Disease relevance of NSC7248

• The initial dose of either the synthetic surfactant (Exosurf, 5 ml per kilogram of body weight) or air (the placebo) was administered less than 24 hours after birth, with a second dose given 12 hours later [1].
• Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group [2].
• Metabolic studies employing Triton WR-1339 and either [(3)H]glycerol or [(3)H]palmitate showed that the hypertriglyceridemia in apoB/BATless mice was due to the increased synthesis and secretion of triglyceride [3].
• Physiologic response and lung distribution of lavage versus bolus Exosurf in piglets with acute lung injury [4].
• We conclude that tyloxapol is potentially useful as a new antiinflammatory therapy for CF lung disease, and could possibly promote clearance of secretions in the CF airway [5].

High impact information on NSC7248

• Results are compatible with the hypothesis that the potentiating effects of Triton WR-1339 on liver damage caused by DMN and other hepatotoxins were due to a modification of the response of liver cells to injury [6].
• In these experiments, we tested two hypothesis: first, that Triton WR-1339, a nonionic detergent which is sequestered in hepatocyte lysosomes, undergoes biliary excretion; and second, that Triton WR-1339, which also alters serum lipid levels and modifies hepatic catabolism of lipoproteins, affects the biliary output of proteins and lipids [7].
• Inhibition of proteolytic degradation of low density lipoprotein in human fibroblasts by chloroquine, concanavalin A, and Triton WR 1339 [8].
• Despite their enrichment in DPPC Survanta and Exosurf exhibited poor surface activity because of low or absent SP-B/C [9].
• We investigated these parameters in Alveofact, Curosurf, Exosurf, and Survanta, and compared them with native bovine (NBS) and porcine (NPS) surfactant [9].

Chemical compound and disease context of NSC7248

• In the basal 7-h fasted state, rosiglitazone (10 micromol.kg(-1).day(-1)) and darglitazone corrected the hypertriglyceridemia by increasing plasma triglyceride (TG) clearance and decreasing hepatic TG production, as assessed using Triton WR 1339 [10].
• ICRF 159 and Triton WR 1339 have been examined for their ability to suppress subcutaneous growth and pulmonary metastases from a transplanted rat epithelioma [11].
• Administration of Triton WR 1339 aggravates chronic aminonucleoside nephrosis [12].
• DESIGN: We reconstituted human nasal mucus obtained from 74 patients with chronic sinusitis and determined the effects of 4 mucokinetic drugs, including acetylcysteine, deoxynuclease I, 2% sodium bicarbonate, and a combination product containing tyloxapol (Alevaire), on rheological properties of reconstituted human nasal mucus (RHNM) [13].
• Hypertriglyceridemia induced by i.v. injection of the lipoprotein lipase inhibitor Triton WR 1339 was reduced without affecting body weight in "Zucker" rats after 3 days on a fat-free diet supplemented with acarbose [14].

Biological context of NSC7248

• Exosurf was ineffective in the treatment of wood smoke inhalation [15].
• Formation of triton WR 1339-filled rat liver lysosomes. II. Involvement of autophagy and of pre-existing lysosomes [16].
• The synthetic surfactant preparation Exosurf containing L-alpha-phosphatidylcholine-dipalmitoyl (DPPC) as the sole lipid ingredient had no statistically significant effect on polymer- and lipid-mediated transfection [17].
• Whereas both 3 and 1 reduced hypercholesterolemic and hypertriglyceridemic serum levels in the Triton WR-1339 induced hyperlipidemic Sprague-Dawley rat to normal, the hydrolysis product of 3, namely 5-chloro-3(2'-hydroxyethoxy)-2-benzofurancarboxylic acid (4), was found to be inactive [18].
• Hepatic TG secretion rates, measured in vivo after blocking lipolysis with Triton WR-1339 in fasting animals, were increased by 33% in both ADR and NA rats as compared to controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)[19]

Anatomical context of NSC7248

• Peroxisomes were separated from lysosomes in a density gradient centrifugation using rats which were injected with Triton WR 1339 [20].
• Tyloxapol also reduces the viscosity of CF sputum (from 463 +/- 133 to 128 +/- 52 centipoise) [5].
• Characterization of exosurf (surfactant)-mediated suppression of stimulated human alveolar macrophage cytokine responses [21].
• In this study, we report that both Exosurf and Survanta suppress TNF mRNA and secretion (85 +/- 4% mean percent inhibition +/- SEM by Exosurf; 71 +/- 6% by Survanta) by endotoxin-stimulated THP-1, a human monocytic cell line [22].
• When macrophages from hosts pretreated with Triton WR 1339 were used, inhibition of the multiplication of mycobacteria within cells infected in vitro or in vivo was very slight, though this compound displayed a marked protective effect in the host [23].

Associations of NSC7248 with other chemical compounds

• We have, therefore, studied the effects of the inhibitor of lipase activity, Triton WR 1339, on the secretion of triacylglycerol by cultured rat hepatocytes [24].
• Preliminary findings from clinical trials suggest that aerosolized delivery of the synthetic surfactant Exosurf (Burroughs Wellcome Co.) reduces mortality in patients with sepsis-induced ARDS [25].
• The effects of exogenous apoE, heparin, Triton WR 1339, and lactoferrin on catabolism of emulsions were also assayed. n-3 TG emulsions were cleared faster from blood and had different extrahepatic tissue targeting compared to n-6 TG emulsions [26].
• Lactone 2, its synthetic tricyclic hemiacetal precursor 4, and clofibrate were investigated for their antilipidemic activity in 7-day treated normal and in Triton WR-1339 induced hyperlipidemic male Sprague-Dawley rats [27].
• Hepatic triglyceride and apolipoprotein B (apoB) production were measured in anesthetized, fasted rats injected intravenously with Triton WR-1339 (400 mg/kg) [28].

Gene context of NSC7248

• Tyloxapol inhibits NF-kappa B and cytokine release, scavenges HOCI, and reduces viscosity of cystic fibrosis sputum [5].
• However, if AMs were preincubated for 24 h in media and then LPS-stimulated, IL-8 secretion was inhibited by Exosurf [25].
• We previously demonstrated that both synthetic (Exosurf) and modified natural surfactant (Survanta) downregulated endotoxin-stimulated inflammatory c ytokine mRNA levels and protein products (tumor necrosis factor-alpha [TNF], interleukin-1-beta [IL-1], interleukin-6 [IL-6]) in human alveolar macrophages [22].
• The effects of Tyloxapol on endotoxin binding and macrophage activation were studied in the macrophage cell line RAW264.7 and CHO cells expressing CD14 [29].
• Involvement of IL-6 and IL-6 receptor in fibrinogen synthesis in the liver of Triton WR-1339-induced hyperlipidemic rats [30].

Analytical, diagnostic and therapeutic context of NSC7248

• Greater than 95% of total proteolysis in homogenates, measured at 37 degrees C from free amino acid generation or the release of [14C]valine in previously labeled livers, was associated with particulate fractions, and it paralleled lysosomal markers closely during graded differential centrifugation after Triton WR-1339 loading [31].
• In fact, immunofluorescence studies and Triton WR-1339 shift experiments suggest a lysosomal localization for this enzyme [32].
• We conclude that Exosurf is more effective when administered by lavage in this lung injury model [4].
• Exosurf, an artificial surfactant, was administered after acute lung injury induced by saline lung lavage in neonatal piglets [4].
• 1. Lipoprotein lipase activity was measured in heart homogenates and in heparin-releasable and non-releasable fractions of isolated perfused rat hearts, after the intravenous injection of Triton WR-1339 [33].

References