1.A Combination of Short and Simple Surfactant Protein B and C Analogues as a New Synthetic Surfactant: In Vitro and Animal Experiments.
Yong Sung CHOI ; Sung Hoon CHUNG ; Chong Woo BAE
Yonsei Medical Journal 2017;58(4):823-828
PURPOSE: Pulmonary surfactants for preterm infants contain mostly animal-derived surfactant proteins (SPs), which are essential for lowering surface tension. We prepared artificial pulmonary surfactants using synthetic human SP analogs and performed in vitro and in vivo experiments. MATERIALS AND METHODS: We synthesized peptide analogues that resemble human SP-B (RMLPQLVCRLVLRCSMD) and SP-C (CPVHLKRLLLLLLLLLLLLLLLL). Dipalmitoylphosphatidylcholine (DPPC), phosphatidylglycerol (PG), and palmitic acid (PA) were added and mixed in lyophilized to render powdered surfactant. Synsurf-1 was composed of DPPC:PG:PA:SP-B (75:25:10:3, w/w); Synsurf-2 was composed of DPPC:PG:PA:SP-C (75:25:10:3, w/w); and Synsurf-3 was composed of DPPC:PG:PA:SP-B:SP-C (75:25:10:3:3, w/w). We performed in vitro study to compare the physical characteristics using pulsating bubble surfactometer and modified Wilhelmy balance test. Surface spreading and adsorption test of the surfactant preparations were measured. In vivo test was performed using term and preterm rabbit pups. Pressure-volume curves were generated during the deflation phase. Histologic findings were examined. RESULTS: Pulsating bubble surfactometer readings revealed following minimum and maximum surface tension (mN/m) at 5 minutes: Surfacten® (5.5±0.4, 32.8±1.6), Synsurf-1 (16.7±0.6, 28.7±1.5), Synsurf-2 (7.9±1.0, 33.1±1.6), and Synsurf-3 (7.1±0.8, 34.5±1.0). Surface spreading rates were as follows: Surfacten® (27 mN/m), Synsurf-1 (43 mN/m), Synsurf-2 (27 mN/m), and Synsurf-3 (27 mN/m). Surface adsorption rate results were as follows: Surfacten® (28 mN/m), Synsurf-1 (35 mN/m), Synsurf-2 (29 mN/m), and Synsurf-3 (27 mN/m). The deflation curves were best for Synsurf-3; those for Synsurf-2 were better than those for Surfacten®. Synsurf-1 was the worst surfactant preparation. Microscopic examination showed the largest aerated area of the alveoli in the Synsurf-3 group, followed by Synsurf-1 and Surfacten®; Synsurf-2 was the smallest. CONCLUSION: Synsurf-3 containing both SP-B and SP-C synthetic analogs showed comparable and better efficacy than commercially used Surfacten® in lowering surface tension, pressure-volume curves, and tissue aerated area of the alveoli.
1,2-Dipalmitoylphosphatidylcholine
;
Adsorption
;
Animal Experimentation*
;
Animals*
;
Humans
;
In Vitro Techniques*
;
Infant, Newborn
;
Infant, Premature
;
Palmitic Acid
;
Pulmonary Surfactant-Associated Proteins
;
Pulmonary Surfactants
;
Reading
;
Surface Tension
2.Study on the biodegradation of perfluorooctanesulfonate (PFOS) and PFOS alternatives.
Bongin CHOI ; Suk Hyun NA ; Jun Hyo SON ; Dong Soo SHIN ; Byung Taek RYU ; Kyun Suk BYEON ; Seon yong CHUNG
Environmental Health and Toxicology 2016;31(1):e2016002-
OBJECTIVES: In this study, we investigated the biodegradation features of 4 perfluorooctanesulfonate (PFOS) alternatives developed at Changwon National University compared to those of PFOS. METHODS: Biodegradation testing was performed with microorganisms cultured in the good laboratory practice laboratory of the Korea Environment Corporation for 28 days following the Organization for Economic Cooperation and Development guidelines for the testing of chemicals (Test No. 301 C). RESULTS: While C₈F₁₇SO₃Na, PFOS sodium salt was not degraded after 28 days, the 4 alternatives were biodegraded at the rates of 20.9% for C₁₅F₉H₂₁S₂O₈Na₂, 8.4% for C₁₇F₉H ₂₅S₂O₈Na₂, 22.6% for C₂₃F₁₈H₂₈S₂O₈Na₂, and 23.6% for C₂₅F₁₇H₃₂O₁₃S₃Na₃. CONCLUSIONS: C₂₅F₁₇H₃₂S₃O₁₃Na₃, C₂₃F₁₈H₂₈S₂O₈Na₂, and C₁₅F₉H₂₁S₂O₈Na₂ were superior to PFOS in terms of biodegradation rates and surface tension, and thus they were considered highly applicable as PFOS alternatives. Environmental toxicity, human toxicity, and economic feasibility of these compounds should be investigated prior to their commercialization.
Gyeongsangnam-do
;
Humans
;
Korea
;
Organisation for Economic Co-Operation and Development
;
Sodium
;
Surface Tension
3.Development of a Synthetic Surfactant Using a Surfactant Protein-C Peptide Analog: In Vitro Studies of Surface Physical Properties.
Chong Woo BAE ; Sung Hoon CHUNG ; Yong Sung CHOI
Yonsei Medical Journal 2016;57(1):203-208
PURPOSE: Pulmonary surfactant (PS) replacement has been the gold standard therapy for neonatal respiratory distress syndrome; however, almost all commercial PSs contain animal proteins. We prepared a synthetic PS by using a human surfactant protein (SP) analog and evaluated its in vitro properties. MATERIALS AND METHODS: A peptide sequence (CPVHLKRLLLLLLLLLLLLLLLL) of human SP-C was chosen to develop the peptide analog (SPa-C). The new synthetic SP-C PS (sSP-C PS) was synthesized from SPa-C, dipalmitoyl phosphatidylcholine, phosphatidyl glycerol, and palmitic acid. Physical properties of the sSP-C PS were evaluated by measuring the maximum and minimum surface tensions (STs), surfactant spreading, and adsorption rate. In addition, we recorded an ST-area diagram. The data obtained on sSP-C PS were subsequently compared with those of purified natural bovine surfactant (PNBS), and the commercial product, Surfacten(R). RESULTS: The sSP-C PS and Surfacten(R) were found to have maximum ST values of 32-33 mN/m, whereas that of PNBS was much lower at 19 mN/m. The minimum ST values of all three products were less than 10 mN/m. The values that were measured for the equilibrium ST of rapidly spreading sSP-C PS, Surfacten(R), and PNBS were 27, 27, and 24 mN/m, respectively. The surface adsorptions were found to be the same for all three PSs (20 mN/m). ST-area diagrams of sSP-C PS and Surfacten(R) revealed similar properties. CONCLUSION: In an in vitro experiment, the physical properties exhibited by sSP-C PS were similar to those of Surfacten(R). Further study is required to evaluate the in vivo efficacy.
1,2-Dipalmitoylphosphatidylcholine/analogs & derivatives
;
Adsorption
;
Amino Acid Sequence/*genetics
;
Animals
;
C-Peptide/*chemistry
;
Cattle
;
Humans
;
Infant, Newborn
;
Pulmonary Surfactant-Associated Protein C/*chemical synthesis/pharmacology
;
Pulmonary Surfactants/*chemical synthesis/pharmacology
;
Respiratory Distress Syndrome, Newborn/*drug therapy
;
*Surface Properties
;
*Surface Tension
;
Surface-Active Agents
4.The use of artificial pulmonary surfactant in neonatal respiratory distress.
Journal of the Korean Medical Association 2015;58(4):330-335
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
5.Effect of bile acids on surface tension of bronchoalveolar lavage fluid in rabbits.
Fei WANG ; Cong ZHAO ; Yinghong TIAN ; Yanru YIN
Journal of Southern Medical University 2014;34(10):1465-1468
OBJECTIVETo observe changes in surface tension of bronchoalveolar lavage fluids (BALF) in rabbits with hyperbilirubinemia and the influence of bile diluents and 5 different bile acids on BALF surface tension to provide better insight into the regulatory role of bile acids on respiratory function.
METHODSBronchoalveolar lavage with 0.9% normal saline was carried out in 30 male New Zealand rabbits and the surface tensions of BALF were measured. The changes in BALF surface tension was measured in rabbits with hyperbilirubinemia. Different concentrations of bile diluents, normal saline, or water solutions of 5 bile acids were added into the collected BALF to test their influence on the surface tension of BALF.
RESULTSThe BALF from rabbits with hyperbilirubinemia showed a significantly increased surface tension (P<0.05). The bile diluents (1:15, 1:10, and 1:5) added into the BALF increased the surface tension of the BALF by 21.15%, 26.09%, and 19.64%, respectively. Among the water solutions of the 5 bile acids, UDCA produced no significant influence on the surface tension of BALF while CDCA, CA, LCA, and DCA increased the surface tension by 16.10%, 21.66%, 14.21%, and 13.05%, respectively.
CONCLUSIONThe surface tension of BALF increases significantly during hyperbilirubinemia. Bile diluents as well as the free bile acids CDCA, CA, LCA and DCA, but not UDCA, can increase the surface tension of BALF, suggesting that these bile acids may emulsify pulmonary alveolar surfactants to increase the alveolar surface tension.
Animals ; Bile ; Bile Acids and Salts ; Bronchoalveolar Lavage Fluid ; Male ; Pulmonary Surfactants ; Rabbits ; Surface Tension
6.New Synthetic Surfactants for Neonates.
Journal of the Korean Society of Neonatology 2012;19(4):184-194
The benefits of exogenous synthetic or animal-derived natural surfactants for treatment of respiratory distress syndrome (RDS) are well established. Although synthetic surfactants have potential safety advantages over animal-derived products, they seem to be clinically inferior to animal-derived natural surfactant, based on the results of numerous comparative trials. In recent years, however, synthetic surfactant has experienced a surge in breakthroughs to the point of rivaling natural surfactant, mainly due to the development of protein-containing synthetic surfactant. This article will review the historical background on the development of artificial pulmonary surfactant, compositional and physicochemical aspects on pulmonary surfactant lipids and proteins, results of comparative trials among natural, protein-free and protein-containing surfactants, and current status of development of protein-containing surfactants for treatment of RDS.
Humans
;
Hyaline Membrane Disease
;
Infant, Newborn
;
Infant, Premature
;
Proteins
;
Pulmonary Surfactants
;
Surface Tension
;
Surface-Active Agents
7.Researches on relationships between main active ingredients and physical and chemical parameters of dangguibuxue decoction.
Jiahua MA ; Xia LI ; Mingling ZHANG ; Nan LI ; Qin ZHENG ; Ming YANG
China Journal of Chinese Materia Medica 2010;35(15):1953-1956
OBJECTIVETo study relationships between the main active ingredients and physical and chemical parameters of dangguibuxue decoction, and to explore the feasibility of characterization the quality of decoction by physical and chemical parameters.
METHODSolutions of ferulic acid and astragaloside with different concentrations were prepared, of which physical and chemical parameters such as surface tension, pH value and conductivity, etc were determined at 25 degrees C. And polynomial regression analysis was used to analyze these data.
RESULTWith the increase of concentration of ferulic acid, pH value was decreased and conductivity was increased. And surface tension was decreased in the aqueous solution of astragaloside. In the combined solution of ferulic acid and astragaloside, ferulic acid was the main influencing pH value and conductivity, while astragaloside was the main factor influencing surface tension.
CONCLUSIONOn one hand, astragaloside concentration has a significant correlation with surface tension, but almost no correlation with pH value and conductivity. On the other hand, ferulic acid concentration has a strong correlation with pH value and conductivity, but almost no correlation with surface tension. In addition, each parameter has strong anti-interference ability and almost didn't change with the addition of another material. These preliminary results suggested that such characteristic parameters could be used to characterize the decoction quality.
Chemical Phenomena ; Coumaric Acids ; analysis ; Drugs, Chinese Herbal ; chemistry ; Surface Tension
8.A Case of Lung Necrosis and Abscess after Paint Thinner Ingestion.
Hyung Min KIM ; Tai Yong HONG ; Kyu Nam PARK ; Kyoung Ho CHOI ; Byung Hak SO
Journal of the Korean Society of Emergency Medicine 2009;20(2):219-222
Paint thinners contain a mixture of volatile organic solvents, including aromatic hydrocarbons such as toluene, xylene, and N-hexane. Hydrocarbon pneumonitis is an acute, intense pneumonitis resulting from the aspiration of volatile hydrocarbon compounds with low viscosity and surface tension. Here we report the case of a 60-year-old man admitted to our hospital with chest pain following the ingestion of paint thinner. Aspiration resulted from inducing emesis after ingestion. Acute chemical pneumonitis developed in the right lower lung. The patient's course was further complicated by lung necrosis, abscess, pleural effusion, and pneumothorax. He was treated with pleural adhesiolysis and a right middle lobe wedge resection via video-assisted thoracoscopic surgery.
Abscess
;
Chest Pain
;
Eating
;
Hexanes
;
Humans
;
Hydrocarbons, Aromatic
;
Lung
;
Lung Abscess
;
Middle Aged
;
Necrosis
;
Paint
;
Pleural Effusion
;
Pneumonia
;
Pneumothorax
;
Solvents
;
Surface Tension
;
Thoracic Surgery, Video-Assisted
;
Toluene
;
Viscosity
;
Volatile Organic Compounds
;
Vomiting
;
Xylenes
9.Comparisons of Physical and Biological Activities between Newfactan(R), Surfacten(R) and Exosurf(R).
Dong Woo LEE ; Min Soo PARK ; Ji Hyun JEON ; Eun Na CHOI ; Kook In PARK ; Ran NAMGUNG ; Chul LEE
Journal of the Korean Society of Neonatology 2006;13(1):1-8
PURPOSE: Neonatal respiratory distress syndrome (RDS) is caused by the deficiency of pulmonary surfactants in the newborn. We aim to determine and compare the physical and biological activities of the three surfactants currently on the market, namely Newfactan(R), Surfacten(R) and Exosurf(R). METHODS: For physical activities, we performed the stable microbubble test (SMR) and Pulsating Bubble Surfactometer (PBS). The minimum and maximum surface tensions measured at 1 and 5 minutes allowed us to create the surface-tension diagrams, from which the compressibility at a surface tension of 10 mN/m was calculated for all three products. The biological activities were compared using the pressure-volume curves measured from premature rabbit fetuses. RESULTS: For all three products, the concentration of surfactant and the number of stable microbubbles exhibited a proportional increase in relationship. For both Newfactan(R) and Surfacten(R), the minimal surface tensions were lower than 10 mN/m at 1 and 5 minutes. Hysteresis was evident at 1 and 5 minutes for both Newfactan(R) and Surfacten(R), and their surface tensions were reduced below 10 mN/m at 20% surface compression. As for Exosurf(R), all the hysteresis measurements were below expectations, and the reduction in surface tension during compression was also minimal. The compressibilities at a surface tension of 10 mN/m and measured at 1 and 5 minutes for Newfactan(R) and Surfacten(R), were less than 0.020 cm/dyne at almost concentrations. The pulmonary surface areas of the fetal rabbits were, after aeration by a maximum of 30 cmH2O, adequately maintained after decompression to 5 cmH2O in the groups treated with Newfactan(R) and Surfacten(R). However, the lung volume was not maintained upon decompression to 5 cmH2O in the groups treated with Exosurf(R). CONCLUSIONS: Newfactan(R) and Surfacten(R) were effective agents in prevention of pulmonary collapse in premature lungs.
Decompression
;
Fetus
;
Humans
;
Infant, Newborn
;
Lung
;
Microbubbles
;
Motor Activity
;
Pulmonary Surfactants
;
Rabbits
;
Respiratory Distress Syndrome, Newborn
;
Surface Tension
;
Surface-Active Agents
10.A case of acute respiratory distress syndrome treated with surfactant and low dose methylprednisolone.
Bo Yeon CHOI ; Kyong Mo KIM ; Jong Seo YOON ; Joon Sung LEE
Korean Journal of Pediatrics 2006;49(4):455-459
The major pathogenesis of acute respiratory distress syndrome (ARDS) is an inflammatory process that results from a diversity of injuries to the body. Due to the various cytokines and vasoactive peptides released from the endothelium, the vascular permeability is increased; the migration of inflammatory cells and the leakage of plasma proteins then occur and edema develops in the alveolus. There is a hypothesis that the impairment of alveolar recruitment in ARDS is caused by a defect of the surfactant system and the resultant increase of alveolar surface tension. This has been studied in pediatric patients in ARDS; after the administration of surfactant, hypoxia, respiratory symptoms and survival chances were improved. To alleviate the major pathogenic mechanism in this disease, that is to say, inflammation of the lung, steroids have been used and studied as another treatment modality for ARDS, and it has been concluded that the administration of low dose methylprednisolone may improve patients' symptoms and survival rates. We report here on a case of a young infant admitted with ARDS, who, after the intratracheal administration of 120 mg/kg surfactant, on PaO(2)/FiO(2) was elevated. Subsequent low doses of methylprednisolone were given, and the symptoms did not recur, and no fibrotic change was shown during the follow-up period of 2 months.
Anoxia
;
Blood Proteins
;
Capillary Permeability
;
Cytokines
;
Edema
;
Endothelium
;
Follow-Up Studies
;
Humans
;
Infant
;
Inflammation
;
Lung
;
Methylprednisolone*
;
Peptides
;
Respiratory Distress Syndrome, Adult*
;
Steroids
;
Surface Tension
;
Survival Rate

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