RESUMEN
OBJECTIVE: To measure plasma nitric oxide (NO), asymmetric dimethylarginine (ADMA) and vascular endothelial growth factor (VEGF) levels and VEGF gene polymorphisms in fetal circulation in severe preeclampsia. METHODS: Cord vessels of singleton gestations complicated with severe preeclampsia 36 weeks or more (n = 31) and controls were sampled upon delivery for analyte measuring. Additionally, DNA was extracted from umbilical vein whole blood to determine the frequency of VEGF gene single nucleotide polymorphisms (SNPs): -2578 A/C, -1498 C/T, -1154 A/G, -634 C/G and +936 C/T. Coefficient correlations between analyte levels and placental and neonatal weight were calculated. RESULTS: NO plasma levels in umbilical vessels (artery and vein) were significantly higher in preeclampsia cases as compared to controls (4.67 ± 3.0 vs. 0.82 ± 0.90; 4.46 ± 3.0 vs. 0.82 ± 0.99 mmol/L, respectively, p = 0.0001 both). ADMA levels displayed a similar increased trend in both fetal vessels, but this did not reach statistical significance (2.57 ± 1.03 vs. 2.34 ± 0.57; 2.74 ± 0.94 vs. 2.42 ± 0.59 mmol/L, respectively, p > 0.05). VEGF was significantly lower in artery but not in vein in preeclampsia cases (200.48 ± 225.62 vs. 338.61 ± 287.03 pg/mL, p = 0.04). A significant positive correlation was found between NO and ADMA levels (artery and vein) among preeclampsia cases. Overall, the frequency of the studied VEGF gene SNPs did not differ among pre-eclamptic cases and controls; nevertheless, a significant trend toward lower umbilical vein VEGF levels was observed in pre-eclampsia cases in the presence of -2578 CC and -1154 AG genotypes. CONCLUSION: Near term gestations complicated with severe preeclampsia presented higher NO levels in fetal circulation, which correlated to ADMA and lower artery VEGF values. More research is warranted to confirm that selected VEGF SNPs may be associated with lower umbilical vein VEGF.
Asunto(s)
Arginina/análogos & derivados , Óxido Nítrico/análisis , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/genética , Adolescente , Adulto , Arginina/sangre , Estudios de Casos y Controles , Femenino , Sangre Fetal/química , Sangre Fetal/metabolismo , Predisposición Genética a la Enfermedad , Humanos , Recién Nacido , Óxido Nítrico/sangre , Óxido Nítrico/metabolismo , Proyectos Piloto , Placenta/irrigación sanguínea , Placenta/química , Placenta/metabolismo , Circulación Placentaria/fisiología , Preeclampsia/sangre , Embarazo , Índice de Severidad de la Enfermedad , Venas Umbilicales/química , Venas Umbilicales/metabolismo , Factor A de Crecimiento Endotelial Vascular/análisis , Adulto JovenRESUMEN
OBJECTIVES: To determine the correlation between ph at birth and venous Doppler parameters in pregnancies with placental dysfunction. METHODS: This was a prospective cohort study of 58 pregnancies with the diagnosis of placental dysfunction between 26 and 34 weeks of gestation. Inclusion criteria were singleton pregnancies, abnormal umbilical artery (UA) Doppler, fetal growth restriction diagnosed by estimated fetal weight <10th centile for gestational age, intact membranes, and absence of fetal congenital abnormalities. The Doppler measurements were the following: UA pulsatility index (PI), ductus venosus (DV) pulsatility index for veins (PIV), intra-abdominal umbilical vein (UV) time-averaged maximum velocity (TAMxV) and blood flow and left portal vein (LPV) time-averaged maximum velocity (TAMxV) and blood flow. All Doppler parameters were transformed into z-scores (SD values from the mean) according to normative references. RESULTS: The UA pH at birth showed a negative significant correlation with the DV-PIV (p = 0.004) and the DV-PIV z-score (p = 0.004), while LPV TAMxV (p = 0.004), LPV TAMxV z-score (p = 0.002), LPV blood flow (p = 0.01), LPV blood flow normalized (p = 0.04) and UV blood flow (p = 0.04) positively correlated with pH at birth. Multiple regression analysis was performed and the DV-PIV z-score was the variable that independently correlated with pH at birth (p = 0.002). CONCLUSIONS: the present results suggest that changes in fetal venous blood flow, mainly DV and LPV are useful in the management of cases with early onset placental insufficiency and that venous Doppler parameters correlate with pH at birth.
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Parto , Enfermedades Placentarias/diagnóstico por imagen , Ultrasonografía Doppler , Venas Umbilicales/química , Venas Umbilicales/diagnóstico por imagen , Adulto , Femenino , Sangre Fetal/química , Sangre Fetal/metabolismo , Feto/irrigación sanguínea , Humanos , Concentración de Iones de Hidrógeno , Recién Nacido , Parto/sangre , Parto/metabolismo , Parto/fisiología , Enfermedades Placentarias/sangre , Enfermedades Placentarias/fisiopatología , Embarazo , Embarazo de Alto Riesgo/fisiología , Ultrasonografía Doppler/métodos , Arterias Umbilicales/química , Arterias Umbilicales/diagnóstico por imagen , Arterias Umbilicales/metabolismo , Venas Umbilicales/metabolismo , Adulto JovenRESUMEN
Umbilical veins (UV) and arteries (UA) of preeclamptic women in Curaçao harbor lower long-chain polyunsaturated fatty acids (LCP). The present aim was to test these findings in Mwanza (Tanzania), whose inhabitants have high LCPomega3 and LCPomega6 intakes from Lake Victoria fish. Women with preeclampsia (n=28) in Mwanza had lower PUFA and higher 20:0 in UV and UA, compared with normotensive/non-proteinuric controls (n=31). Their UV 22:6omega3, 22:4omega6, LCPomega6, omega6, and LCPomega3+omega6 were lower, while saturated FA, potentially de novo synthesized FA (Sigmade novo) and (Sigmade novo)/(LCPomega3+omega6) ratio were higher. Their UA had higher 16:1omega7, omega7, 18:0, and 16:1omega7/16:0. Umbilical vessels in Mwanza had higher 22:6omega3, LCPomega3, omega3, and 16:0, and lower 22:5omega6, 20:2omega6, 18:1omega9, and omega9, compared to those in Curaçao. Preeclampsia in both Mwanza and Curaçao is characterized by lower LCP and higher Sigmade novo. An explanation of this might be placental dysfunction, while the similarity of umbilical vessel FA-abnormalities in preeclamptic and diabetic pregnancies suggests insulin resistance as a common denominator.
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Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-6/análisis , Ácidos Grasos/análisis , Productos Pesqueros , Preeclampsia/metabolismo , Cordón Umbilical/química , Adolescente , Adulto , Grasas Insaturadas en la Dieta/metabolismo , Ácidos Grasos Insaturados/análisis , Femenino , Humanos , Antillas Holandesas , Embarazo , Tanzanía , Arterias Umbilicales/química , Venas Umbilicales/química , Adulto JovenRESUMEN
Plasma amino acid levels have never been studied in the placental intervillous space of preterm gestations. Our objective was to determine the possible relationship between plasma amino acids of maternal venous blood (M), of the placental intervillous space (PIVS) and of the umbilical vein (UV) of preterm newborn infants. Plasma amino acid levels were analyzed by ion-exchange chromatography in M from 14 parturients and in the PIVS and UV of their preterm newborn infants. Mean gestational age was 34 +/- 2 weeks, weight = 1827 +/- 510 g, and all newborns were considered adequate for gestational age. The mean Apgar score was 8 and 9 at the first and fifth minutes. Plasma amino acid values were significantly lower in M than in PIVS (166%), except for aminobutyric acid. On average, plasma amino acid levels were significantly higher in UV than in M (107%) and were closer to PIVS than to M values, except for cystine and aminobutyric acid (P < 0.05). Comparison of the mean plasma amino acid concentrations in the UV of preterm to those of term newborn infants previously studied by our group showed no significant difference, except for proline (P < 0.05), preterm > term. These data suggest that the mechanisms of active amino acid transport are centralized in the syncytiotrophoblast, with their passage to the fetus being an active bidirectional process with asymmetric efflux. PIVS could be a reserve amino acid space for the protection of the fetal compartment from inadequate maternal amino acid variations.
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Aminoácidos/sangre , Vellosidades Coriónicas/química , Recien Nacido Prematuro/sangre , Venas Umbilicales/química , Adulto , Cromatografía por Intercambio Iónico , Femenino , Edad Gestacional , Humanos , Recién Nacido , Masculino , Intercambio Materno-Fetal , EmbarazoRESUMEN
Plasma amino acid levels have never been studied in the placental intervillous space of preterm gestations. Our objective was to determine the possible relationship between plasma amino acids of maternal venous blood (M), of the placental intervillous space (PIVS) and of the umbilical vein (UV) of preterm newborn infants. Plasma amino acid levels were analyzed by ion-exchange chromatography in M from 14 parturients and in the PIVS and UV of their preterm newborn infants. Mean gestational age was 34 ± 2 weeks, weight = 1827 ± 510 g, and all newborns were considered adequate for gestational age. The mean Apgar score was 8 and 9 at the first and fifth minutes. Plasma amino acid values were significantly lower in M than in PIVS (166 percent), except for aminobutyric acid. On average, plasma amino acid levels were significantly higher in UV than in M (107 percent) and were closer to PIVS than to M values, except for cystine and aminobutyric acid (P < 0.05). Comparison of the mean plasma amino acid concentrations in the UV of preterm to those of term newborn infants previously studied by our group showed no significant difference, except for proline (P < 0.05), preterm > term. These data suggest that the mechanisms of active amino acid transport are centralized in the syncytiotrophoblast, with their passage to the fetus being an active bidirectional process with asymmetric efflux. PIVS could be a reserve amino acid space for the protection of the fetal compartment from inadequate maternal amino acid variations.
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Adulto , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Aminoácidos/sangre , Vellosidades Coriónicas/química , Recien Nacido Prematuro/sangre , Venas Umbilicales/química , Cromatografía por Intercambio Iónico , Edad Gestacional , Intercambio Materno-FetalRESUMEN
Von Willebrand Factor is a multimer produced by endothelial cells and megakaryocytes, being stored in intracellular organelles, such as the Weibel-Palade bodies and alpha-granules in endothelial cells and platelets, respectively. This molecule acts as a carrier protein for factor VIIIc, involved in the intrinsic pathway of blood coagulation maintaining its stability in circulation. Von Willebrand Factor also plays an important role in platelet aggregation and adhesion to injured vessel wall. It interacts with platelets through two distinct glycoproteins, GPIb and GPIIb/IIIa. We raised two monoclonal antibodies, ECA-3 and ECA-4, against human umbilical vascular endothelial cells that recognize and immunoprecipitate von Willebrand Factor. Interestingly, ECA-4 monoclonal antibody is able to completely inhibit platelet agglutination induced by ristocetin, suggesting that it binds to von Willebrand Factor close to platelet GPIb binding site. The use of monoclonal antibodies to identify von Willebrand Factor binding regions to factor VIII or platelets has been reported by others. In pulmonary hypertension, abnormalities have been detected on the multimeric structure of the molecule as well as on its proteolytic fragments, by using monoclonal antibodies. Moreover, monoclonal antibodies raised against specific regions of von Willebrand Factor molecule may allow studies of functional abnormalities of this protein in inherited and acquired disorders like subtypes of von Willebrand's disease.
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Anticuerpos Monoclonales/química , Factor de von Willebrand/inmunología , Animales , Anticuerpos Monoclonales/farmacología , Afinidad de Anticuerpos , Técnicas de Cultivo de Célula , Endotelio Vascular/química , Endotelio Vascular/citología , Humanos , Hibridomas/inmunología , Immunoblotting , Técnicas para Inmunoenzimas , Leucocitos Mononucleares/química , Ratones , Ratones Endogámicos BALB C , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Precipitina , Ristocetina/farmacología , Células Tumorales Cultivadas , Venas Umbilicales/química , Venas Umbilicales/citologíaRESUMEN
OBJECTIVE: To investigate whether the steady decline in the maternal essential fatty acids (EFA) status during pregnancy observed in Dutch pregnant women is a local or general phenomenon. DESIGN: The EFA status was measured during uncomplicated, singleton pregnancy of healthy women from the Netherlands, Hungary, Finland, England and Ecuador. In addition, the EFA status of their neonates were measured at birth. Fatty acid profiles were analyzed in phospholipids isolated from maternal plasma and from umbilical plasma and cord vessel walls. RESULTS: Considerable differences between these centers were observed in the maternal EFA levels and EFA status indexes. However, the change in the absolute as well as relative amounts of the EFAs followed a similar course in the five populations during pregnancy. The neonatal EFA profiles reflected the differences found in maternal plasma during pregnancy and shortly after delivery. Comparable correlations were found, particularly, between the neonatal and the maternal n-3 fatty acids in the participating groups. CONCLUSIONS: It seems that the reduction in maternal EFA status during pregnancy is a general phenomenon, and is largely independent of differences in dietary habits and ethnic origin. Since the lowest values for certain maternal EFAs in a given country were significantly higher than the highest value of these EFAs throughout pregnancy in other countries, the functional implications of the pregnancy-associated reduction in the maternal EFA status for the fetal and neonatal development is not obvious and needs to be further elucidated.