RESUMEN
Maternal overweight in pregnancy alters the metabolic environment and generates chronic low-grade inflammation. This affects fetal development and programs the offspring's health for developing cardiovascular and metabolic disease later in life. MME (membrane-metalloendopeptidase, neprilysin) cleaves various peptides regulating vascular tone. Endothelial cells express membrane-bound and soluble MME. In adults, the metabolic environment of overweight and obesity upregulates endothelial and circulating MME. We here hypothesized that maternal overweight increases MME in the feto-placental endothelium. We used primary feto-placental endothelial cells (fpEC) isolated from placentas after normal vs. overweight pregnancies and determined MME mRNA, protein, and release. Additionally, soluble cord blood MME was analyzed. The effect of oxygen and tumor necrosis factor α (TNFα) on MME protein in fpEC was investigated in vitro. Maternal overweight reduced MME mRNA (-39.9%, p < 0.05), protein (-42.5%, p = 0.02), and MME release from fpEC (-64.7%, p = 0.02). Both cellular and released MME protein negatively correlated with maternal pre-pregnancy BMI. Similarly, cord blood MME was negatively associated with pre-pregnancy BMI (r = -0.42, p = 0.02). However, hypoxia and TNFα, potential negative regulators of MME expression, did not affect MME protein. Reduction of MME protein in fpEC and in cord blood may alter the balance of vasoactive peptides. Our study highlights the fetal susceptibility to maternal metabolism and inflammatory state.
Asunto(s)
Regulación hacia Abajo , Células Endoteliales/enzimología , Sangre Fetal/enzimología , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Neprilisina/biosíntesis , Obesidad Materna/enzimología , Placenta/enzimología , Adulto , Línea Celular , Células Endoteliales/patología , Femenino , Humanos , Obesidad Materna/patología , Placenta/patología , EmbarazoRESUMEN
BACKGROUND: Elevated stearoyl-CoA desaturase 1 (SCD-1) activity showed associations with obesity in cross-sectional studies. In non-pregnant populations, nutrition regulates SCD-1 transcription and activity. OBJECTIVE: To investigate the longitudinal associations of maternal and fetal SCD-1 activity markers with infant anthropometry up to 2 years of age, and to explore how selected dietary intakes modulate SCD-1 activity in pregnancy. METHODS: As a secondary analysis from the ROLO intervention study, which was conducted in a population at risk for macrosomia, non-esterified fatty acids (NEFA) from maternal plasma at 13 and 28 weeks' gestation and in cord blood were measured via liquid-chromatography-mass-spectrometry. Fatty acid ratios 18:1/18:0 and 16:1/16:0 were used as markers for SCD-1 activity ('desaturation indices', DIs). Relationships of DIs with infant anthropometry up to 2 years of age and maternal dietary parameters during pregnancy were investigated using adjusted linear regression models and p-values correction for multiple testing. RESULTS: 18:1/18:0, but not 16:1/16:0, was associated with measures of infant anthropometry at birth (maternal and fetal markers) and up to 2 years of age (maternal markers only). Dietary intakes did not show strong associations with 18:1/18:0, but 16:1/16:0 was associated with absolute and relative dietary intakes. CONCLUSIONS: In a population at risk for macrosomia, maternal SCD-1 activity measured via 18:1/18:0 was involved in the fetal programming of infant obesity, but could not be substantially modulated by short-term diet in pregnancy. CLINICAL TRIAL REGISTRATION: ISRCTN Registration number: ISRCTN54392969 (http://www.isrctn.com/ISRCTN54392969).
Asunto(s)
Desarrollo Infantil , Dieta , Ácidos Grasos/sangre , Sangre Fetal/enzimología , Fenómenos Fisiologicos Nutricionales Maternos , Obesidad Infantil/etiología , Efectos Tardíos de la Exposición Prenatal , Estearoil-CoA Desaturasa/sangre , Adiposidad , Adulto , Factores de Edad , Antropometría , Biomarcadores/sangre , Preescolar , Femenino , Humanos , Recién Nacido , Estudios Longitudinales , Obesidad Infantil/sangre , Obesidad Infantil/enzimología , Obesidad Infantil/fisiopatología , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de RiesgoRESUMEN
We previously reported that triglyceride (TG) levels in small-for-gestational age (SGA) newborns were significantly higher than those in appropriate-for-gestational age (AGA) newborns. Stearoyl-CoA desaturase (SCD) activity is required for TG synthesis, while lipoprotein lipase mass (LPLm) facilitates TG clearance. The purpose of this study is to reveal whether SCD activity or LPLm is the cause of high TG levels in SGA newborns. Fifty-five newborns were classified as AGA (nâ¯=â¯42) and SGA (nâ¯=â¯13). Serum LPLm, TG and fatty acids in umbilical cord blood were analyzed. Then, [16:1 (n-7)]/ [16:0] and [18:1 (n-9)]/ [18:0] were calculated as SCD16 and SCD18 activities, respectively. The SGA group showed significantly higher TG levels and significantly lower LPLm levels than the AGA group. However, SCD16 and 18 activities were lower in SGA newborns than in AGA newborns. In conclusion, LPLm, rather than SCD activity may be involved in the increased TG levels in SGA newborns.
Asunto(s)
Sangre Fetal/enzimología , Recién Nacido Pequeño para la Edad Gestacional/sangre , Lipoproteína Lipasa/sangre , Estearoil-CoA Desaturasa/sangre , Adulto , Femenino , Edad Gestacional , Humanos , Recién Nacido , MasculinoRESUMEN
INTRODUCTION: Recent studies indicate that alkaline phosphatase (ALP) may affect expression and activity of fatty acid (FA) transport proteins in placenta and other tissues. OBJECTIVE: To evaluate if disturbed FA profile in offspring of gestational diabetes mellitus (GDM) with different maternal pregestational weight could be related to maternal or neonatal ALP. METHODS: Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 lean-GDM, 20 obese-GDM). Fetal ultrasound was performed. At delivery, FAs were analyzed in placenta, maternal, and venous cord blood. Western blotting analysis of lipid carriers was performed in placenta. RESULTS: Newborns from obese-GDM tended to higher birthweight (p = 0.059) than those from both lean-GDM and controls. ALP in maternal blood tended to be lower in GDM (p = 0.170) while increased significantly in cord blood of obese-GDM with respect to controls (p = 0.039). Saturated FA percentages in cord blood were significantly higher (p < 0.000), while polyunsaturated FA (PUFA) percentages were lower (p = 0.003) in both GDM, which could be due to a lower expression of major family domain 2a receptor (MFSD2a) in the placenta. Plasma ALP in the offspring of obese-GDM was inversely associated to cord essential PUFAs (ß = -6.18, p = 0.005) and to placental MFSD2a (ß = -38.46, p = 0.014). CONCLUSIONS: Cord PUFA and placental MFSD2a are decreased in both lean and obese-GDM pregnancies. Higher ALP in cord blood of obese-GDM could play a role in the FA levels in these pregnancies.
Asunto(s)
Fosfatasa Alcalina/sangre , Diabetes Gestacional/enzimología , Ácidos Grasos Insaturados/análisis , Sangre Fetal/enzimología , Obesidad/enzimología , Adulto , Estudios de Casos y Controles , Ácidos Grasos Insaturados/sangre , Femenino , Sangre Fetal/química , Humanos , Obesidad/complicaciones , Placenta/química , Embarazo , Tercer Trimestre del Embarazo , Estudios ProspectivosRESUMEN
Our research shows that the newborns of vitamin D-deficient mothers have higher serum alkaline phosphatase (ALP) activity compared with those of vitamin D-non-deficient mothers, which is likely related to increased bone turnover rather than just being a marker for bone formation. This has a potential negative impact on fetal bone development and subsequent skeletal growth. PURPOSE/INTRODUCTION: Low maternal serum 25-hydroxy vitamin D (25(OH)D) level during pregnancy contributes to vitamin D deficiency in infants at birth, which is associated with multiple potential adverse effects on fetal skeletal mineralization and growth. We studied the relationship between maternal 25(OH)D level and newborn serum alkaline phosphatase activity (ALP) at term. METHODS: In this prospective cross-sectional hospital-based study, venous blood samples of healthy pregnant mothers were drawn to measure 25(OH)D levels within 6 h of delivery. Cord blood samples were examined for calcium, phosphorus levels, and ALP activity immediately after birth. In addition, we also recorded the newborns' anthropometric measurements. RESULTS: Seventy-two percent (n = 108/150) of mothers in our study were vitamin D-deficient (serum 25(OH)2D < 25 nmol/l). In a multivariate logistic regression model, young maternal age (odds ratio (OR) = 0.94, 95% CI 0.88-0.99, p = 0.04) and increased weight (OR = 1.03, 95% CI 1.01-1.07, p = 0.02) as well as decreased milk intake (OR = 0.31, 95% CI 0.13-0.74, p = 0.009) were all significantly associated with maternal vitamin D deficiency. ALP activity was significantly higher in newborns of vitamin D-deficient compared with vitamin D-non-deficient mothers (median = 176 (IQR = 139-221) and 156 (IQR = 132-182), respectively, p = 0.04). A significant inverse correlation (Pearson's coefficient = - 0.18, p = 0.03) was observed between maternal 25(OH)D levels and babies' ALP activities. This association persisted in a multivariate logistic regression model (OR = 3.46, 95% CI 1.18-10.18, p = 0.024). CONCLUSIONS: Our findings indicate that newborns of vitamin D-deficient mothers have higher serum ALP activity than those of non-deficient mothers, which might be related to increased bone turnover rather than just being a marker for bone formation. This could have a potential negative impact on fetal bone development and subsequent skeletal growth.
Asunto(s)
Fosfatasa Alcalina/sangre , Complicaciones del Embarazo/epidemiología , Efectos Tardíos de la Exposición Prenatal , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Adulto , Calcio/sangre , Estudios Transversales , Femenino , Sangre Fetal/enzimología , Humanos , Recién Nacido , Madres , Fósforo/sangre , Embarazo , Complicaciones del Embarazo/sangre , Estudios Prospectivos , Arabia Saudita/epidemiología , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Adulto JovenAsunto(s)
Amnios/enzimología , Vellosidades Coriónicas/enzimología , Pruebas de Enzimas/métodos , Sangre Fetal/enzimología , Enfermedades por Almacenamiento Lisosomal/diagnóstico , Diagnóstico Prenatal/métodos , Amniocentesis , Amnios/citología , Células Sanguíneas/enzimología , Células Sanguíneas/metabolismo , Células Cultivadas , Muestra de la Vellosidad Coriónica , Femenino , Sangre Fetal/citología , Humanos , Recién Nacido , Enfermedades por Almacenamiento Lisosomal/enzimología , Enfermedades por Almacenamiento Lisosomal/patología , Masculino , Tamizaje Neonatal , Embarazo , Cultivo Primario de Células/métodos , Estudios Retrospectivos , Enfermedad de Sandhoff/diagnóstico , Enfermedad de Sandhoff/enzimología , Enfermedad de Tay-Sachs/diagnóstico , Enfermedad de Tay-Sachs/enzimología , TurquíaRESUMEN
Mesenchymal stem cells (MSCs) are multipotent adult stem cells that present immunosuppressive effects in experimental and clinical trials targeting various rare diseases including inflammatory bowel disease (IBD). In addition, recent studies have reported tryptophanyl-tRNA synthetase (WRS) possess uncanonical roles such as angiostatic and anti-inflammatory effects. However, little is known about the function of WRS in MSC-based therapy. In this study, we investigated if a novel factor, WRS, secreted from MSCs has a role in amelioration of IBD symptoms and determined a specific mechanism underlying MSC therapy. Experimental colitis was induced by administration of 3% DSS solution to 8-week-old mice and human umbilical cord blood-derived MSCs (hUCB-MSCs) were injected intraperitoneally. Secretion of WRS from hUCB-MSCs and direct effect of WRS on isolated CD4ï¼ T cells was determined via in vitro experiments and hUCB-MSCs showed significant therapeutic rescue against experimental colitis. Importantly, WRS level in serum of colitis induced mice decreased and recovered by administration of MSCs. Through in vitro examination, WRS expression of hUCB-MSCs increased when cells were treated with interferon-γ (IFN-γ). WRS was evaluated and revealed to have a role in inhibiting activated T cells by inducing apoptosis. In summary, IFN-γ- mediated secretion of WRS from MSCs has a role in suppressive effect on excessive inflammation and disease progression of IBD and brings new highlights in the immunomodulatory potency of hUCB-MSCs. [BMB Reports 2019; 52(5): 318-323].
Asunto(s)
Colitis/terapia , Interferón gamma/farmacología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/enzimología , Triptófano-ARNt Ligasa/metabolismo , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Colitis/inmunología , Colitis/patología , Modelos Animales de Enfermedad , Sangre Fetal/citología , Sangre Fetal/enzimología , Sangre Fetal/inmunología , Humanos , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/inmunología , Ratones , Ratones Endogámicos C57BL , Células MadreRESUMEN
In umbilical cord blood transplantation (UCBT), the number of cluster of differentiation (CD)34+ cells and colonyforming units (CFUs) in the cord blood (CB) graft positively correlate with patient survival. Therefore, these parameters are currently used for quality assessment of the cryopreserved CB cells in the attached segment that is considered representative of the CB in the main bag prior to UCBT. Since aldehyde dehydrogenase (ALDH) activity is high in hematopoietic stem cells, the number of ALDHbright (ALDHbr) cells was examined in comparison with the number of CD34+ cells and CFUs for the quality assessment of CB units. In the cryopreserved main bag, the number of ALDHbr cells in the CB unit exhibited positive correlation with the number of CD34+ cells, and with CFUgranulocytes/macrophages and total CFU counts. Furthermore, the concentration of ALDHbr cells in the cryopreserved attached segment was not significantly different compared to that of the main bag, suggesting that the attached segment is representative of the main bag. In conclusion, the present study suggested that ALDHbr cell counts in the cryopreserved attached segments may serve as a quality assessment indicator for CB units prior to UCBT.
Asunto(s)
Aldehído Deshidrogenasa/genética , Diferenciación Celular/genética , Criopreservación , Sangre Fetal/enzimología , Antígenos CD34/genética , Linaje de la Célula/genética , Ensayo de Unidades Formadoras de Colonias , Trasplante de Células Madre de Sangre del Cordón Umbilical , Citometría de Flujo , Regulación Enzimológica de la Expresión Génica/genética , Granulocitos/citología , Granulocitos/enzimología , Células Madre Hematopoyéticas/metabolismo , Humanos , Macrófagos/citología , Macrófagos/enzimología , Células Madre/metabolismoRESUMEN
Alzheimer's Disease (AD) is the leading cause of dementia in the elderly. In healthy individuals, amyloid precursor protein (APP) is cleaved by α-secretase, generating soluble α-amyloid precursor protein (sAPPα), which contributes neuroprotective functions in the neuronal environment. In contrast, in the neurodegenerative environment of AD patients, amyloid-ß-peptide (Aß) of either 40 or 42 residues are generated by increased activity of ß- and γ-secretase. These proteins amalgamate in specific regions of the brain, which disrupts neuronal functions and leads to cognitive impairment. Human umbilical cord blood cells (HUCBC) have proven useful as potential immunomodulatory therapies in various models of neurodegenerative diseases, including AD. Our most recent work studied the impact of umbilical cord blood serum (CBS) on modulation of sAPPα production. Heat-sensitive CBS significantly promoted sAPPα production, indicating that heat-sensitive factor(s) play(s) a role in this process. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to determine the molecular source of α-secretase in purified CBS and aged blood serum (AgBS) fraction. Of the proteins identified, the subunits of C1 complex (C1q, C1r, and C1s) and alpha-2-macroglobulin showed significantly greater levels in purified α-CBS fraction (α-CBSF) compared with the AgBS fraction (AgBSF). Specifically, C1 markedly increased sAPPα and alpha-carboxyl-terminal fragment (α-CTF) production in a dose-dependent fashion, whereas C1q alone only minimally increased and C3 did not increase sAPPα production in the absence of sera. Furthermore, C1q markedly increased sAPPα and α-CTF, while decreasing Aß, in CHO/APPwt cells cultured in the presence of whole sera. These results confirm our initial assumption that APP α-secretase activity in human blood serum is mediated by complement C1, opening a potential therapeutic modality for the future of AD.
Asunto(s)
Secretasas de la Proteína Precursora del Amiloide/metabolismo , Complemento C1/metabolismo , Sangre Fetal/enzimología , Anciano , Envejecimiento/sangre , Péptidos beta-Amiloides/metabolismo , Animales , Células CHO , Complemento C1/aislamiento & purificación , Complemento C3b/metabolismo , Cricetinae , Cricetulus , Calor , Humanos , Ratones , ProteómicaAsunto(s)
Cloropirifos/toxicidad , Eritrocitos/efectos de los fármacos , Sangre Fetal/efectos de los fármacos , Insecticidas/toxicidad , Neonicotinoides/toxicidad , Aldehídos/toxicidad , Catalasa/metabolismo , Eritrocitos/enzimología , Eritrocitos/metabolismo , Sangre Fetal/enzimología , Sangre Fetal/metabolismo , Humanos , Fragilidad Osmótica/efectos de los fármacos , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Cord blood units (CBUs) are processed, frozen, and thawed before use in hematopoietic stem cell (HSC) transplantation. The manipulations affect HSC functionality, that is, induce apoptosis and reduce viability. HSC content, commonly expressed as CBU potency, that is, the expected ability of a CBU to restore hematopoiesis, is traditionally approximated through viable CD34+ cells and the colony-forming unit (CFU) cell cultivation assay. Alternative approaches, for example, the aldehyde dehydrogenase (ALDH) enzyme-based assay, are also forthcoming. We hypothesized that the ALDH assay might exclude apoptotic cells since it is based on enzyme activity. To investigate this, we designed a protocol for simultaneous staining of viable and apoptotic CD34+ and ALDH+ cells using 7-aminoactinomycin (7-AAD) and annexin V, in frozen-thawed CBUs. Results were correlated with results from the colony-forming unit-granulocyte/macrophage (CFU-GM) assay. STUDY DESIGN AND METHODS: Samples from 57 CBUs were thawed and simultaneously analyzed for CD34+ cells, ALDH+ cells, viability (7-AAD), and apoptosis (annexin V) using flow cytometry. Enumeration of CFUs was also performed. RESULTS: No nonviable and few apoptotic cells (mean 0.7%) were identified in the ALDH+ population compared to the viable CD34+ population (mean 3.6%). The total number of ALDH+ cells correlated better than viable CD34+ cells (r = 0. 72 vs. r = 0.66; p < 0.0001) with the results of the CFU assay. CONCLUSION: The ALDH assay excludes nonviable and apoptotic cells, and therefore correlates better with CFU enumeration compared to the number of viable CD34+ cells. We propose that the ALDH assay might replace the CFU-GM method in CBU potency measurements.
Asunto(s)
Aldehído Deshidrogenasa/metabolismo , Apoptosis , Protocolos Clínicos/normas , Sangre Fetal/citología , Antígenos CD34/sangre , Almacenamiento de Sangre/métodos , Supervivencia Celular , Ensayo de Unidades Formadoras de Colonias , Pruebas de Enzimas/métodos , Pruebas de Enzimas/normas , Sangre Fetal/enzimología , HumanosRESUMEN
BACKGROUND: Lactic acid dehydrogenase (LDH) is a valuable marker for some of the most important diseases in newborns and the plasma LDH activity in newborns correlates well with conditions such as asphyxia. If LDH should be considered as a useful tool also in obstetric care, key factors associated with maternal health before and during pregnancy which could affect umbilical cord LDH activity need to be known. The aims of this study were to explore relationships between selected maternal conditions and arterial lactic acid dehydrogenase activity (aLDH) in umbilical cord blood at delivery. METHODS: A prospective observational study was conducted at Sodersjukhuset, Stockholm, Sweden. Included in the study were 1247 deliveries, and cord blood samples from each were analyzed for aLDH. Background, delivery and neonatal data were collected from the medical records. RESULTS: Higher median values of aLDH were found (P=0.001) among women with chronic disorders not related to pregnancy but there was no increased frequency of high aLDH levels (>612 µ/L, P=0.30). No difference in aLDH was identified between infants born to women with pregnancy-related disorders compared with healthy women, neither in median values, nor in high values (>612 µ/L, P=0.95). CONCLUSION: Newborn infants born to women with non-pregnancy-related chronic disorders had a somewhat higher median value of aLDH in cord blood at delivery. The influence of common maternal conditions and diseases on umbilical cord arterial LDH levels is small compared to the increase reported in fetal distress and several other critical conditions in the newborn.
Asunto(s)
Sangre Fetal/enzimología , L-Lactato Deshidrogenasa/sangre , Adolescente , Adulto , Enfermedad Crónica , Femenino , Sufrimiento Fetal/sangre , Hemólisis , Humanos , Recién Nacido , Masculino , Salud Materna , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/sangre , Estudios Prospectivos , Valores de Referencia , Factores de Riesgo , Suecia , Adulto JovenRESUMEN
OBJECTIVE: To evaluate a relationship between preeclampsia and prolidase enzyme activity. METHODS: A prospective cohort study of 41 pregnant women diagnosed with preeclampsia and 31 healthy pregnant women as control group was selected at Harran University Hospital Department of Obstetrics and Gynecology. The prolidase enzyme activity was analyzed in maternal and umbilical cord plasma, amniotic fluid and placental and umbilical cord tissues by Chinard method in addition to maternal serum levels of lactate dehydrogenase (LDH), serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT). RESULTS: A significant relationship was found between plasma prolidase activity (635 ± 83 U/L) (p = 0.007), umbilical cord plasma prolidase activity (610 ± 90 U/L) (p = 0.013), amniotic fluid prolidase activity (558 ± 100 U/L) (p = 0.001), umbilical cord tissue prolidase activity (4248 ± 1675 U/gr protein) (p = 0.013) and placental tissue prolidase activity (2116 ± 601 U/gr protein) (p = 0.001) in preeclamptic group when compared to healthy pregnant women. CONCLUSION: There is a strong correlation between prolidase enzyme activity and preeclampsia. Prolidase enzyme activity may play a role in preeclampsia.
Asunto(s)
Dipeptidasas/metabolismo , Placenta/enzimología , Preeclampsia/enzimología , Adulto , Líquido Amniótico/enzimología , Estudios de Casos y Controles , Dipeptidasas/sangre , Femenino , Sangre Fetal/enzimología , Humanos , Preeclampsia/etiología , Embarazo , Estudios Prospectivos , Estadísticas no Paramétricas , Cordón Umbilical/enzimologíaRESUMEN
Axl encodes the tyrosine-protein kinase receptor, participating in the proliferation and migration of many cells. This study examined the role of Axl in functions of endothelial progenitor cells (EPCs). Axl was detected by RT-PCR and Western blotting in both placentas and EPCs from normal pregnancy and preeclampsia patients. The Axl inhibitor, BMS777-607, was used to inhibit the Axl signalling pathway in EPCs. Cell proliferation, differentiation, migration and adhesion were measured by CCK-8 assay, cell differentiation assay, Transwell assay, and cell adhesion assay, respectively. Results showed the expression levels of Axl mRNA and protein were significantly higher in both placentas and EPCs from preeclampsia patients than from normal pregnancy (P<0.05). After treatment with BMS777-607, proliferation, differentiation, migration and adhesion capability of EPCs were all significantly decreased. Our study suggests Axl may play a role in the function of EPCs, thereby involving in the pathogenesis of preeclampsia.
Asunto(s)
Células Endoteliales de la Vena Umbilical Humana/enzimología , Preeclampsia/genética , Proteínas Proto-Oncogénicas/genética , ARN Mensajero/genética , Proteínas Tirosina Quinasas Receptoras/genética , Células Madre/enzimología , Adulto , Aminopiridinas/farmacología , Presión Sanguínea , Estudios de Casos y Controles , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Sangre Fetal/citología , Sangre Fetal/enzimología , Regulación de la Expresión Génica , Edad Gestacional , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Placenta/metabolismo , Placenta/fisiopatología , Preeclampsia/sangre , Preeclampsia/fisiopatología , Embarazo , Cultivo Primario de Células , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/metabolismo , Piridonas/farmacología , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/metabolismo , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/metabolismo , Células Madre/efectos de los fármacos , Células Madre/patología , Tirosina Quinasa del Receptor AxlRESUMEN
The investigation of fetal cord blood (FCB) during child delivery has created a novel topic in the field of psychiatric research. The umbilical vein receives nutrients and oxygen from the mother's circulation and transports them to the fetal circulation. Investigating fetal cord blood during delivery is beneficial for understanding the fetal environment. Depression in pregnancy is associated with medical and emotional burdens. In this study, we aimed to investigate glutathione peroxidase (Gpx) and myeloperoxidase (MPO) activity in the FCB of depressed mothers and healthy controls. Our study included 45 depressed mothers and 59 healthy controls. The FCB samples were collected from the umbilical vein during delivery. We found that Gpx levels were significantly decreased in the FCB of depressed mothers than healthy controls, medians were 0.14 U/ml and 0.16 U/ml respectively, Z: -3.567 and p < 0.001. MPO levels were similar in both groups, medians were 1.0 U/L and 1.2 U/L respectively, Z: -1.837 and p:0.066. Depression in pregnancy may be associated with decreased antioxidant levels, and this condition may cause an oxidative load, which may lead to improper brain development. Future studies should be performed in larger samples to clarify our preliminary results.
Asunto(s)
Depresión/sangre , Depresión/enzimología , Sangre Fetal/enzimología , Glutatión Peroxidasa/sangre , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/enzimología , Adulto , Peso al Nacer , Cesárea , Femenino , Humanos , Recién Nacido , Madres/psicología , Peroxidasa/sangre , Embarazo , Escalas de Valoración PsiquiátricaRESUMEN
AIM: Fetal blood contains higher concentrations of glutamate-oxaloacetate transaminase (GOT; a blood enzyme able to metabolize glutamate) than maternal blood. The aim of this study was to determine the relationship between GOT and glutamate levels in arterial blood samples from umbilical cord in control newborn infants and newborn infants with hypoxic-ischaemic insult and/or symptoms of hypoxia-ischemia after delivery. METHOD: A total of 46 newborn infants (28 females, 18 males) were prospectively included in the study. Twenty-three infants (18 females, five males) were included as control participants and 23 (10 females, 13 males) were included as newborn infants at risk of adverse neurological outcome (defined as umbilical blood with pH <7.1). RESULTS: Analysis of glutamate concentration and GOT activity in umbilical blood samples showed that newborn infants with pH <7.1 had higher levels of glutamate (142.4 µmol/L [SD 61.4] vs 62.8 µmol/L [SD 25.5]; p<0.001) and GOT (83.1 U/L [SD 60.9] vs 34.9 U/L [SD 18.2]; p<0.001) compared to newborn infants without fetal distress. Analysis of Apgar scores and blood pH values (markers of perinatal distress) showed that conditions of severe distress were associated with higher glutamate and GOT levels. INTERPRETATION: During fetal development, the ability of GOT to metabolize glutamate suggests that this enzyme can act as an endogenous protective mechanism in the control of glutamate homeostasis.
Asunto(s)
Aspartato Aminotransferasas/sangre , Asfixia Neonatal/sangre , Sangre Fetal/metabolismo , Ácido Glutámico/sangre , Hipoxia-Isquemia Encefálica/sangre , Asfixia Neonatal/enzimología , Estudios Transversales , Femenino , Sangre Fetal/enzimología , Humanos , Hipoxia-Isquemia Encefálica/enzimología , Recién Nacido , Masculino , Neuroprotección/fisiología , Neurotoxinas/sangreRESUMEN
OBJECTIVE: To compare ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) concentrations in umbilical cord blood of neonates who develop Sarnat stage II-III hypoxic-ischemic encephalopathy (HIE) to healthy controls, and to relate the concentrations to the severity of neurology and long-time outcomes. MATERIAL AND METHODS: Cord sera of 15 neonates with HIE II-III and 31 matched controls were analyzed for UCH-L1 and GFAP. Comparisons were performed for cord artery pH, amplitude-integrated electroencephalography (aEEG), stage of HIE, and death or sequelae up to an age of 6 years. Parametric and non-parametric statistics were used with a two-sided p < 0.05 considered significant. RESULTS: Among controls no associations between biomarker concentrations and gestational age, birthweight, length of storage of cord sera and degree of hemolysis were found. No significant differences in biomarker concentrations were found between HIE neonates and controls, and no differences were found with regard to HIE stage, cord acidemia, severity of aEEG changes, or persistent sequelae or death. CONCLUSIONS: No differences in cord blood UCH-L1 and GFAP concentrations were found between HIE neonates and controls, and no associations were found between the biomarker concentrations and the severity of disease, or whether the condition developed into a permanent or fatal injury.
Asunto(s)
Peso al Nacer , Proteína Ácida Fibrilar de la Glía/sangre , Hipoxia-Isquemia Encefálica/sangre , Ubiquitina Tiolesterasa/sangre , Acidosis/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Sangre Fetal/enzimología , Edad Gestacional , Hemólisis , Humanos , Recién Nacido , Masculino , Manejo de EspecímenesRESUMEN
OBJECTIVE: To evaluate the association between fetal and maternal catechol-O-methyltransferase (COMT) Val158Met and methyl tetrahydrofolate reductase (MTHFR) C677T functional polymorphisms and preeclampsia, examining its influence on placental COMT and in maternal 2-methoxyestradiol (2-ME) plasma levels. DESIGN: Prospective case-control study. SETTING: University hospital. PATIENT(S): A total of 53 preeclamptic and 72 normal pregnant women. INTERVENTION(S): Maternal and cord blood samples and placental tissue samples were obtained. MAIN OUTCOME MEASURE(S): Maternal and fetal COMT and MTHFR polymorphisms were genotyped. Maternal plasma 2-ME and homocysteine levels, and expression and activity of placental COMT were measured. RESULT(S): The odds ratio for the risk of preeclampsia for fetal COMT Met/Met was 3.22, and it increased to 8.65 when associated with fetal MTHFR TT. Placental COMT activity and expression were influenced by genotype, but COMT activity in preeclamptic placentas did not differ from control pregnancies. There was no association between any genotypes and maternal 2-ME. Homocysteine levels were higher in women with preeclampsia than in normal pregnancies, and were inversely correlated with 2-ME plasma levels, indicating that its altered metabolism may lower COMT activity in vivo. CONCLUSION(S): Fetal Met-Met COMT genotype reduces COMT placental expression and activity in vitro and increases preeclampsia, risk but it does not explain the difference in maternal 2-ME levels between preeclamptic and normal pregnancies. However, the preeclamptic patients had elevated homocysteine levels that correlated inversely with 2-ME, indicating that an altered methionine-homocysteine metabolism may contribute to reduce COMT activity in vivo and explain the decreased levels of 2-ME in preeclamptic women.
Asunto(s)
Presión Sanguínea/genética , Catecol O-Metiltransferasa/genética , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , 2-Metoxiestradiol , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Catecol O-Metiltransferasa/sangre , Distribución de Chi-Cuadrado , Estradiol/análogos & derivados , Estradiol/sangre , Femenino , Sangre Fetal/enzimología , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Homocisteína/sangre , Hospitales Universitarios , Humanos , Modelos Logísticos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Análisis Multivariante , Oportunidad Relativa , Fenotipo , Placenta/enzimología , Preeclampsia/sangre , Preeclampsia/diagnóstico , Preeclampsia/enzimología , Preeclampsia/fisiopatología , Embarazo , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , EspañaRESUMEN
OBJECTIVE: Targeted screening for glucose-6-phosphate dehydrogenase deficiency (G6PDdef) using fluorescent spot test (FST) is done in our newborn nursery (NN) and now in our NICU. Premature infants have higher G6PD levels than term infants. FST may result in under diagnosis of G6PDdef in preterms. We sought to determine if FST is appropriate for diagnosis of G6PDdef at<35 weeks and assess screening in NICU. STUDY DESIGN: Retrospective chart review of male, inborn infants<35 weeks in NICU from 2008 to 2011. Difference in G6PDdef incidence<5% between NN and NICU was acceptable for equivalence. RESULTS: Out of 679 subjects, 442 were screened for G6PDdef and 11.3% had abnormal results. Binomial testing comparing 11.3% (95% confidence interval (CI) 8.5 to 14.6) incidence of G6PDdef in NICU and reported incidence in NN (11%) demonstrated no difference. 12.2% of Black/African American males were not screened. CONCLUSION: FST is appropriate for screening all at-risk newborns. A number of at-risk premature males were not screened.
Asunto(s)
Sangre Fetal/enzimología , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Recien Nacido Prematuro/sangre , Tamizaje Neonatal , Femenino , Glucosafosfato Deshidrogenasa/sangre , Deficiencia de Glucosafosfato Deshidrogenasa/epidemiología , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Ohio , Estudios RetrospectivosRESUMEN
This study was conducted to determine the association of Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency among neonates admitted with jaundice at the neonatal intensive care unit, well baby nursery and neonatal step down nursery of the Aga Khan University Hospital, Karachi, Pakistan, from January to June 2010. A total of 205 neonates following the selection criteria were included. All selected neonates have their venous blood drawn, saved in EDTA bottle and sent to laboratory of The Aga Khan University Hospital (AKUH). The laboratory results of whether G-6-PD deficiency was present or not was recorded in the proforma. G-6-PD was deficient in 19 neonates (9.3%). All neonates were male.