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Bronchopulmonary dysplasia(BPD)is the main cause of chronic respiratory diseases in preterm infants.The research on the prophylaxis and treatment of BPD has been a concern of neonatologists because of its high incidence and poor prognosis in preterm infants.Glucocorticoid is a major therapy in the treatment of BPD because the pathological changes of BPD are characterized by persistent lung inflammation.Until now, a large number of clinical studies including different types and administration methods of glucocorticoids have been conducted.Compared with other types of glucocorticoids, low-dose and short-course dexamethasone has its unique advantages in the treatment of BPD.This article reviews the role of inflammation in the pathogenesis of BPD and the research progress of glucocorticoids in the prophylaxis and treatment of BPD.
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The aim of this study was to investigate the clinical characteristics of neonates born to SARS-CoV-2 infected mothers and increase the current knowledge on the perinatal consequences of COVID-19. Nineteen neonates were admitted to Tongji Hospital from January 31 to February 29, 2020. Their mothers were clinically diagnosed or laboratory-confirmed with COVID-19. We prospectively collected and analyzed data of mothers and infants. There are 19 neonates included in the research. Among them, 10 mothers were confirmed COVID-19 by positive SARS-CoV-2 RT-PCR in throat swab, and 9 mothers were clinically diagnosed with COVID-19. Delivery occurred in an isolation room and neonates were immediately separated from the mothers and isolated for at least 14 days. No fetal distress was found. Gestational age of the neonates was 38.6 ± 1.5 weeks, and average birth weight was 3293 ± 425 g. SARS-CoV-2 RT-PCR in throat swab, urine, and feces of all neonates were negative. SARS-CoV-2 RT-PCR in breast milk and amniotic fluid was negative too. None of the neonates developed clinical, radiologic, hematologic, or biochemical evidence of COVID-19. No vertical transmission of SARS-CoV-2 and no perinatal complications in the third trimester were found in our study. The delivery should occur in isolation and neonates should be separated from the infected mothers and care givers.
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Adult , Female , Humans , Infant, Newborn , Pregnancy , Betacoronavirus , Coronavirus Infections , Diagnostic Imaging , Infectious Disease Transmission, Vertical , Mothers , Pandemics , Pneumonia, Viral , Diagnostic Imaging , Prospective Studies , Tomography, X-Ray ComputedABSTRACT
Objective To determine the dynamic changes in adenosine monophosphate-activated protein kinase (AMPK) in neurons of neonatal rats suffering from hypoxic ischemic brain injury.Methods Twenty-four-hour old and seven-day old neonatal rats were used in this study.A classic primary cortical neuron oxygen glucose deprivation (OGD) model and neonatal rat hypoxic ischemic encephalopathy (HIE) model were employed.Lactic dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) were used to evaluate neuron viability and damage.The expression of phosphorylated adenosine monophosphate-activated protein kinase (P-AMPK),phosphorylated activated protein kinase (P-Akt) and Cleaved Caspase-3 in neurons and brain tissue was measured by Western blot at different time points after OGD or HIE.The Student-t test was used for statistical analysis.Results (1) Compared with the control group,LDH levels at 2,4,8 and 24 h after OGD were higher (all P＜0.05) and optical absorption levels of MTT were lower (all P＜0.05).(2) Levels of P-AMPK in the OGD group were higher than those in the control group,and showed a time-dependent increase at 30 min and 2,4,8 and 24 h (all P＜0.05).The expression levels of P-AMPK in the HIE group were higher than those in the control group (0.345 ± 0.038,0.387 ± 0.112 and 0.618 ± 0.075 at 1,3 and 7 days after HIE,and 0.132±0.032 in the control group,all P＜0.05).(3) The levels of P-Akt increased above the control levels at 30 min (0.991 ±0.134 vs 0.304±0.050),reached a maximum level at 2 h (1.183± 0.107),and then gradually declined,whereas the levels of Cleaved Caspase-3 started to increase at 30 min,and remained elevated at 24 h (all P＜0.05).Conclusion Following hypoxic ischemic brain damage,the expression of P-AMPK is significantly increased in both in vivo and in vitro studies in a time-dependent manner.
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Objective To investigate the neuroprotective effects and mechanisms of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ IMP cyclohydrolase(AICAR) supplement (AMPK activator) in different stages of neonatal rats sufferring from hypoxia-ischemia encephalopathy ( HIE). Methods Neonatal rat hypoxia-ischemia brain injury model was employed in this study. A total of 160 neonatal rats were distributed into five groups: sham, model control,AICAR30 min, AICAR24 h and AICAR72 h. The neuroprotective effects of AICAR supplement (30 min, 24 h, 72 h post operation) were compared by cresyl violet staining; Expressions of P-AMPK,AMPK in the brain tissue were measured by Western blotting.Foot-faults method was used to evaluate the long-term prognosis of the rats. Results Compared with the sham group, the survival of rats brain in model control group was significantly decreased [(100.0± 0.1)% and (45.3± 6.3)%, P0.05). Compared with the sham group, the expression of P-AMPK significantly increased about three times, while ATP level decreased close to the same. Conclusion Early AICAR treatment can protect hypoxia-ischemia brain injury by increasing AMPK-ATP level.
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Objective To investigate the diagnosis,treatment and prognosis of neonates with severe acute respiratory distress syndrome (ARDS) according to Berlin definition.Methods A retrospective study was carried to analyze the clinical features about diagnosis,treatment,chest X-ray findings,mortality,complications and ventilator parameters in 86 neonates with severe ARDS admitted in the NICU from January 2005 to December 2013.Results (1)Among the 86 cases,55 were cured,and 31 died with 36.0％ mortality.(2) Chest X-ray showed there was decreased lucency of bilateral lungs with ground-glass appearance,lung texture with thick chaos or dot flakes or patchy shadows in 36 neonates; diffuse infiltrates and extensive confluent consolidation shadows in bilateral lungs along with peripheral air brornchograms in 26 cases; heart shadow and diaphragmatic surface disappeared like a white lung change in 24 cases.(3) Persistent pulmonary hypertension of newborn as a complication occurred in 68 cases with 79.1％ incidence.(4) Eighty-six cases were categorized into survival group and death group.The results showed compared with the survival group,the neonates in death group required higher FiO2,and PaO2,and lower PaO2/FiO2 before mechanical ventilation (P ＜ 0.01),but needed higher initial PIP of mechanical ventilation (P ＜ 0.01).Conclusions Neonatal ARDS is still a kind of critical condition with high mortality and lack of evidence-based diagnostic criteria so far.The therapeutic strategy for neonatal ARDS should be a comprehensive measures in addition to appropriate respiratory support.
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Objective To investigate the efficacy and safety of aminophylline,caffeine citrate and aminophylline combined with naloxone in prevention of apnea of prematurity(AOP).Methods Ninety-four infants with a birth weight ＜ 1 500 g and gestational age ＜ 34 weeks admitted to Department of Pediatrics,Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology between Jan.2010 and Jan.2012 were randomly divided into 3 groups.(1) Aminophylline group (n =30):30 infants received a loading dose of 4-5 mg/kg of aminophylline and then maintained by a dose of 2 mg/kg,with intravenous drip q12 h.(2) Caffeine citrate group(n =32):a loading dose of 20 mg/kg of caffeine citrate was followed by a daily maintained dose of 5 mg/kg,with intravenous drip per day.(3) Aminophylline combined naloxone group (observation group,n =32):32 infants were treated with Aminophylline combined with naloxone.After 6 hours of the first dose of aminophylline,a dose of 0.1 mg/kg naloxone was injected,q12 h.Then the two drugs were used alternately.The mortality and incidence of AOP,bronchopulmonary dysplasia(BPD),retinopathy of prematurity (ROP) and brain injury were evaluated,and drug-related side effects were recorded.Results 1.There was no significant difference in gender,gestational age,birth weight,maternal antenatal glucocorticoid application,pregnancy (including multiple pregnancy) and delivery,5 min Apgar score,oxygen therapy,and the application of positive airway pressure as well as pulmonary surfactant among the 3 groups(all P ＞0.05).2.Compared with aminophylline group,the incidence of apnea of caffeine group and observation group were significantly lower (F =6.704,P ＜ 0.05),but there was no significant difference between caffeine group and observation group (P ＞0.05).3.There was no statistically significant difference in mortality,duration of oxygen therapy,the incidence of ROP,brain injury and hearing loss,postmenstrual age,body weight at discharge,the duration and cost of hospitalization among the 3 groups(all P ＞0.05).4.The BPD incidence in caffeine group[9.4％ (3/32 cases)] and observation group [12.5％ (4/32 cases)] were lower than that in Aminophylline group [20.0％ (6/30 cases)],but there was no statistical significance among the 3 groups(P ＞ 0.05).5.No drug-related side effects were recorded in the 3 groups.Conclusions It is safe and effective to use aminophylline combined with naloxone in prevention of AOP,and its efficiency is similar to caffeine citrate.
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This study investigated the effects of hyperoxia on dynamic changes of thioredoxin-1 (Trx1) and thioredoxin reductase-1 (TrxR1) in alveolar type II epithelial cells (AECII) of premature rats. Pregnant Sprague-Dawley rats were sacrificed on day 19 of gestation. AECII were isolated and purified from the lungs of premature rats. When cultured to 80% confluence, in vitro cells were randomly divided into air group and hyperoxia group. Cells in the hyperoxia group were continuously exposed to 95% O(2)/5% CO(2) and those in the air group to 95% air/5% CO(2). After 12, 24 and 48 h, cells in the two groups were harvested to detect their reactive oxygen species (ROS), apoptosis, TrxR1 activity and the expressions of Trx1 and TrxR1 by corresponding protocols, respectively. The results showed that AEC II exposed to hyperoxia generated excessive ROS and the apoptosis percentage in the hyperoxia group was increased significantly at each time points as compared with that in the air group (P0.05). Western blotting showed the changes of Trx1 protein expressions in the hyperoxia group paralleled those of Trx1 mRNA expressions revealed by RT-PCR. It was concluded that hyperoxia can up-regulate the protective Trx1/TrxR1 expressed by AECII in a certain period, however, also cause dysfunction of the cytoplasmic thioredoxin system by decreasing TrxR1 activity, which may contribute to the progression of oxidative stress and cell apoptosis and finally result in lung injury.
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This study examined the effects of retinoic acid (RA), PD98059, SP600125 and SB203580 on the hyperoxia-induced expression and regulation of matrix metalloproteinase-2 (MMP-2) and metalloproteinase-2 (TIMP-2) in premature rat lung fibroblasts (LFs). LFs were exposed to hyperoxia or room air for 12 h in the presence of RA and the kinase inhibitors PD98059 (ERK1/2), SP600125 (JNK1/2) and SB203580 (p38) respectively. The expression levels of MMP-2 and TIMP-2 mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). MMP-2 activity was measured by zymography. The amount of p-ERK1/2, REK1/2, p-JNK1/2, JNK1/2, p-p38 and p38 was determined by Western blotting. The results showed that: (1) PD98059, SP600125 and SB203580 significantly inhibited p-ERK1/2, p-JNK1/2 and p-p38 respectively in LFs; (2) The expression of MMP-2 mRNA in LFs exposed to hyperoxia was decreased after treatment with RA, SP600125 and SB203580 respectively (P0.05). Meanwhile, RA, PD98059, SP600125 and SB203580 had no effect on the expression of TIMP-2 mRNA in LFs exposed to room air or hyperoxia (P>0.05); (3) The expression of pro- and active MMP-2 experienced no change after treatment with RA or SP600125 in LFs exposed to room air (P>0.05), but decreased remarkably after hyperoxia (P<0.01 or 0.05). SB203580 inhibited the expression of pro- and active MMP-2 either in room air or under hyperoxia (P<0.01). PD98059 exerted no effect on the expression of pro- and active MMP-2 (P<0.05). It was suggested that RA had a protective effect on hyperoxia-induced lung injury by down-regulating the expression of MMP-2 through decreasing the JNK and p38 activation in hyperoxia.
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To investigate the protective effect of retinoic acid (RA) on hyperoxic lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs), gastation 21 d Sprague-Dawley (SD) fetuses (term = 22 d) were delivered by hysterotomy. Within 12-24 h of birth, premature rat pups were randomly divided into 4 groups (n=12 each): air-exposed control group (group I); hyperoxia-exposed group (group II), air-exposed plus RA group (group III), hyperoxia-exposed plus RA group (group IV). Group I, III were kept in room air, and group II, IV were placed in 85 % oxygen. The pups in groups III and IV were intraperitoneally injected with RA (500 microg/kg every day). All lung tissues of premature rat pups were collected at the 4th day after birth. Terminal transferase d-UTP nick end labeling (TUNEL) staining was used for the detection of cell apoptosis. The expression of PCNA was immunohistochemically detected. Western blot analysis was employed for the determination of phosphorylated and total nonphosphorylated ERKs, JNKs or p38. Our results showed that lungs from the pups exposed to hyperoxia for 4 d exhibited TUNEL-positive nuclei increased markedly throughout the parenchyma (P0.05), whereas activation of these MAPKs was markedly altered by hyperoxia and RA. After hyperoxia exposure, p-ERK1/2, p-JNK1/2 and p-p38 were dramatically increased (P<0.01), whereas p-JNK1/2 and p-p38 were markedly declined and p-ERK1/2 was further elevated by RA treatment (P<0.01). It is concluded that RA could decrease cell apoptosis and stimulate cell proliferation under hyperoxic condition. The protection of RA on hyperoxia-induced lung injury was related to the regulation of MAP kinase activation.
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To investigate the protective effect of retinoicacid (RA) on hyperoxic lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs), gastation 21 d SpragueDawley (SD) fetuses (term=22d) were delivered by hysterotomy. Within 12-24 h of birth,premature rat pups were randomly divided into 4 groups (n=12 each): air-exposed control group (group Ⅰ); hyperoxia-exposed group ( group Ⅱ), air-exposed plus RA group (group Ⅲ ), hyperoxia-exposed plus RA group (group Ⅳ). Group Ⅰ ,Ⅲ were kept in room air, and group Ⅱ , Ⅳwere placed in 85 % oxygen. The pups in groups Ⅲ and Ⅳ were intraperitoneally injected with RA (500 μg/kg every day). All lung tissues of premature rat pups were collected at the 4th day after birth. Terminal transferase d-UTP nick end labeling (TUNEL) staining was used for the detection of cell apoptosis. The expression of PCNA was immunohistochemically detected. Western blot analysis was employed for the determination of phosphorylated and total nonphosphorylated ERKs,JNKs or p38. Our results showed that lungs from the pups exposed to hyperoxia for 4 d exhibited TUNEL-positive nuclei increased markedly throughout the parenchyma (P＜0.01),and decreased significantly after RA treatment (P＜0.01). The index of PCNA-positive cells was significantly decreased (P＜0.01), and was significantly increased by RA treatment (P＜0.01).The air-space size was significantly enlarged, secondary crests were markedly decreased in hyperoxia-exposed animals. RA treatment improved lung air spaces and secondary crests in air-exposed pups, but had no effect on hyperoxia-exposure pups. Western blotting showed that the amounts of JNK, p38 and ERK proteins in hyperoxia-exposure or RA-treated lung tissues were same as those in untreated lung tissues (P＞0.05), whereas activation of these MAPKs was markedly altered by hyperoxia and RA. After hyperoxia exposure, p-ERK1/2, p-JNK1/2 and p-p38 were dramatically increased (P＜0.01), whereas p-JNK1/2 and p-p38 were markedly declined and p-ERK1/2 was further elevated by RA treatment (P＜0.01). It is concluded that RA could decrease cellapoptosis and stimulate cell proliferation under hyperoxic condition. The protection of RA on hyperoxia-induced lung injury was related to the regulation of MAP kinase activation.
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To explore the relationship between Insulin-like growth factor (IGF)-I , -II and lung development in neonatal rats. 80 timed pregnant Sprague-Dawley (SD) rats were randomly divided into 4 groups (n=20): group A (Control group), group B (Dexamethasone (DEX) 1 group), group C (DEX 2 group), group D (retinoic acid (RA) group). 20 pregnant rats in group A, B and D were injected subcutaneously or intraperitoneally with vehicle (NS), DEX, or RA respectively during gestational day 16 to 18. All newborn rats in group C were subcutaneously injected with DEX at day 1 to 3 after birth. The lung tissue was obtained at the following times: fetuses at gestational ages of 18, 20 and 21 days, and 1, 3, 5, 7, 10, 14 and 21 days after birth. Lung tissues were used for histopathological study, the polypeptides analysis of IGF- I, -II (immunohistochemistry and Western blot) and mRNA analysis ( RT- PCR). The results showed that the strongest expression of IGF- I in group A and D occurred at ages of 5-7 days (alveolar stage). The stronger their expressions, the better the alveolar develop. The peak stage of expression in group B occurred earlier, on the day 3 after birth. Compared with group A, the expression of IGF-I during gestation age of 18 days to age of 3 days in group B were significantly higher (P<0.01), but significantly lower at other time points (P<0.01). The expression of IGF-I was lower in group C all the time and always higher in group D than those in group A (P<0.01). The peak expression of IGF-II took place at the gestation age of 18 days, then gradually dropped to trace. During 18 days of gestation to age of 3 days, the expression of IGF-II in group B was significantly higher than that in group A (P<0.01). No difference was found among all other groups. The change in the expression of IGF-I, -II mRNA in all 4 groups was similar to that of their polypeptides. The results suggested that there is a close linking between IGF-I , -II and lung development in newborns. The IGF-II works at early stage and the that of IGF- I works at the stage of new septa formation and alveoli maturation. The stronger their expressions, the more mature the lung development.
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Animals , Female , Male , Pregnancy , Rats , Animals, Newborn , Dexamethasone , Pharmacology , Insulin-Like Growth Factor I , Genetics , Insulin-Like Growth Factor II , Genetics , Lung , Embryology , Metabolism , RNA, Messenger , Genetics , Random Allocation , Rats, Sprague-Dawley , Tretinoin , PharmacologyABSTRACT
The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats were randomly assigned to two groups: control group and RA group. The rats in RA group was intraperitoneally injected with all trans-retinoic acid (500 microg/kg every day) for consecutive 3 days after birth, while those in the control group were not subjected to intervention. Immunohistochemical assay was performed to locate the expression of PDGF. mRNA levels of PDGF were measured by reverse transcription polymerase chain reaction (RT-PCR) at age of 1, 3, 5, 7, 10, 14, 21 days. The method of radial alveolar counts (RAC) was used to measure the amount of the alveoli of the lungs. It was found that with increasing days, levels of PDGF-A and PDGF-B changed to verying degrees. RA could elevate significantly the expression levels of PDGF-A mRNA and protein (P<0.01), but not affect the expression levels of PDGF-B mRNA and protein markedly (P>0.05). It is suggested that PDGF might play an important role in lung development. RA can stimulate lung development through increasing the expression levels of PDGF-A mRNA and protein.
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Animals , Rats , Animals, Newborn , Lung , Metabolism , Platelet-Derived Growth Factor , Genetics , RNA, Messenger , Genetics , Random Allocation , Rats, Sprague-Dawley , Tretinoin , PharmacologyABSTRACT
Objective To investigate the diagnostic value of dynamic level of TNF ?、IL 8、IL 1? and IL 6 in lung lavage fluid obtained from preterm infants with chronic lung disease (CLD). Methods Lung lavage were serially collected from 29 ventilated infants hospitalized in NICU from December 1999 to November 2002. Total cell counts, neutrophilic granulocyte counts, malondialdehyde, protein, TNF ?、IL 8、IL 1? and IL 6 in lung lavage fluid were examined. Among the 29 cases, 10 developed pneumonia, 6 HMD, 7 CLD and 6 without lung disease as control. Results Total cell counts(7.9?10 9/L), neutrophilic granulocyte counts(6.4?10 9/L), TNF ?(13.88 pmol/L)、IL 8(376.92 mg/L)、IL 1?(2.96 ?g/L)and IL 6(1.72 ?g/L) in lung lavage fluid in infants who developed CLD were higher than the others on day 5( P
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Objective To explore the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in hyperoxia-induced lung injury in preterm rats. Methods At the 2 nd postnatal day Sprague-Dawley preterm rats were randomly assigned to air group and hyperoxia group (exposed to about 85% of O 2). At 3,7,14 and 21 days after exposure, six rats of each group were used to assess lung histologic changes and expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in lungs by immunohistochemistry. At 3,7 and 14 days after exposure, gelatinase activity in bronchoalveolar lavage fluid (BALF) of another six rats in each group by gelatin zymography was examed. Results Except 3 d after exposure, hyperoxia group showed lung injury characterized by subacute alveolitis and inhibition of lung development. Expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in hyperoxia group was stronger than that in air group at every time (P