PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “surfactant dysfunction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2005

Reversibility of lung inflammation caused by SP-B deficiency.

Whereas decreased concentrations of surfactant protein (SP)-B are associated with lung injury and respiratory distress, potential causal relationships between SP-B deficiency and lung inflammation remain unclear. A transgenic mouse in which human SP-B expression was placed under conditional control of doxycycline via the CCSP promoter was utilized to determine the role of SP-B in the initiation of pulmonary inflammation. Adult mice, made SP-B deficient by removal of doxycycline, developed severe respiratory failure within 4 days. Deficiency of SP-B was associated with increased minimal surface tension of the surfactant and perturbed lung mechanics. Four days of SP-B deficiency did not alter SP-C content or surfactant phospholipid content or composition. SP-B deficiency was associated with lung inflammation and increased soluble L-selectin, STAT-3, and phosphorylated STAT-3 in alveolar macrophages and alveolar epithelial cells. Alveolar IL-6, IL-1beta, and macrophage inflammatory protein-2 concentrations were increased after removal of doxycycline, indicating pulmonary inflammation. Restoration of SP-B expression following administration of doxycycline rapidly reversed SP-B-dependent abnormalities in lung mechanics and inflammation. SP-B deficiency is sufficient to cause lung dysfunction and inflammation in adult mice. SP-B reversed inflammation and maintained lung function in vivo, indicating its potential utility for the prevention and treatment of pulmonary injury and surfactant deficiency.

Animals↗
PubMed1996

Lung preservation: the importance of endothelial and alveolar type II cell integrity.

The practice of lung transplantation is constrained by a shortage of suitable donor organs. Furthermore, even "optimal" donor lung grafts are at risk of significant dysfunction perioperatively. Significant insights into the cellular and molecular mechanisms of pulmonary ischemia-reperfusion injury have occurred since the publication of previous reviews on lung preservation 3 to 4 years ago. Recent evidence indicates that the endothelium plays an essential role in regulating the dynamic interaction between pulmonary vasodilatation and vasoconstriction and is a major target during lung injury. In addition, the composition, function, and metabolism of pulmonary surfactant produced by alveolar type II cells are increasingly being recognized as important factors in pulmonary ischemia-reperfusion injury. We hypothesize that reperfusion after a period of pulmonary ischemia results in significant endothelial and alveolar type II cell dysfunction and that an important strategy in lung preservation is to preserve the integrity of these cells in the face of this injury. Given the persistent shortage of lungs available for transplantation, laboratory studies need to focus also on the "rescue" of compromised donor lungs that would have been previously regarded as unsuitable. Importantly, innovative work from the laboratory needs to be translated into clinical practice via prospective, randomized trials to ensure that the prevalence of postoperative lung graft dysfunction is reduced and the shortage of lung grafts for transplantation is alleviated.

Animals↗
PubMed2006

An X-ray diffraction study of alterations in bovine lung surfactant bilayer structures induced by albumin.

Lung surfactant (LS) is an extra-cellular lipid-protein system responsible for maintaining low surface tension in the lung and alveolar stability. Serum proteins cause dysfunction of this material, e.g. in adult respiratory distress syndrome (ARDS). BLES is a clinically used LS consisting of most of the lipids and associated proteins from bovine lung lavage. Aqueous phases of BLES at 30% and 70% hydration, with and without 5% by weight of bovine serum albumin (BSA), calculated on the amount of lipids, were studied using X-ray diffraction during cooling from 42 to 5 degrees C. The diffraction curves are consistent with a transition from a lamellar liquid crystalline phase to a gel phase transition at cooling in the interval 30-20 degrees C. The long-spacings correspond to a reduction of the bilayer thickness during this transition. The wide-angle region shows a peak at 4.1 A below 25 degrees C, which is characteristic of the hexagonal chain packing of the gel phase. The perturbation of the bilayers by the presence of BSA seems to induce a significant decrease of the bilayer thickness. Calculations on the observed limits of swelling (taking place in the range 50-60%) indicate that BSA is closely associated with the BLES bilayers, probably due to electrostatic interaction with the cationic surfactant proteins SP-B and SP-C. This study show that the LS lipid structural organizations are extremely susceptible to small amounts of serum albumin, which may have implications in surfactant related lung disease and clinical applications of surfactant therapy.

Animals↗
PubMedDate not supplied

Prenatal theophylline and necrotizing enterocolitis in premature newborn infants.

To determine whether prenatal theophylline therapy would increase the incidence of neonatal necrotizing enterocolitis (NEC) we studied bowel dysfunction in 59 consecutive premature infants (g.s. < 34 weeks), whose mothers were treated with theophylline as a tocolytic during the last trimester, or as surfactant synthesis inductor, for at least three days prior to premature labor (Group A). As case-control we considered the premature, matched for gestational age born immediately before, and whose was untreated with theophylline (Group B). NEC occurred in one patient from group A during the second postnatal week, and surgery was performed. First passage of meconium and start of enteral feeding were comparable in groups A and B, while gastric residuals lasting more than 4 days were found statistically increased (p < 0.03) in antenatally treated group A prematures. Furthermore, 18 out of 49 prematures postnatally treated with theophylline had gastric residuals (36%) with respect to 5 out of 69 untreated (7%) (p < 0.001). Also the premature infants treated ante and postnatally with theophylline showed a statistically significant increase of lasting gastric residuals with respect to the untreated, 13/16 vs 5/7, respectively (p < 0.03). Antenatal theophylline administered to high risk mothers, when maternal diseases do not allow the use of steroids, does not appear to later increase the risk of NEC in premature infants, and provides a chance to avoid the risks related to premature birth. Inhibitory activity on gut motility and gastric irritability are only detectable during the first postnatal days, enhanced by gut immaturity of preterm infants.

Case-Control Studies↗
PubMed2002

Hyperoxia and nitric oxide reduce surfactant components (DSPC and surfactant proteins) and increase apoptosis in adult and fetal rat type II pneumocytes.

Nitric oxide (NO) alone or in conjunction with hyperoxia can have protective or detrimental effects on the lung. Our hypothesis was that hyperoxia in conjunction with NO would result in increased cellular dysfunction and apoptotic cell death in adult and fetal Type II pneumocytes (TIIP) in a dose-dependent manner. The TIIP were obtained from adult and 19-day fetal rat lungs. The TIIP were then exposed to 100, 200 and 500 micro M of the NO-donor, Glyco-SNAP-2, alone or in conjunction with 95% oxygen for 24 h. While low-dose NO exposure alone did not increase cytotoxicity, in conjunction with hyperoxia, there was a significant dose-dependent increase in apoptotic cell death of adult TIIP as well as fetal TIIP. Choline incorporation into disaturated phosphatidylcholine was markedly decreased in adult TIIP while the fetal TIIP had similar values as controls. However, the mRNAs of surfactant proteins A, B and C as well as iNOS were significantly reduced in fetal TIIP. Exogenous peroxynitrite also increased nitrotyrosine formation in fetal TIIP as did hyperoxia and NO. The effect of hyperoxia and NO could be abrogated with catalase and superoxide dismutase. These findings may have significant clinical implications in the use of NO in premature infants.

Animals↗
PubMed2005

Survival prolongation of microencapsulated allogeneic islet by nanosized nordihydroguaiaretic acid.

Immunoisolation such as alginate-poly-L-lysine-alginate (APA) microencapsulation may protect entrapped islet graft cells from destruction by cellular and humoral immunities, but cannot avoid aggregation of macrophages and fibroblasts around microcapsules, which has been known to cause late dysfunction. Nordihydroguaiaretic acid (NDGA) is a lipoxygenase inhibitor that prevents the activation and chemotaxis of macrophages. In this study, we used the dialysis method without surfactant to prepare poly (DL-lactide-co-glycolide) (PLGA) nanoparticles to entrap NDGA. We determined the formulation conditions suitable for sustained release when coencapsulated with the islets. Nanoparticle sizes of 0.2-0.3 microm were suitable for sustained release in electromagnetic driven APA microcapsules. In the toxicity study, we coincubated islets with PLGA-NDGA nanoparticles in vitro for 2 and 4 weeks. The glucose stimulated insulin secretion and insulin contents of islets were not influenced significantly. To test whether nanosized NDGA provides extra protection for APA islets, about 160-200 allogeneic islets of C57BL/6 mice were either encapsulated alone using APA or coencapsulated with PLGA-NDGA. At 2 and 4 weeks after implantation into the peritoneal cavities of healthy BALB/c mice, the intraperitoneal islet grafts were recovered using lavage. Mice that received islets of APA-PLGA-NDGA preparations showed a higher recovery rate of functioning grafts than those that received islets prepared using APA alone (10.1%, n = 4 vs 5.2%, n = 3). In conclusion, nanosized NDGA prolonged the graft survival of APA microencapsulated allogeneic islets.

Animals↗
PubMed2000

Cell biology of tubotympanum in relation to pathogenesis of otitis media - a review.

The sterility of the eustachian tube and tympanic cavity of normal individuals is maintained not only by the adaptive immune system, but also by the mucociliary system and the antimicrobial molecules of innate immunity. Mucin production and periciliary fluid homeostasis are essential for normal mucociliary function and dysfunction of this system is an important risk factor for otitis media. The secreted antimicrobial molecules of the tubotympanum include lysozyme, lactoferrin, beta defensins, and the surfactant proteins A and D (SP-A, SP-D). Defects in the expression or regulation of these molecules may also be the major risk factor for otitis media.

Animals↗
PubMed2005

[The protective effects of Fufang Biejiafang on bleomycin-induced pulmonary fibrosis in rats].

OBJECTIVE: To explore the possible effects and mechanism of Fufang Biejiafang on a single intratracheal instillation (IT) of bleomycin-induced lung fibrosis model. METHOD: SD rats were treated with a single IT dose of bleomycin or control saline. Chinese medicine group were poured into the stomach after the first day of operation with high dosage, middle dosage and low dosage. On days 7, 14 and 28 following IT bleomycin or saline, 4 mL blood were taken from the abdominal aorta for arterial blood gas analysis. The left lung was fixed for routine light microscopic examination. Bronchoalveolar lavage fluid (BALF) from the right lung was tested the activity of pulmonary surfactant (PS) by the Whihelmy Film Balance, then the right lung was frozen immediately in liquid nitrogen for determination of hydroxyproline concentration. RESULT: Model rats had obviously changes of body weight and hypoxemia and dysfunction of PS on days 7 and improved on days 14. Compared with three dose groups, the middle dose group some degreely improved and PS function. It ameliorate fibrosis because of inhibition of inflammation. CONCLUSION: (1) PS dysfunction resulted in hypoxemia after bleomycin injured alveolar type II (AT II). Fufang biejiafang-middle dose-group ameliorate hypoxemia by remission AT-II injury. (2) Fufang biejiafang may inhibit exudation inflammation and ameliorate fibrosis.

Animals↗
PubMed2002

[Detergent-like effects of the lipofuscin retinoid component A2-E in retinal pigment epithelial cells].

PURPOSE: Several lines of evidence suggest that excessive accumulation of lipofuscin in postmitotic retinal pigment epithelial (RPE) cells with age and in various hereditary retinal diseases, plays a pathogenetic role. The lipofuscin retinoid component A2-E (N-retinylidene-N-retinylethanolamine) inhibits lysosomal degradation. Here we sought to evaluate additional toxic mechanisms of A2-E, whereby possible detergent-like effects on various membranes in human RPE cells were investigated by latency measurements. METHODS: A postnuclear supernatant prepared from cultured human RPE cells was used to isolate intact lysosomes by fractionation of cellular organelles in two sequential gradients. Destabilization of the lysosomal membrane was tested by incubating the purified lysosomal fraction in the presence of A2-E and subsequent measurement of the latency of the lysosomal luminal marker beta-hexosaminidase. In order to compare the effect of A2-E on other cellular membranes, latencies of the specific markers succinate dehydrogenase and UDP-galactosyltransferase were assessed using partially purified mitochondria and microsomes. Intactness of the plasma membrane was tested by including A2-E in the culture medium before leakage of lactate dehydrogenase into the medium was determined. RESULTS: A more than 100-fold purification of the lysosomal fraction was achieved. Except for a minor activity of the mitochondrial marker, no contamination with other cell fractions was observed. Intactness of the purified lysosomes was well preserved during incubation in isotonic media and provided the basis for investigations on a possible detergent-like action of A2-E on lysosomal integrity. At concentrations above 2 microM A2-E, progressive leakage of the lysosomal marker was observed. In comparison leakage of the mitochondrial marker was induced at significantly lower concentrations (1 microM), whereas ER/Golgi membranes and the plasma membrane were relatively insensitive to a detergent effect of the retinoid. CONCLUSIONS: The described practical and fast methodology to obtain highly purified and intact lysosomes from RPE cells, provides a very suitable tool for investigations on compounds affecting the lysosomal structure. The results suggest that A2-E causes disintegration of the lysosomal membrane at relatively low concentrations which may implicate an involvement of such a mechanism in triggering lipofuscin-induced dysfunction of aged RPE in vivo. Secondary to disintegration of the lysosomal membrane, damage to mitochondria might be an additional pathogenic mechanism. Our data provide evidence for surfactant-like properties of A2-E on biomembranes which might be operative in retinal diseases associated with excessive lipofuscin accumulation including age-related macular degeneration.

Aged↗
PubMed2002

Isolation of intact lysosomes from human RPE cells and effects of A2-E on the integrity of the lysosomal and other cellular membranes.

BACKGROUND: Accumulation of lipofuscin in RPE cells occurs with age and in association with various retinal diseases. Lipofuscin and its major retinoid compound and fluorophore A2-E interfere with the cellular metabolism of RPE cells in various ways. One of these mechanisms is thought to be related to detergent properties of A2-E. METHODS: We isolated pure and intact lysosomes from RPE cell cultures and investigated detergent-like effects of the lipofuscin compound A2-E on the integrity of lysosomal membrane and other cellular membranes, using latency measurements. A postnuclear supernatant prepared from cultured human RPE cells was used to isolate intact lysosomes by fractionation of cellular organelles in two sequential gradients. Destabilization of the lysosomal membrane was tested by incubating the purified lysosomal fraction in the presence of A2-E and subsequent measurement of the latency of the lysosomal luminal marker beta-hexosaminidase. In order to compare the effect of A2-E on other cellular membranes, latencies of the specific markers succinate dehydrogenase and UDP-galactosyltransferase were assessed using partially purified mitochondria and microsomes. Intactness of the plasma membrane was tested by including A2-E in the culture medium before leakage of lactate dehydrogenase into the medium was determined. RESULTS: A more than 100-fold purification of the lysosomal fraction was achieved. Except for a minor activity of the mitochondrial marker, no contamination with other cell fractions was observed. Intactness of the purified lysosomes was well preserved upon incubations in isotonic media providing the base for investigations on a possible detergent-like action of A2-E on lysosomal integrity. At concentrations above 2 microM A2-E, progressive leakage of the lysosomal marker was observed. In comparison, leakage of the mitochondrial marker was induced at significantly lower concentrations (1 microM), whereas ER/Golgi membranes and the plasma membrane were relatively insensitive to a detergent effect of the retinoid. The described methodology to obtain highly purified and intact lysosomes from RPE cells provides a suitable tool for investigations on compounds affecting lysosomal structure. A2-E was shown to cause desintegration of the lysosomal membrane at relatively low concentrations, which may implicate an involvement of such mechanism in triggering lipofuscin-induced dysfunction of RPE in vivo. Secondary to disintegration of the lysosomal membrane, damage to mitochondria might be an additional pathogenic mechanism. CONCLUSIONS: Our data provide evidence for surfactant-like properties of A2-E on biomembranes which might be operative in retinal diseases associated with excessive lipofuscin-accumulation, such as age-related macular degeneration.

Cell Membrane↗
PubMed2001

Surfactant proteins A and D in Eustachian tube epithelium.

Surfactant protein (SP) A and SP-D are collectins that have roles in host defense. The Eustachian tube (ET) maintains the patency between the upper airways and the middle ear. Dysfunction of local mucosal immunity in ET may predispose infants to recurrent otitis media. We recently described preliminary evidence of the expression of SP-A and SP-D in the ET. Our present aim was to establish the sites of SP-A and SP-D expression within the epithelium of the ET in vivo. With in situ hybridization, electron microscopy, and immunoelectron microscopy, the cells responsible for SP-A and SP-D expression and storage were identified. SP-A expression was localized within the ET epithelium, and the protein was found in the electron-dense granules of microvillar epithelial cells. Being concentrated in the epithelial lining, only a few cells revealed intracellular SP-D, and it was not associated with granules. The SP-A and SP-D immunoreactivities in ET lavage fluid, as shown by Western blot analyses, were similar to those in bronchoalveolar lavage fluid. We propose that there are specialized cells in the ET epithelium expressing and secreting SP-A and SP-D. SP-A and SP-D may be important for antibody-independent protection of the middle ear against infections.

Animals↗
PubMed2005

ABC proteins: key molecules for lipid homeostasis.

Forty-nine ABC protein genes exist on human chromosomes. Eukaryotic ABC proteins were originally recognized as drug efflux pumps involved in the multidrug resistance of cancer cells. However, it is now realized that one of their major physiological roles is cellular lipid transport and homeostasis, and their dysfunction is often associated with human diseases. ABCA1 and ABCA7 mediate the apolipoprotein-dependent formation of a high-density lipoprotein-cholesterol complex. ABCA3 is indispensable for pulmonary surfactant secretion. ABCG5 and ABCG8 are involved in the secretion of plant sterols and cholesterol into bile. However, the primary substrates and mechanism of action of these ABC proteins have not been precisely defined. In this review article, we first describe the general structure and functions of eukaryotic ABC proteins. The current model of ABCA1 functionality is then explained based on studies on a topological model, subcellular localization, apoA-I dependence of HDL formation, functional defects of Tangier disease mutants, and ATP hydrolysis of purified ABCA1. ABCA1 is supposed to function as a transporter of lipids as well as a receptor for apoA-I. ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures.

ATP-Binding Cassette Transporters↗
PubMed1984

Prolonged bleeding time in preterm infants receiving indomethacin for patent ductus arteriosus.

Sequential bleeding times were performed on 25 preterm infants receiving intravenous indomethacin for closure of the patent ductus arteriosus. Prolongation of bleeding time was observed after the initial dose of indomethacin, with an increase from a pretreatment mean of 3.6 minutes to 8.7 minutes. The bleeding time was not further prolonged at the end of the three-dose course of indomethacin, but was still elevated 48 hours after the completion of therapy. Clinical bleeding developed in six of the patients, but was generally limited to occult hematuria. Serial echoencephalography during indomethacin therapy showed progression from mild periventricular-intraventricular hemorrhage to moderate or severe grades in five of 21 infants at risk for this complication. However, no clear temporal relationship between indomethacin administration and intraventricular hemorrhage extension was observed, and no difference in the degree of bleeding time prolongation was noted between infants with and without hemorrhage extension. Other factors, including surfactant deficiency, amount of volume expansion used, and lowest PO2 in the first day of life, did distinguish those with hemorrhage extension. The results suggest that indomethacin-induced platelet dysfunction is not associated with major hemorrhagic complications in the majority of preterm infants with patent ductus arteriosus.

Bleeding Time↗
PubMed2003

Infarct-induced chronic heart failure increases bidirectional protein movement across the alveolocapillary barrier.

Chronic heart failure (CHF) is associated with adaptive structural changes at the alveolocapillary barrier that may be associated with altered protein permeability. Bidirectional protein movement across the barrier was studied in anesthetized rats with infarct-induced CHF by following (125)I-labeled albumin ((125)I-albumin) flux into the alveoli and the leakage of surfactant protein (SP)-B from the alveoli into the circulation. Three groups were studied: controls [0% left ventricular (LV) infarction], moderate infarct (25-45% LV infarction), and large infarct (>46% LV infarction). Wet and dry lung weights increased in the large infarct group (both P < 0.001), consistent with increased lung water and solid lung tissue. (125)I-albumin flux increased across the endothelial (P < 0.001) and epithelial (P < 0.01) components of the alveolocapillary barrier in the large infarct group. Plasma SP-B increased 23% with moderate infarcts (P < 0.05) and 97% with large infarcts (P < 0.001), independent of alveolar levels. Lavage fluid immune cells (P < 0.01) and myeloperoxidase activity (P < 0.05) increased in the large infarct group, consistent with inflammation. Bidirectional protein movement across the alveolocapillary barrier is increased in CHF, and alveolar inflammation may contribute to this pathophysiological defect.

Animals↗
PubMed1996

Congenital diaphragmatic hernia: an overview.

Understanding the complex multisystem dysfunction in the infant with a congenital hernia of the posterolateral diaphragm is still evolving and has changed radically during the last decade. The reduction in lung mass, in conjunction with surfactant deficiency and diminished compliance, leads to initial deficiencies in oxygenation and carbon dioxide (CO2) removal. This may then be potentiated by an extremely reactive hypoplastic pulmonary arterial system. Treatment no longer is focused on the operative repair but rather on the components of the pathophysiological process that are potentially reversible. Thus, extracorporeal membrane oxygenation and delay of repair until resolution of pulmonary artery hypertension have become mainstays of therapy and are probably responsible for increasing the survival rate in the patient who presents early with respiratory distress from 50% to 65%. Still far from acceptable, these results are giving impetus to new approaches to therapy including drugs such as nitric oxide, fetal intervention including open repair, and lung transplantation.

Extracorporeal Membrane Oxygenation↗
PubMed2002

Acute ingestion poisoning with insecticide formulations containing the pyrethroid permethrin, xylene, and surfactant: a review of 48 cases.

BACKGROUND: Forty-eight patients poisoned with insecticide formulations containing permethrin (a Type I pyrethroid insecticide), xylene, and surfactants are reported here. These patients were diagnosed and treated in the Chang Gung Memorial Hospital in Taiwan from January 1987 to June 1999. Ten patients ingested permethrin in error and 38 patients attempted suicide. Gastrointestinal tract signs and symptoms were most common (35/48; 73%), and included sore throat, mouth ulcerations, dysphagia, epigastric pain, and vomiting. Pulmonary abnormalities were documented in 29% (14/48) of patients. Aspiration pneumonitis occurred in eight patients, including onefatal case. Pulmonary edema was observed in two patients. Sixteen patients (33%) had central nervous system involvement including confusion (6/48; 13%), coma (10/48; 21%), and seizures (4/48; 8%). Cardiovascular symptoms in 3/48 (7%) patients were limited to arrhythmias and shock. Mild renal and hepatic dysfunction was found in 5/48 (10%) and 3/48 (6%) of patients, respectively. Leukocytosis occurred in 16 patients (33%) but was not associated with infection. Only one death occurred during this 12.5-year period. CONCLUSION: Poisoning caused by ingesting insecticides containing permethrin, xylene, and surfactant manifests primarily gastrointestinal tract symptoms and signs. The involvement of the central nervous system and lungs were less common, but clinically more significant. The relative contributions of the 20% permethrin, 70% xylene, and 10% surfactant to these toxic manifestations, however, is uncharacterized.

Adult↗
PubMed1996

Microvascular pressures in isolated perfused immature lamb lungs: effects of flow rate, left atrial pressure and surfactant therapy.

To determine the effect of some physical factors on microvascular pressures in immature lungs, we studied the lungs of 125-day gestation immature lambs (term 150 days). Lambs were delivered and ventilated for 30 min prior to isolation of the lungs. Nine had surfactant (Survanta, 100 mg/kg) instilled into the lungs prior to delivery, and 7 did not (control group). Lungs were kept distended with airway pressure at 20 cm H2O and perfused with autologous blood, using a steady flow pump. Papaverine was added to the blood to eliminate vasomotion. We measured pulmonary artery and arterial, double and venous occlusion pressures, with flow at 100, 200 and 260 ml.kg-1.min-1 and left atrial pressure (Pla) at 0, 10 and 15 mm Hg. We found that the vascular pressure profile was similar in control and surfactant-treated lungs under similar conditions of flow and Pla. Our data show that elevation of Pla results in significant increases in capillary (double occlusion) pressure; however, the preterm lung accommodates increases in flow with little change in capillary pressure. An increase in flow rate in the presence of elevated Pla had the greatest effect on capillary pressure. All lungs became hemorrhagic when capillary pressure exceeded 30 mm Hg. We speculate that in preterm infants, stress failure of pulmonary capillaries and hemorrhage will occur when there is marked elevation of capillary pressures resulting from increased blood flow in the presence of pulmonary venous construction or left ventricular dysfunction.

Animals↗