• Clinical and Experimental Pediatrics
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• v.53 no.12
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• pp.979-984
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• 2010

Recent progress in neonatal medicine has enabled survival of many extremely low-birth-weight infants. Prenatal steroids, surfactants, and non-invasive ventilation have helped reduce the incidence of the classical form of bronchopulmonary dysplasia characterized by marked fibrosis and emphysema. However, a new form of bronchopulmonary dysplasia marked by arrest of alveolarization remains a complication in the postnatal course of extremely low-birth-weight infants. To better understand this challenging complication, detailed alveolarization mechanisms should be delineated. Proper alveolarization involves the temporal and spatial coordination of a number of cells, mediators, and genes. Cross-talk between the mesenchyme and the epithelium through soluble and diffusible factors are key processes of alveolarization. Lung interstitial cells derived from the mesenchyme play a crucial role in alveolarization. Peak alveolar formation coincides with intense lung interstitial cell proliferation. Myofibroblasts are essential for secondary septation, a critical process of alveolarization, and localize to the front lines of alveologenesis. The differentiation and migration of myofibroblasts are strictly controlled by various mediators and genes. Disruption of this finely controlled mechanism leads to abnormal alveolarization. Since arrest in alveolarization is a hallmark of a new form of bronchopulmonary dysplasia, knowledge regarding the role of lung interstitial cells during alveolarization and their control mechanism will enable us to find more specific therapeutic strategies for bronchopulmonary dysplasia. In this review, the role of lung interstitial cells during alveolarization and control mechanisms of their differentiation and migration will be discussed.

• Neonatal Medicine
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• v.18 no.2
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• pp.165-176
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• 2011

The pathologic hallmark of new bronchopulmonary dysplasia (BPD) is an arrest in alveolarization and vascular development. Alveoli are the fully mature gas-exchange units and alveolarization denotes the process through which the developing lung attains its fully mature structure. In human, alveolarization is mainly a postnatal event and begins in utero around 35 postmenstrual weeks and continues to 2 postnatal years. Beginning of respiration with very immature lungs as a result of preterm delivery renders the immature lung to be exposed to various injuries such as mechanical stretch, hyperoxia, infection/inflammation and leads to a disruption of normal alveolarization process, which is a main pathologic finding of BPD. Better understanding of the control mechanisms of normal alveolarization process should help us to figure out the pathophysiology of BPD and discover effective preventive or therapeutic measures for BPD. In this review, the pathologic evolution of BPD from 'old' to 'new' BPD, the detailed mechanisms of normal alveolarization, and the factors that disrupt normal alveolarization will be discussed.

• Korean Journal of Environmental Biology
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• v.21 no.3
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• pp.297-302
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• 2003

This study was designed to determine whether selenium (Se) nutrition affects pulmonary glutathione peroxidase and alveolarization in the neonatal rat. Twenty-four female Sprague Dawley rats were bred and fed a semipurified Se-deficient (0.04 ppm, Se-) or a Se-adequate (0.5 ppm, Se+) diet through pregnancy and lactation. Pulmonary DNA synthesis was slightly higher in Se+ pups than in Se- pups on d 6 and d 9 of lactation, but significant difference was not found. As pulmonary alveolarization progressed, mean air space size decreased and internal surface area and lung volume increased. No difference in pulmonary alveolarization was found between Se- and Se+ pups by age. Pulmonary Se concentration was higher in Se+ pups than in Se- pups at all age. Glutathione peroxidase activity in lung tissur reflected Se status and was lower in Se- pups than in Se+ pups. In conclusion, selenium has no significant effect on alveolarization of neonatal lungs. but it is necessary for adequate supply of pulmonary antioxidant, glutathione peroxidase.

• Clinical and Experimental Pediatrics
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• v.64 no.1
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• pp.37-43
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• 2021

Background: Animal studies have shown that a leukocyte influx precedes the development of bronchopulmonary dysplasia (BPD) in premature sheep. The CXC chemokine receptor 2 (CXCR2) pathway has been implicated in the pathogenesis of BPD because of the predominance of CXCR2 ligands in tracheal aspirates of preterm infants who later developed BPD. Purpose: To test the effect of CXCR2 antagonist on postnatal systemic and pulmonary inflammation and alveolarization in a newborn Sprague-Dawley rat model of BPD. Methods: Lipopolysaccharide (LPS) was injected intraperitoneally (i.p.) into the newborn rats on postnatal day 1 (P1), P3, and P5 to induce systemic inflammation and inhibit alveolarization. In the same time with LPS administration, CXCR2 antagonist (SB-265610) or vehicle was injected i.p. to investigate whether CXCR2 antagonist can alleviate the detrimental effect of LPS on alveolarization by attenuating inflammation. On P7 and P14, bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) were collected from the pups. To assess alveolarization, mean cord length and alveolar surface area were measured on 4 random nonoverlapping fields per animal in 2 distal lung sections at ×100 magnification. Results: Early postnatal LPS administration significantly increased neutrophil counts in BALF and PB and inhibited alveolarization, which was indicated by a greater mean cord length and lesser alveolar surface area. CXCR2 antagonist significantly attenuated the increase of neutrophil counts in BALF and PB and restored alveolarization as indicated by a decreased mean cord length and increased alveolar surface area in rat pups exposed to early postnatal systemic LPS. Conclusion: CXCR2 antagonist preserved alveolarization by alleviating pulmonary and systemic inflammation induced by early postnatal systemic LPS administration. These results suggest that CXCR2 antagonist can be considered a potential therapeutic agent for BPD that results from disrupted alveolarization induced by inflammation.

• Speech Sciences
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• v.8 no.4
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• pp.109-118
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• 2001

This study was designed to evaluate the phonological characteristics in profound hearing-impaired children. 10 males and 10 females participated in this study and all were prelingually hearing impaired. 7 children were educated at deaf school and 13 children at general elementary school with private clinic. Their hearing levels were more than 95dB HL and did not appear any wave by ABR. The results can be summarized as following: The articulation accuracy of hearing impaired children was 54.19% and most distinguished phonological patterns of the hearing impaired children were alveolarization and stop assimilation. The accurate articulation phonation was significantly different from education system between deaf school and general school. The error articulation degrees in profound hearing impaired children at general school seemed meaningfully smaller than those in hearing impaired children at deaf school.

• Phonetics and Speech Sciences
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• v.7 no.2
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• pp.19-28
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• 2015

This study investigated final consonant error characteristics at word-medial position in children with functional articulation disorder. Data was collected from 11 children with functional articulation and 11 normal children, ages 4 to 5. The speech samples were collected from a naming test. Seventy-five words with every possible bi-consonants matrix at the word-medial position were used. The results of this study were as follows : First, percentage of correct word-medial final consonants of functional articulation disorder was lower than normal children. Second, there were significant differences between two groups in omission, substitution and assimilation error. Children with functional articulation disorder showed a high frequency of omission and regressive assimilation error, especially alveolarization in regressive assimilation error most. However, normal children showed a high frequency of regressive assimilation error, especially bilabialization in regressive assimilation error most. Finally, the results of error analysis according to articulation manner, articulation place and phonation type of consonants of initial consonant at word-medial, both functional articulation disorder and normal children showed a high error rate in stop sound-stop sound condition. The error rate of final consonant at word-medial position was high when initial consonant at word-medial position was alveolar sound and alveopalatal sound. Futhermore, when initial sounds were fortis and aspirated sounds, more errors occurred than linis sound was initial sound. The results of this study provided practical error characteristics of final consonant at word-medial position in children with speech sound disorder.

• Neonatal Medicine
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• v.15 no.1
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• pp.22-31
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• 2008

Purpose : Bronchopulmonary dysplasia (BPD) is characterized by arrested vascular and alveolar growth in the premature lung. Considering the consequences of arrested lung growth, the idea of administering bone marrow cells to enhance the inborn repair mechanism is promising as this may reduce the morbidity and mortality of BPD. We followed enhanced green fluorescent protein (EGFP)-labeled bone marrow cells (BMC) injected intraperitoneally into non-EGFP mice in order to determine their fate after transplantation. Methods : An angiogenesis inhibitor, SU1498, was injected subcutaneously on day 3 in non-EGFP C57BL/6 newborn mice to create a model of arrested alveolar development. On the following day, $1{\times}10^6$ BMCs isolated from major histocompatibility complex (MHC)- matched syngenic EGFP mice were injected intraperitoneally to non-EGFP BPD mice. Morphometric analysis, immunostaining, and confocal microscopy were performed to determine the fate of EGFP-positive stem cells in the injured lung. Results : SU1498 injection reduced alveolar surface area and mean alveolar volume in newborn mice. BMC injection resulted in recovery of lung structure comparable to controls. EGFP-positive BMCs were identified in the lungs of the recipient mice after intraperitoneal injection. The injected EGFP cells were co-stained with endothelial and epithelial cells of the developing lung as determined by confocal microscopy. Conclusion : Our results illustrated that EGFP-positive BMCs engrafted and trans-differentiated into epithelial and endothelial cells after intraperitoneal injection in a mouse model of arrested alveolar development.