No abstract available.
Pulmonary Surfactants*

PURPOSE: Respiratory distress syndrome(RDS) is caused by a deficiency of pulmonary surfactant, which is a lipoprotein complex. Both low levels of surfactant protein A(SP-A) and SP-A alleles have been associated with RDS. However, the genes underlying susceptibility to RDS are insufficiently known. The candidate-gene approach was used to study the association between the SP-A gene locus and RDS in the genetically homogeneous Korean population. METHODS: A PCR-cRFLP-based methodology was used to detect SP-A genotype. Twenty four neonates with RDS were matched pairwise to those without RDS. RESULTS: The frequencies of specific genotypes such as 6A(2), 1A(0) were increased, but the frequency of specific 1A(2) genotype was increased in control group. 6A(2)/1A(0) were also increased in the RDS group. Infants who did not have RDS develop, despite prematurity and lack of steroid therapy, had a higher frequency of the 1A(2) allele than infants who had received steroid therapy and had RDS develop. However, infants who had received steroid therapy and had RDS develop had a higher frequency of the 1A(0) allele than infants who did not have RDS develop, despite prematurity and lack of steroid therapy. CONCLUSION: SP-A alleles/haplotypes are susceptible(6A(2), 1A(0), 6A(2)/1A(0)) or protective(1A(2)) factors for RDS. We conclude that the SP-A gene locus is an important determinant for predisposition to RDS in neonates
Alleles ; Genotype ; Humans* ; Infant ; Infant, Newborn* ; Lipoproteins ; Pulmonary Surfactants ; Steroids

The pathophysiology of meconium aspiration syndrome(MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. Meconium is also suggested to cause functional deterioration of pulmonary surfactant. Recent studies have reported that meconium inhibits the physical surface properties of pulmonary surfactant, and that administration of exogenous surfactant may provide therapeutic benefits in animal models or infants with respiratory distress due to MAS. To assess the effects of meconium on physical surface properties, especially the changes on the air-liquid interface and hypophase of pulmonary surfactant in vitro, we studied the following findings; a) the surface spreading rate(SSR) and the surface adsorption rate(SAR), b) the viscosity, c) the electron microscopic changes, on a series of mixtures with various concentrations of lyophilized human meconium and Surfactant-TA(SurfactenTM). The human meconium has significantly increased the surface tension of SSR and the viscosity of pulmonary surfactant, but had decreased the surface pressure of SAR of surfactant, and changed the electron microscopic findings of surfactant. We have concluded that these findings support the concept that meconium-induced surfactant dysfunction may play a role in the pathophysiology of MAS.
Human ; Infant, Newborn ; Meconium/*metabolism ; Pulmonary Surfactants/*metabolism

PURPOSE: With the recent advent of surfactant replacement therapy, there is an increasing need for a rapid and reliable test to predict respiratory distress syndrome (RDS) immediately before or at birth. There are many investigations and methods for the detection of RDS in prenatal or postnatal period. The stable microbubble rating test (SMR-test) developed by pattle et al. is rapid and simple test performed on amniotic fluid and gastric aspirates which reflects the adequacy of pulmonary surfactant with higher diagnostic accuracy. To determine the relation of the SMR and surfactant derivatives [Surfacten : phospholipid (PL), Exosurf : dipalmitoyl-phosphatidyl choline (DPPC) concentration in vitro, author performed SMR test according to 15 groups of surfactant derivatives concentration by using modified Pattle's method. METHODS: Surfacten & Exosurf were diluted each concentration (0, 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100microgram/ml) by dilutional fluid. We enveloped test tube by paraffin paper for protection of evaporation. When we performed SMR test, we shaked test tube vigorously by Vlotex shaker. We performed SMR test according to 15 groups of Surfactant concentration by using modified Pattle's method. RESULTS: 1) The number of SMR according to 15 groups of surfactant derivatives concentration were 2, 1/mm2 in 4.2microgram/ml of PL and 3.1microgram/ml of DPPC, 279, 1104/mm2 in 83.3microgram/ml of PL and 61.8microgram/ml DPPC. 2) The regression curve of SMR and surfactant derivatives concentration showed statistically significant relation (p<0.005). CONCLUSION: The SMR test was a good method in estimation of surfactant concentration in vitro and also in diagnosis of RDS recognized as a surfactant deficiency.
Amniotic Fluid ; Choline ; Diagnosis ; Female ; Microbubbles* ; Paraffin ; Parturition ; Pulmonary Surfactants

PURPOSE: To produce a new generation of artificial pulmonary surfactant(PS), surfactant protein (SP)-B from human PSwas isolated, and the amino acid sequences of these proteins were studied. Artificial peptides of human SP-B were synthesized. New artificial PS preparations which were cornposed of phospholopids and two artificial synthetic SP-B peptides were made, and the surface physical properties of these new PS preparations were tested. METHODS: The purities of SP-B were assessed by SDS-polyacrylamide gel and the amino acid sequences of these proteins were determined. We synthetized two peptides SP-1 and SP-2 and the amino acid sequences were as follows,' SP-1: RMLPQLVCRLVLRCSMD, SP-2: RMLP- QLVCRLVLRCSM. Surface physical properties of newly artificial PSs, which were composed of a mixture of phospholipid(PL) and SP-1 or SP-2(sample A; PL+SP-1, sample B; PL+SP-2), were measured by surface spreading, adsorption rate, and surface tension-area diagram. RESULTS: The amino acid sequence of human SP-B was obtained. We produced the artificial peptides of SP-B and prepared the new generation PS(sample A and sample B). The order of the superiority of spreading and adsorption rate was Surfacten Absorption ; Adsorption ; Amino Acid Sequence ; Humans ; Peptides* ; Pulmonary Surfactants

In the present study, the composition and content of pulmonary surfactant (PS) were analyzed to explore the hypoxia adaptation mechanism in plateau zokors (Myospalax baileyi) and plateau pikas (Ochotona curzoniae). 36 plateau zokors and plateau pikas were trapped alive at the Laji Mountain in Guide County, Qinghai Province (at the altitude of about 3 600 m), and 36 Sprague-Dawley (SD) rats were purchased from the experimental animal center of Lanzhou University (at the altitude of about 1 500 m). All animals were lavaged after laboratory anesthesia, the blood in lung tissues was fully washed out and the lung tissues were then taken out to obtain the bronchoalveolar lavage fluid by bronchoalveolar lavage. The composition and content of phospholipids in the PS of three different kinds of animals were analyzed by using high performance liquid chromatography; the protein composition, content and types in the PS were analyzed by G-250 Coomassie brilliant blue method, polyacrylamide gel electrophoresis (PAGE) and mass spectrometry; the dissolved oxygen in the PS solutions were determined by using dissolved oxygen electrode. The results showed that the total contents of phospholipids in the PS were successively increased among plateau zokors, plateau pikas and SD rats (P < 0.05), while the total content of proteins successively decreased (P < 0.05). There were five phospholipids identified in the PS, including linoleic palmitoylphosphatidylcholine (LPPC), dipalmitoylphosphatidylcholine (DPPC), phosphatidylglyerol (PG), phosphatidylinositol (PI) and phosphatidylserine (PSe), but the relative contents of these phospholipids were different. The relative content of LPPC was successively increased among plateau zokors, plateau pikas and SD rats (P < 0.01). The relative contents of DPPC, PG and PI in the PS of plateau zokors were significantly higher than those of plateau pikas (P < 0.01), while insignificant differences between plateau pikas and SD rats (P > 0.05). The relative content of PSe had no significant differences between plateau zokors and plateau pikas (P > 0.05), but both were significantly higher than that of SD rats (P < 0.01). The serum albumin (SA) was identified in the PS of three kinds of animals, including homologous tetramer protein containing heme, which is composed of hemoglobin β subunit, in plateau zokors and plateau pikas. Immunoglobulin (Ig) heavy chain was found in PS of plateau zokors and SD rats. The content of Ig heavy chain in plateau zokor was significantly higher than that in SD rats (P < 0.01), and the content of protein containing heme was significantly higher than that in plateau pikas (P < 0.05). The amount of dissolved oxygen was successively decreased in the PS among plateau zokors, plateau pikas and SD rats (P < 0.01), but it was significantly higher than that in saline (P < 0.01). These results suggest that the total content of proteins in the PS of plateau zokors and plateau pikas was significantly higher, while the total content of phospholipids was significantly decreased. There were high content of homologous tetramer protein containing heme in the PS of plateau zokors and plateau pikas. The relative content of DPPC, the main component of phospholipids, was significantly increased in plateau zokors. The changes of PS component and content improve the adaptability of the two plateau animals in hypoxia environment.
Altitude ; Animals ; Hypoxia ; Lagomorpha ; Pulmonary Surfactants ; Rats ; Rats, Sprague-Dawley

In order to observe the effects of serum albumin and fibrinogen on biophysical surface properties and the morphology of pulmonary surfactant in vitro, we measured the surface adsorption rate, dynamic minimum and maximum surface tension (min-, max-ST) by Pulsating Bubble Surfactometer, and demonstrated ultrastructures on a series of mixtures with varying concentrations of albumin or fibrinogen and Surfactant-TA. The albumin and fibrinogen significantly inhibited the adsorption rate and ST-lowering properties of surfactant through increasing STs of adsorption rate, min-ST, and max-ST. The characteristic morphology of the Surfactant-TA changed from lamellar rod-like structure with open ends into spherical structures with loss of their open ends by mixing with albumin or fibrinogen. These inhibitory effects of albumin and fibrinogen on surface properties of surfactant were dependent upon the increasing concentration of albumin or fibrinogen. We concluded that albumin and fibrinogen significantly altered surfactant function and its ultrastructural morphology in vitro. These findings support the concept that albumin and fibrinogen-induced surfactant dysfunction may play an important role in the pathophysiology of adult respiratory distress syndrome, and this adverse effect of albumin and fibrinogen on surfactant might be overcome by administration of large doses of exogenous surfactant.
Adsorption ; Animal ; Cattle ; Fibrinogen/pharmacology* ; Human ; Pulmonary Surfactants/ultrastructure* ; Pulmonary Surfactants/drug effects ; Serum Albumin, Bovine/pharmacology* ; Surface Properties

In Korea, pulmonary surfactant (PS) replacement therapy in respiratory distress syndrome (RDS) was started in 1991 since when Surfacten(R) was imported from Japan. At the present time, Surfacten(R), Newfactan(R), Curosurf(R), and Infasurf(R) are available in Korea. The governmental health insurance covers the expense for multiple dose treatment since 2002 and the early prophylactic treatment (BW: <1,250 g or GP: <30 wks) since 2011. We undertook a multi-institutional collective study to evaluate the outcomes of PS over past 20 years in Korea (Period-I; 1990/91, P-II; 1996, P-III; 2002, and P-IV; 2007, P-V; 2010). There were 60 RDS neonates with PS treatment in P-I (16 hospitals), 1,179 in P-II (64), 1,595 in P-III (62), 1,921 in P-IV (57), and 3,160 in P-V (72). Decreased mortality rate, defined as the percentage of neonates who died within 28 days of birth, was seen between periods, P-V vs P-I, II, III, and IV (mortality rate: 10.1% vs. 40.0%, 30.0%, 18.7%, and 14.3%). We conclude that PS therapy contributed to improve remarkable outcome in RDS neonates over the last 20 years in Korea. However, more efforts should be made to optimize PS therapy for better outcome. Multiple PS doses for relapse and poor response, early prophylactic use, and better supportive care for pre-term infants are mandatory.
Humans ; Infant ; Infant, Newborn ; Insurance, Health ; Japan ; Korea ; Parturition ; Pulmonary Surfactants ; Recurrence

Pulmonary surfactant instillation is the treatment of choice in neonatal respiratory distress syndrome. The development of artificial surfactant has three decades of history. Animal-derived artificial surfactant is used in most countries and consists of 80% phospholipids and glycerol. 10% of the formulation is comprised of surfactant proteins, which have the critical role in surfactant function of lowering surface tension in the alveoli. Synthetic surfactants are made using synthetic peptide analogues as the surfactant protein counterparts. These are not the same as the human surfactant protein sequences; however, researchers are attempting to find the ideal synthetic peptide sequence for use in synthetic surfactants. Prophylactic and rescue surfactant therapy are two main therapeutic options. A recent recommendation emphasizes the importance of rescue therapy with continuous positive nasal airway pressure, rather than prophylactic use immediate after birth. This article briefly reviews the history and physiology of surfactant use, as well as clinical practice of surfactant and future studies.
Glycerol ; Humans ; Parturition ; Phospholipids ; Physiology ; Pulmonary Surfactants* ; Respiratory Distress Syndrome, Newborn ; Surface Tension ; Surface-Active Agents

BACKGROUND: Surfactant proteins are important in the regulation of the surfactant secretion, synthesis and recycling. Glucocorticoids are known to have primary or secondary effects on gene expression and can alter the rate of gene transcription. The hydrophilic and hydrophobic surfactant protein have been shown to be upregulated by glucocorticoids in vitro but its regulation in vivo, however, is not well established. The authors carried out nuclear run on assays to determine wheather glucocorticoids altered the transcription rate of SP-A, SP-B and SP-C genes. METHODS: Adult rats were given the 2 mg/kg dose of subcutaneous dexamethasone for 2 days and sacrified at 2 days. The transcription rate of SP-A, SP-B and SP-C genes were measured by nuclear run on assays. RESULTS: Treatment with 2 mg/kg dexamethasone increased transcription of SP-A gene (1.6-fold) and SP-C gene (1.3-fold) compared to the control for SP-A and SP-C after 2 days, which were not statistically significant. The rate of gene transcription for SP-B at 2 days after 2 mg/kg dexamethasone administration was significantly increased by 5.3-fold compared to the control for SP-B (p<0.005). The rates of gene transcription for hydrophilic and hydrophobic surfactant proteins, even in the hydrophobic surfactant proteins SP-B and SP-C were different. CONCLUSIONS: The authors conclude that the difference in dexamethasone sensitivity may indicate that the three surfactant protein genes contain glucocorticoid response elements with different affinities for receptor in vivo.
Adult ; Animals ; Dexamethasone ; Gene Expression ; Glucocorticoids ; Humans ; Pulmonary Surfactants ; Rats ; Recycling ; Response Elements