Most of perinatological phenomenona and diseases are closely related with immune reaction. Most of initial immune responses occur through innate immunity and most causes, such as mechanical damage, hypoxia, and hyperoxia, are self and microorganisms are non-self, all of which are related with immune reaction concept. However, researches on perinatology are mainly focused on specific one or two causes of perinatal diseases, so often there is limitation to understand the basic concepts and phenomenona of the perinatal diseases. Through understanding of immune reaction concept, we can apply immune reaction theory to researches in perinatology and we can understand phenomenona in perinatology through knowledge of immune reaction. Therefore it is essential to understand historical development of immunology and concept of immune reaction for researches and treatment of perinatology.
Allergy and Immunology ; Anoxia ; Hyperoxia ; Immunity, Innate ; Perinatology*

Animals ; Cecum/microbiology* ; Hyperoxia/blood* ; Microbiota ; Rats

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.
Bronchopulmonary Dysplasia ; Humans ; Hyperoxia ; Infant, Newborn ; Lung ; Respiration

No abstract available.
Animals ; Extracellular Matrix* ; Hyaluronic Acid* ; Hyperoxia* ; Lung Injury* ; Lung* ; Rats*

PURPOSE: To investigate the effect of curcumin, known to inhibit hypoxia-inducible factor-1, on retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). METHODS: OIR was induced by exposing C57BL/6 mice on postnatal day 7 (P7) to 75% hyperoxia for 5 days, followed by 5 days in a room with normal oxygen level. Curcumin was administered intraperitoneally once a day for 5 days from P12 or intravitreally once on P13. Mice retinas on P17 were analyzed for retinal neovascularization, which was compared between curcumin-treated and control mice. RESULTS: After intraperitoneal and intravitreal administration of curcumin, qualitative assessment of retinal neovascularization of flat-mounted retina showed no significant difference compared to control retinas. Quantitative assessment of retinal neovascularization also showed no significant difference between curcumin-treated and control mice. CONCLUSIONS: Both intraperitoneal and intravitreal administration of curcumin did not reduce retinal neovascularization in an OIR mouse model. Further investigation including development of new formulations is required for the use of curcumin as an anti-angiogenic agent for retinal neovascularization.
Animals ; Curcumin* ; Hyperoxia ; Mice* ; Oxygen ; Retina ; Retinal Neovascularization ; Retinopathy of Prematurity

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 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 ( < 0.001), and was significantly higher in hyperoxic+VD (125 times) than in hyperoxia + VD (1250 times) group ( < 0.01). The alveolar secondary protrusion count was significantly higher in hyperoxic+VD (1250 times) group than in hyperoxic+saline group ( < 0.001), and was significantly higher in hyperoxia+VD (125 times) group than in hyperoxia + VD (1250 times) group ( < 0.01). Compared with that in air + saline group, VEGFR2 expression was significantly lowered in hyperoxia+saline group ( < 0.05) and in air+VD group ( < 0.05); VEGFR2 expression was significantly higher in hyperoxia+VD (1250 times) group than in hyperoxia+saline group ( < 0.001) and hyperoxia+VD (125 times) group ( < 0.001); VEGFR2 expression was significantly higher in hyperoxia+VD (125 times) group than in hyperoxia+ saline group ( < 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.
Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; Hyperoxia ; Lung ; Mice ; Vitamin D

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.
Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; Hyperoxia ; Lung ; MicroRNAs ; Rats ; Triterpenes

PURPOSE: Lung injury imposed by hyperoxia is the most important cause of bronchopulmonary dysplasia (BPD) in premature lungs, and hyperoxia has the chief biological effect of inducing cell death. The objective of this study was to investigate the response of cell death in fetal alveolar type II cells (FATIICs) exposed to different concentrations of hyperoxia for 36 h. METHODS: FATIICs were isolated on embryonic day 19 and exposed to 65%- or 85%-oxygen for 36 h. Cells in room air were used as controls. FACScan was performed in hyperoxic and control samples at 0/6/12/24/36 h, and the patterns of cell death were compared at each time point using flow-cytometry. RESULTS: Cell necrosis as measured by selective propidium iodide staining increased significantly from 12 h of 65%-hyperoxia and 6 h of 85%-hyperoxia, respectively. Cell necrosis increased 1.6-fold, 3.0-fold and 4.6-fold after 12 h, 24 h, and 36 h, respectively during 65%-hyperoxia and increased by 2.4-fold, 3.1-fold, 6.3-fold, and 8.8-fold after 6 h, 12 h, 24 h, and 36 h, respectively during 85%-hyperoxia compared to controls. Apoptotic cells as measured by selective Annexin-V staining peaked at 1.3% at 24 h of 65%-hyperoxia and peaked at 1.2% at 6 h of 85%-hyperoxia, respectively and then decreased rapidly. CONCLUSION: This study shows that exposure to sublethal and lethal hyperoxia increases necrosis of FATIICs remarkably from the early stage of hyperoxia. These findings support the idea that short-term exposure to oxygen from birth may contribute to the evolution of "new" BPD in preterm lungs.
Bronchopulmonary Dysplasia ; Cell Death ; Humans ; Hyperoxia ; Infant, Newborn ; Lung ; Lung Injury ; Necrosis ; Oxygen ; Parturition ; Propidium

PURPOSE: In the treatrnent of respiratory distress syndrome, Infants are often exposed to hyperoxia. It can generate oxygen free radical, damage to lung and bronchi, and inactivate pulmonary surfactant(PS). Antioxidant therapy in animal and human models has been tried to overcome this detrimental effects. We hypothesized that the addition of oxygen free radical such as hydrogen peroxide(H) could compromise surface active properties(SAP) of PS and that further addition of antioxidant such as catalaseR(CAT, Sigma chemical, St. Louis) could recover SAP. METHODS: We prepared combinations of mixtures with SurfactenR(S-TA, Tokyo Tanabe, Japan), H202 and CAT. 1)0.625mgPL(phospholipids)/ml or 1.25mgPL/ml S - TA and H202 were mixed to the final concentrations of 0.1 and 1mM H respectively, and incubated at 37C for one hour. 2) 0.625mgPL/rnl S - TA, H202 and CAT 10U were mixed to the final concentrations of lmM H202, and incubated at 37 degree C for one hour. We used Pulsating Bubble Surfactometer (Electronetics, NY) measure in vitro minimum and maximum surface tensions(ST) and area-surface tension relationship. RESULTS: 1) For 0.625mgPL/ml S-TA and 1mM H mixture minimum. ST after 5 min of pulsation increased significantly(P=0.007) and the area-surface tension curve was deformed. But they were comparable to control levels for 1.25mgPL/ml S-TA. 2) When CAT was added to 0.625mgPL/ml S-TA and 1mM H mixture, the resultant minimum ST after 5 min of pulsation dropped to the control levels with recovery of hysteresis curve(P=0.0001). CONCLUSION: PS could be inactivated by addition of high concentrations of H but SAP can be recovered either by increasing PS concentration or by further addition of antioxidant CAT. Therefore, we suggest that in case of suspected surfactant inactivation an increase in surfactant concentration or administration of antioxidant must be considered.
Animals ; Bronchi ; Catalase* ; Cats ; Humans ; Hydrogen Peroxide* ; Hydrogen* ; Hyperoxia ; Infant ; Lung ; Oxygen

The effect of hyperoxia and smoking on retinal and optic nerve head microcirculation, and O2 reactivity in smokers and non-smokers were investigated using HRF(Heidelberg Retinal Flowmeter). 10 eyes of 10 young healthy non-smoking volunteers and 10 eyes of 10 young healthy smoking volunteers were investigated. Blood flow measurements were performed using HRF before and after 100% oxygen was applied to the subjects. In the non-smoking group, retinal flow was reduced by 33%, retinal volume by 24%, optic nerve head flow by 16% and optic nerve head volume by 18%. In the smoking group, retinal flow was reduced by 19%, retinal volume by 16%, optic nerve head flow by 16% and optic nerve head volume by 16%. The difference of O 2 reactivity between smokers and non-smokers was statistically significant in the retinal blood flow and volume, but not significant in the optic nerve head flow and volume. These results indicate that hyperoxia leads to a decrease in capillary blood flow of the retina and optic nerve head secondary to vasoconstriction, and that smoking decreases O2 reactivity in retinal microcirculation. The findings might be based on the long term effects of nicotine on the vascular system in smokers.
Capillaries ; Hyperoxia* ; Microcirculation ; Nicotine ; Optic Disk* ; Optic Nerve* ; Oxygen ; Retina ; Retinaldehyde* ; Smoke* ; Smoking ; Vasoconstriction ; Volunteers