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

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

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

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

Pulmonary hypoplasia(PH) commonly occurs in association with oligohydramnios and other congenital anomalies, especially congenital diaphragmatic hernia (CDH). Pulmonary hypoplasia is an important factor, as persistent pulmonary hypertension, in the prognosis of CDH. In some reports, there is a decrement of pulmonary surfactant in PH accompanying CDH. Recently, there are some reports that exogenous pulmonary surfactant therapy is effective in experimental animal model and neonatal respiratory distress with PH. We report a case of a 5 day-old male neonate, who had shown dyspnea and diagnosed as left pulmonary hypoplasia accompanying CDH. The CDH was surgically treated and the ipsilateral PH, with intratracheal administration of exogenous pulmonary surfactant postoperatively. After exogenous pulmonary surfactant application, the left lung volume was increased on chest roentgenogram and lung perfusion scan findings, and there was an improvement in oxygenation and clinical manifestations. We suggest that postoperative exogenous pulmonary surfactant replacement therapy is effective in the case of PH and further trials are needed to clarify the optimal dose and timing of supplementation of surfactant for treatment of infants with PH accompanying CDH.
Case Report ; Hernia, Diaphragmatic/*congenital ; Human ; Infant, Newborn ; Lung/*abnormalities ; Male ; Pulmonary Surfactants/*therapeutic use

Conflicting results have been reported regarding the effects of ether anesthesia on the surfactant system of the lung, and little has been known on the effects of methoxyflurane anesthesia on the activity of the pulmonary surfactant. In the present study, an effort was made to observe and clarify possible effects of ether and methoxyflurane anesthesia on the activity of surfactant of the rabbit lung extracts, subjecting the rabbit to the light or deep anesthesia with the anesthetics by the non-rebreathing system. Tension-area (T-A) diagram of the lung extract was recorded automatically by a modified Langmuir-Wilhelmy balance with a synchronized recording system. The arterial blood pressure and heart rate during the entire stages of anesthesia were also recorded. The surface tension of the lung extracts, arterial blood pressure and heart rate thus obtained were compared with those of the non-anesthetized control group, and the results are summarized as follows: 1, The maximal surface tension, minimal surface tension, width of the T-A diagram at the surface area of 40% and stability index of the control group were 35.15+/-4.49 dynes/cm, 12.40+/-2.73 dynes/cm, 18.15+/-4.0 dynes/cm and 0.96+/-0.23, respectively.2. No significant difference was observed in the activity of surfactant of the lung extract prepared from the rabbit anesthetized with ether or methoxyflurane throughout the entire experiment. 3. In the ether anesthesia group, arterial blood pressure decreased gradually from the control value of 102.38+/-10.99 mmHg as the anesthesia deepened. The heart rate was slightly elevated in light stages of ether anesthesia from the control value of 284.95+/-35.91/min, but 120 min after deep anesthesia the heart rate returned to the control value. 4. Anesthesia with methoxyflurane produced a significantly decreased arterial blood pressure from the beginning and throughout the entire anesthesia stage. The heart rate did not change significantly througbout the entire anesthesia compripg with the control. 5. The above results suggest that the inhalation anesthesia with ether or methoxyflurane do not produce any significant change in the activity of pulmonary surfactant.
Anesthesia* ; Anesthesia, Inhalation ; Anesthetics ; Arterial Pressure ; Ether* ; Heart Rate ; Lung ; Methoxyflurane* ; Pulmonary Surfactants* ; Rabbits* ; Surface Tension

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