RESUMEN
The high costs of artificial pulmonary surfactants, ranging in hundreds per kilogram of body weight, used for treating the respiratory distress syndrome (RDS) premature babies have limited their applications. We have extensively studied soy lecithins and higher alcohols as lipid alternatives to expensive phospholipids such as DPPC and PG. As a substitute for the proteins, we have synthesized the peptide Hel 13-5D3 by introducing D-amino acids into a highly lipid-soluble, basic amphiphilic peptide, Hel 13-5, composed of 18 amino acid residues. Analysis of the surfactant activities of lipid-amphiphilic artificial peptide mixtures using lung-irrigated rat models revealed that a mixture (Murosurf SLPD3) of dehydrogenated soy lecithin, fractionated soy lecithin, palmitic acid (PA), and peptide Hel 13-5D3 (40:40:17.5:2.5, by weight) superior pulmonary surfactant activity than a commercially available pulmonary surfactant (beractant, Surfacten®). Experiments using ovalbumin-sensitized model animals revealed that the lipid-amphiphilic artificial peptide mixtures provided significant control over an increase in the pulmonary resistance induced by premature allergy reaction and reduced the number of acidocytes and neutrophils in lung-irrigated solution. The newly developed low-cost pulmonary surfactant system may be used for treatment of a wide variety of respiratory diseases.
Asunto(s)
Aminoácidos/metabolismo , Asma/tratamiento farmacológico , Hemólisis/efectos de los fármacos , Pulmón/efectos de los fármacos , Péptidos/farmacología , Surfactantes Pulmonares/farmacología , Animales , Dicroismo Circular , Interacciones Hidrofóbicas e Hidrofílicas , Pulmón/patología , Péptidos/química , Ratas , Ratas Endogámicas BN , Ratas WistarRESUMEN
The artificial pulmonary surfactant composition in the present study is characterized by a lipid mixture system composed of higher aliphatic alcohol, egg yolk phosphatidylcholine (egg PC), soy lecithin and higher aliphatic acid as the major components or a peptide-lipid mixture system composed of a combination of the lipid mixture system to which a peptide is added. Three peptides with amphiphilic surface-staying, membrane spanning, and both properties were designed and synthesized. The evaluation of pulmonary surfactant assay was performed by a hysteresis curve drawn upon the measurement for the surface tension-area curve with the Wilhelmy surface tensometer in vitro and the recovery of lung compliance for the pulmonary surfactant-deficient rat models in vivo. Lipid-mixture systems composed of octadecanol or soy lecithins containing no peptide were favorable hysteresis curves as compared with commercially available Surfacten, but were not prominent. The peptide-lipid mixture systems composed of a combination of the lipid mixture of alkyl alcohol or soy lecithin to which peptides designed were added were desirable hysteresis curves similar to Surfacten and amphiphilic Hel 13-5 peptide-lipids mixture systems were much more effective than the lipid mixture system. Particularly, the recovery of lung compliance treated with hydrogenated soy lecithin-fractionated soy lecithin PC70-palmitic acid-peptide Hel 13-5 (40:40:17.5:2.5, w/w) was comparable to that with Surfacten. Because the artificial pulmonary surfactant compositions of this study can be prepared at lower costs, they are useful for the treatment of respiratory distress syndrome and acute respiratory distress syndrome as well as for inflammatory pulmonary diseases, dyspnea caused by asthma, etc.
Asunto(s)
Alcoholes/química , Lecitinas/química , Lípidos/química , Péptidos/química , Surfactantes Pulmonares/administración & dosificación , Surfactantes Pulmonares/síntesis química , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Inyecciones Intraperitoneales , Instilación de Medicamentos , Surfactantes Pulmonares/economía , Ratas , Ratas Wistar , Pruebas de Función Respiratoria , Glycine max/química , Tensión Superficial , Factores de TiempoRESUMEN
This report documents a new endoscopic management modality for congenital membranous stenosis in the third portion of the duodenum. Standard approaches to duodenal stenosis in newborns include a laparotomy with an enteroenterostomy, bypassing the obstruction, or a duodenoduodenostomy with excision. We successfully developed a modification of the endoscopic treatment modality for congenital duodenal diaphragm.
Asunto(s)
Obstrucción Duodenal/congénito , Duodenoscopía/métodos , Obstrucción Duodenal/cirugía , Humanos , Recién Nacido , MasculinoRESUMEN
OBJECTIVE: To examine the obstetrical risk factors for death and brain injury among extremely-low-birth-weight (ELBW) infants (birth weight <1000 g). STUDY DESIGN: Study subjects were 121 ELBW infants born at a single tertiary perinatal center. Death among ELBW infants was considered to have occurred when subjects died within their corrected age of 40 weeks. In the sub-analysis of the 91 ELBW infants who survived their corrected age of 40 weeks, brain injury was defined as present when criteria based on ultrasound and/or MRI were substantiated. RESULTS: A birth weight of <800 g [adjusted odds ratio (OR), 14.57; 95% confidence interval (CI), 4.72-56.98], a younger gestational age of <26 weeks (adjusted OR, 4.64; 95% CI, 1.60-14.90), and a low Apgar score of <5 (adjusted OR, 3.88; 95% CI, 1.32-12.45) were significantly associated with death among ELBW infants. A maternal age of 30 years or older (adjusted OR, 3.71; 95% CI, 1.19-13.35) was only associated with brain injury among surviving ELBW infants. CONCLUSION: Obstetrical care should be aimed at preventing or predicting premature delivery especially at <26 weeks of gestation.
Asunto(s)
Peso al Nacer , Lesiones Encefálicas/etiología , Mortalidad Infantil , Recien Nacido con Peso al Nacer Extremadamente Bajo , Complicaciones del Embarazo , Femenino , Edad Gestacional , Humanos , Recién Nacido , Masculino , Embarazo , Resultado del Embarazo , Factores de RiesgoRESUMEN
An unusual case of biliary atresia with jejunal atresia is herein described. Only 12 cases demonstrating biliary atresia associated with a jejunal atresia have been previously reported in Japan. The pathogenesis of biliary atresia is thought to be secondary to the influence of jejunal atresia.