RESUMEN
BACKGROUND: Neonatal encephalopathy following perinatal asphyxia is a leading cause for neonatal death and disability, despite treatment with therapeutic hypothermia. 2-Iminobiotin is a promising neuroprotective agent additional to therapeutic hypothermia to improve the outcome of these neonates. METHODS: In an open-label study, pharmacokinetics and short-term safety of 2-iminobiotin were investigated in neonates treated with therapeutic hypothermia. Group A (n = 6) received four doses of 0.16 mg/kg intravenously q6h. Blood sampling for pharmacokinetic analysis and monitoring of vital signs for short-term safety analysis were performed. Data from group A was used to determine the dose for group B, aiming at an AUC0-48 h of 4800 ng*h/mL. RESULTS: Exposure in group A was higher than targeted (median AUC0-48 h 9522 ng*h/mL); subsequently, group B (n = 6) received eight doses of 0.08 mg/kg q6h (median AUC0-48 h 4465 ng*h/mL). No changes in vital signs were observed and no adverse events related to 2-iminobiotin occurred. CONCLUSION: This study indicates that 2-iminobiotin is well tolerated and not associated with any adverse events in neonates treated with therapeutic hypothermia after perinatal asphyxia. Target exposure was achieved with eight doses of 0.08 mg/kg q6h. Optimal duration of therapy for clinical efficacy needs to be determined in future clinical trials.
Asunto(s)
Asfixia Neonatal/terapia , Biotina/análogos & derivados , Inhibidores Enzimáticos/farmacocinética , Hipotermia Inducida , Hipoxia-Isquemia Encefálica/prevención & control , Óxido Nítrico Sintasa/antagonistas & inhibidores , Asfixia Neonatal/diagnóstico , Asfixia Neonatal/enzimología , Biotina/administración & dosificación , Biotina/efectos adversos , Biotina/farmacocinética , Esquema de Medicación , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Femenino , Humanos , Hipotermia Inducida/efectos adversos , Hipoxia-Isquemia Encefálica/diagnóstico , Hipoxia-Isquemia Encefálica/enzimología , Recién Nacido , Infusiones Intravenosas , Masculino , Países Bajos , Óxido Nítrico Sintasa/metabolismo , Estudios Prospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Multi-organ injury causes leakage of several intracellular enzymes into the circulation. We evaluated the correlation between the serum-leaked intracellular enzyme levels at the beginning of treatment and the outcome in perinatally stressed neonates. MATERIALS AND METHODS: We retrospectively studied neonates whose 1 minute Apgar score was < 7. We collected initial venous blood sample data, including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, and correlated these with patient short-term outcomes. RESULTS: Of 60 neonates, nine patients were treated with therapeutic hypothermia, and 32 needed mechanical ventilation. The therapeutic hypothermia group showed significantly larger base deficit, and higher lactate, AST, ALT, LDH, and CK (all p < 0.01). The duration of mechanical ventilation significantly correlated with AST, ALT, LDH, and CK levels (all p < 0.01). CONCLUSION: Initial enzyme levels are useful for predicting the duration of mechanical ventilation in stressed neonates.
Asunto(s)
Asfixia Neonatal/embriología , Recién Nacido/metabolismo , Síndrome de Aspiración de Meconio/enzimología , Taquipnea/enzimología , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Asfixia Neonatal/sangre , Asfixia Neonatal/enzimología , Creatina Quinasa/sangre , Femenino , Humanos , L-Lactato Deshidrogenasa/sangre , Ácido Láctico/sangre , Síndrome de Aspiración de Meconio/sangre , Embarazo , Estudios Retrospectivos , Taquipnea/sangreRESUMEN
Introducción: la asfixia perinatal es un problema de salud que puede acarrear alteraciones del neurodesarrollo en los recién nacidos. Las determinaciones en suero de enolasa específica de neurona, lactato deshidrogenasa y aspartato amino transferasa han sido utilizadas como marcadores de asfixia perinatal. Objetivos: evaluar el valor de las determinaciones en suero de lactato deshidrogenasa, aspartato amino transferasa y enolasa específica de neurona como marcadores moleculares de la asfixia perinatal. Métodos: se realizó un estudio observacional descriptivo de corte transversal. Se trabajó con una muestra intencional de 41 recién nacidos asfícticos, clasificados con distintos grados de encefalopatía hipóxico-isquémica según los criterios de Sarnat. Se tomaron muestras de suero al momento del nacimiento y a las 72 horas siguientes. Las determinaciones en suero de enolasa específica de neurona se realizaron por ELISA. Se cuantificó lactato deshidrogenasa y aspartato amino transferasa por espectrofotometría. Resultados: todos los pacientes presentaron valores elevados en suero, de los tres analitos, a las 24 y 72 horas de nacidos. Los valores enzimáticos no variaron significativamente entre las 24 y 72 horas de nacidos sin tomar en cuenta el grado de encefalopatía hipóxico-isquémica. Existe correlación positiva entre los valores enzimáticos a las 24 y a las 72 horas de enolasa específica de neurona y lactato deshidrogenasa. No fue posible diferenciar el grado de encefalopatía hipóxico-isquémica a través de los niveles en suero de estas enzimas. Conclusiones: los valores de estas determinaciones enzimáticas contribuyen a describir desde el punto de vista bioquímico el cuadro del neonato con asfixia perinatal(AU)
Introduction: perinatal asphyxia is a health problem which may cause neurodevelopmental alterations in newborns. Serum determinations of neuron-specific enolase, lactate dehydrogenase, and aspartate aminotransferase have been used as markers of perinatal asphyxia. Objectives: evaluate the value of serum determinations of lactate dehydrogenase, aspartate aminotransferase and neuron-specific enolase as molecular markers of perinatal asphyxia. Methods: a cross-sectional observational descriptive study was conducted of 41 asphyxiated newborns classified as different grades of hypoxic-ischemic encephalopathy according to Sarnat's scale. Serum samples were taken at birth and 72 hours later. Serum determinations of neuron-specific enolase were obtained by ELISA. Lactate dehydrogenase and aspartate aminotransferase were quantified by espectrophotometry. Results: all the patients had high serum values of the three analytes 24 and 72 hours after birth. Enzyme values did not vary significantly from 24 to 72 hours after birth, not considering the grade of hypoxic-ischemic encephalopathy. A positive correlation was found between enzyme values for neuron-specific enolase and lactate dehydrogenase at 24 and 72 hours. It was not possible to differentiate the grade of hypoxic-ischemic encephalopathy via the serum levels of these enzymes. Conclusions: the values of these enzyme determinations contribute to describe the status of neonates with perinatal asphyxia from a biochemical point of view(AU)
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Asfixia Neonatal/enzimología , Fosfopiruvato Hidratasa , Aspartato Aminotransferasas/uso terapéutico , Epidemiología Descriptiva , Estudios Transversales , Estudios Observacionales como AsuntoRESUMEN
Introducción: la asfixia perinatal es un problema de salud que puede acarrear alteraciones del neurodesarrollo en los recién nacidos. Las determinaciones en suero de enolasa específica de neurona, lactato deshidrogenasa y aspartato amino transferasa han sido utilizadas como marcadores de asfixia perinatal. Objetivos: evaluar el valor de las determinaciones en suero de lactato deshidrogenasa, aspartato amino transferasa y enolasa específica de neurona como marcadores moleculares de la asfixia perinatal. Métodos: se realizó un estudio observacional descriptivo de corte transversal. Se trabajó con una muestra intencional de 41 recién nacidos asfícticos, clasificados con distintos grados de encefalopatía hipóxico-isquémica según los criterios de Sarnat. Se tomaron muestras de suero al momento del nacimiento y a las 72 horas siguientes. Las determinaciones en suero de enolasa específica de neurona se realizaron por ELISA. Se cuantificó lactato deshidrogenasa y aspartato amino transferasa por espectrofotometría. Resultados: todos los pacientes presentaron valores elevados en suero, de los tres analitos, a las 24 y 72 horas de nacidos. Los valores enzimáticos no variaron significativamente entre las 24 y 72 horas de nacidos sin tomar en cuenta el grado de encefalopatía hipóxico-isquémica. Existe correlación positiva entre los valores enzimáticos a las 24 y a las 72 horas de enolasa específica de neurona y lactato deshidrogenasa. No fue posible diferenciar el grado de encefalopatía hipóxico-isquémica a través de los niveles en suero de estas enzimas. Conclusiones: los valores de estas determinaciones enzimáticas contribuyen a describir desde el punto de vista bioquímico el cuadro del neonato con asfixia perinatal(AU)
Introduction: perinatal asphyxia is a health problem which may cause neurodevelopmental alterations in newborns. Serum determinations of neuron-specific enolase, lactate dehydrogenase, and aspartate aminotransferase have been used as markers of perinatal asphyxia. Objectives: evaluate the value of serum determinations of lactate dehydrogenase, aspartate aminotransferase and neuron-specific enolase as molecular markers of perinatal asphyxia. Methods: a cross-sectional observational descriptive study was conducted of 41 asphyxiated newborns classified as different grades of hypoxic-ischemic encephalopathy according to Sarnat's scale. Serum samples were taken at birth and 72 hours later. Serum determinations of neuron-specific enolase were obtained by ELISA. Lactate dehydrogenase and aspartate aminotransferase were quantified by espectrophotometry. Results: all the patients had high serum values of the three analytes 24 and 72 hours after birth. Enzyme values did not vary significantly from 24 to 72 hours after birth, not considering the grade of hypoxic-ischemic encephalopathy. A positive correlation was found between enzyme values for neuron-specific enolase and lactate dehydrogenase at 24 and 72 hours. It was not possible to differentiate the grade of hypoxic-ischemic encephalopathy via the serum levels of these enzymes. Conclusions: the values of these enzyme determinations contribute to describe the status of neonates with perinatal asphyxia from a biochemical point of view(AU)
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Asfixia Neonatal/enzimología , Fosfopiruvato Hidratasa/inmunologíaRESUMEN
OBJECTIVES: Acute kidney injury (AKI) is defined as a decrease in glomerular filtration rate with an increase in serum creatinine (sCr). Perinatal asphyxia (PNA) may be etiological factor for AKI with oxidative stress also implicated. Paraoxonase 1 (PON1) activity has been reported to be decreased in renal disease. The aim of our study was to evaluate paraoxonase 1 (PON1) activity and oxidative stress during the first hours and first days of life and to determine if these parameters could discriminate neonates having AKI from those who do not. METHODS: Serum samples at different time points after birth were obtained from 64 preterm newborns with PNA (45 defined as having AKI, 19 as non-AKI). Clinical markers, sCr, total oxidant status (TOS), total antioxidant status (TAS) and PON1 activity were measured. RESULTS: The AKI group had more newborns with hypoxic ischemic encephalopathy, significantly higher serum creatinine (sCr) at 3 and 7d, total antioxidant status (TAS) at 7d; decreased PON1 at 4h, 6h and 7d than the non-AKI group. Within the AKI group, significant positive correlations were found between PON1 activity at 2h and TAS at 2h, PON1 activity at 4h and base deficit (BD); whereas negative correlations between PON1 activity at 2h and ΔsCr (at 24h and at 3d), PON1 activity at 7d and ΔsCr (at 24h and 3d). Oxidative stress status parameters indicated excellent discriminative potential at 4h, 6h and 7d. CONCLUSIONS: AKI neonates were characterised by a marked decrease in PON1 activity. PON1 activity may be an important factor for discrimination of newborns having AKI from those that do not.
Asunto(s)
Lesión Renal Aguda/sangre , Lesión Renal Aguda/complicaciones , Arildialquilfosfatasa/sangre , Asfixia Neonatal/sangre , Asfixia Neonatal/complicaciones , Estrés Oxidativo , Lesión Renal Aguda/enzimología , Lesión Renal Aguda/patología , Área Bajo la Curva , Asfixia Neonatal/enzimología , Asfixia Neonatal/patología , Biomarcadores/sangre , Biomarcadores/metabolismo , Creatinina/sangre , Femenino , Edad Gestacional , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Modelos Logísticos , Masculino , Embarazo , Nacimiento Prematuro , Curva ROC , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: To evaluate the biochemical consequences and platelet counts of birth asphyxia in neonates. STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Department of Child Health, Nishter Medical College and Hospital, Multan, from September to November 2015. METHODOLOGY: The data of 50 (50%) asphyxiated neonates and 50 (50%) non-asphyxiated neonates, with age range less than 1 month, was collected from Children Ward of Nishtar Hospital, Multan, Pakistan. Data on platelet count in blood, kidney function tests (creatinine, urea), liver function tests (bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and cardiac enzyme test (lactate dehydrogenase (LDH)) were analysed by paired sample t-test by SPSS software. Sociodemographic data of those neonate's mothers was also collected. RESULTS: In asphyxiated neonates LDH, ALT, AST, creatinine, bilirubin, urea levels were higher than healthy infants, while the platelet count was smaller in asphyxiated neonates than healthy infants. CONCLUSION: There was a higher rate of alteration in platelet count, levels of LDH, AST, ALT, urea creatinine and bilirubin in asphyxiated infants. These alterations may be correlated with damage of vital organ of asphyxiated neonates.
Asunto(s)
Asfixia Neonatal/sangre , Asfixia Neonatal/enzimología , Biomarcadores/sangre , Recuento de Plaquetas/estadística & datos numéricos , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Asfixia Neonatal/epidemiología , Bilirrubina/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Creatinina/sangre , Humanos , Recién Nacido , Pruebas de Función Renal , L-Lactato Deshidrogenasa/sangre , Pruebas de Función Hepática , Pakistán/epidemiologíaRESUMEN
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
Perinatal asphyxia (PA) is a leading cause of neuronal damage in newborns, resulting in long-term neurological and cognitive deficits, in part due to impairment of mesostriatal and mesolimbic neurocircuitries. The insult can be as severe as to menace the integrity of the genome, triggering the overactivation of sentinel proteins, including poly (ADP-ribose) polymerase-1 (PARP-1). PARP-1 overactivation implies increased energy demands, worsening the metabolic failure and depleting further NAD(+) availability. Using a global PA rat model, we report here evidence that hypoxia increases PARP-1 activity, triggering a signalling cascade leading to nuclear translocation of the NF-κB subunit p65, modulating the expression of IL-1ß and TNF-α, pro-inflammatory molecules, increasing apoptotic-like cell death in mesencephalon of neonate rats, monitored with Western blots, qPCR, TUNEL and ELISA. PARP-1 activity increased immediately after PA, reaching a maximum 1-8 h after the insult, while activation of the NF-κB signalling pathway was observed 8 h after the insult, with a >twofold increase of p65 nuclear translocation. IL-1ß and TNF-α mRNA levels were increased 24 h after the insult, together with a >twofold increase in apoptotic-like cell death. A single dose of the PARP-1 inhibitor nicotinamide (0.8 mmol/kg, i.p.), 1 h post delivery, prevented the effect of PA on PARP-1 activity, p65 translocation, pro-inflammatory cytokine expression and apoptotic-like cell death. The present study demonstrates that PA leads to PARP-1 overactivation, increasing the expression of pro-inflammatory cytokines and cell death in mesencephalon, effects prevented by systemic neonatal nicotinamide administration, supporting the idea that PARP-1 inhibition represents a therapeutic target against the effects of PA.
Asunto(s)
Asfixia Neonatal/metabolismo , Asfixia/metabolismo , Mesencéfalo/metabolismo , Niacinamida/administración & dosificación , Poli(ADP-Ribosa) Polimerasas/metabolismo , Transducción de Señal , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Asfixia/enzimología , Asfixia Neonatal/enzimología , Humanos , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Mesencéfalo/efectos de los fármacos , Mesencéfalo/enzimología , Proteínas de Neoplasias/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Poli(ADP-Ribosa) Polimerasa-1 , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Thioredoxin (Trx) family proteins are crucial mediators of cell functions via regulation of the thiol redox state of various key proteins and the levels of the intracellular second messenger hydrogen peroxide. Their expression, localization and functions are altered in various pathologies. Here, we have analyzed the impact of Trx family proteins in neuronal development and recovery, following hypoxia/ischemia and reperfusion. METHODS: We have analyzed the regulation and potential functions of Trx family proteins during hypoxia/ischemia and reoxygenation of the developing brain in both an animal and a cellular model of perinatal asphyxia. We have analyzed the distribution of 14 Trx family and related proteins in the cerebellum, striatum, and hippocampus, three areas of the rat brain that are especially susceptible to hypoxia. Using SH-SY5Y cells subjected to hypoxia and reoxygenation, we have analyzed the functions of some redoxins suggested by the animal experiment. RESULTS AND CONCLUSIONS: We have described/discovered a complex, cell-type and tissue-specific expression pattern following the hypoxia/ischemia and reoxygenation. Particularly, Grx2 and Trx1 showed distinct changes during tissue recovery following hypoxia/ischemia and reoxygenation. Silencing of these proteins in SH-SY5Y cells subjected to hypoxia-reoxygenation confirmed that these proteins are required to maintain the normal neuronal phenotype. GENERAL SIGNIFICANCE: These findings demonstrate the significance of redox signaling in cellular pathways. Grx2 and Trx1 contribute significantly to neuronal integrity and could be clinically relevant in neuronal damage following perinatal asphyxia and other neuronal disorders.
Asunto(s)
Asfixia Neonatal/enzimología , Encéfalo/enzimología , Glutarredoxinas/metabolismo , Hipoxia-Isquemia Encefálica/enzimología , Neuronas/enzimología , Tiorredoxinas/metabolismo , Animales , Asfixia Neonatal/patología , Encéfalo/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Glutarredoxinas/genética , Humanos , Hipoxia-Isquemia Encefálica/patología , Masculino , Neuronas/patología , Oxidación-Reducción , Oxígeno/metabolismo , Fenotipo , Interferencia de ARN , Ratas Sprague-Dawley , Transducción de Señal , Tiorredoxinas/genética , Factores de Tiempo , TransfecciónRESUMEN
Because of hypoxemia, different organ systems of the body are affected in perinatal asphyxia. In this study, the functional status of liver of the asphyxiated babies was assessed through estimation of liver enzymes to see any correlation existing between enzyme changes and severity of perinatal asphyxia. A total of 70 full-term asphyxiated newborns (study group) were studied during January'2008 to December'2008 in the department of Paediatrics, Mymensingh Medical College Hospital. After enrollment these babies were grouped according to Sarnat & Sarnat stages of Hypoxic-ischemic encephalopathy (HIE) as stage I, II & III. Babies who are small for gestational age, having severe jaundice, sepsis or congenital anomalies of the hepatobiliary system were excluded from the study. Another 50 healthy newborns were also studied as control group. Venous blood was analyzed between 2nd and 5th day of life to estimate serum AST, ALT & alkaline phosphatase (ALP). Unpaired student's 't' test and Spearman's rank correlation was used for data analysis and P value of <0.05 were considered significant. Mean AST, ALT and ALP of the asphyxiated babies were 76.27±37.44, 82.16±48.08 & 369.59±123.05 U/L and that of normal babies were 23.46±8.45, 26.54±7.76 & 208.20±46.95 U/L respectively and these rise were statistically significant (p<0.001). The levels of transaminases and ALP were positively correlated with the severity of asphyxia and these correlations were also statistically significant (p<0.001). So, this study concludes that AST, ALT & ALP significantly elevated in perinatal asphyxia and this elevation was proportional to the severity of hypoxia.
Asunto(s)
Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Aspartato Aminotransferasas/metabolismo , Asfixia Neonatal/enzimología , Hipoxia/metabolismo , Hígado/enzimología , Asfixia Neonatal/complicaciones , Humanos , Hipoxia/etiología , Recién Nacido , Índice de Severidad de la EnfermedadRESUMEN
The frequency of GSTT1 and GSTM1 gene deletion polymorphism was determined in a case-control study of full-term Ukrainian newborns including patients with perinatal asphyxia. Multiplex polymerase chain reaction was used for genotyping 245 full-term newborns. The investigated full-term newborns with perinatal asphyxia were subdivided in the subgroups depending of severity of perinatal asphyxia and neonatal outcome. No significant differences in allele frequencies of homorygous null genotypes of GSTT1 and GSTM1 gene were detected among newborns with moderate perinatal asphyxia and healthy control. However, association with the development of severe perinatal asphyxia was detected for the deletion polymorphism in GSTT1 gene and the combination of the GSTT1 absent/GSTM1 absent in the newborns. The study shows that severe perinatal asphyxia may develop in the consequence of genetic predisposition to this condition as compare with moderate.
Asunto(s)
Asfixia Neonatal/genética , Eliminación de Gen , Predisposición Genética a la Enfermedad , Glutatión Transferasa/genética , Polimorfismo Genético , Asfixia Neonatal/enzimología , Estudios de Casos y Controles , Homocigoto , Humanos , Recién Nacido , Reacción en Cadena de la Polimerasa , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: To present a term newborn with severe asphyxial status due to dysrrhythmia induced by the neonatal form of carnitine palmitoyltransferase II deficiency (CPT II). RESULTS: Term newborn delivered spontaneously (birth weight 3450 grams, birth length 52 cm, values of Apgar score 10/10) with good direct adaptation, on second day of life he manifested severe asphyxial status followed by cardiorespiratory insufficiency with circulatory failure. After prolonged resuscitation of 3 hours, the child was admitted to our neonatological department. Diagnosis of CPT II was confirmed (free carnitine level in blood 12.2 micromol/l; ratio (C16+C18):1/C2 was 0.760 by tandem mass spectrometry; activity of CPT II in leukocytes was 0.082 micromol/min x gram protein). After appropriate treatment the patient survived the critical period. CONCLUSIONS: Neonatal form of CPT II deficiency is the most severe form and is considered to be invariably fatal. This kind of metabolic disease is congenital, but cardiac problems are not detectable during the prenatal period. Fasting in the early newborn period is a main trigger of CPT II deficiency signs. The authors emphasise the relevance of investigating acylcarnitine profiles and carnitine in serum in all cases of severe postnatal asphyxia and in cases of unusual newborn arrhythmias since some forms of disturbances in beta oxidation of fatty acids are partially treatable.
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Asfixia Neonatal/enzimología , Asfixia Neonatal/genética , Carnitina O-Palmitoiltransferasa/deficiencia , Asfixia Neonatal/terapia , Reanimación Cardiopulmonar , Insuficiencia Cardíaca/etiología , Humanos , Recién Nacido , Masculino , Insuficiencia Respiratoria/etiología , Espectrometría de Masas en TándemRESUMEN
It is difficult to make a retrospective diagnosis of perinatal asphyxia in symptomatic neonates delivered non-institutionally. We studied serum creatine kinase muscle-brain fraction (CK-MB), lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (SGOT) and glutamic pyruvate transaminase (SGPT) for differentiating asphyxiated (n=25) from non-asphyxiated (n=20) neonates who present with non-specific signs of sickness. CK-MB was assayed at 8 and 24 h; and LDH, SGOT and SGPT at 72 h of life. On comparing cases and controls, median 8-hr CK-MB [80 U/L vs. 26 U/L respectively, P< 0.001], median 24-hr CK-MB [33.5 U/L vs. 21.5 U/L respectively, P=0.009] and median LDH [965 U/L vs. 168 U/L respectively, P< 0.001] were higher in asphyxiated neonates. Raised LDH had 100% sensitivity, while CK-MB had 100% specificity for asphyxia. LDH had the highest area under ROC curve (0.998). We conclude that LDH at 72 hr of life is most accurate at differentiating asphyxiated from non-asphyxiated symptomatic neonates.
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Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Asfixia Neonatal/sangre , Asfixia Neonatal/enzimología , Creatina Quinasa/sangre , L-Lactato Deshidrogenasa/sangre , Humanos , Recién Nacido , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
AIM: To investigate: 1) the occurrence of hypoxic hepatitis in full-term infants after birth asphyxia, 2) the temporal enzyme pattern in asphyxiated newborn infants, and 3) whether the degree of hypoxic hepatitis, as reflected by the rise in aminotransferase, correlates with the severity of the asphyxia and CNS symptomatology. METHODS: Serum aminotransferases, lactate dehydrogenase, gamma-glutamyl transferase, total and conjugated bilirubin, cholinesterase activity, albumin, international normalized ratio (INR), and nucleated red blood cell count were prospectively measured in full-term asphyxiated newborn infants (n=26). Samples were collected three times during the first 72 h and once between days 6 and 12 after birth. Samples from healthy newborns (n=56), collected 24-172 h after birth, served as controls. RESULTS: In 12 of the 26 asphyxiated infants, a serum alanine aminotransferase (S-ALAT) pattern compatible with hypoxic hepatitis was found. Five infants showed increased S-ALAT activity but with a different pattern. Similar patterns were seen in serum aspartate aminotransferase (S-ASAT). S-ALAT and -ASAT concentrations 0-72 h after birth correlated significantly with severity of hypoxic-ischaemic encephalopathy. CONCLUSION: Birth asphyxia can induce an enzyme pattern in serum compatible to hypoxic hepatitis. There seems to be a correlation between aminotransferases in serum and the extent of CNS injury.
Asunto(s)
Asfixia Neonatal/complicaciones , Asfixia Neonatal/enzimología , Hepatitis/enzimología , Hepatitis/etiología , Hipoxia Encefálica/enzimología , Hipoxia Encefálica/etiología , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Asfixia Neonatal/sangre , Femenino , Hepatitis/sangre , Humanos , Hipoxia Encefálica/sangre , Recién Nacido , L-Lactato Deshidrogenasa/sangre , MasculinoRESUMEN
AIM: To measure serial cardiac troponin-T, creatine kinase, creatine kinase-MB, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels in asphyxiated newborn infants during the first 15 d of life. METHODS: Troponin-T, creatine kinase, creatine kinase-MB, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase (LDH) concentrations were measured prospectively in blood samples obtained from 45 asphyxiated and 15 healthy term neonates within the first 2-4 h, third, seventh and 15th days. RESULTS: Infants with severe asphyxia had significantly higher cardiac troponin-T levels than grade I and II asphyxiated and healthy neonates within the first 2-4 h of life (0.34+/-0.21 ag/ml vs 0.07+/-0.03 ag/ml, 0.12+/-0.07 ag/ml, 0.04+/-0.02 ag/ml, respectively). Troponin-T levels remained high on days 3 and 7 in severely asphyxiated neonates. The creatinine kinase-MB levels were significantly higher in grade II and III asphyxiated neonates than grade I asphyxiated and healthy neonates within the first 2-4 h. No difference was found in creatinine kinase-MB on day 3. There was cardiac involvement in 12 (80%) newborns of group III on B mode echocardiographic images on day 1. However, no echocardigraphic pathology was found in the seventh- and 15th-day echocardiographic analysis in any groups. CONCLUSION: Our results suggest that asphyxia-related cardiac changes were significant but reversible in severely asphyxiated neonates, and troponin T is a good determinant of the degree of injury to the heart within the first week of life. Cardiac troponin T also has a wider diagnostic frame than other diagnostic markers of myocardial damage.
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Asfixia Neonatal/sangre , Isquemia Miocárdica/sangre , Troponina T/sangre , Análisis de Varianza , Asfixia Neonatal/enzimología , Biomarcadores , Estudios de Casos y Controles , Humanos , Recién Nacido , Isquemia Miocárdica/enzimología , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: This prospective study aimed to compare serum creatine kinase MB isoenzyme (CK-MB) mass concentrations and cardiac troponin T (cTnT) concentrations during the first 48 h of life in asphyxiated term infants. METHODS: Serum cTnT and CK-MB mass concentrations of 50 term infants with clinical features of perinatal asphyxia were measured at birth and at 12, 24 and 48 h of age by chemiluminescence immunoassay. These infants were followed up until discharge or death. Cord blood CK-MB and cTnT concentrations of 50 healthy term infants were also assayed. RESULTS: At birth, asphyxiated infants had significantly higher concentrations of cTnT and CK-MB than controls (P < 0.0001). Serum cTnT of asphyxiated infants with low ejection fraction <60% was significantly higher at 12 and 24 h than those with normal ejection fraction (P < 0.05). Asphyxiated infants with congestive cardiac failure had significantly higher serum cTnT concentration during the first 48 h of life than those without congestive cardiac failure (P
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Asfixia Neonatal/sangre , Creatina Quinasa/sangre , Troponina T/sangre , Asfixia Neonatal/enzimología , Forma MB de la Creatina-Quinasa , Femenino , Humanos , Recién Nacido , Isoenzimas/sangre , Malasia , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVES: Magnesium sulfate has been recognized as a neuroprotective agent against hypoxia-ischemia, mainly by the protection from the excitotoxicity associated with increased glutamate concentration. However, the mechanism of MgSO4 action is not fully understood and is considerably controversial. DESIGN AND METHODS: During the 2 first hours of life, the asphyxiated full-term newborns were treated intravenously with one dose of MgSO4 250 mg/kg body weight. At birth, after 6 and 48 h of life the activity of ATP-dependent enzymes in erythrocyte membranes: Mg2+-ATPase, Ca2+-ATPase, protein kinases A and C, were determined. Using monoclonal antibodies, the band 3 and its phosphotyrosine level were also assayed. RESULTS: The time-dependent decrease of Ca2+-ATPase activity was detected in untreated newborns, whereas MgSO4 prevented this reduction. After 48 h, protein kinases activities differed in MgSO4-treated and untreated groups. Magnesium therapy increased the amount of band 3 and diminished proteolytic degradation of this protein. CONCLUSION: Our results demonstrated, for the first time, that magnesium sulfate treatment significantly altered the activities of some important enzymes in erythrocyte membrane from asphyxiated newborns. It also reduced the post-asphyxial damages of membrane compounds. These data may partly explain the molecular mechanisms of MgSO4 action in asphyxiated newborns.
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Asfixia Neonatal/tratamiento farmacológico , Membrana Eritrocítica/efectos de los fármacos , Sulfato de Magnesio/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Proteína 1 de Intercambio de Anión de Eritrocito/análisis , Asfixia Neonatal/enzimología , ATPasa de Ca(2+) y Mg(2+)/sangre , ATPasas Transportadoras de Calcio/sangre , Proteínas Quinasas Dependientes de AMP Cíclico/sangre , Membrana Eritrocítica/enzimología , Humanos , Recién Nacido , Magnesio/sangre , Fosfotirosina/sangre , Proteína Quinasa C/sangreRESUMEN
A new aspect on delivery as "physiological stress" provides the possibility for assessing its influence in asphyxial newborns. Asphyxia is characterized by hypoxic ischemic damage of organs with subsequent damage due to reoxygenation and reperfusion. The aim of the study was to compare the activity of liver enzymatic systems of healthy newborns with asphyxial newborns. Reference values of the AST on the 1st day of life 0.80 +/- 0.12 microkat/l and on the 5th day of life 0.78 +/- 0.11 microkat/l, of the ALT on the 1st day of life 0.29 +/- 0.04 microkat/l and on the 5th day of life 0.54 +/- 0.21 microkat/l and of the quotient of DeRitis on the 1(st) day of life 3.35 +/- 0.6 and on the 5th day of life 2.14 +/- 0.22 were established. The quotient of DeRitis expresses better the influence of stress on healthy term newborns since isolated evaluation of liver enzymes and their dynamics, which is decreased on the 5th day of life shows stabilization of the baby and improvement of liver cell function in comparison with the 1st day of life. The authors found that delivery is considered to be a certain form of physiological stress.
Asunto(s)
Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Asfixia Neonatal/enzimología , Parto Obstétrico , Humanos , Recién Nacido , Hígado/enzimologíaRESUMEN
The aim of this study was to evaluate serum concentrations of neuron-specific enolase (NSE) as a marker of the severity of hypoxic ischemic encephalopathy (HIE) and to elucidate the relation among the concentrations of NSE, grade of HIE and short-term outcome. Forty-three asphyxiated full-term newborn infants who developed symptoms and signs of HIE (Group 1) and 29 full-term newborn infants with meconium-stained amniotic fluid but with normal physical examination (Group 2) were studied with serial neurological examination, Denver developmental screening test (DDST), electroencephalogram and computerized cerebral tomography (CT) for neurological follow-up. Thirty healthy infants were selected as the control group. In the patient groups, two blood samples were taken to measure NSE levels, one between 4 and 48 h and the other 5-7 days after birth. Serum NSE levels were significantly higher in infants with HIE compared to those infants in Group 2 and control group. The mean serum concentrations of the second samples decreased in all groups studied but they were significantly higher in Group 1 compared to those in Group 2. Serum NSE concentrations of initial samples were significantly higher in patients with stage III HIE than in those with stages II and I. The sensitivity and specificity values of serum NSE as a predictor of HIE of moderate or severe degree (cut-off value 40.0 microg/l) were 79 and 70%, respectively, and as a predictor of poor outcome (cut-off value 45.4 microg/l) were calculated as 84 and 70%, respectively. The predictive capacity of serum NSE concentrations for poor outcome seems to be better than predicting HIE of moderate or severe degree. However, earlier and/or CSF samples may be required to establish serum NSE as an early marker for the application of neuroprotective strategies.