Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.2.1.7 (BAL)
1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe respiratory failure is always associated with a defect in the surfactant system. Surfactant substitution in newborn infants with respiratory distress syndrome (RDS) has gained worldwide acceptance. In the present study, we have evaluated whether surfactant diagnostics are of use in choosing recipients of exogenous surfactant. In addition, we studied whether factors apparently unrelated to surfactant influence the degree of respiratory failure and surfactant responsiveness. In small preterm infants, the surfactant indices in amniotic fluid (L/S ratio and phosphatidylglycerol), within 3 days of birth, predicted the risk of RDS with a sensitivity of 90-100%, and a specificity of 50-85%. The surfactant indices, measured in BAL, predicted the risk of ARDS (which became evident 1 to 7 days later) with a sensitivity of 50-60% and a specificity of 59-65%. In small preterm infants with RDS, the amount of fluids given during the first day correlated positively with the degree of respiratory failure and negatively with the degree of surfactant responsiveness. According to an experimental study, in hydrostatic lung edema, exogenous surfactant is diluted by edema fluid and becomes sensitive to inhibitors of surfactant function. Beside dosage, quality, and time of administration, the management of patients largely dictates the responsiveness to exogenous surfactant.
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PMID:Lung surfactant in respiratory distress syndrome. 192 23

Oxygen radicals play an important role in the mechanism of acute lung injury. The 21-aminosteroid lazaroid, U-78518F, is a potent antioxidant. We examined the effect of intravenous U-78518F on acute lung injury in septic guinea pigs over 8 h. The experimental groups (n = 6) were 1) saline control, 2) Escherichia coli (2 x 10(9)/kg i.v.), 3) pretreatment (U-78518F 5 mg/kg bolus + 1 mg.kg-1 x h-1, 15 min before E. coli injection), and 4) posttreatment (U-78518F 30 min after E. coli injection). We measured wet-to-dry weight ratio (W/D) as an index of pulmonary edema and concentration ratios of 125I-labeled albumin in lung tissue and bronchoalveolar lavage fluid compared with plasma (L/P and BAL/P, respectively) as indexes of lung protein fluxes. In septic guinea pigs, pretreatment with U-78518F attenuated W/D, L/P, and BAL/P and posttreatment attenuated W/D and BAL/P (P < 0.05 for each). Furthermore, we studied the effect of U-78518F on human neutrophil oxygen radical production (ORP) by using flow cytometry to assess intracellular ORP and lucigenin-dependent chemiluminescence to assess extracellular ORP. Neutrophils (5 x 10(5) were stimulated with 0.5 micrograms/ml of phorbol myristate acetate. With flow cytometry, we measured intracellular ORP, cross-sectional cell area, and degranulation in neutrophils. U-78518F (minimum concn 1.0 microM) decreased intracellular ORP (n = 4; P < 0.05) when the dihydrorhodamine 123 assay was used. U-78518F (minimum concn 1.0 microM) inhibited phorbol myristate acetate-induced neutrophil chemiluminescence (n = 4; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Attenuation of acute lung injury and oxygen radical production by the 21-aminosteroid, U-78518F. 833 43

ARDS includes a complex series of events leading to alveolar damage, high permeability pulmonary edema, and respiratory failure. The endogenous pulmonary surfactant system is crucial to maintaining normal lung function, and only recently has it been appreciated that alterations in the surfactant system significantly contributed to the pathophysiology of the lung injury of patients with ARDS. Through a combination of analyzing BAL samples from patients with ARDS and extensive animal studies, there have been significant insights into the variety of surfactant abnormalities that can occur in injured lungs. These include altered surfactant composition and pool sizes, abnormal surfactant metabolism, and inactivation of alveolar surfactant by serum proteins present within the airspace. Positive effects of exogenous surfactant administration on acute lung injury have been reported. There is now a prospective, randomized clinical trial evaluating the efficacy of aerosolized exogenous surfactant in patients with ARDS. This trial has demonstrated improvements in gas exchange and a trend toward decreased mortality in response to the surfactant. Despite these encouraging results, there are multiple factors requiring further investigation in the development of optimal surfactant treatment strategies for patients with ARDS. Such factors include the development of optimal surfactant delivery techniques, determining the ideal time for surfactant administration during the course of injury, and the development of optimal exogenous surfactant preparations that will be used to treat these patients. With further clinical trials and continued research efforts, exogenous surfactant administration should play a useful role in the future therapeutic approach to patients with ARDS.
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PMID:Surfactant and the adult respiratory distress syndrome. 842 Apr 22

Bronchoalveolar lavage fluids (BALF) were analyzed for surfactant abnormalities in 153 patients with acute respiratory failure necessitating mechanical ventilation. Diagnoses were acute respiratory distress syndrome (ARDS) in the absence of lung infection (n = 16), severe pneumonia (PNEU; n = 88), ARDS and PNEU (n = 36), and cardiogenic lung edema (CLE; n = 13). The PNEU group was subdivided into groups with alveolar PNEU (n = 35), bronchial PNEU (n = 16), interstitial PNEU (n = 18) and nonclassified PNEU (n = 19). Comparison with healthy controls (n = 20) was undertaken. Total phospholipids (PL), proteins, PL classes (HPTLC) and surfactant apoproteins SP-A and SP-B (ELISA) were quantified in the original BALF. The 48,000 x g pellet from centrifugation of the BAL was used to assess the percentage of large surfactant aggregates (LSA) and the biophysical properties of the surfactant (pulsating bubble surfactometer). All groups with inflammatory lung injury (PNEU and/or ARDS) showed some decrease in the lavageable PL pool, a reduced LSA content in BALF, and a manifold increase in alveolar protein load. Marked changes in the PL profile were noted throughout the groups (a decrease in phosphatidylcholine (PC) and phosphatidylglycerol (PG) and an increase in phosphatidylinositol [PI] and sphingomyelin [SPH]). Concentrations of SP-A but not of SP-B in BALF were reduced. Minimum surface-tension values approached 0 mN/m in controls, and ranged from 10 to 25 mN/m in the absence of supernatant protein and from 20 to 35 mN/m in recombination with leaked protein in the groups with ARDS and/or PNEU. Abnormalities in alveolar PNEU surpassed those in bronchial PNEU, and interstitial PNEU presented a distinct pattern with extensive metabolic changes. All surfactant changes were absent in CLE except for a slight inhibition of surface activity by proteins. We conclude that pronounced surfactant abnormalities, comparable to those in ARDS in the absence of lung infection, occur in different entities of severe PNEU, but not in CLE.
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PMID:Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema. 854 13

Activated neutrophils (PMN) have been implicated in the pathogenesis of adult respiratory distress syndrome (ARDS). Granulocyte colony-stimulating factor (G-CSF) is essential for PMN production and activation of PMN functions. We have recently shown that levels of G-CSF mRNA in a rat model of hemorrhagic shock correlated with severity of shock, PMN infiltration, pulmonary edema, and hypoxia. To determine whether increased tissue levels of G-CSF contribute to PMN recruitment and PMN-mediated injury, we instilled G-CSF into the lungs by intratracheal injection. Animals treated with G-CSF became hypoxic, hypocapnic, and alkalotic and demonstrated increased BAL fluid cellularity compared with control animals. The wet-to-dry ratio increased significantly after G-CSF instillation and peaked at 12 h. Histological examination of the lungs from G-CSF-treated rats revealed marked edema and increased PMN within the interstitium and alveoli. These results indicate that the presence of G-CSF alone in the lung can lead to recruitment of PMN, lung injury, and impaired pulmonary function, suggesting that local production of G-CSF may contribute to the development of lung damage and possibly ARDS in the setting of resuscitated hemorrhagic shock.
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PMID:G-CSF instillation into rat lungs mediates neutrophil recruitment, pulmonary edema, and hypoxia. 946 75

Practical approaches to the initial evaluation of solid organ transplant patients, BMT patients, and HIV-infected patients with pulmonary disease are summarized in Figures 2, 3, and 4. These algorithms are meant to be used as guidelines for the clinician. The clinical setting will ultimately determine the extent and speed of the evaluation. Patients who are recipients of solid organ transplants and have pulmonary symptoms may have focal or diffuse changes or may have normal chest radiographs. In all these groups, sputum is obtained by expectation. If a pathogen is found in any of the groups, it is treated. When no pathogen is found on sputum examination in patients with focal disease, empiric antibiotic therapy is given. If the patients do not improve on the empiric antibiotics, then bronchoscopy is performed. Some centers proceed directly to bronchoscopy before antibiotics are started in the hope of directing antibiotic therapy. Patients who have a normal CXR or diffuse infiltrates and no identified pathogen on examination of sputum undergo bronchoscopy, and the protocol is followed until a diagnosis is made (see Fig. 2). Patients who have received a BMT and who present with pulmonary symptoms are treated as shown in Figure 3. The CXR will reveal if the infiltrate is focal or diffuse. Those with focal infiltrates are treated with broad-spectrum antibiotics for 48 to 72 hours. If the symptoms and signs do not show some resolution, then bronchoscopy is usually performed. The effect of diffuse infiltrates in BMT patients depends to a large extent how far along in recovery from the transplant the patient is when they develop the infiltrates. During the first 30 days posttransplant, pulmonary edema commonly occurs, and the infiltrates may resolve with diuresis. If the patient is not clinically fluid overloaded or they do not respond to the diuretic therapy, then bronchoscopy with BAL is indicated. Finally, many HIV-infected patients may present with pulmonary symptoms. They may have a normal CXR or a diffuse or focal pattern (Fig. 4). All patients are subjected to sputum induction to identify a pathogen. If one is identified, it is treated. Should the patient not respond to treatment adequately or a pulmonary pathogen is not found, then bronchoscopy with BAL, protected specimen brush, or a transbronchial biopsy is attempted. The above schema is a general guideline to the initial evaluation of pulmonary disorders in the ICP. The respiratory abnormality is found in most of the cases if these algorithms are closely followed. If the patient does not improve or deteriorates further, additional diagnostic procedures such as video-assisted thorascopic lung biopsy or CT-directed transthoracic needle biopsy may be needed.
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PMID:The initial pulmonary evaluation of the immunocompromised patient. 1007 78

Initiated by numerous factors, acute lung injury is marked by epithelial and endothelial cell perturbation and inflammatory cell influx that leads to surfactant disruption, pulmonary edema, and atelectasis. This syndrome has been associated with a myriad of mediators including cytokines, oxidants, and growth factors. To better understand gene-environmental interactions controlling this complex process, the sensitivity of inbred mouse strains was investigated following acute lung injury that was induced by fine nickel sulfate aerosol. Measuring survival time, protein and neutrophil concentrations in BAL fluid, lung wet-to-dry weight ratio, and histology, we found that these responses varied between inbred mouse strains and that susceptibility is heritable. To assess the progression of acute lung injury, the temporal expression of genes and expressed sequence tags was assessed by complementary DNA microarray analysis. Enhanced expression was noted in genes that were associated with oxidative stress, antiprotease function, and extracellular matrix repair. In contrast, expression levels of surfactant proteins (SPs) and Clara cell secretory protein (ie, transcripts that are constitutively expressed in the lung) decreased markedly. Genome-wide analysis was performed with offspring derived from a sensitive and resistant strain (C57BL/6xA F(1) backcrossed with susceptible A strain). Significant linkage was identified for a locus on chromosome 6 (proposed as Aliq4), a region that we had identified previously following ozone-induced acute lung injury. Two suggestive linkages were identified on chromosomes 1 and 12. Using haplotype analysis to estimate the combined effect of these regions (along with putative modifying loci on chromosomes 9 and 16), we found that five loci interact to account for the differences in survival time of the parental strains. Candidate genes contained in Aliq4 include SP-B, aquaporin 1, and transforming growth factor-alpha. Thus, the functional genomic approaches of large gene set expression (complementary DNA microarray) and genome-wide analyses continue to provide novel insights into the genetic susceptibility of lung injury.
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PMID:Acute lung injury: functional genomics and genetic susceptibility. 1189 92

Current testing conventions for inhalation toxicity studies require that solid and non-volatile liquid compounds are converted to respirable aerosol, which is often achieved by laboratory-specific technical methodologies. So far, internationally harmonized approaches are lacking that would allow comparison of results from inhalation studies with 'contrived' test aerosols taking into account the actual particle size of the product as it might be encountered in normal handling and use. The focus of this paper is to consider aerosols of irritant substances eliciting their mode of action on sites of initial deposition within the respiratory tract of rats. Assessment is based on conventional endpoints, such as mortality (LC(50)), and sublethal endpoints that include an analysis for the concentration-effect relationship of protein in bronchoalveolar lavage fluid (BAL-protein) as a sensitive, early marker of lung edema. This retrospective analysis also addresses whether common denominators can be found for different aerosol sizes of direct and indirect irritants, such as monomeric and polymeric diphenylmethane-4,4'-diisocyanate (mMDI and pMDI), naphthylene diisocyanate (NDI), dicyclohexylmethane-4,4'-diisocyanate (HMDI), 2,4-triisopropyl-benzene-diisocyanate (TRIDI) and substances (e.g., chlorofluoroalkyl side-chain fungicides) known to decompose to irritant intermediates in the lining fluids of the airways. Collectively, this analysis shows that for irritant aerosols both the concentration and the particle size are equally important for the outcome of the test, independent of whether the endpoint chosen is lethality or BAL protein. The scientific value of 1-h exposures to high aerosol concentrations, as required by some regulations, could be challenged because high concentrations and high respirability of aerosol appear to be mutually exclusive, as shown for mMDI and NDI (LC(50 )>2000 mg/m(3)). Thus, for a meaningful risk characterization, test results from inhalation studies with 'contrived properties' due to the specific techniques employed need to be compared with the real properties of substances as marketed, handled and used.
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PMID:Acute inhalation studies with irritant aerosols: technical issues and relevance for risk characterization. 1505 6

The purpose of the present study was to investigate: (1) the acute effects of sulfur mustard on airway, lung, and surface tension of bronchoalveolar lavage fluid (BALfluid) in guinea pigs following intratracheal (i.t.) exposure to 1LD50 of an aerosolized solution of sulfur mustard in saline, and (2) the therapeutic efficacy of i.t. administration of the natural surfactant Curosurf and the broncholytic Salbutamol. Intratracheally aerosolized sulfur mustard solution induced two clinically relevant symptoms, that is, asthmalike symptoms reflected by an early bronchoconstriction and "late asthmatic responses" (LAR), and ARDS-like symptoms, that is, pulmonary edema and damage to the lung surfactant. The respiratory minute volume (RMV) was enhanced. Histologically, inflammation and severe epithelial injury in the upper airways were observed, whereas the lungs were homogeneously affected. The surface tension of BAL fluid derived at 24 h after sulfur mustard exposure was much higher (20 +/- 1 mN/m) than that of unexposed control animals (about 1.0 +/- 0.5 mN/m), indicating that the lung surfactant had been altered, and justifying treatment with exogenous surfactant. Intratracheal nebulization of a Salbutamol solution (10 microg/kg), or i.t. bolus administration of Curosurf (62.5 or 125 mg/kg), tended to reduce mortality, although Salbutamol appeared to be more effective than Curosurf in this respect. Although the present study does not give a definite answer to the question of whether the animal model used would be the most relevant for humans, a number of considerations in favor of i.t. aerosolization of sulfur mustard are discussed. Since it was noticed that sulfur mustard exposure induced damage to the lung surfactant, severe bronchoconstriction, and inflammation of the respiratory tract, the effectiveness of a combined treatment consisting of exogenous surfactant, anti-inflammatory drugs, and broncholytics is recommended to be further investigated.
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PMID:Asthmalike symptoms following intratracheal exposure of Guinea pigs to sulfur mustard aerosol: therapeutic efficacy of exogenous lung surfactant curosurf and salbutamol. 1520 45

Pneumonia is common in those patients placed in intensive care units, especially in mechanically ventilated patients. The high mortality rate of ventilator-associated pneumonia requires a rapid initiation of the appropriate antibiotic treatment. Patients who do not respond to initial antibiotic regimens could have the additional benefit of the use of invasive techniques such as bronchoalveolar lavage. Moreover, BAL is of clinical use to identify several non-infectious pulmonary conditions that may mimic pneumonia in these patients. Such conditions include pulmonary haemorrhages, acute eosinophilic pneumonia, malignancy, drug-induced toxicity, adult respiratory distress syndrome and cardiogenic pulmonary oedema. It is important to distinguish these conditions from pneumonia because the management and prognosis of these entities is quite different.
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PMID:Bronchoalveolar lavage in intensive care units. 1536 35


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