[Show abstract][Hide abstract] ABSTRACT: Background
Epidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.Methods
An IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.ResultsMaternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.Conclusions
These findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.
Respiratory Research 11/2014; 15(1):137. · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic hypoxia pulmonary hypertension (CH-PHT) in adulthood is likely to be of fetal origin following intrauterine growth retardation (IUGR). Oxygen (O2)-sensitive voltage-gated potassium channels (Kv channels) in resistance pulmonary artery smooth muscle cells (PASMCs) play an important role in scaling pulmonary artery pressure. Expression and functional changes of Kv channels are determined, in part, by embryonic development. We hypothesized that O2-sensitive Kv channels play an important role in exaggerated CH-PHT following IUGR. We established a rat model of IUGR by restricting maternal food during the entire pregnancy and exposed IUGR rats and their age-matched controls aged12 weeks to hypoxia for 2 weeks. We found that hypoxia exposure significantly induced increased pulmonary artery (PA) pressure and thicker smooth muscle layer in the IUGR group relative to controls. We compared the constriction of the resistance PA to inhibitors of K(+) channels, 4-aminopyridine (4-AP), tetraethylammonium (TEA), and barium chloride (BaCl2). Despite the thickness of the smooth muscle layer, the constriction to 4-AP was significantly reduced in the IUGR group exposed to hypoxia. Consistent with these changes in pulmonary vascular reactivity, 2 weeks of hypoxia induced weaker 4-AP-sensitive Kv currents in a single IUGR PASMC. Moreover, after 2 weeks of hypoxia, Kv1.5 expression in resistance PAs decreased significantly in the IUGR group. Overexpression of Kv1.5 in cultured PASMCs could offset hypoxia-induced cell proliferation and hypoxia-inhibited Kv currents in the IUGR group. These results suggest that the inhibited expression of Kv1.5 in PASMCs contribute to the development of exaggerated CH-PHT in IUGR rats during adulthood.
[Show abstract][Hide abstract] ABSTRACT: To observe the effects of neurally adjusted ventilatory assist (NAVA) on the patient-ventilator synchrony, gas exchange, and ventilatory parameters in preterm infants with respiratory distress syndrome (RDS) during mechanical ventilation.
Ten preterm infants with RDS received mechanical ventilation in NAVA mode for 60 minutes and in synchronized intermittent mandatory ventilation (SIMV) mode for 60 minutes, and the two modes were given in a random order. The vital signs, patient-ventilator synchrony, blood gas values, and ventilatory parameters were compared between the two ventilation modes.
Inspiratory trigger delay was significantly shorter with NAVA than with SIMV (P<0.05). There were no significant differences in arterial pH, PaCO2, PaO2 and PaO2/FiO2 between the two modes. The spontaneous respiratory rate, peak inspiratory pressure (PIP), electrical activity of the diaphragm and work of breathing were significantly lower in NAVA than in SIMV (P<0.05).
Compared with SIMV, NAVA appears to improve patient-ventilator synchrony, decrease PIP, and reduce diaphragmatic muscle load and work of breathing in preterm infants with RDS during mechanical ventilation.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 09/2013; 15(9):709-12.
[Show abstract][Hide abstract] ABSTRACT: To assess the diagnostic value of amplitude-integrated electroencephalography (aEEG) in predicting outcome of newborns who were at high risk for central nervous system without severe hypoxic-ischemic encephalopathy.
Forty-two consecutive patients at risks for neurological disorders referred to our level-III NICU were prospectively enrolled in the study over a period of 3 years. They were classified on the basis of their primary diagnoses including hypoglycemic brain damage, meningoencephalitis, bilirubin encephalopathy, and metabolic disease. Clinical data were collected. Amplitude-integrated and raw EEG tracings were assessed for background pattern, sleep-wake cycling, and epileptiform activity. The neuromotor development of survivors was assessed by using the Infant Neurological International Battery (INFANIB).
The characteristic of aEEG tracings in 42 infants showed continuous normal voltage (CNV)(n = 15), discontinuous voltage (DC)(n = 9), burst-suppression (BS) BS(+) (n = 6), BS(-)(n = 7), flat (FT, n = 5); mature sleep-wake cycling (SWC, n = 4), immature SWC (n = 14), no SWC (n = 24); 30 infants (71.4%) had electrical seizures: single seizure (n = 6); repetitive seizures (n = 7), and status epilepticus (SE) (n = 17).aEEG of 20 infants who had poor outcome showed FT (n = 5), BS(-)/SE (n = 6), BS(-)/ repetitive seizures (n = 1) , BS(+)/SE (n = 1), BS(+)/repetitive seizures (n = 1), DC/SE(n = 6). Chi-square analysis and Spearman rank correlation analysis showed the classification of aEEG background pattern, SWC and comprehensive score (score system was developed by evaluation of the above 3 variables) were correlated with the outcome of these infants at high neurological risks.
Amplitude-integrated electroencephalography can provide important information of the status of cerebral function in neonates at high neurological risk and help to predict their outcome.
Zhonghua er ke za zhi. Chinese journal of pediatrics 08/2013; 51(8):614-20.
[Show abstract][Hide abstract] ABSTRACT: To explore the value of the score for neonatal acute physiology (score for neonatal acute physiology, SNAP) in predicting outcome and risk of surgery of necrotizing enterocolitis (NEC).
A total of 62 NEC patients in neonatal intensive care unit (NICU) of Zhejiang University Children's Hospital were reviewed from October 2001 to October 2011. All the patients were classified into surgery group and non-surgery group according to whether the patient had the surgical intervention. Also the patients were divided into death group and alive group according to the outcome. Data on gestational age at birth, gender, birth weight, early clinical manifestations, treatment and prognosis of all patients were collected. SNAP-II and score for neonatal acute physiology and perinatal extension II (SNAPPE-II) were calculated on the day of diagnosis.
Abdominal distension, which was seen in 91.9% of the cases, was the commonest early clinical manifestation. The next was residual and bloody stool. SNAP-II and SNAPPE-II score in surgery group (26.5,26.5) were higher than that of the non-surgery group (13.0, 13.0,P = 0.002, 0.006). And the same scores in death group (29.0,32.0) were higher than those in the alive group (8.0, 8.0) (P = 0.000, 0.000). Measuring the scores as a predictor of surgery, the area under ROC curve for SNAP-II was 0.745, and was 0.714 for SNAPPE-II. The area under ROC curve for SNAP-II was 0.916, and was 0.929 for SNAPPE-II.The best positive point of SNAP-II and SNAPPE-II for predicting surgery was 22 and 28. The best positive point of SNAP-II and SNAPPE-II for predicting death was 18.5 and 22.
The SNAP-II and SNAPPE-II score may be used to predict the prognosis and the risk of surgery in the NEC patients. The scores are also good predictors of mortality in the early period when NEC occurs.
Zhonghua er ke za zhi. Chinese journal of pediatrics 05/2013; 51(5):326-30.
[Show abstract][Hide abstract] ABSTRACT: To characterize amplitude-integrated electroencephalo graphic (aEEG) traces in neonates with acute bilirubin encephalopathy (ABE), explore the value of aEEG in early diagnosis and prediction of neurological outcome of ABE.
aEEG records of 10 cases with ABE (Oct 2009-Nov 2011) were reviewed to identify neonates with a diagnosis of ABE. Clinical data were collected. The aEEG traces were classified according to background activity (normal, moderate, or severely abnormal), presence of seizures and sleep-wake cycling (SWC). Brainstem auditory evoked potential (BAEP) and magnetic resonance imaging (MRI) were studied. The neuromotor development of survivors with ABE was assessed by using the Infant Neurological International Battery (INFANIB).
The characteristics of aEEG tracings in these infants with ABE were shown continuous normal voltage (CNV, n = 5), discontinuous voltage (DNV, n = 4), discontinuous voltage with burst-suppression (BS)BS+ (n = 1); mature SWC (n = 2), immature SWC (n = 5), no SWC (n = 3); 8 infants (80%) had electrical seizures: single seizure (n = 2); repetitive seizures (n = 2), and status epilepticus (SE) (n = 4). Among the 10 infants with ABE, no infants had normal aEEG, 3 had mildly abnormal aEEG, and 7 had severely abnormal aEEG. Eight infants accepted BAEP test, 2 were mildly abnormal and 6 were severely abnormal. Six infants accepted MRI, 1 was normal and 5 were abnormal. By chi-square analysis and Spearman rank correlation analysis, the results of aEEG classification were correlated with the phase of ABE and the severity of BAEP. These infants were followed up for more than 6 months (range 6 months to 1 year). In 3 infants with mildly abnormal aEEG, 2 were normal and 1 was transit in infanib score at 6 months of age. Of 7 infants with severely abnormal aEEG, 1 died, 3 were abnormal (2 Spastic dyskinesia and 1 hypotonia), 2 were transit in infanib score at 6 months old. 1 lost to follow-up.
Amplitude-integrated electroencephalography can provide important information of the status of cerebral function in neonates with ABE and help to predict its neurological outcome.
Zhonghua er ke za zhi. Chinese journal of pediatrics 03/2013; 51(3):221-6.
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidence reveals that intrauterine growth retardation (IUGR) can cause varying degrees of pulmonary arterial hypertension (PAH) later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR.
The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC) were isolated from the rat lungs by magnetic-activated cell sorting (MACS). We investigated epigenetic regulation of the endothelin-1 (ET-1) gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia.
The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α) binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling.
These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.
Respiratory research 01/2013; 14:20. · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The history of clinical application of extracorporeal membrane oxygenation (ECMO) has been more than 30 years. But in China, there were only a few ECMO centers with limited successful cases reported by the end of twentieth century. The high morbidities and mortalities in current pediatric ECMO practice are noted in China. Therefore, it is necessary to review the experience on rescue use of ECMO in critically ill pediatric patients.
A retrospective analysis was done for patients who had been receiving ECMO treatment to rescue refractory cardiorespiratory failure from different causes in a hospital between July 2007 and May 2011.
A total of 12 patients were treated with ECMO; 7 of them were male and 5 female, they aged 6 days to 11 years, weighed 2.8 - 35 (17.21 ± 11.64) kg. The underlying causes of cardiorespiratory failure were as follows: two cases with acute respiratory distress syndrome (ARDS) leading to respiratory failure, 4 with failure of weaning from cardiopulmonary bypass, 3 with fulminant myocarditis, 1 with right ventricular cardiomyopathy leading to repeated cardiac arrest, 1 with preoperative severe hypoxemia, and 1 with anaphylactic shock complicated with massive pulmonary hemorrhage and severe hypoxemia. Of the 12 cases, 3 were established ECMO (E-CPR) while underwent chest compression cardiopulmonary resuscitation (CPR). The mean ECMO support time was 151.75 (15 - 572) h. Seven patients (58.33%) were weaned from ECMO, 6 patients (50.00%) were successfully discharged. Six cases had bleeding from sutures, 2 cases with severe bleeding underwent thoracotomy hemostasis, 2 presented with acute renal failure. Infection was documented in 3 cases, hyperbilirubinemia in 2 cases, lower limb ischemia in 1 case, hyperglycemia in 3 cases, disseminated intravascular coagulation in 1 case, membrane lung leakage in 2 cases, systemic hemolysis in 3 cases, oxygenator failure in 2 cases and oxygenator thrombosis in one case. During the follow-up between 6 months and 4.5 years, 5 patients survived with good quality of life, without any documented central nervous system disorders. One case survived with the right lower extremity disorder from ischemic damage. His motor function has been improved following orthopedic operation at one year after discharge.
ECMO is a justifiable alternative treatment for reversible severe cardiopulmonary failure in critically ill children.
Zhonghua er ke za zhi. Chinese journal of pediatrics 09/2012; 50(9):649-52.
[Show abstract][Hide abstract] ABSTRACT: Previous reports indicated that mutations in the adenosine triphosphate (ATP)-binding cassette transporter A3 (ABCA3) cause fatal respiratory failure in term infants, and common ABCA3 gene polymorphisms have been characterized at the population level in Caucasians. But the role of ABCA3 in relation to respiratory distress syndrome (RDS) in newborns has not been evaluated within a Chinese population. The aim of this study was to analyze eight single-nucleotide polymorphisms (SNPs) of the ABCA3 gene, and to assess the ABCA3 gene as a candidate gene for susceptibility to RDS in newborns.
Eight SNPs were selected and genotyped in 203 newborns. The data analysis and statistical tests were used for allele frequencies, haplotype and Hardy-Weinberg equilibrium pairwise linkage disequilibrium measures.
There was a haplotype association with SNP rs313909 and SNP rs170447, but no haplotype association was observed among the newborns with and without RDS (P > 0.05). The minor allele frequency (G) of the coding SNP (cSNP) rs323043 (P585P) was significantly increased in preterm infants with RDS.
There is an association between a synonymous cSNP rs323043 and the development of RDS.
Chinese medical journal 05/2012; 125(9):1594-8. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pulmonary arterial hypertension (PAH) is diagnosed as a sustained elevation of pulmonary arterial pressure to more than 25 mm Hg at rest or to more than 30 mm Hg with exercise. PAH is an intrinsic disease of the pulmonary vascular smooth muscle and endothelial cells in association with plexiform lesions, medial thickening, concentric laminar intimal fibrosis and thrombotic lesions. Pulmonary vascular remodeling is the characteristic pathological change of PAH. The pathogenesis of PAH has been studied at the level of smooth muscle and endothelial cells. Existing research does not adequately explain susceptibility to the disease, and recent evidence reveals that epigenetic alterations may be involved in PAH. Epigenetics refers to all heritable changes in phenotype or in gene expression states, including chromatin remodeling, DNA methylation, histone modification and RNA interference, which are not involved in the DNA sequence itself. This review will focus on recent advances in epigenetics related to PAH, including epigenetic changes of superoxide dismutase, endothelial nitric oxide synthase and the bone morphogenetic protein signaling pathway. This will provide new insight for improved treatment and prevention of PAH. Future work aimed at specific epigenetic treatments may prove to be an effective therapy for patients with PAH.
Hypertension Research 06/2011; 34(9):981-6. · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Effective treatment and/or prevention strategies for neonatal persistent pulmonary hypertension of the newborn (PPHN) have been an important topic in neonatal medicine. However, mechanisms of impaired pulmonary vascular structure in hypoxia-induced PPHN are poorly understood and consequently limit the development of effective treatment. In this study, we aimed to explore the molecular signaling cascades in the lungs of a PPHN animal model and used primary cultured rat pulmonary microvascular endothelial cells to analyze the physiological benefits of ghrelin during the pathogenesis of PPHN. Randomly selected newborn rats were exposed to hypoxia (10-12%) or room air and received daily s.c. injections of ghrelin (150 μg/kg) or saline. After 2 weeks, pulmonary hemodynamics and morphometry were assessed in the rats. Compared with the control, hypoxia increased pulmonary arterial pressure, right ventricle (RV) hypertrophy, and arteriolar wall thickness. Ghrelin treatment reduced both the magnitude of PH and the RV/(left ventricle+septum (Sep)) weight ratio. Ghrelin protected neonatal rats from hypoxia-induced PH via the upregulation of phosphorylation of glycogen synthase kinase 3β (p-GSK3β)/β-catenin signaling and associated with β-catenin translocation to the nucleus in the presence of growth hormone secretagogue receptor-1a. Our findings suggest that s.c. administration of ghrelin improved PH and attenuated pulmonary vascular remodeling after PPHN. These beneficial effects may be mediated by the regulation of p-GSK3β/β-catenin expression. We propose ghrelin as a novel potential therapeutic agent for PPHN.
Journal of Molecular Endocrinology 04/2011; 47(1):33-43. · 3.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: captopril is well tolerated in most patients. There is no report of acute deterioration in renal function after administration of captopril in neonates with congestive heart failure secondary to congenital heart defects with large left-to-right shunts.
we report a premature neonate with double outlet right ventricle and congestive heart failure who developed acute renal failure after administration of captopril at a low dose of 0.1 mg/kg per 8 hours.
on the third day after captopril therapy, the levels of serum creatinine and blood urea nitrogen increased to 2.6 mg/dl and 73 mg/dl respectively, and hyperkalemia appeared. Captopril was discontinued immediately. On the fourth day, the infant developed oliguria which persisted for 24 hours and resolved on the fifth day when the serum potassium normalized to 4.5 mmol/L. The level of serum creatinine peaked at 3.9 mg/dL on the sixth day and gradually decreased to normal on the ninth day after administration of captopril. The captopril-induced acute renal failure resolved completely after cessation of the drug.
attention should be given to captopril therapy in premature neonates with congestive heart failure secondary to congenital heart disease with large left-to-right shunts. Routine hemodynamic examination and biochemical monitoring are suggested before and during captopril therapy.
World Journal of Pediatrics 02/2011; 7(1):89-91. · 1.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Persistent pulmonary hypertension of the newborn (PPHN) is a major clinical problem. Nitric oxide produced by endothelial nitric oxide synthase (eNOS) in endothelial cells plays an important role in the pathogenesis of PPHN. The eNOS expression in endothelial cells is controlled by epigenetic regulation. The aim of this study was to investigate the epigenetic regulatory mechanisms of the eNOS gene in PPHN.
The rat model of PPHN was induced by hypoxia and indomethacin. Pulmonary vascular endothelial cells were isolated from the fetal rat lungs by magnetic-activated cell sorting. Chromatin immunoprecipitation and bisulfite sequencing methods were used to analyze epigenetic regulation.
The levels of acetylated histone H3 and acetylated histone H4 at the proximal promoter of the eNOS gene in pulmonary vascular endothelial cells from PPHN were significantly higher than those from the control group (P < 0.01, respectively). Total methylation percentage of the eNOS gene promoter in PPHN rat was slightly lower than that of control, but there was no statistically significant difference between the two groups (24.7 ± 2.0 vs. 27.3 ± 2.3%, P = 0.408). These changes of epigenetic modifications at the eNOS gene promoter were consistent with increased levels of eNOS mRNA and protein in PPHN.
The increased expression of eNOS in PPHN was associated with epigenetic regulation.
Journal of Hypertension 11/2010; 28(11):2227-35. · 4.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To review the role of epigenetic regulation in neonatal diseases and better understand Barker's "fetal origins of adult disease hypothesis".
The data cited in this review were mainly obtained from the articles published in Medline/PubMed between January 1953 and December 2009.
Articles associated with epigenetics and neonatal diseases were selected.
There is a wealth of epidemiological evidence that lower birth weight is strongly correlated with an increased risk of adult diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular disease. This phenomenon of fetal origins of adult disease is strongly associated with fetal insults to epigenetic modifications of genes. A potential role of epigenetic modifications in congenital disorders, transient neonatal diabetes mellitus (TNDM), intrauterine growth retardation (IUGR), and persistent pulmonary hypertension of the newborn (PPHN) have been studied.
Acknowledgment of the role of these epigenetic modifications in neonatal diseases would be conducive to better understanding the pathogenesis of these diseases, and provide new insight for improved treatment and prevention of later adult diseases.
Chinese medical journal 10/2010; 123(20):2948-54. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The severity of respiratory distress was associated with neonatal prognosis. This study aimed to explore the clinical characteristics, therapeutic interventions and short-term outcomes of late preterm or term infants who required respiratory support, and compare the usage of different illness severity assessment tools.
Seven neonatal intensive care units in tertiary hospitals were recruited. From November 2008 to October 2009, neonates born at ≥ 34 weeks' gestational age, admitted at < 72 hours of age, requiring continuous positive airway pressure (CPAP) or mechanical ventilation for respiratory support were enrolled. Clinical data including demographic variables, underlying disease, complications, therapeutic interventions and short-term outcomes were collected. All infants were divided into three groups by Acute care of at-risk newborns (ACoRN) Respiratory Score < 5, 5 - 8, and > 8.
During the study period, 503 newborn late preterm or term infants required respiratory support. The mean gestational age was (36.8 ± 2.2) weeks, mean birth weight was (2734.5 ± 603.5) g. The majority of the neonates were male (69.4%), late preterm (63.3%), delivered by cesarean section (74.8%), admitted in the first day of life (89.3%) and outborn (born at other hospitals, 76.9%). Of the cesarean section, 51.1% were performed electively. Infants in the severe group were more mature, had the highest rate of elective cesarean section, Apgar score < 7 at 5 minutes and resuscitated with intubation, the in-hospital mortality increased significantly. In total, 58.1% of the patients were supported with mechanical ventilation and 17.3% received high frequency oscillation. Adjunctive therapies were commonly needed. Higher rate of infants in severe group needed mechanical ventilation or high frequency oscillation, volume expansion, bicarbonate infusion or vasopressors therapy (P < 0.05). The incidence of complications was also increased significantly in severe group (P < 0.05). The in-hospital mortality in the severe group was significantly higher than other two groups (P < 0.05). ACoRN Respiratory Score was correlated with Score for Neonatal Acute Physiology-Version II (SNAP-II) (P < 0.01). High gestational age, high SNAP-II score and oxygenation index (OI), and Apgar score at 5 minutes < 5 were independent risks for death.
Neonatal respiratory distress is still a common cause of hospitalization in China. Illness severity assessment is important for the management. ACoRN Respiratory Score which correlated with SNAP-II score is easy to use and may be helpful in facilitating the caregivers in local hospital to identify the early signs and make the transfer decision promptly.
Chinese medical journal 10/2010; 123(20):2776-80. · 1.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: With the widespread application of peripherally inserted central catheters (PICC) in neonatal intensive care unit (NICU), the incidence of invasive fungal infections increased significantly than ever. The present study aimed to explore the clinical significance of oral fluconazole in premature infants with gestational age ≤ 32 weeks and/or birth weight ≤ 1500 grams who had catheter insertions.
This study enrolled 118 infants admitted between January 2006 and December 2007 who did not receive fluconazole prophylaxis (control group) and 106 infants admitted between January 2008 and June 2009 who received oral fluconazole prophylaxis (prophylaxis group). Statistical analyses were performed by using SPSS 11.5 software. The clinical characteristics and the risk factors for invasive fungal infection between the two groups were compared. Liver functions (alanine transaminase, ALT and direct bilirubin) were monitored to evaluate the safety of fluconazole prophylaxis.
Except for the proportion of infants born via vaginal delivery in the control group (56/118, 47.5%) was significantly lower than that in prophylaxis group (69/106, 65.1%, P = 0.007), there were no significant significant differences in the demographics and other baseline clinical characteristics between the two groups. There were no significant differences in the risk factors for invasive fungal infection between the two groups either. Nine infants developed invasive fungal infection in control group (7.6%), while no invasive fungal infection was found in prophylaxis group (0%, P = 0.01). Compared to infants in control group, those in prophylaxis group showed no significant changes in alanine transaminase ALT and direct bilirubin levels at 2 weeks and 4 weeks after fluconazole prophylaxis: the incidences of abnormal ALT and direct bilirubin levels were 8.5% (10/118) and 6.8% (8/118) in control group compared to 11.3% (12/106) and 8.5% (9/106) in prophylaxis group after 2 weeks (P = 0.47 and 0.63); the incidences of abnormal ALT and direct bilirubin levels were 3.4% (4/118) and 3.4% (4/118) in control group compared to 5.7% (6/106) and 8.5% (9/106) in prophylaxis group after 4 weeks (P = 0.62 and 0.15).
For infants with PICC insertions and gestational ages at birth ≤ 32 weeks and/or low birth weight ≤ 1500 grams, oral fluconazole is effective to prevent invasive fungal infection. Oral fluconazole in premature infants neither affected the liver function, nor increased the incidence of cholestasis.
Zhonghua er ke za zhi. Chinese journal of pediatrics 07/2010; 48(7):510-3.
[Show abstract][Hide abstract] ABSTRACT: This study sought to determine the effect of combined treatment of hypoxia plus indomethacin on pulmonary vascular remodeling in fetal rats.
Hypoxia and indomethacin were used to treat pregnant rats during 19-21 days of gestation. The adventitia, media, and intima of pulmonary arteries from fetal rats were assessed. Western blots were used for determining the abundance of smooth muscle specific alpha-actin protein (α-SMA), elastin, and endothelial nitric oxide synthase (eNOS) in lung tissues. Plasma brain-type natriuretic peptide (BNP) levels, reflecting the increased right ventricular load or pulmonary arterial pressure, were detected.
The ratio of left ventricular free wall plus septum to right ventricular weight significantly increased in hypoxia plus indomethacin-treated group. The medial thickness percentage of pulmonary arteries of < 100 μm and ≥100 μm in diameter from hypoxia plus indomethacin-treated group was higher than that from control or single treatment group. Vascular elastin area percentage and immunostaining density of eNOS from the combined-treated group were higher than other groups. The relative abundance of α-SMA, elastin, and eNOS and plasma BNP levels in hypoxia plus indomethacin-treated group also significantly increased compared with other groups.
Hypoxia and indomethacin had synergistic effect on fetal pulmonary vascular remodeling. This rat model induced by combined treatments can mimic human persistent pulmonary hypertension of the newborn.
The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 05/2010; 24(1):172-82. · 1.36 Impact Factor