/80 alone. However, small but significantly elevated amounts of histamine appeared in the placental effluent when compound 48/80 was given 10 minutes after the initial 50 mcg dose of HFB. This agent also caused a slight increase in placental perfusion pressure after each administration. Results obtained with morphine do not appear to support the hypothesis that significant amounts of histamine are released by this agent in the perfused human placenta.

Female↗
PubMed1998

Absence of human placental lactogen and placental growth hormone (HGH-V) during pregnancy: PCR analysis of the deletion.

Human placental lactogen (HPL) is produced in large amounts in normal pregnancies. We report a pregnancy with complete lack of HPL and the placental variant of the human growth hormone HGH-V. The pregnancy resulted in a severely growth-retarded but otherwise normal male baby. PCR analysis of DNA extracted from the placenta showed that the HPL encoding genes hPL-4 and hPL-3 were deleted along with the human growth hormone variant gene (hGH-V), which is located between these two active hPL genes and also expressed in the normal placenta. Of the five members of this multigene family, hGH-N, which is expressed in the pituitary gland, and hPL-1, a presumed pseudogene, were left intact. The latter (hPL-1) was expressed as RNA transcripts only at very low levels as is usually reported in normal pregnancies. Analysis of the parents' DNA showed that both of them carried a different heterozygous deletion at the 3' end of the hGH/hPL locus.

Adult↗
PubMed2004

Tumor necrosis factor-alpha allele lymphotoxin-alpha+250 is associated with the presence and severity of placental inflammation among preterm births.

Histologic inflammation of placenta has been associated with increased risk for bronchopulmonary dysplasia and periventricular leukomalacia among preterm infants. Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the regulation of inflammation. Some alleles of TNF (LT-alpha+250, TNF-alpha-308, and TNF-alpha-238) have been associated with susceptibility and/or severity of many diseases characterized by inflammation and/or involving the immune system. To determine whether alleles of TNF-alpha affect the risk and/or the severity of chorioamnionitis, we examined the placentas of 101 preterm births (birth weight <or=1250 g) for the presence of inflammation. Maternal and fetal chorioamnionitis (MCA and FCA, respectively) were graded for severity and staged for location of inflammatory infiltrate. Analysis for TNF-alpha alleles was done using PCR-restriction fragment length polymorphism technique on DNA extracted from infants' whole blood. MCA and FCA were seen in 45 and 38 placentas, respectively (p = 0.64). Genotypes of TNF-alpha-308 did not affect the development or the severity of placental inflammation. However, the AA genotype of LT-alpha+250 occurred more often when MCA and FCA were present compared with placentas without inflammation (p = 0.016 and p = 0.007, respectively). The GA genotype of TNF-alpha-238 was more common in placentas with severe MCA than with mild MCA (p = 0.015). The number of A alleles of LT-alpha+250 (GG = 0, GA = 1, AA = 2) correlated directly and significantly with grades and stages of MCA and FCA (p < 0.05). The AA genotype of LT-alpha+250 is associated with the development of chorioamnionitis among preterm births. The A allele of LT-alpha+250 seems to worsen the degree of placental inflammation.

Adult↗
PubMed1987

Protein translocation across wheat germ microsomal membranes requires an SRP-like component.

Different wheat germ extracts were tested for the presence of membranes capable of translocating and processing nascent secretory proteins. One lysate was found in which nascent prehuman-placental lactogen (phPL) was translocated and processed to mature human placental lactogen (hPL). Processing was found to occur concomitant with translocation across membranes. Translocation across the wheat germ membrane required a component which is similar to the mammalian signal recognition particle (SRP). It bound to DEAE-Sepharose, had a sedimentation coefficient of 11S and contained a 7S RNA. In addition to hPL, the plant protein zein and the bacterial protein beta-lactamase were translocated across and processed by wheat germ membranes. Transport was found to occur only co-translationally. Our results show that the wheat germ protein translocation system is similar to the mammalian one. Unlike the mammalian SRP, the particle purified from wheat germ did not arrest elongation of nascent secretory proteins.

Journal Article↗
PubMed1975

[Isolation and characterization of a high molecular weight placental protein (PPg)(author's transl)].

The isolation and characterization of a high molecular weight protein (PP6) from human placentae is described. The protein which apparently has some steroid-binding properties shows the mobility of an alpha1-globulin and has a molecular weight of around 1 X 10(6) daltons. The molecule is composed of several different subunits with molecular weights ranging from 200,000-35,000 daltons which are held together by non-covalent bonds. Immunofluorescent studies revealed that the placental protein PP6 is localized in the nuclei of the syncytiotrophoblast. But PP6 is not specific for the placenta; this protein is also found in extracts from other human tissues as well as in the erythrocytes. PP6 usually is not present in normal sera but in some cases it could be detected in concentrations ranging from 1-3 mg per 100 ml in sera from pregnant women and in sera from patients with malignant tumors.

Alpha-Globulins↗
PubMed1986

The fibronectin content of canine lungs is increased in bleomycin-induced fibrosis.

Fibronectin (Fn), a high molecular weight glycoprotein, was found to constitute 0.43% of the normal adult beagle dog lung. The tissue Fn (TFn) was solubilized by sequential chemical extractions and quantified by ELISA (enzyme-linked immunoabsorbent assay). Subsequent plasmin digestion did not appear to solubilize significantly more Fn. Since 70% of the lung tissue was solubilized by the extractions and plasmin digestions, the TFn quantified represented the bulk of lung Fn. The TFn was identical to plasma fibronectin in the ELISA and one can infer that the Fn molecule is not significantly altered as it is incorporated into the lung connective tissue matrix. Lungs from beagles in which fibrosis had been induced with bleomycin contained 0.99% Fn, more than a twofold increase over normal. In the ELISA TFn from fibrotic lungs gave an inhibition curve of the same shape as did TFn from normal lungs. Thus, Fn from fibrotic lungs is not different qualitatively from Fn from normal lungs in any way detectable with this antiserum. The TFn content of plasmin digests of intact lung was less than that of extracts, which was the converse of results obtained on placenta (B. A. Bray (1985) Biochem. J. 226, 811-815). This difference between lung TFn and placental TFn may be due to differences in degree of glycosylation, which determines susceptibility to proteases.

Animals↗
PubMed1996

Localization of 17beta-hydroxysteroid dehydrogenase and characterization of testosterone in the brain of the male frog.

Several enzymes involved in the formation of steroids of the pregnene and pregnane series have been identified in the brain, but the biosynthesis of testosterone has never been reported in the central nervous system. In the present study, we have investigated the distribution and bioactivity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) (EC 1.1.1.62; a key enzyme that is required for the formation of testosterone and estradiol) in the brain of the male frog Rana ridibunda. By using an antiserum against human type I placental 17beta-HSD, immunoreactivity was localized in a discrete group of ependymal glial cells bordering the telencephalic ventricles. HPLC analysis of telencephalon and hypothalamus extracts combined with testosterone radioimmunoassay revealed the existence of two peaks coeluting with testosterone and 5alpha-dihydrotestosterone. After HPLC purification, testosterone was identified by gas chromatography/mass spectrometry. Incubation of telencephalon slices with [3H]pregnenolone resulted in the formation of metabolites which coeluted with progesterone, 17alpha-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, and 5alpha-dihydrotestosterone. The newly synthesized steroid comigrating with testosterone was selectively immunodetected by using testosterone antibodies. These data indicate that 17beta-HSD is expressed in a subpopulation of gliocytes in the frog telencephalon and that telencephalic cells are capable of synthesizing various androgens, including dehydroepiandrosterone, androstenedione, testosterone, and 5alpha-dihydrotestosterone.

17-Hydroxysteroid Dehydrogenases↗
PubMed1975

Peripheral metabolism of insulin, proinsulin, and C-peptide in the pregnant rat.

To clarify alterations in carbohydrate metabolism which occur in pregnancy, metabolic clearance rates of insulin, proinsulin, and C-peptide were measured by the constant infusion technique in term-pregnant rats and in virgin littermates. In addition, placental permeability to these peptides was evaluated by simultaneous determination of their concentration in fetal blood, amniotic fluid, and maternal arterial blood and the renal extraction and excretion of insulin and C-peptide were determined during simultaneous studies of renal hemodynamics. The metabolic clearance rate (MCR) of insulin was higher (P less than 0.005) in pregnant animals (61.5+/-1.7 ml/min per kg nonconceptus body weight) than in virgin littermates (51.5+/-2.2 ml/min per kg). Insulin disappearance from the circulation after both single injection and discontinuance of a constant infusion was also faster in gravid animals. In contrast, the MCR of proinsulin and C-peptide, and the disappearance of C-peptide from the circulation were similar in pregnant and control rats. The placenta was virtually impermeable to each of the three polypeptides since their mean levels in both fetal blood and amniotic fluid did not exceed 2.5 ng/ml and were only minimally influenced by pharmacological concentrations as high as 60 ng/ml in the maternal circulation. The renal clearance of insulin (renal arteriovenous insulin difference X renal plasma flow) was lower, and its contribution to insulin MCR was less in pregnant animals than in controls (19.4+/-1.5% vs. 28.7+/-3.7%, P less than 0.05), whereas the renal clearance and renal clearance/MCR of C-peptide were similar in pregnant rats and virgin littermates. These results indicate that the peripheral metabolism of insulin is accelerated in pregnancy, while that of pro-insulin and C-peptide is unaffected. Since transplacental passage of insulin is negligible and its renal clearance is not increased, the enhanced MCR of insulin in pregnancy is due to increased metabolism at an extrarenal site probably within the placenta itself.

Amniotic Fluid↗
PubMed2000

Bovine placental protease specificity toward muscle connective tissue proteins.

Enzymes currently used to tenderize meat are not substrate-specific, resulting in extensive myofibrillar protein degradation that often produces an undesirable texture. Bovine placental metalloproteases, which selectively hydrolyze connective tissue proteins while leaving myofibrillar proteins intact, may tenderize meat without causing texture problems. Therefore, our objective was to extract and crudely purify bovine metalloproteases from bovine placenta for possible use as tenderizers in meat systems. Enzymes were extracted from homogenized tissue and purified by ammonium sulfate precipitation. Samples were collected before (crude enzyme) and after gel filtration on a Sephadex G-100 column. Spectrophotometric analysis identified one major peak (filtered enzyme). Gelatin, casein, and type I acid-soluble collagen zymography were used to determine substrate specificity. Beef myofibrillar proteins were incubated with crude and filtered enzyme fractions, enzymes quenched, and substrate degradation visualized using SDS-PAGE. Active gelatinases and collagenases exhibiting molecular weights of 57 to 65 kDa were detected on zymograms. Banding patterns from crude enzyme indicated two enzymes with both gelatinase and collagenase activity and a third enzyme with gelatinase activity only. Banding patterns from filtered enzyme indicated two enzymes with both gelatinase and collagenase activity. Proteolytic activity was not detected with casein, actin, or myosin heavy-chain substrates. Due to specificity for collagen and gelatin, these enzymes may be capable of improving the tenderness of certain cuts relatively high in connective tissue, while avoiding myofibrillar protein hydrolysis.

Animals↗
PubMed2004

Maternal-fetal transplacental leakage of mitochondrial DNA in bovine nuclear transfer pregnancies: potential implications for offspring and recipients.

The synepitheliochorial placenta of ruminants is constructed of multiple tissue layers that separate maternal and fetal blood. In nuclear transfer cloned ruminants, however, placental anomalies such as abnormal vascular development and hemorrhagic cotyledons have been reported. We have investigated the possible exchange of genetic material between somatic cell nuclear transfer cloned (SCNT) bovine fetuses and recipients at day 80 of gestation using mitochondrial DNA (mtDNA) as a marker. Twenty-three recovered SCNT-fetuses and their recipients were screened for divergent and thus informative mtDNA combinations. Twenty-one fetuses generated by in vitro fertilization (IVF) or multiple ovulation embryo transfer (MOET) and the corresponding recipients served as controls. A search for recipient mtDNA haplotype in DNA extracts from fetal blood by PCR-RFLP analysis revealed three cases of chimerism (two SCNT, one IVF) among a total of 19 informative fetus-recipient pairs (eight SCNT, seven IVF, four MOET). Placental anomalies have also been observed in some IVF fetuses and the present data therefore suggests transplacental leakage of cell components or cells from the recipient into some fetuses generated by in vitro techniques. Further studies are necessary to determine (i) the nature of leaked material, (ii) whether there is bi-directional leakage, and (iii) whether leaked material is present in recipients and calves after parturition, i.e. whether leakage takes place in vivo. If recipients were chimeric for DNA or cells derived from genetically modified SCNT (or IVF) embryos, their subsequent utilization might be affected.

Animals↗
PubMedDate not supplied

Vitamin C and aloe vera supplementation protects from chemical hepatocarcinogenesis in the rat.

The effects of vitamin C and aloe vera gel extract supplementation on induced hepatocarcinogenesis in male Sprague-Dawley rats (120-150 g) by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) was investigated. The severity of the carcinogenesis process was determined by measuring gamma-glutamyl transpeptidase (GGT) and the placental form of glutathione S-transferase (GSTP) histochemically in situ and in plasma and liver fractions. In addition, plasma alkaline phosphatase (ALP) and liver microsomal uridine diphosphate glucuronyl transferase (UDPGT) activity were also determined. Administration of DEN/AAF caused an increase in the surface area and number of enzyme-positive foci (both GGT and GSTP) compared with control. Supplementation of vitamin C or aloe vera gel extract to the cancer-induced rats suppressed this increase significantly (P < 0.05; P < 0.001). Increases in liver UDPGT, GGT, and GSTP activities were also observed with cancer induction that were again suppressed with either vitamin C or aloe vera gel supplementation. Plasma GGT in the DEN/AAF rats were determined monthly for the duration of the experiment and found to be reduced as early as 1 mo with aloe vera gel supplementation and 2 mo with vitamin C supplementation. In conclusion, vitamin C and aloe vera gel extract supplementation were found to be able to reduce the severity of chemical hepatocarcinogenesis.

2-Acetylaminofluorene↗