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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 24-30, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948520

RESUMO

OBJECTIVE: To study the expression of microRNA-495-5p (miRNA-495-5p) in the serum of preterm infants with bronchopulmonary dysplasia (BPD) based on a bioinformatics analysis, and to provide a theoretical basis for further research on the association between miRNA-495-5p and BPD. METHODS: A total of 40 preterm infants who were admitted to the neonatal intensive care unit from January 2015 to December 2016 were enrolled. Among these infants, 20 with early clinical manifestations of BPD were enrolled as the BPD group, and 20 without such manifestations were enrolled as the control group. Peripheral blood samples were collected. The miRNA microarray technique was used to screen out differentially expressed miRNAs in serum between the two groups. RT-PCR was used for validation of results. TargetScan, miRDB, and miRWalk databases were used to predict the target genes of miRNA-495-5p. The DAVID database was used to perform gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the target genes. RESULTS: Compared with the control group, the BPD group had a significant increase in the expression of miRNA-495-5p in serum (P<0.05). A total of 117 target genes of miRNA-495-5p were predicted by the above three databases and they were involved in several molecular functions (including transcriptional regulatory activity, transcriptional activation activity, and transcription cofactor activity), biological processes (such as metabolic regulation, DNA-dependent transcriptional regulation, and vascular pattern), and cell components (including nucleoplasm, membrane components, and insoluble components) (P<0.05). As for signaling pathways, these genes were significantly enriched in the mTOR signaling pathway (P<0.05). CONCLUSIONS: MiRNA-495-5p may be involved in the development and progression of BPD by regulating angiogenesis, stem cell differentiation, apoptosis, and autophagy, which provides clues for further research on the role and functional mechanism of miRNA-495-5p in BPD.


Assuntos
Displasia Broncopulmonar , MicroRNAs/genética , Biologia Computacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Transcrição Genética
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 71-76, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31948528

RESUMO

OBJECTIVE: To study the protective effect of asiaticoside against hyperoxia-induced bronchopulmonary dysplasia in neonatal rats based on the microRNA-155 (miR-155)/suppressor of cytokine signaling-1 (SOCS1) axis. METHODS: Neonatal rats were randomly divided into a control group, a model group, a low-dose asiaticoside group (10 mg/kg), a middle-dose asiaticoside group (25 mg/kg), a high-dose asiaticoside group (50 mg/kg), and a budesonide group (1.5 mg/kg), with 12 rats in each group. All rats except those in the control group were exposed to a high concentration of oxygen for 14 days to establish a neonatal rat model of bronchopulmonary dysplasia. The low-, middle-, and high-dose asiaticoside groups were given asiaticoside at different doses by gavage, and those in the budesonide group were given budesonide aerosol treatment. Hematoxylin and eosin staining was used to observe lung tissue development and measure radial alveolar count (RAC) and mean linear intercept (MLI). Superoxide dismutase (SOD) and malondialdehyde (MDA) detection kits were used to measure the levels of SOD and MDA in lung tissue. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SOCS1 in lung tissue. Western blotting was used to measure the protein expression of SOCS1 in lung tissue. RESULTS: Compared with the control group, the model group had the symptoms of bronchopulmonary dysplasia such as a disordered structure of lung tissue, enlargement of alveolar fusion, uneven alveolar septa, enlargement of average alveolar space, and a reduction in alveolar number. The model group also had significant increases in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05) and significant reductions in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Compared with the model group, the low-, middle-, and high-dose asiaticoside groups and the budesonide group had significant improvement in the above symptoms of bronchopulmonary dysplasia, significant reductions in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05), and significant increases in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Asiaticoside improved the above symptoms and indices in a dose-dependent manner. There were no significant differences in the above indices between the high-dose asiaticoside and budesonide groups (P>0.05). CONCLUSIONS: Asiaticoside can alleviate inflammation injury induced by hyperoxia in neonatal rats and improve the symptoms of bronchopulmonary dysplasia in a dose-dependent manner, possibly by down-regulating the expression of miR-155 and up-regulating the expression of SOCS1.


Assuntos
Displasia Broncopulmonar , Hiperóxia , Animais , Animais Recém-Nascidos , Pulmão , MicroRNAs , Ratos , Triterpenos
3.
Orv Hetil ; 161(5): 183-192, 2020 Feb.
Artigo em Húngaro | MEDLINE | ID: mdl-31984771

RESUMO

Introduction: Over the last few years, in the development of neonatology, the limits to which it is possible to sustain the lives of premature babies have been extended, and thus the proportion of survivors with chronic morbidities has increased. Retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH) and bronchopulmonary dysplasia (BPD), all of which deeply influence the quality of life, life expectancy and social integration, are the most significant morbidities among premature newborns. Aim: Description of psychomotor development of low birth weight (<2500 g) premature infants at the age of 2 years, in relation to the most common chronic morbidities. Method: Psychomotor development (Brunet-Lézine scale, 1980) of low-birth-weight preterm infants at the age of 2 years (n = 200) was measured and the neonatal final reports were analysed retrospectively. Results: After age correction, birth weight positively correlated with the developmental quotient (DQ), while the length of stay in hospital correlated negatively. Grades I/II of neonatal IVH were not significant predictors of lower DQ, while the opposite was true for grades III/IV. We identified a similar relationship with the stages of ROP. According to the result of the homogeneity test, we can consider the independent effects of significant diseases. We also observed that the more diagnoses the premature baby received, the more they are at risk of later developmental delay at the age of 2 years. Conclusions: We recommend the early childhood interventions of the most vulnerable children of ≤1500 g birth weight with severe ROP and IVH - to reduce deficiencies in capabilities and prevent future mental and motor difficulties. Orv Hetil. 2020; 161(5): 183-192.


Assuntos
Displasia Broncopulmonar , Hemorragia Cerebral Intraventricular , Desenvolvimento Infantil/fisiologia , Recém-Nascido Prematuro , Desempenho Psicomotor/fisiologia , Qualidade de Vida/psicologia , Retinopatia da Prematuridade , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Morbidade , Destreza Motora/fisiologia , Gravidez , Estudos Retrospectivos
4.
Zhonghua Er Ke Za Zhi ; 57(12): 934-942, 2019 Dec 02.
Artigo em Chinês | MEDLINE | ID: mdl-31795560

RESUMO

Objective: To study the short-term outcomes and their related risk factors of extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI) in Guangdong province. Methods: The neonatal and corresponding maternal medical records of 2 392 cases of EPI and ELBWI discharged from 26 tertiary hospitals in Guangdong province during 2013-2017 were collected. Chi-square test or linear-by-linear association chi-square was used to analyze the following data on an annual basis: (1) the proportion of EPI and ELBWI in all discharged infants and preterm infants; (2) the difference in survival rate of EPI and ELBWI in different regions and types of hospital; and (3) the difference in incidence of complications. A binary Logistic regression model was established to analyze the death-related risk factors. Results: From 2013 to 2017, the enrolled infants each year were 331, 418, 458, 574 and 611, respectively. Totally, there were 1 352 (56.5%) male infants. The gestational age was (27.7±1.9) weeks, and the birth weight was (919±158) g. The proportion of EPI and ELBWI in all discharged infants increased from 2013 to 2017 (χ(2)=68.636, P<0.01), and so did the proportion in all discharged preterm infants (χ(2)=73.463, P<0.01). The overall survival rate was 60.4% (1 445/2 392), which increased from 2013 to 2017 (χ(2)=11.424, P<0.01). Besides, the survival rate was higher in the Pearl River Delta region than that in the non-Pearl River Delta region (61.7% (1 325/2 146) vs. 48.8% (120/246), χ(2)=15.505, P<0.01), and also higher in women and children specialist hospitals than that in general hospitals (66.5% (702/1 056) vs. 55.6% (743/1 336), χ(2)=29.104, P<0.01). The overall incidence of complications was 89.0% (2 130/2 392) for neonatal respiratory distress syndrome (NRDS), 72.2% (1 041/1 442) for bronchopulmonary dysplasia (BPD), 40.5% (625/1 544) for retinopathy of prematurity (ROP), 12.3% (237/1 922) for necrotizing enterocolitis (NEC), 31.0% (578/1 865) for periventricular-intraventricular hemorrhage (PV-IVH), 34.1% (656/1 922) for nosocomial infection, 26.9% (625/2 327) for patent ductus arteriosus (PDA), and 4.4% (82/1 865) for periventricular leukomalacia (PVL). From 2013 to 2017, the incidence of PVL decreased (χ(2)=6.093, P=0.014), but the incidence of BPD and PDA increased (χ(2)=24.476 and 11.741, respectively, both P<0.01). Multivariate Logistic regression analysis showed that Apgar score ≤7 at 5-minute (OR=1.830, 95%CI 1.373-2.437, P<0.01), NRDS (OR=1.407, 95%CI 1.222-1.621, P<0.01), invasive assisted ventilation (OR=1.825, 95%CI 1.241-2.683, P<0.01), maternal cervical insufficiency (OR=2.044, 95%CI 1.002-4.169, P=0.049), and medical care withdrawal (OR=25.532, 95%CI 18.867-34.553, P<0.01) increased the risk of early neonatal death, while the increase in gestational age (OR=0.869, 95%CI 0.802-0.941, P<0.01), discharged from Guangzhou and Shenzhen (OR=0.606, 95%CI 0.451-0.813, P<0.01), antenatal use of steroids (OR=0.624, 95%CI 0.471-0.828, P<0.01), premature rupture of membranes (OR=0.667, 95%CI 0.466-0.955, P=0.027), and pulmonary surfactant treatment (OR=0.532, 95%CI 0.419-0.676, P<0.01) could decrease the risk. For the mortality in the late or post-neonatal period, placenta previa (OR=2.355, 95%CI 1.006-5.516, P=0.048), cervical insufficiency (OR=3.306, 95%CI 1.259-8.679, P=0.015), PV-IVH (OR=1.486, 95%CI 1.135-1.946, P<0.01), invasive assisted ventilation (OR=2.143, 95%CI 1.208-3.801, P<0.01), and medical care withdrawal (OR=286.532, 95%CI 87.840-934.661, P<0.01) increased the risk, while the increase of birthweight (OR=0.997, 95%CI 0.996-0.999, P<0.01) decreased the risk. Conclusions: The survival rate of EPI and ELBWI increases annually, but the incidence of complications is still high. Invasive assisted ventilation, medical care withdrawal and maternal cervical insufficiency are associated with mortality in both early and late neonatal or post-neonatal period.


Assuntos
Displasia Broncopulmonar/epidemiologia , Enterocolite Necrosante/epidemiologia , Mortalidade Infantil , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Lactente Extremamente Prematuro , Retinopatia da Prematuridade/epidemiologia , China , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Fatores de Risco
5.
Medicine (Baltimore) ; 98(52): e18493, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876736

RESUMO

Bronchopulmonary dysplasia (BPD) is a common disease of premature infants with very low birth weight. The mechanism is inconclusive. The aim of this study is to systematically explore BPD-related genes and characterize their functions.Natural language processing analysis was used to identify BPD-related genes. Gene data were extracted from PubMed database. Gene ontology, pathway, and network analysis were carried out, and the result was integrated with corresponding database.In this study, 216 genes were identified as BPD-related genes with P < .05, and 30 pathways were identified as significant. A network of BPD-related genes was also constructed with 17 hub genes identified. In particular, phosphatidyl inositol-3-enzyme-serine/threonine kinase signaling pathway involved the largest number of genes. Insulin was found to be a promising candidate gene related with BPD, suggesting that it may serve as an effective therapeutic target.Our data may help to better understand the molecular mechanisms underlying BPD. However, the mechanisms of BPD are elusive, and further studies are needed.


Assuntos
Displasia Broncopulmonar/genética , Mineração de Dados , Algoritmos , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/metabolismo , Biologia Computacional/métodos , Mineração de Dados/métodos , Ontologia Genética , Genes/genética , Genes/fisiologia , Predisposição Genética para Doença/genética , Humanos , Recém-Nascido , Redes e Vias Metabólicas/genética , Processamento de Linguagem Natural , Transdução de Sinais/genética
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(12): 1153-1158, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31874651

RESUMO

OBJECTIVE: To study the effect of bronchopulmonary dysplasia (BPD) on lung function in preterm infants. METHODS: According to the presence/absence or the severity of BPD, 72 preterm infants were divided into non-BPD group (n=44), mild BPD group (n=15) and moderate BPD group (n=13). Lung function was assessed by plethysmography on days 7, 14 and 28 after birth. RESULTS: The preterm infants in the three groups had gradual increases in tidal volume per kilogram (TV/kg), functional residual capacity (FRC), ratio of time to peak tidal expiratory flow to total expiratory time (%T-PF) and ratio of volume to peak tidal expiratory flow to total expiratory volume (%V-PF) on days 7, 14 and 28 after birth, while there were gradual reductions in effective airway resistance per kilogram (Reff/kg) and respiratory rate (RR) (P<0.05). Compared with the non-BPD group on days 7, 14 and 28 after birth, the mild and moderate BPD groups had significantly lower TV/kg, FRC, %T-PF, and %V-PF and significantly higher Reff/kg and RR (P<0.05). On day 7 after birth, the moderate BPD group had significantly higher airway resistance, Reff/kg and FRC/kg than the mild BPD group (P<0.05). CONCLUSIONS: There is a certain degree of pulmonary function impairment in preterm infants with BPD. Dynamic monitoring of lung function by plethysmography is useful for assessing lung development in the neonatal period in these infants.


Assuntos
Displasia Broncopulmonar , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Pulmão , Pletismografia , Testes de Função Respiratória
7.
Lakartidningen ; 1162019 Oct 08.
Artigo em Sueco | MEDLINE | ID: mdl-31593285

RESUMO

The recently documented high survival of extremely preterm infants in Sweden is related to a high degree of centralization of pre- and postnatal care and to recently issued national consensus guidelines providing recommendations for perinatal care at 22-24 gestational weeks. The prevalence of major neonatal morbidity remains high and exceeded 60 % in a recent study of extremely preterm infants born at < 27 gestational weeks delivered in Sweden in 2014-2016 and surviving to 1 year of age. Damage to immature organ systems inflicted during the neonatal period causes varying degrees of functional impairment with lasting effects in the growing child. There is an urgent need for evidence-based novel interventions aiming to prevent neonatal morbidity with a subsequent improvement of long-term outcome.


Assuntos
Lactente Extremamente Prematuro , Doenças do Prematuro , Nascimento Prematuro , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/prevenção & controle , Serviços Centralizados no Hospital , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/prevenção & controle , Ventrículos Cerebrais/irrigação sanguínea , Ventrículos Cerebrais/diagnóstico por imagem , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/fisiopatologia , Enterocolite Necrosante/prevenção & controle , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/fisiopatologia , Doenças do Prematuro/prevenção & controle , Assistência Perinatal/organização & administração , Gravidez , Nascimento Prematuro/mortalidade , Retinopatia da Prematuridade/sangue , Retinopatia da Prematuridade/epidemiologia , Retinopatia da Prematuridade/fisiopatologia , Retinopatia da Prematuridade/prevenção & controle , Taxa de Sobrevida , Suécia/epidemiologia
8.
Eur. respir. j ; 54(3)Sept. 2019.
Artigo em Inglês | BIGG | ID: biblio-1026259

RESUMO

This document provides recommendations for monitoring and treatment of children in whom bronchopulmonary dysplasia (BPD) has been established and were discharged from the hospital, or who were older than 36 weeks of postmenstrual age. The guideline was based on pre-defined Population, Intervention, Comparison and Outcomes (PICO) questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. After considering the balance of desirable (benefits) and undesirable (burden, adverse effects) consequences of the intervention, the certainty of the evidence, and values, the Task Force made conditional recommendations for monitoring and treatment of BPD based on very low to low quality of evidence. We suggest monitoring with lung imaging using ionising radiation in a subgroup only, for example severe BPD or recurrent hospitalisations, and monitoring with lung function in all children. We suggest to give individual advice to parents regarding day care attendance. With regards to treatment, we suggest to use bronchodilators in a subgroup only, for example asthma-like symptoms, or reversibility in lung function, no treatment with inhaled or systemic corticosteroids, natural weaning of diuretics by the relative decrease in dose with increasing weight gain if diuretics are started in the neonatal period, and to treat with supplemental oxygen with a saturation target range of 90­95%. A multidisciplinary approach for children with established severe BPD after the neonatal period into adulthood is preferable. These recommendations should be considered until new and urgently needed evidence becomes available.


Assuntos
Humanos , Masculino , Feminino , Criança , Broncodilatadores/uso terapêutico , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/terapia , Administração dos Cuidados ao Paciente/métodos , Nascimento Prematuro/enfermagem
9.
Clin Drug Investig ; 39(11): 1093-1107, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414269

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the need for oxygen therapy at 36 weeks postmenstrual age (PMA). Sildenafil has been shown to enhance the lung alveolarization and vascularization in newborn animal models after lung injury and has possible therapeutic potential for the prevention of BPD. OBJECTIVE: To perform a proof-of-concept, Phase II, pilot randomized, double-blind, clinical trial to study the efficacy of sildenafil in preventing BPD, in postnatal (< 24 h), extremely and very preterm infants. METHODS: This Phase II, pilot randomized, double-blind, clinical trial was conducted in the Neonatal Intensive Care Unit of Women's Wellness and Research Center, Doha, Qatar during 2012-2014. Infants of 240/7-296/7 weeks' gestation were eligible if they needed respiratory or oxygen support ≥ 25% at randomization, and if they were at a postnatal age of < 24 h at randomization. Forty preterm infants were randomly assigned to receive off-label oral sildenafil (0.5 mg/kg every 6 h) or a placebo solution, for one week. The primary endpoints were the incidence of BPD and death at 36 weeks PMA, and the side effects. Secondary outcomes included the incidence of BPD and the respiratory support at day 28 of life, duration of oxygen use, fraction of inspired oxygen use at 36 weeks and 28 days of life, duration of hospitalization, and the incidence of significant retinopathy of prematurity, severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and late sepsis. RESULTS: No significant differences were observed between the sildenafil and placebo study groups in mortality at 36 weeks PMA (10% vs 20%, p = 1), respiratory support at 36 weeks (30% vs 25%, p = 0.57), and side effects (0% vs 0%). For all other secondary outcomes, no significant differences were detected. CONCLUSIONS: While not associated with side effects, off-label oral sildenafil did not demonstrate benefits in the prevention of BPD or death in the extreme and very preterm infants. Future studies of dosing and efficacy that target different regimens of sildenafil are warranted before sildenafil is recommended for the prevention of BPD.


Assuntos
Displasia Broncopulmonar/prevenção & controle , Recém-Nascido Prematuro , Profilaxia Pré-Exposição/métodos , Estudo de Prova de Conceito , Citrato de Sildenafila/administração & dosagem , Vasodilatadores/administração & dosagem , Displasia Broncopulmonar/diagnóstico , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Masculino , Projetos Piloto , Fatores de Risco
10.
BMC Pulm Med ; 19(1): 145, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409326

RESUMO

BACKGROUND: Aerosol administration is increasingly being used as a therapeutic intervention for mechanically ventilated preterm infants. However, the effects of inhalation therapy on retinopathy of prematurity (ROP) have not yet been explored. METHODS: A retrospective cohort study was conducted in a tertiary level neonatal intensive care unit (NICU) from 2011 to 2013. All preterm infants with a gestational age (GA) of 24~29 weeks receiving invasive intubation for more than 1 week in the NICU were included. Infants with severe congenital anomalies were excluded. ROP was defined as stage II or greater according to medical records by ophthalmologists. A multivariate logistic regression model was used to estimate the risk of ROP in relation to inhalation therapy after adjusting for confounders. RESULTS: In total, 205 infants were enrolled in this study, including 154 with inhalation therapy and 51 without inhalation therapy. Univariate analyses showed an association of inhalation with the following characteristics: sex (p = 0.047), GA (p = 0.029), sepsis (p = 0.047), bronchopulmonary dysplasia (BPD) (p < 0.001), and ROP (p = 0.001). Furthermore, logistic regression analysis indicated that inhalation therapy was an independent risk factor for ROP (odds ratio (OR) = 2.639; 95% confidence interval (CI) = 1.050~6.615). In addition, infants with a GA of 24~25 weeks (OR = 6.063; 95% CI = 2.482~14.81) and 26~27 weeks (OR = 3.825; 95% CI = 1.694~8.638) were at higher risk of ROP than those with a GA of 28~29 weeks. Other factors - including sex, sepsis, BPD, and delivery mode - did not carry significant risk. CONCLUSION: Aerosol therapy with pure oxygen delivery is associated with ROP. Clinicians should exercise great caution when conducting aerosol therapy with excess oxygen in mechanically ventilated preterm infants.


Assuntos
Displasia Broncopulmonar/induzido quimicamente , Recém-Nascido Prematuro , Oxigenoterapia/efeitos adversos , Oxigenoterapia/métodos , Retinopatia da Prematuridade/induzido quimicamente , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Modelos Logísticos , Masculino , Análise Multivariada , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Taiwan
12.
BMC Pulm Med ; 19(1): 138, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362742

RESUMO

BACKGROUND: Caffeine therapy for apnea of prematurity reduces the incidence of bronchopulmonary dysplasia (BPD) in premature neonates. Several mechanisms, including improvement in pulmonary mechanics underly beneficial effects of caffeine in BPD. As vascular development promotes alveologenesis, we hypothesized that caffeine might enhance angiogenesis in the lung, promoting lung growth, thereby attenuating BPD. METHODS: C57Bl/6 mice litters were randomized within 12 h of birth to room air (RA) or 95%O2 to receive caffeine (20 mg/kg/day) or placebo for 4 days and recovered in RA for 12wks. The lung mRNA and protein expression for hypoxia-inducible factors (HIF) and angiogenic genes performed on day 5. Lung morphometry and vascular remodeling assessed on inflation fixed lungs at 12wks. RESULTS: Caffeine and hyperoxia in itself upregulate HIF-2α and vascular endothelial growth factor gene expression. Protein expression of HIF-2α and VEGFR1 were higher in hyperoxia/caffeine and angiopoietin-1 lower in hyperoxia. An increase in radial alveolar count, secondary septal count, and septal length with a decrease in mean linear intercept indicate an amelioration of hyperoxic lung injury by caffeine. An increase in vessel surface area and a significant reduction in smooth muscle thickness of the pulmonary arterioles may suggest a beneficial effect of caffeine on vascular remodeling in hyperoxia, especially in male mice. CONCLUSIONS: Postnatal caffeine by modulating angiogenic gene expression early in lung development may restore the pulmonary microvasculature and alveolarization in adult lung.


Assuntos
Cafeína/farmacologia , Hiperóxia/complicações , Lesão Pulmonar/tratamento farmacológico , Neovascularização Fisiológica , Alvéolos Pulmonares/efeitos dos fármacos , Angiopoietina-1/metabolismo , Animais , Animais Recém-Nascidos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/metabolismo , Modelos Animais de Doenças , Pulmão/patologia , Lesão Pulmonar/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Alvéolos Pulmonares/metabolismo , Distribuição Aleatória , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
Eur J Pharmacol ; 860: 172588, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31377154

RESUMO

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that often occurs in preterm infants. However, there is still no effective treatment for BPD. Recent studies demonstrated that connective tissue growth factor (CTGF) is involved in the development of BPD in experimental models. CTGF, also known as CCN2, is the second member of the CCN family and is necessary for normal lung development. The expression of CTGF is increased in lung tissues in infants with BPD. Hyperoxia, inflammation and mechanic ventilation increase CTGF expression which may promote fibroblast proliferation, matrix production and vascular remodeling. Conditional overexpression of CTGF in alveolar epithelial type II cells disrupts alveolarization and vascular development, induces vascular remodeling, and results in pulmonary hypertension, the pathological hallmarks of severe BPD. Further studies have shown that inhibition of CTGF by a CTGF monoclonal antibody improved alveolarization and vascular development, and decreased pulmonary vascular remodeling and pulmonary hypertension in a rodent model of BPD induced by hyperoxia. CTGF may be a novel target for BPD therapy in preterm infants.


Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Terapia de Alvo Molecular/métodos , Animais , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patologia , Humanos
14.
J Perinat Med ; 47(6): 671-676, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31365347

RESUMO

Background Antioxidant enzymes may play a significant role in the development of bronchopulmonary dysplasia (BPD). The aim of the study was to assess the relationship between the level of extracellular superoxide dismutase (SOD3) in the serum at days 1 and 7 of life and the risk of developing BPD. Methods The study comprised 103 neonates born before 32 weeks' gestation with a birth weight of ≤1500 g. Results In the investigated group, the median serum SOD3 level at day 1 of life was 4.01 ng/mL [interquartile range (IQR) 2.59-5.09 ng/mL] and at day 7 of life 3.13 ng/mL (IQR 2.49-4.34 ng/mL). A statistically significant decrease in the serum SOD3 level was found in the first week of life, P < 0.0001. No correlation was found between the serum SOD3 level at day 1 of life and gestational age R = 0.07, P = 0.4543 and birth weight R = 0.10, P = 0.3083. No statistically significant correlation was found between the dynamics of change in the SOD3 level in serum at days 1 and 7 of life and the risk of BPD development for the definition of BPD at day 28 of life, P = 0.8764 nor at 36 weeks' postmenstrual age, P = 0.6598. Conclusion The study revealed a statistically significant decrease in the serum SOD3 level in the first week of life in very and extremely low birth weight infants born before 32 weeks of gestation. In the clinical setting, no relationship was observed between the level of SOD3 in serum and the risk of developing BPD.


Assuntos
Displasia Broncopulmonar , Recém-Nascido de Peso Extremamente Baixo ao Nascer/sangue , Recém-Nascido Prematuro/sangue , Superóxido Dismutase/sangue , Peso ao Nascer , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/epidemiologia , Correlação de Dados , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Polônia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
15.
Orv Hetil ; 160(32): 1270-1278, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31387373

RESUMO

Introduction: During recent decades, the perinatal mortality of extremely low-birth weight infants has decreased. An important task is to recognize complications of prematurity. Aim: We made an attempt to explore the relationship between complications of prematurity and neonatal hyperglycemia. Method: From 1 January 2014 to 31 December 2017, 188 infants with birth weight below 1000 g were admitted. For each infant, the frequencies of hyperglycemia (blood glucose >8.5 mmol/l), retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia were determined. Animal studies were performed in Sprague Dawley rats. Hyperglycemia was achieved by intraperitoneal injection of streptozotocin (100 mg/kg). On the 7th day of life, aorta sections were prepared and stained with hematoxylin eosin. Wall thickness was measured using QCapture Pro 7 image analysis software. Results: The mean ± SD gestational age and birth weight were 27.1 ± 2.2 weeks and 814.9 ± 151.9 g; 33 infants (17.5%) died. Hyperglycemia was confirmed in 62 cases (32.9%), and insulin treatment was given to 43 infants (22.8%). The gestational age and birth weight of the hyperglycemic infants were significantly lower (p<0.001), the incidence of severe retinopathy (p = 0.012) and the mortality of insulin-treated patients were higher (p = 0.02) than in normoglycemic infants. Among survivors (n = 155), we found by logistic regression analysis that hyperglycemia was a risk factor for severe retinopathy (p<0.001). In the rat model, neonatal hyperglycemia caused significant thickening of the aortic wall. Conclusion: Our studies indicate that hyperglycemia is common in extremely low birth-weight infants. Monitoring of these infants for retinopathy of prematurity, kidney dysfunction, and hypertension is recommended. Orv Hetil. 2019; 160(32): 1270-1278.


Assuntos
Diabetes Mellitus Experimental , Hiperglicemia , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Doenças do Prematuro , Retinopatia da Prematuridade/etiologia , Animais , Peso ao Nascer , Displasia Broncopulmonar/epidemiologia , Hemorragia Cerebral Intraventricular/epidemiologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Gravidez , Ratos , Ratos Sprague-Dawley , Retinopatia da Prematuridade/epidemiologia
16.
Medicina (Kaunas) ; 55(7)2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324065

RESUMO

Pulmonary hypertension (PH) is a complication of bronchopulmonary dysplasia (BPD). The underlying pathophysiology of BPD-associated PH is complex and poorly understood. Echocardiogram may underestimate the severity of pulmonary hypertensive vascular disease in severe BPD. Digital subtraction pulmonary angiography (DSPA) is a potentially useful imaging modality for evaluating changes in the pulmonary vasculature of BPD-associated PH. In this study, we objectively quantified the pulmonary hypertensive vascular changes demonstrated by DSPA using a novel pulmonary vascular underperfusion score (PVUS) and correlated the scoring system with echocardiography parameters and cardiac hemodynamics by right heart catheterization.


Assuntos
Displasia Broncopulmonar/classificação , Hipertensão Pulmonar/classificação , Recém-Nascido Prematuro/fisiologia , Angiografia Digital/métodos , Displasia Broncopulmonar/complicações , Estudos Transversais , Ecocardiografia/métodos , Humanos , Hipertensão Pulmonar/complicações , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Escala de Gravidade do Ferimento , Pulmão/anormalidades , Pulmão/fisiopatologia
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(7): 816-822, 2019 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-31340915

RESUMO

OBJECTIVE: To investigate the protective effect of vitamin D (VD) against hyperoxia-induced bronchopulmonary dysplasia (BPD) in newborn mice and explore the mechanism. METHODS: Thirty-six newborn mice were randomly divided into air + VD group, air + saline group, hyperoxia + VD group, and hyperoxia + saline group. In all the groups, saline or VD was administered on a daily basis via intramuscular injection. After 3 weeks of treatment, the mice were weighed and cardiac blood was collected for measurement of serum VD level using ELISA, and histological examination of the lungs was performed. Radial alveolar counting (RAC) and alveolar secondary interval volume density were measured using image analysis software. The expression levels of vascular endothelial cell growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in the lung tissues were detected using Western blotting. RESULTS: The weight gain rate of the mice and the weight of the lungs were significantly higher in air + saline group and air + VD group than in the hyperoxia + saline group. The RAC was significantly lower in hyperoxic+saline group than that in hyperoxia+VD group (P < 0.001), and was significantly higher in hyperoxic+VD (125 times) than in hyperoxia + VD (1250 times) group (P < 0.01). The alveolar secondary protrusion count was significantly higher in hyperoxic+VD (1250 times) group than in hyperoxic+saline group (P < 0.001), and was significantly higher in hyperoxia+VD (125 times) group than in hyperoxia + VD (1250 times) group (P < 0.01). Compared with that in air + saline group, VEGFR2 expression was significantly lowered in hyperoxia+saline group (P < 0.05) and in air+VD group (P < 0.05); VEGFR2 expression was significantly higher in hyperoxia+VD (1250 times) group than in hyperoxia+saline group (P < 0.001) and hyperoxia+VD (125 times) group (P < 0.001); VEGFR2 expression was significantly higher in hyperoxia+VD (125 times) group than in hyperoxia+ saline group (P < 0.05). CONCLUSIONS: In newborn mice with BPD, VD supplement can increase the weight of the lungs and promote lung maturation, and a higher concentration of VD can better protect the lungs and promote the growth of pulmonary blood vessels.


Assuntos
Displasia Broncopulmonar , Hiperóxia , Animais , Animais Recém-Nascidos , Pulmão , Camundongos , Vitamina D
18.
BMJ Case Rep ; 12(7)2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350226

RESUMO

This case report is about a boy born extremely preterm at gestational age of 24 weeks, with extremely low birth weight, developing severe bronchopulmonary dysplasia and in need of mechanical ventilation for 155 days. He also had five recurrent infections with group B streptococcus (GBS) within 4 months from birth, and his respiratory condition clearly deteriorated with every GBS infection. It was difficult to wean him from mechanical ventilation. Finally he was extubated when he was 7 months old and kept out of mechanical ventilation after receiving high-dose methylprednisolone, given according to international recommendations. After GBS was cultured for the fifth time, he received oral rifampicin along with intravenous penicillin and after this treatment, GBS did not occur again. At the age of 22 months, the boy no longer needed any respiratory support and he was about 6 months late in his neurological development.


Assuntos
Antibacterianos/uso terapêutico , Displasia Broncopulmonar/fisiopatologia , Respiração Artificial , Infecções Respiratórias/fisiopatologia , Infecções Estreptocócicas/fisiopatologia , Streptococcus agalactiae/isolamento & purificação , Displasia Broncopulmonar/imunologia , Displasia Broncopulmonar/terapia , Deficiências do Desenvolvimento , Humanos , Lactente , Recém-Nascido de Peso Extremamente Baixo ao Nascer/imunologia , Lactente Extremamente Prematuro/imunologia , Recém-Nascido , Masculino , Metilprednisolona/uso terapêutico , Penicilinas/uso terapêutico , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/terapia , Rifampina/uso terapêutico , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/terapia , Streptococcus agalactiae/efeitos dos fármacos , Resultado do Tratamento
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(7): 619-623, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31315757

RESUMO

Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases in neonates especially in preterm infants. It is also the main reason leading to a poor prognosis. The prognosis of the neonates with BPD is unsatisfactory with current treatment strategies. Recent clinical trails have found that mesenchymal stem cell (MSC) transplantation might be effective and promising for treatment of BPD in neonates. This article outlines the characteristics of MSC and the potential mechanisms of MSC transplantation for BPD in vivo, and the safety and feasibility of MSC transplantation in BPD neonates, as well as the challenges in clinical trials on MSC transplantation for treatment of BPD.


Assuntos
Displasia Broncopulmonar , Transplante de Células-Tronco Mesenquimais , Displasia Broncopulmonar/terapia , Humanos , Recém-Nascido Prematuro
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(7): 624-628, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31315758

RESUMO

OBJECTIVE: To investigate the physical development, incidence of common respiratory diseases, and motor development during infancy in preterm infants with bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was performed on the clinical features and infantile outcomes of preterm infants with BPD who were admitted to the neonatal intensive care unit between January 2012 and December 2015. Preterm infants without BPD were used as controls who were admitted to the neonatal intensive care unit during the same period and had similar gestational age and birth weight. Physical development, number of hospital stays, the incidences of pneumonia and wheezing, and motor development during infancy were compared between the two groups. RESULTS: Compared with the control group, BPD infants had a significantly higher incidence of extrauterine growth retardation at discharge (48% vs 41%; P<0.05); BPD infants were more susceptible to pneumonia, wheezing, eczema and rhinitis; BDP infants also had a significantly higher number of readmissions due to respiratory tract infection (P<0.05). BPD infants had a significantly smaller head circumference than the control group at corrected ages of 3, 6, and 12 months (P<0.05). BPD infants had significantly delayed gross, fine, and overall motor development than the control group at corrected ages of 6 and 9 months (P<0.05). CONCLUSIONS: Infants with BPD are susceptible to extrauterine growth retardation at discharge. Their head circumference growth is relatively slow. They are susceptible to pneumonia and wheezing during infancy. Moreover, they have delayed motor development when compared with those without BPD at corrected ages of 6 and 9 months.


Assuntos
Displasia Broncopulmonar , Criança , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Prognóstico , Estudos Retrospectivos
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