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1.
J Med Chem ; 66(22): 15141-15170, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-37963811

RESUMO

A lack of the T cell-inflamed tumor microenvironment limits the efficacy of immune checkpoint inhibitors (ICIs). Activation of stimulator of interferon genes (STING)-mediated innate immunity has emerged as a novel therapeutic approach in cancer therapy. 2',3'-Cyclic GMP-AMP (cGAMP) is a natural STING agonist; however, cGAMP is subjected to endogenous degradation by ecto-nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1). To improve the ICI response rate, we developed 29f, a novel ENPP1 inhibitor with phthalazin-1(2H)-one as the core scaffold. 29f inhibited the cGAMP hydrolysis by ENPP1 in vitro (IC50 = 68 nM) and enhanced the STING-mediated type I interferon response in both immune and tumor cells. 29f demonstrated excellent metabolic stability and bioavailability (F = 65%). Orally administered 29f promoted tumor growth inhibition in a CT26 syngeneic model and increased the anti-PD-L1 response. Furthermore, 29f-induced immunological memory prevented the tumor relapse against tumor rechallenge, suggesting the promising therapeutic potential of 29f.


Assuntos
Neoplasias , Diester Fosfórico Hidrolases , Humanos , Diester Fosfórico Hidrolases/metabolismo , Neoplasias/terapia , Pirofosfatases , Imunoterapia , Microambiente Tumoral
2.
Arch Orthop Trauma Surg ; 138(6): 771-776, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29470637

RESUMO

INTRODUCTION: To evaluate the prevalence of medial collateral ligament (MCL) injury of the knee among ankle-fracture patients and to determine the risk factors associated with MCL injury in this patient group. MATERIALS AND METHODS: 303 patients (303 affected ankles) who underwent surgical treatment for an ankle fracture were assessed. Supination versus pronation injury, Danis-Weber classification, age, sex, body mass index (BMI), limb dominance, and mechanism of injury were reviewed to identify factors related to MCL injury. RESULTS: Prevalence of MCL injury of the knee among the total number of patients with an ankle fracture was 3.96% (12 out of 303 injuries). Multivariable logistic and linear regression analysis with adjustment of possible confounding factors confirmed that female sex and pronation injury were associated significantly (p < 0.05) with MCL injury. CONCLUSIONS: The prevalence of MCL injury among females and the pronation type of ankle injury was 8.19% (10 out of 122 females) and 10.75% (10 out of 93 pronation injuries), respectively. More careful physical examination of the knee joint is strongly recommended in patients with ankle fractures, especially if the patient is female or the ankle-fracture pattern corresponds to the pronation type of injury.


Assuntos
Fraturas do Tornozelo/cirurgia , Traumatismos do Tornozelo/cirurgia , Traumatismos do Joelho/terapia , Ligamento Colateral Médio do Joelho/lesões , Adolescente , Adulto , Idoso , Fraturas do Tornozelo/complicações , Traumatismos do Tornozelo/complicações , Feminino , Humanos , Traumatismos do Joelho/complicações , Masculino , Ligamento Colateral Médio do Joelho/cirurgia , Pessoa de Meia-Idade , Prevalência , Pronação , Fatores de Risco , Supinação , Adulto Jovem
3.
Pediatr Int ; 59(1): 34-40, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27337221

RESUMO

BACKGROUND: Both histologic chorioamnionitis (HCAM) and Ureaplasma infection are considered important contributors to perinatal lung injury. We tested the hypothesis that coexistence of maternal HCAM and perinatal Ureaplasma exposure increases the risk of prolonged mechanical ventilation in extremely low-birthweight (ELBW) infants. METHODS: A retrospective cohort study was carried out of all ELBW infants born between January 2008 and December 2013 at a single academic center. Placental pathology and gastric fluid Ureaplasma data were available for all infants. Culture and polymerase chain reaction were used to detect Ureaplasma in gastric fluid. Prolonged mechanical ventilation was defined as mechanical ventilation that began within 28 days after birth and continued. RESULTS: Of 111 ELBW infants enrolled, 84 survived beyond 36 weeks of postmenstrual age (PMA) and were included in the analysis. Eighteen infants (21.4%) had both HCAM and Ureaplasma exposure. Seven infants (8.3%) required mechanical ventilation beyond 36 weeks of PMA. Coexistence of HCAM and Ureaplasma in gastric fluid was significantly associated with prolonged mechanical ventilation after adjustment for gestational age, sex, mode of delivery, and use of macrolide antibiotics (OR, 8.7; 95%CI: 1.1-67.2). CONCLUSIONS: Coexistence of maternal HCAM and perinatal Ureaplasma exposure significantly increases the risk of prolonged mechanical ventilation in ELBW infants.


Assuntos
Corioamnionite/microbiologia , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Complicações Infecciosas na Gravidez/microbiologia , Respiração Artificial/estatística & dados numéricos , Infecções por Ureaplasma/complicações , Ureaplasma/isolamento & purificação , Técnicas Bacteriológicas , Displasia Broncopulmonar/microbiologia , Displasia Broncopulmonar/terapia , Estudos de Coortes , DNA Bacteriano/genética , Feminino , Humanos , Recém-Nascido , Doenças do Prematuro/microbiologia , Doenças do Prematuro/terapia , Masculino , Reação em Cadeia da Polimerase , Gravidez , Estudos Retrospectivos
4.
Pediatr Crit Care Med ; 17(12): 1142-1146, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27918385

RESUMO

OBJECTIVES: The aim of the present study was to report possible improvements in ventilator variables associated with a transition from synchronized intermittent mandatory ventilation to neurally adjusted ventilatory assist in preterm infants with bronchopulmonary dysplasia who required a high level of mechanical ventilatory support in a single center. DESIGN: Retrospective study. SETTING: Neonatal ICU. PATIENTS: Twenty-nine preterm infants with a median gestational age of 25.4 weeks (range, 23.4-30.3 wk) and a median birth weight of 680 g (range, 370-1,230 g) and who were supported with a mechanical ventilator for more than 4 weeks and had a respiratory severity score greater than four during conventional mechanical ventilation prior to conversion to neurally adjusted ventilatory assist. INTERVENTIONS: Comparison of ventilatory variables, work of breathing, and blood gas values during conventional ventilation and at various time intervals after the change to neurally adjusted ventilatory assist. MEASUREMENTS AND MAIN RESULTS: The values of various ventilatory variables and other measurements were obtained 1 hour before neurally adjusted ventilatory assist and 1, 4, 12, and 24 hours after conversion to neurally adjusted ventilatory assist. During neurally adjusted ventilatory assist, the peak inspiratory pressure (20.12 ± 2.93 vs 14.15 ± 3.55 cm H2O; p < 0.05), mean airway pressure (11.15 ± 1.29 vs 9.57 ± 1.27 cm H2O; p < 0.05), and work of breathing (0.86 ± 0.22 vs 0.46 ± 0.12 J/L; p < 0.05) were significantly decreased, and the blood gas values were significantly improved. Significantly lower FIO2 and improved oxygen saturation were observed during neurally adjusted ventilatory assist compared with conventional ventilation support. The RSS values decreased and sustained during neurally adjusted ventilatory assist (4.85 ± 1.63 vs 3.21 ± 1.01; p < 0.001). CONCLUSIONS: The transition from synchronized intermittent mandatory ventilation to neurally adjusted ventilatory assist ventilation was associated with improvements in ventilator variables, oxygen saturation, and blood gas values in infants with bronchopulmonary dysplasia in a single center. This study suggests the possible clinical utility of neurally adjusted ventilatory assist as a weaning modality for bronchopulmonary dysplasia patients in the neonatal ICU.


Assuntos
Displasia Broncopulmonar/terapia , Terapia Intensiva Neonatal/métodos , Suporte Ventilatório Interativo/métodos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Estudos Retrospectivos , Resultado do Tratamento
5.
J Pediatr ; 179: 49-53.e1, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27692860

RESUMO

OBJECTIVE: To describe the clinical course and risk factors for pulmonary arterial hypertension (PAH) after ibuprofen treatment to close patent ductus arteriosus. STUDY DESIGN: All neonates weighing < 1500 g at birth who received ibuprofen to close patent ductus arteriosus and were admitted to Seoul National University Children's Hospital's neonatal intensive care unit in 2010-2014 were eligible for this study. The study population was divided into the PAH and non-PAH groups, and medical records were retrospectively reviewed. RESULTS: Of the 144 eligible infants, 10 developed PAH (6.9%). Relative to the non-PAH group, the PAH group exhibited greater respiratory severity and more frequent severe bronchopulmonary dysplasia or death before 36 weeks postmenstrual age. Multivariable analysis demonstrated that lower gestational age, birth weight in less than the third percentile for age, maternal hypertension of pregnancy, and oligohydramnios were risk factors for developing PAH after ibuprofen treatment. CONCLUSION: A high incidence of PAH after ibuprofen treatment was observed in the study population. Furthermore, younger gestational age and several prenatal conditions were identified as risk factors for developing PAH after ibuprofen treatment. Additional large cohort studies are necessary to confirm our results.


Assuntos
Inibidores de Ciclo-Oxigenase/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Hipertensão Pulmonar/induzido quimicamente , Ibuprofeno/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Estudos Retrospectivos
6.
Neonatology ; 110(3): 181-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27172918

RESUMO

BACKGROUND: The long-term cardiovascular outcomes of pulmonary hypertension (PH) in preterm infants with bronchopulmonary dysplasia (BPD) are uncertain. OBJECTIVES: The purpose of this study was to assess outcomes of PH in prematurely born children diagnosed with moderate to severe BPD. METHODS: We retrospectively reviewed the medical records of patients born before 32 weeks of gestation and diagnosed with moderate to severe BPD from June 2004 to April 2008. Patients were recruited for a cross-sectional study from August to October 2014 and underwent echocardiography. RESULTS: Forty-two children were enrolled. Their mean gestational age and birth weight were 26.2 ± 1.7 weeks and 753.1 ± 172.5 g, respectively. Sixteen patients (38%) were diagnosed with PH at a mean age of 3.3 ± 1.6 months, and the PH improved after a median of 12.3 months (range 0.7-46.6). Cardiovascular function was reassessed at a mean age of 7.7 ± 0.9 years, at which time 1 patient was taking a medication for recurrent PH, and 12 (28.6%) patients exhibited elevated blood pressure. Conventional 2-dimensional and Doppler echocardiography indicated normal ventricular function in all children. However, right ventricular longitudinal strains were decreased in children with previous PH. CONCLUSIONS: Subclinical ventricular dysfunction was detectable using sensitive echocardiographic techniques in children with previous BPD-associated PH. Long-term follow-up and meticulous cardiovascular function assessment are required in this population.


Assuntos
Displasia Broncopulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/epidemiologia , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Disfunção Ventricular/diagnóstico por imagem , Peso ao Nascer , Criança , Pré-Escolar , Estudos Transversais , Ecocardiografia Doppler , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , República da Coreia , Estudos Retrospectivos
7.
Neonatology ; 110(2): 148-54, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27105356

RESUMO

BACKGROUND: White matter injury (WMI) is the most common form of brain injury in preterm infants. It could be induced by a systemic inflammatory response in preterm infants. OBJECTIVES: We hypothesized that surgical necrotizing enterocolitis (surgNEC) results in more severe WMI than spontaneous intestinal perforation (SIP) on brain magnetic resonance imaging (MRI) at term-equivalent age (TEA). METHODS: The medical records of 33 preterm infants born at less than 32 weeks of gestation who underwent surgery due to either NEC or SIP were reviewed retrospectively. White matter abnormality (WMA) on brain MRI was scored according to the diagnosis of surgNEC or SIP. RESULTS: Nine patients were diagnosed with SIP and 24 with surgNEC. The median (range) gestational age of the SIP and surgNEC groups was 26+6 (23+3-27+6) and 25+5 weeks (23+3-31+2), respectively (p = 0.454). There were no differences in 1- and 5-min Apgar scores, mode of delivery, use of antenatal steroids, histologic chorioamnionitis, or incidence of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) between the two groups. Males were more prevalent in the surgNEC group (75.0 vs. 33.3%, p = 0.044), and the incidence of sepsis was higher in the surgNEC group than in the SIP group (75.0 vs. 33.3%, p = 0.044). Multivariate regression showed that the difference in WMA scores between the two groups remained significant (estimated difference = 2.418; 95% CI 0.107-4.729). CONCLUSION: In preterm infants at less than 32 weeks of gestation, those with surgNEC showed more severe WMI than infants with SIP on brain MRI at TEA.


Assuntos
Enterocolite Necrosante/complicações , Enterocolite Necrosante/cirurgia , Perfuração Intestinal/complicações , Perfuração Intestinal/cirurgia , Substância Branca/patologia , Feminino , Idade Gestacional , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Imageamento por Ressonância Magnética , Masculino , Análise Multivariada , Análise de Regressão , República da Coreia , Estudos Retrospectivos , Substância Branca/diagnóstico por imagem
8.
J Korean Med Sci ; 30 Suppl 1: S104-10, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26566351

RESUMO

This study was done to evaluate respiratory syncytial virus (RSV) related readmission (RRR) and risk factors of RRR in preterm infants < 34 weeks gestational age (GA) within 1 yr following discharge from the neonatal intensive care unit (NICU). Infants (n = 1,140) who were born and admitted to the NICUs of 46 hospitals in Korea from April to September 2012, and followed up for > 1 yr after discharge from the NICU, were enrolled. The average GA and birth weight of the infants was 30(+5) ± 2(+5) weeks and 1,502 ± 474 g, respectively. The RRR rate of enrolled infants was 8.4% (96/1,140), and RSV accounted for 58.2% of respiratory readmissions of infants who had laboratory tests confirming etiological viruses. Living with elder siblings (odd ratio [OR], 2.68; 95% confidence interval [CI], 1.68-4.28; P < 0.001), and bronchopulmonary dysplasia (BPD) (OR, 2.95; 95% CI, 1.44-6.04; P = 0.003, BPD vs. none) increased the risk of RRR. Palivizumab prophylaxis (OR, 0.06; 95% CI, 0.03-0.13; P < 0.001) decreased the risk of RRR. The risk of RRR of infants of 32-33 weeks' gestation was lower than that of infants < 26 weeks' gestation (OR, 0.11; 95% CI, 0.02-0.53; P = 0.006). This was a nationwide study that evaluated the rate and associated risk factors of RRR in Korean preterm infants. Preterm infants with BPD or living with siblings should be supervised, and administration of palivizumab to prevent RRR should be considered.


Assuntos
Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Antivirais/uso terapêutico , Peso ao Nascer , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/patologia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Razão de Chances , Palivizumab/uso terapêutico , Alta do Paciente , Readmissão do Paciente , República da Coreia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Fatores de Risco , Irmãos
9.
J Korean Med Sci ; 30(10): 1476-82, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26425046

RESUMO

Conflicting results on the influences of histologic chorioamnionitis (HC) on neonatal morbidities might be partly originated from using different definition of HC. The aim of this study was to determine the relationship between HC and neonatal morbidities using definition of HC that reflects the site and extent of inflammation. This was a retrospective cohort study of 261 very low birth weight (VLBW) infants admitted at a tertiary academic center. Based on the site of inflammation, HC was categorized: any HC; amnionitis; funisitis; amnionitis+funisitis. The extent of inflammation in each site was reflected by sub-defining high grade (HG). The incidences of morbidities in infants with and without HC were compared. The bronchopulmonary dysplasia (BPD) rate was significantly higher in infants with amnionitis and the severe retinopathy of prematurity (ROP) rate was significantly higher in infants with any HC and funisitis. After adjustment for both gestational age and birth weight, the respiratory distress syndrome (RDS) rate was significantly lower in infants with all categories of HC except for HG amnionitis and HG funisitis, which are not associated with lower RDS rate. HG amnionitis was significantly associated with increased BPD rate but the association of HC with severe ROP disappeared. In conclusion, HC is significantly associated with decreased RDS and HG amnionitis with increased BPD while lacking association with other neonatal morbidities in VLBW infants. The association with HC and neonatal morbidities differs by the site and extent of chorioamnionitis.


Assuntos
Displasia Broncopulmonar/epidemiologia , Corioamnionite/epidemiologia , Recém-Nascido de muito Baixo Peso , Pré-Eclâmpsia/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Retinopatia da Prematuridade/epidemiologia , Adulto , Peso ao Nascer , Displasia Broncopulmonar/complicações , Corioamnionite/classificação , Corioamnionite/patologia , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Infiltração de Neutrófilos/imunologia , Placenta/patologia , Pré-Eclâmpsia/patologia , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Retinopatia da Prematuridade/complicações , Estudos Retrospectivos , Centros de Atenção Terciária
10.
Pediatr Neonatol ; 56(5): 317-23, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26328892

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH) is a well-known complication of prematurity; however, the additional impact of a left-to-right interatrial shunt on this condition remains poorly understood. The aim of the present study was to identify the significance of atrial left-to-right shunt lesions in PH infants with moderate or severe BPD. METHODS: The medical records of 383 preterm infants (gestational age of < 32 weeks) who were diagnosed with BPD between 2005 and 2013 were retrospectively reviewed. Baseline characteristics such as interatrial shunts and outcomes were compared between the infants who developed PH (n = 50) and infants who did not (n = 144). Infants with hemodynamically significant residual patent ductus arteriosus were excluded. Among the infants diagnosed with PH (n = 50), the outcomes were compared between the patients with (n = 21) and without atrial shunts (n = 29) at 36 weeks corrected postmenstrual age. RESULTS: Fifty (15%) preterm infants with BPD were diagnosed with PH. The number of infants with a history of atrial shunt lesions was significantly higher in the PH group than in the non-PH group (42% vs. 15.3%, respectively). The adjusted odds ratio for PH in the atrial shunt group was 3.8 (95% confidence interval, 1.8-8.0), compared to PH-BPD infants without an atrial shunt. CONCLUSION: The presence of an atrial left-to-right shunt was associated with PH in preterm infants with moderate or severe BPD. Close follow up is needed for infants with interatrial shunts, and a more tailored prognostic evaluation and treatment are recommended.


Assuntos
Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/fisiopatologia , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/fisiopatologia , Doenças do Prematuro/fisiopatologia , Displasia Broncopulmonar/diagnóstico , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico , Masculino , Prevalência , Estudos Retrospectivos
11.
Nat Commun ; 6: 8087, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-26290419

RESUMO

Many proteins are known to promote ciliogenesis, but mechanisms that promote primary cilia disassembly before mitosis are largely unknown. Here we identify a mechanism that favours cilium disassembly and maintains the disassembled state. We show that co-localization of the S/G2 phase kinase, Nek2 and Kif24 triggers Kif24 phosphorylation, inhibiting cilia formation. We show that Kif24, a microtubule depolymerizing kinesin, is phosphorylated by Nek2, which stimulates its activity and prevents the outgrowth of cilia in proliferating cells, independent of Aurora A and HDAC6. Our data also suggest that cilium assembly and disassembly are in dynamic equilibrium, but Nek2 and Kif24 can shift the balance toward disassembly. Further, Nek2 and Kif24 are overexpressed in breast cancer cells, and ablation of these proteins restores ciliation in these cells, thereby reducing proliferation. Thus, Kif24 is a physiological substrate of Nek2, which regulates cilia disassembly through a concerted mechanism involving Kif24-mediated microtubule depolymerization.


Assuntos
Cílios/fisiologia , Cinesinas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Carcinogênese , Ciclo Celular , Linhagem Celular Tumoral , Regulação da Expressão Gênica/fisiologia , Humanos , Cinesinas/genética , Quinases Relacionadas a NIMA , Fosforilação , Proteínas Serina-Treonina Quinases/genética
12.
Eur J Radiol ; 84(10): 2024-31, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26159485

RESUMO

INTRODUCTION: This study aimed to assess the therapeutic results of ultrasound (US)-guided water-soluble contrast enema in very low birth weight (VLBW) preterm infants (<1,500 g) with meconium obstruction and to study factors that affect therapeutic results. METHODS: This study included a total of 33 consecutive VLBW infants with clinically diagnosed meconium obstruction underwent US-guided water-soluble contrast enema, from April 2007 to March 2014. Patients were classified into two groups based on to procedure outcome: the success group (evacuation of the meconium plug resolution followed by improved bowel distention within 2 days of the procedure, without additional interventions), and the failure group (the contrast enema failed to relieve the obstruction, or other procedure-related complications occurred). Patient- and mother-related clinical factors and procedure-related factors were compared between both groups. RESULTS: Overall success rate was 54.5%, with 18 successful (M:F=10:8), and 15 failure (M:F=7:8) cases. When compared with the failure group, the success group patients showed statistically significant older gestational age (29(+1) vs. 27 weeks; p=0.028), larger birth weight (1023.1g vs. 790.3g; p=0.048), and higher body weight on the day of the procedure (1036.2g vs. 801.6g, p=0.049). However, no statistically significant differences were seen between other patient and maternal factors. Among the procedure-related factors, retrial of contrast injection during the procedure was associated with significantly higher success than the single trial (p=0.027). The presence of refluxed contrast into the distal ileum was the statistically significant predictor for success of the procedure (p=0.038). There were three cases of bowel perforation (9.1% per person). CONCLUSION: US-guided water-soluble contrast enema in VLBW infants with meconium obstruction showed a 54.5% success rate and a 9.1% perforation rate per person. Among the procedure-related factors, retrial of contrast injection during the procedure and the presence of refluxed contrast into the distal ileum were related to the success of the procedure.


Assuntos
Catárticos/uso terapêutico , Meios de Contraste/uso terapêutico , Enema/métodos , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Obstrução Intestinal/terapia , Mecônio , Ultrassonografia de Intervenção/métodos , Acetilcisteína/uso terapêutico , Peso ao Nascer , Diatrizoato de Meglumina/uso terapêutico , Expectorantes/uso terapêutico , Feminino , Idade Gestacional , Humanos , Doenças do Íleo/diagnóstico por imagem , Recém-Nascido , Obstrução Intestinal/diagnóstico por imagem , Perfuração Intestinal/etiologia , Ácido Iotalâmico/análogos & derivados , Ácido Iotalâmico/uso terapêutico , Masculino , Mecônio/diagnóstico por imagem , Radiografia , Retratamento , Cloreto de Sódio/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
13.
J Korean Med Sci ; 30(4): 456-62, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25829814

RESUMO

Late-onset hyponatremia (LOH), hyponatremia occurring after two weeks of age with the achievement of full feeding, is the result of a negative sodium balance caused by inadequate salt intake or excessive salt loss due to immature renal or intestinal function in preterm infants. The aims of our study were to identify the risk factors for LOH and its influence on neonatal outcomes. This was a retrospective cohort analysis of 161 preterm infants born before 34 weeks of gestation between June 2009 and December 2010 at Seoul National University Hospital. LOH was defined as a sodium level ≤ 132 mEq/L or 133-135 mEq/L with oral sodium supplementation. LOH occurred in 49 (30.4%) of the studied infants. A lower gestational age, a shorter duration of parenteral nutrition, the presence of respiratory distress syndrome, the use of furosemide, and feeding with breast milk were significant risk factors for LOH. In terms of neonatal outcomes, the infants with LOH had longer hospital stays and higher risks of bronchopulmonary dysplasia and retinopathy of prematurity requiring surgery. LOH lasting at least 7 days significantly increased moderate to severe bronchopulmonary dysplasia, periventricular leukomalacia, and extra-uterine growth retardation. LOH is commonly observed in preterm infants; it may be a risk factor for bronchopulmonary dysplasia and retinopathy of prematurity or a marker of illness severity.


Assuntos
Hiponatremia/etiologia , Displasia Broncopulmonar/etiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de Risco
14.
Yonsei Med J ; 55(1): 99-106, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24339293

RESUMO

PURPOSE: We tested whether rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-γ agonist, can restore alveolar development and vascular growth in a rat model of bronchopulmonary dysplasia (BPD). MATERIALS AND METHODS: A rat model of BPD was induced through intra-amniotic delivery of lipopolysaccharide (LPS) and postnatal hyperoxia (80% for 7 days). RGZ (3 mg/kg/d, i.p.) or vehicle was given daily to rat pups for 14 days. This model included four experimental groups: No BPD+vehicle (V), No BPD+RGZ, BPD+V, and BPD+RGZ. On D14, alveolarization, lung vascular density, and right ventricular hypertrophy (RVH) were evaluated. RESULTS: Morphometric analysis revealed that the BPD+RGZ group had significantly smaller and more complex airspaces and larger alveolar surface area than the BPD+V group. The BPD+RGZ group had significantly greater pulmonary vascular density than the BPD+V group. Western blot analysis revealed that significantly decreased levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 by the combined exposure to intra-amniotic LPS and postnatal hyperoxia were restored by the RGZ treatment. RVH was significantly lesser in the BPD+RGZ group than in the BPD+V group. CONCLUSION: These results suggest that RGZ can restore alveolar and pulmonary vascular development and lessen pulmonary hypertension in a rat model of BPD.


Assuntos
Displasia Broncopulmonar/tratamento farmacológico , PPAR gama/agonistas , Tiazolidinedionas/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Feminino , Hipertensão Pulmonar/tratamento farmacológico , Imuno-Histoquímica , Pulmão/efeitos dos fármacos , Pulmão/patologia , Ratos , Ratos Sprague-Dawley , Rosiglitazona
15.
Korean J Pediatr ; 55(11): 438-44, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23227064

RESUMO

Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of ß-D-hexosaminidase and α-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.

16.
J Korean Med Sci ; 27(4): 395-401, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22468103

RESUMO

The aim of our study was to investigate the differential effects of dexamethasone (DXM) and hydrocortisone (HCS) on somatic growth and postnatal lung development in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was induced by administering intra-amniotic lipopolysaccharide (LPS) and postnatal hyperoxia. The rats were treated with a 6-day (D1-D6) tapering course of DXM (starting dose 0.5 mg/kg/day), HCS (starting dose 2 mg/kg/day), or an equivalent volume of normal saline. DXM treatment in a rat model of BPD induced by LPS and hyperoxia was also associated with a more profound weight loss compared to control and LPS + O(2) groups not exposed to corticosteroid, whereas HCS treatment affected body weight only slightly. Examination of lung morphology showed worse mean cord length in both LPS + O(2) + DXM and LPS + O(2) + HCS groups as compared to the LPS + O(2) alone group, and the LPS + O(2) + DXM group had thicker alveolar walls than the LPS + O(2) group at day 14. The HCS treatment was not significantly associated with aberrant alveolar wall thickening and retarded somatic growth. The use of postnatal DXM or HCS in a rat model of BPD induced by intra-amniotic LPS and postnatal hyperoxia appeared detrimental to lung growth, but there was less effect in the case of HCS. These findings suggest that effect of HCS on somatic growth and pulmonary outcome may be better tolerated in neonates for preventing and/or treating BPD.


Assuntos
Anti-Inflamatórios/farmacologia , Dexametasona/farmacologia , Hidrocortisona/farmacologia , Hiperóxia , Pneumopatias/patologia , Alvéolos Pulmonares/efeitos dos fármacos , Âmnio/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Lipopolissacarídeos/toxicidade , Oxigênio/metabolismo , Alvéolos Pulmonares/crescimento & desenvolvimento , Alvéolos Pulmonares/patologia , Ratos , Ratos Sprague-Dawley
17.
Neonatology ; 101(4): 278-84, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22286224

RESUMO

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is known to mobilize endothelial progenitor cells (EPCs) from bone marrow. EPCs reportedly promote neovascularization and participate in the repair of lung structure in adult animals. OBJECTIVE: We tested the hypothesis that G-CSF contributes to alveolar growth by increasing the production of angiogenic growth factor in the lungs of hyperoxia-exposed neonatal mice. METHODS: Neonatal mice were exposed to hyperoxia (80%) or room air (RA) for 7 days and treated with G-CSF (50 µg/kg/day) or vehicle for 5 days. Blood was subjected to flow cytometry to gate for CD45(dim/-)/Sca-1(+)/CD133(+)/vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2) to define the EPC population at day 7. RESULTS: The percentage of EPCs in the peripheral blood and VEGF and VEGFR2 levels in the lungs of neonatal mice exposed to hyperoxia were significantly reduced compared to those of mice kept in RA. G-CSF significantly increased EPCs in the peripheral blood, and VEGF and VEGFR2 levels in the lungs of both mice exposed to hyperoxia and mice kept in RA. G-CSF restored alveolarization inhibited by hyperoxia without altering normal alveolarization under RA. CONCLUSION: G-CSF restored alveolarization inhibited by hyperoxia in the developing lungs and this alveolarization-enhancing effect of G-CSF is associated with mobilization of EPCs and upregulation of VEGF signaling.


Assuntos
Indutores da Angiogênese/metabolismo , Indutores da Angiogênese/farmacologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Hiperóxia/complicações , Alvéolos Pulmonares/efeitos dos fármacos , Animais , Contagem de Células , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Hiperóxia/patologia , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Pulmão/crescimento & desenvolvimento , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Alvéolos Pulmonares/embriologia , Alvéolos Pulmonares/crescimento & desenvolvimento , Alvéolos Pulmonares/metabolismo , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Regulação para Cima/efeitos dos fármacos
18.
Neonatology ; 101(1): 40-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21791938

RESUMO

BACKGROUND: Despite the potential importance of pulmonary artery hypertension (PAH) in preterm infants with bronchopulmonary dysplasia (BPD), little is known about the risk factors for PAH. OBJECTIVES: To investigate the risk factors for PAH in preterm infants with BPD. METHODS: Infants diagnosed with BPD were assigned to the PAH group or non-PAH group except for infants with mild BPD who had no PAH. PAH was diagnosed on the basis of echocardiograms demonstrating elevated right ventricle pressure beyond the postnatal age of 2 months. Logistic regression analysis was done for the multivariate assessment of the risk factors for PAH in preterm infants with moderate or severe BPD. RESULTS: A total of 98 infants among 145 infants with BPD were divided into a PAH group (n = 25) or non-PAH group (n = 73), while the remaining 47 infants had mild BPD with no PAH. Among the study patients, survival rate of the PAH group was significantly lower than that of the non-PAH group. Infants with PAH had more severe cases of BPD and underwent longer durations of oxygen therapy, conventional or high-frequency ventilation, and hospitalization compared to those without PAH. Low 5-min Apgar scores (≤6; relative risk (RR) 6.2; 95% confidence interval (CI) 1.4-28.0; p = 0.017) and oligohydramnios (RR 7.7; 95% CI 2.0-29.6; p = 0.030) were found to be significant risk factors for PAH according to multivariate analysis. CONCLUSIONS: The present study shows that oligohydramnios is a specific risk factor for PAH in preterm infants with moderate or severe BPD.


Assuntos
Displasia Broncopulmonar/epidemiologia , Hipertensão Pulmonar/epidemiologia , Recém-Nascido Prematuro , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/fisiopatologia , Comorbidade , Ecocardiografia , Hipertensão Pulmonar Primária Familiar , Feminino , Ventilação de Alta Frequência , Hospitalização , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Recém-Nascido , Masculino , Oxigenoterapia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco
19.
Korean J Pediatr ; 54(5): 219-23, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21829414

RESUMO

McKusick-Kaufman syndrome (MKS) is an autosomal recessive multiple malformation syndrome characterized by hydrometrocolpos (HMC) and postaxial polydactyly (PAP). We report a case of a female child with MKS who was transferred to the neonatal intensive care unit of Seoul National University Children's Hospital on her 15th day of life for further evaluation and management of an abdominal cystic mass. She underwent abdominal sonography, magnetic resonance imaging, genitography and cystoscopy which confirmed HMC with a transverse vaginal septum. X-rays of the hand and foot showed bony fusion of the left third and fourth metacarpal bones, right fourth dysplastic metacarpal bone and phalanx, right PAP and hypoplastic left foot with left fourth and fifth dysplastic metatarsal bones. In addition, she had soft palate cleft, mild hydronephroses of both kidneys, hypoplastic right kidney with ectopic location and mild rotation, uterine didelphys with transverse vaginal septum and low-type imperforated anus. She was temporarily treated with ultrasound-guided transurethral aspiration of the HMC. Our patient with HMC and PAP was diagnosed with MKS because she has two typical abnormality of MKS and she has no definite complications of retinal disease, learning disability, obesity and renal failure that develop in Bardet-Biedl syndrome, but not in MKS until 33 months of age. Here, we describe a case of a Korean patient with MKS.

20.
Free Radic Res ; 45(9): 1024-32, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21651454

RESUMO

Currently, bronchopulmonary dysplasia (BPD) occurs almost exclusively in pre-term infants. In addition to prematurity, other factors like oxygen toxicity and inflammation can contribute to the pathogenesis. This study aimed to compare urinary inflammatory and oxidative stress markers between the no/mild BPD group and moderate/severe BPD group and between BPD cases with significant early lung disease like respiratory distress syndrome (RDS) ('classic' BPD) and with minimal early lung disease ('atypical' BPD). A total of 60 patients who were a gestational age < 30 weeks or a birth weight < 1250 g were included. Urine samples were obtained on the 1(st), 3(rd) and 7(th) day of life and measured the levels of leukotriene E(4) (LTE(4)) and 8-hydroxydeoxyguanosine (8-OHdG). The 8-OHdG values on the 3(rd) day showed significant correlation to duration of mechanical ventilation. The 8-OHdG levels on the 7(th) day were the independent risk factor for developing moderate/severe BPD. In 'classic' BPD, the 8-OHdG values on the 3(rd) day were higher than those of 'atypical' BPD. In 'atypical' BPD, the LTE(4) values on the 7(th) day were higher than the values in 'classic' BPD. These results suggest that oxidative DNA damage could be the crucial mechanism in the pathogenesis of current BPD and the ongoing inflammatory process could be an important mechanism in 'atypical' BPD.


Assuntos
Displasia Broncopulmonar/metabolismo , Recém-Nascido de muito Baixo Peso/metabolismo , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , Biomarcadores/metabolismo , Biomarcadores/urina , Displasia Broncopulmonar/urina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Desoxiguanosina/urina , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso/urina , Inflamação/urina , Leucotrieno E4/metabolismo , Leucotrieno E4/urina , Masculino , Estatística como Assunto
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