Glycaemic control boosts glucosylated nanocarrier crossing the BBB into the brain.

Recently, nanocarriers that transport bioactive substances to a target site in the body have attracted considerable attention and undergone rapid progression in terms of the state of the art. However, few nanocarriers can enter the brain via a systemic route through the blood-brain barrier (BBB) to efficiently reach neurons. Here we prepare a self-assembled supramolecular nanocarrier with a surface featuring properly configured glucose. The BBB crossing and brain accumulation of this nanocarrier are boosted by the rapid glycaemic increase after fasting and by the putative phenomenon of the highly expressed glucose transporter-1 (GLUT1) in brain capillary endothelial cells migrating from the luminal to the abluminal plasma membrane. The precisely controlled glucose density on the surface of the nanocarrier enables the regulation of its distribution within the brain, and thus is successfully optimized to increase the number of nanocarriers accumulating in neurons.There are only a few examples of nanocarriers that can transport bioactive substances across the blood-brain barrier. Here the authors show that by rapid glycaemic increase the accumulation of a glucosylated nanocarrier in the brain can be controlled.

Hypocapnic alkalosis enhances oxidant-induced apoptosis of human alveolar epithelial type II cells.

Apoptosis of alveolar epithelial type II (AEC-II) cells induced by reactive oxygen species (ROS) contributes to extensive alveolar damage during acute lung injury. Hypercapnic acidosis and hypocapnic alkalosis are known to modulate ROS-mediated lung damage. This study assessed the effects of acid-base balance disturbances on hydrogen peroxide (H2O2)-induced apoptosis of the AEC-II-like human cell line A549, which was cultured under different conditions of pH and CO2 tension (normal pH and CO2, hypercapnic acidosis, metabolic acidosis, hypocapnic alkalosis and metabolic alkalosis). H2O2-induced apoptosis was assessed by a dye-uptake bioassay and induction of caspase activity, which were quantified using analytical digital photomicroscopy. Acidosis or alkalosis of the culture medium alone did not induce A549 cell apoptosis. Hypocapnic alkalosis significantly increased H2O2-induced apoptosis and caspase activation of A549 cells. Metabolic alkalosis non-significantly increased H2O2-induced A549 cell apoptosis and caspase activation. These data suggest that hypocapnic alkalosis intensifies oxidative-induced apoptosis of alveolar epithelial cells.

Effects of phosphodiesterase-III inhibitors on sevoflurane-induced impairment of rat diaphragmatic function.

BACKGROUND: Volatile anesthetics are known to cause diaphragmatic dysfunction using a whole body model. The first aim of the current study was to compare the impairing effect of halothane and sevoflurane on diaphragmatic contractile functions under unfatigued and fatigued conditions. The second purpose was to determine whether phosphodiesterase-III inhibitors can attenuate sevoflurane-potentiated reduction of contractility after fatigue. METHODS: Using rat-isolated muscle strips, diaphragmatic twitch characteristics and tetanic contractions were measured before and after muscle fatigue, which was induced by repetitive tetanic contraction with or without exposure to halothane (1-3 MAC) or sevoflurane (1-3 MAC). Diaphragmatic functions were further assessed with exposure to 3 MAC sevoflurane in the presence and absence of milrinone, or olprinone. Cyclic adenosine monophosphate (cAMP) concentrations in the fatigued diaphragm were also measured. RESULTS: Halothane (1-3 MAC) or sevoflurane (1-2 MAC) did not induce a direct inotropic effect under unfatigued and fatigued conditions. Sevoflurane at 3 MAC enhanced fatigue-induced impairment of twitch and tetanic tensions. Clinically relevant concentrations of olprinone improved the sevoflurane-induced potentiation of diaphragmatic dysfunction following fatigue, accompanied by restoration of diaphragmatic cAMP levels, although milrinone failed to do so. CONCLUSION: Our findings suggest that sevoflurane has a greater decreasing effect on diaphragmatic contractility after fatigue than halothane, and that the clinical dose of olprinone surmounts the disadvantage of sevoflurane in various conditions where diaphragmatic fatigue is predisposed.

Effects of edaravone on human neutrophil function.

BACKGROUND: Neutrophils play a crucial role in the antibacterial host defence system. Edaravone is used in critically ill patients who are often immuno-compromised secondary to concomitant disease or immunosuppressive therapy. The aim of the current study was to assess the effect of edaravone, a novel free-radical scavenger, on several aspects of human neutrophil function using an in vitro system. METHODS: Chemotaxis, phagocytosis, reactive oxygen species (ROS) production by neutrophil (cellular) and xanthine-xanthine oxidase (acellular) systems, and intracellular calcium ion levels ([Ca(2 +) ]i) were measured in the absence and in the presence (at a clinically relevant concentration, and 0.1-fold, and 10-fold this concentration) of edaravone. RESULTS: The clinically relevant concentration of edaravone did not inhibit chemotxais, phagocytosis, or superoxide production of neutrophils. Even at its ordinary clinical plasma concentration, the drug inhibited hydrogen peroxide (H(2)O(2)) and hydroxyl radical (OH*) generation in the cellular (neutrophil) as well as in the cell-free (xanthine-xanthine oxidase) system (P < 0.05). Edaravone did not affect elevation of [Ca(2 +) ]i in neutrophils stimulated by a chemotactic factor. CONCLUSIONS: These findings suggest that edaravone quenched H(2)O(2), and OH* generated rather than impaired the ability of neutrophils to produce the ROS. However, further studies using in vivo systems are required to elucidate the effects of edaravone on neutrophil function in clinical settings.

Serum gamma-glutamyltransferase and development of impaired fasting glucose or type 2 diabetes in middle-aged Japanese men.

OBJECTIVE: To investigate the association between serum gamma-glutamyltransferase (GGT) and risk for development of diabetes. DESIGN: Longitudinal study (followed from 1994 to 2001). SETTING: A work site in Japan. SUBJECTS: A total of 2918 Japanese male office workers aged 35-59 years who did not have impaired fasting glucose (IFG) (a fasting plasma glucose concentration of 6.1-6.9 mmol L-1), type 2 diabetes (a fasting plasma glucose concentration of >/=7.0 mmol L-1 or receipt of hypoglycaemic medication), medication for hypertension or hepatitis, alanine aminotransferase concentrations higher than three times the upper limit of the reference range or a history of cardiovascular disease at study entry. MAIN OUTCOME MEASURE: Incidence of IFG or type 2 diabetes over a 7-year period. RESULTS: With adjustment for potential risk factors for diabetes, the relative risk for IFG compared with serum GGT <16 U L-1 was 1.23 (95% CI, 0.79-1.90), 1.50 (CI, 0.97-2.32) and 1.70 (CI, 1.07-2.71) with serum GGT of 16-24, 25-43 and >/=44 U L-1, respectively (P for trend = 0.014). The respective relative risks for type 2 diabetes compared with serum GGT <16 U L-1 were 2.54 (CI, 1.29-5.01), 2.64 (CI, 1.33-5.23) and 3.44 (CI, 1.69-6.70) (P for trend = 0.002). From stratified analyses by body mass index (BMI) and alcohol intake, a stronger linear association between serum GGT and development of IFG or type 2 diabetes was found in men with a BMI >/=23.2 kg m-2 in both those who drank <46 and >/=46 g day-1 of ethanol. CONCLUSIONS: The risk for development of IFG or type 2 diabetes increased in a dose-dependent manner as serum GGT increased in middle-aged Japanese men. The increased relative risk for IFG or type 2 diabetes associated with serum GGT was more pronounced in obese men.

Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

Effects of ropivacaine on human neutrophil function: comparison with bupivacaine and lidocaine.

BACKGROUND AND OBJECTIVE: Neutrophils are important both for the immunological defence system and for the inflammatory tissue autoinjury mechanism. However, many local anaesthetics impair certain neutrophil functions. The aim was to assess the effects of ropivacaine, bupivacaine and lidocaine on human neutrophils from adult volunteers. METHODS: Chemotaxis, phagocytosis, reactive oxygen species production, intracellular calcium ion ([Ca2+]i) concentrations and protein kinase C activity were measured in the absence and presence of ropivacaine, bupivacaine or lidocaine. The lowest concentrations of the local anaesthetics were similar to those clinically observed in the plasma. RESULTS: Bupivacaine did not affect any neutrophil function (P > 0.05). Ropivacaine failed to change chemotaxis or phagocytosis, while lidocaine suppressed both these neutrophil functions. Ropivacaine (15, 150 microg mL(-1)) and lidocaine (20, 200 microg mL(-1)) impaired neutrophil production of O2-, H2O2 and OH- (P < 0.05) at similar rates (by 7-10%). These same concentrations of ropivacaine and lidocaine suppressed [Ca2+1i elevation. Finally, neither ropivacaine nor bupivacaine inhibited protein kinase C activity, while lidocaine did. CONCLUSIONS: Suppression of the [Ca2+]i response in neutrophils by ropivacaine may represent one of the mechanisms responsible for the impairment of neutrophil functions. It should be emphasized that the inhibitory effects of ropivacaine are minor and are attained only at high concentrations, which may minimize the clinical implication of ropivacaine-associated impairment of reactive oxygen species production. Further studies using in vivo systems are required to identify the inhibitory effects of ropivacaine on reactive oxygen species production in clinical settings.

Hours of work and the risk of developing impaired fasting glucose or type 2 diabetes mellitus in Japanese male office workers.

OBJECTIVE: To investigate the association between duration of overtime and the development of impaired fasting glucose (IFG) or type 2 diabetes mellitus (DM). METHODS: A cohort of 1266 Japanese male office workers aged 35-59 years and free of IFG (fasting plasma glucose concentration 6.1-6.9 mmol/l), type 2 DM (fasting plasma glucose concentration of 7.0 mmol/l or more or taking hypoglycaemic medication), history of diabetes, or medication for hypertension were re-examined over 5 successive years after their initial examinations in 1994. RESULTS: 138 men developed IFG or type 2 DM during the 5736 person-years of follow up. After controlling for potential predictors of diabetes, the relative risks of IFG or type 2 DM, compared with those who worked <8.0 hours a day, were 0.82 (95% confidence interval (95% CI) 0.54 to 1.26), 0.69 (95% CI 0.38 to 1.26), 0.63 (95% CI: 0.37 to 1.09), and 0.50 (95% CI: 0.25 to 0.98) for those who worked 8.0-8.9, 9.0-9.9, 10.0-10.9, and of 11.0 hours or more a day, respectively (p for trend=0.020). 87 and 54 men developed IFG and type 2 DM during the 5817 and 5937 person-years of follow up, respectively. The multivariate adjusted relative risks of IFG tended to decrease with an increase in hours of overtime work a day, but did not reach significance (p for trend=0.202). On the other hand, the multivariate adjusted relative risks of type 2 DM significantly decreased with an increase in hours of overtime work a day (p for trend=0.014). CONCLUSION: Longer overtime is a negative risk factor for the development of IFG or type 2 DM in Japanese male office workers.

A comparison of atenolol, labetalol, esmolol, and landiolol for altering human neutrophil functions.

IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense system. Atenolol, labetalol, esmolol, and landiolol at clinically relevant concentrations failed to change neutrophil functions. Our findings indicate that we may be able to use these beta-antagonists without great caution in clinical settings.

ONO-1714, a new inducible nitric oxide synthase inhibitor, attenuates diaphragmatic dysfunction associated with cerulein-induced pancreatitis in rats.

OBJECTIVES: Acute experimental pancreatitis (induced by cerulein) recently has been reported to cause marked diaphragmatic dysfunction, which may contribute to respiratory distress in this setting. In cerulein-induced acute pancreatitis, expression of inducible nitric oxide synthase is induced to produce a large amount of nitric oxide. Nitric oxide excessively produced has been implicated in diaphragmatic dysfunction induced by a variety of etiologies. The aims of the current study were, first, to examine whether nitric oxide overproduced through inducible nitric oxide synthase is involved in cerulein-induced impairment of diaphragmatic function, and second, if demonstrated, to assess effects of ONO-1714, an inducible nitric oxide synthase inhibitor, on diaphragmatic dysfunction associated with cerulein-induced acute pancreatitis. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Ninety-one male Sprague-Dawley rats, weighing 200-250 g. INTERVENTIONS: Rats were randomly divided into seven groups (n = 8 each): CONT-SAL, CAER-SAL, CONT-ONO, CAER-DEX, CAER-AMI, CAER-ONOhigh, and CAER-ONOlow. Groups labeled CAER received two consecutive intraperitoneal doses (50 microg/kg) of cerulein, whereas groups labeled CONT received two consecutive intraperitoneal injections of saline. Groups labeled SAL received intraperitoneal saline before cerulein or saline. The group labeled DEX received 2 mg/kg intraperitoneal dexamethasone, and the group labeled AMI received 100 mg/kg intraperitoneal aminoguanidine. The groups labeled ONO, ONOhigh, and ONOlow received ONO-1714 at 0.1 mg/kg, 0.1 mg/kg, and 0.03 mg/kg, respectively, before cerulein or saline. MEASUREMENTS AND MAIN RESULTS: Diaphragmatic contractility and fatigability were assessed in vitro by using muscle strips excised from the costal diaphragms 6 hrs after the first dose of cerulein or saline. Expression of inducible nitric oxide synthase protein in the diaphragm was assessed by immunohistochemistry by using anti-inducible nitric oxide synthase antibody. Plasma concentrations of nitrite plus nitrate and diaphragmatic concentrations of malondialdehyde were measured. With another set of rats (n = 5 each group), diaphragmatic inducible nitric oxide synthase activity was determined. Twitch and tetanic tensions and tensions generated during fatigue trial were lower in group CAER-SAL than in group CONT-SAL. Cerulein increased diaphragmatic malondialdehyde and plasma nitrite plus nitrate concentrations. Positive immunostaining for inducible nitric oxide synthase protein was found in group CAER-SAL. Dexamethasone and aminoguanidine attenuated the diaphragmatic mechanical damages. A high dose of ONO-1714 attenuated cerulein-induced impairment of diaphragmatic contractility and endurance capacity, although a low dose of the drug failed to do so. CONCLUSIONS: Cerulein-induced diaphragmatic dysfunction was attributable, in part, to nitric oxide overproduced via inducible nitric oxide synthase. Pretreatment with ONO-1714 at a dose of 0.1 mg/kg attenuated diaphragmatic dysfunction associated with cerulein-induced pancreatitis in rats assessed by contractile profiles and endurance capacity. This beneficial effect of ONO-1714 may be attributable, in part, to inhibition of diaphragmatic lipid peroxidation induced by nitric oxide-derived free radicals.

Propofol attenuates diaphragmatic dysfunction induced by septic peritonitis in hamsters.

BACKGROUND: Sepsis or peritonitis impairs diaphragmatic contractility and endurance capacity. Peroxynitrite, a powerful oxidant formed by superoxide and nitric oxide, has been implicated in the pathogenesis. Propofol scavenges this reactive molecule. The authors conducted the current study to evaluate whether propofol prevents diaphragmatic dysfunction induced by septic peritonitis. METHODS: Forty male Golden-Syrian hamsters (120-140 g) were randomly classified into five groups. Groups sham and sham-propofol 50 underwent sham laparotomy alone, whereas groups sepsis, sepsis-propofol 25, and sepsis-propofol 50 underwent cecal ligation with puncture. Groups sham and sepsis received infusion of intralipid, whereas groups sham-propofol 50, sepsis-propofol 25, and sepsis-propofol 50 received propofol at rates of 50, 25, and 50 mg.kg(-1).h(-1), respectively. Intralipid or propofol was subcutaneously infused from 3 h before surgery until 24 h after operation, when all hamsters were killed. Diaphragmatic contractility and fatigability were assessed in vitro using diaphragm muscle strips. Peroxynitrite formation in the diaphragm was assessed by nitrotyrosine immunostaining. Plasma nitrite-nitrate concentrations and diaphragmatic concentrations of malondialdehyde were determined. Using another set of animals, diaphragmatic inducible nitric oxide synthase activity was also measured. RESULTS: Twitch, tetanic tensions, and tensions during fatigue trials were reduced in group sepsis compared with group sham. In group SEPSIS, diaphragm malondialdehyde and inducible nitric oxide synthase activity, and plasma nitrite-nitrate concentrations increased, and positive immunostaining for nitrotyrosine residues was found. Propofol attenuated these changes. CONCLUSIONS: Pretreatment with propofol attenuated diaphragmatic dysfunction induced by septic peritonitis in hamsters assessed by contractile profiles and endurance capacity. This beneficial effect of propofol may be caused, in part, by inhibition of lipid peroxidation in the diaphragm caused by the powerful oxidant.

Therapeutic time-window of a group IIA phospholipase A2 inhibitor in rabbit acute lung injury: correlation with lung surfactant protection.

OBJECTIVE: We attempted to determine whether group IIA secretory phospholipase A2 (sPLA2-IIA) blockade after the onset of lung injury exerted therapeutic efficacy in the treatment of oleic acid (OA)-induced acute lung injury by using S-5920/LY315920Na, a novel specific inhibitor of sPLA2-IIA, with special interest in the changes of lung surfactant. DESIGN: Prospective animal study. SETTING: University laboratory. SUBJECTS: Forty Japanese white rabbits. INTERVENTIONS: The rabbits, under anesthesia, were endotracheally intubated and mechanically ventilated and then were divided into the following groups: OA + vehicle groups, intravenous infusion of OA for the first 2 hrs (0.1 mL x kg(-1) x hr(-1)) with the addition of vehicle (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); OA + S-5920/LY315920Na groups, treated identically to the OA control with the addition of S-5920/LY315920Na (1 mg/kg bolus followed by infusion at 0.5 mg x kg(-1) x hr(-1)) after OA (1 or 2 hrs after OA administration, each n = 9, total 18 rabbits); saline control groups, treated with saline instead of OA with the addition of vehicle (1 hr after OA administration, 4 rabbits). Arterial blood gas, lung mechanics, lung inflammation, lung surfactant phospholipids, and production of inflammatory mediators in the lung were measured. MEASUREMENTS AND MAIN RESULTS: Treatment with S-5920/LY315920Na 1 hr after OA infusion, but not 2 hrs after infusion, significantly attenuated the lung injury, as estimated by hypoxemia, decreased lung compliance, pulmonary edema, and vascular permeability. The therapeutic efficacy was similar to that found in our previous pretreatment study. The treatment after 1 hr dramatically inhibited OA-induced surfactant degradation in the bronchoalveolar lavage fluid (BALF), without affecting the concentrations of thromboxane A2, leukotriene B4, and interleukin-8 in BALF. The degree of surfactant degradation in BALF paralleled well with the severity of the lung injury. Furthermore, recombinant human sPLA2-IIA reproduced the similar hydrolysis pattern of isolated surfactant in vitro, which was inhibited by S-5920/LY315920Na. CONCLUSIONS: Our results indicate that therapeutic blockade of sPLA2-IIA ameliorated lung dysfunction via protection of surfactant degradation in an animal model of acute lung injury, and they suggest a new strategy in treating clinical acute lung injury.

ONO1714, a new inducible nitric oxide synthase inhibitor, attenuates sepsis-induced diaphragmatic dysfunction in hamsters.

UNLABELLED: Sepsis causes impairment of diaphragmatic contractility and endurance capacity. Nitric oxide (NO) produced via inducible NO synthase (iNOS) has been implicated in the pathogenesis. Peroxynitrite, a NO-derived powerful oxidant, may be responsible for infection-induced diaphragmatic muscle failure. Therefore, we examined whether ONO1714, a new selective iNOS inhibitor, prevents sepsis-induced diaphragmatic dysfunction. Fifty male Golden-Syrian hamsters were randomly divided into five groups: hamsters that underwent sham laparotomy alone and received saline injection (Group Sham), those that underwent cecal ligation with puncture (CLP) and received saline injection (Group Sepsis), those that underwent sham laparotomy and received injection of ONO1714 0.3 mg/kg (Group Sham-ONO1714high), those that underwent CLP and received ONO1714 0.1 mg/kg (Group Sepsis-ONO1714low), and those that underwent CLP and received ONO1714 0.3 mg/kg (Group Sepsis-ONO1714high). ONO1714 or saline was intraperitoneally injected 10 min before surgery. Diaphragmatic contractility was assessed in vitro using diaphragm muscle strips excised 24 h after operation. Diaphragm fatigability was assessed by time until tension decreased to 50% of the initial value (T50%) during fatigue trials. Twitch, tetanic tensions, and T50% during fatigue trials were reduced in Group Sepsis. Pretreatment with ONO1714 dose-dependently attenuated sepsis-induced diaphragmatic contractile profiles and endurance capacity. CLP increased plasma nitrite/nitrate (NOx; stable NO metabolites), and diaphragm malondialdehyde (MDA; a product of lipid peroxidation), positive immunostaining for nitrotyrosine (peroxynitrite footprint), and iNOS activity. ONO1714 attenuated the increase. This beneficial effect of ONO1714 may be attributable, in part, to inhibition of peroxynitrite-induced lipid peroxidation in the diaphragm. IMPLICATIONS: Sepsis impairs diaphragmatic contractility and endurance capacity, which may be involved in acute respiratory failure. Pretreatment with ONO1714, a new selective inducible nitric oxide synthase inhibitor, attenuated sepsis-induced diaphragmatic dysfunction in hamsters.

The effects of lidocaine on nitric oxide production from an activated murine macrophage cell line.

UNLABELLED: Nitric oxide (NO), overproduced by activated macrophages, is important in the pathogenesis of various diseases, including septic shock and inflammatory tissue injury, as well as antibacterial host defense mechanisms. We examined the effects of lidocaine on NO production and the expression of inducible NO synthase (iNOS) protein and messenger RNA (mRNA) in activated macrophages. Murine macrophage-like cell line RAW 264 was stimulated for 8 h with lipopolysaccharide (10 mg/mL) and interferon-gamma (50 U/mL) in the presence of various concentrations of lidocaine (0-500 mg/mL). NO production was assessed by measuring levels of the stable metabolites, nitrite and nitrate (NOx), in the culture medium with an automatic analyzer using the Griess reaction. Expression of iNOS mRNA in harvested RAW 264 was quantified by Northern blot analysis using mouse iNOS complementary DNA probe. Expression of iNOS protein in the cells was assessed by Western blot analysis using anti-iNOS antibody. Lidocaine dose-dependently attenuated the increase in NOx levels in response to the stimulants. The drug at any concentration failed to decrease iNOS mRNA expression in RAW 264. Lidocaine at 500 mg/mL decreased iNOS protein levels. These data suggest that lidocaine reduced NO production in activated macrophages at multiple levels after transcription. The inhibitory site appeared to vary with the dose of lidocaine. IMPLICATIONS: Lidocaine dose-dependently inhibited nitric oxide production by activated macrophages, presumably at levels after transcription. The attenuating effect of lidocaine on organ injuries previously reported may be explained by the ability of the drug to suppress this inflammatory mediator.

Effect of methylprednisolone on phospholipase A(2) activity and lung surfactant degradation in acute lung injury in rabbits.

Glucocorticoids are the most potent and widely used anti-inflammatory agents, but they are not particularly effective against early phase of acute respiratory distress syndrome. We investigated whether methylprednisolone, a synthetic glucocorticoid, could inhibit increase of phospholipase A(2) activity in the lung and lead to protection against a model of acute respiratory distress syndrome in rabbits. Infusion of oleic acid (0.1 ml/kg/h, i.v. for 2 h) provoked pulmonary hemorrhage and edema, protein leakage and massive neutrophil infiltration, resulted in severe hypoxemia and impaired lung compliance, accompanying the increase of phospholipase A(2) activity and interleukin-8, and degradation of surfactant in the bronchoalveolar lavage fluid. Infusion of methylprednisolone (60 mg/kg/h, i.v. for 30 min before the oleic acid and then 0.5 mg/kg/h, i.v. for 6 h) did not improve the above described lung injury induced by oleic acid, nor did it suppress phospholipase A(2) activity and degradation of surfactant in bronchoalveolar lavage fluid, while it strongly reduced interleukin-8 levels in both plasma and bronchoalveolar lavage fluid. We conclude that methylprednisolone did not attenuate oleic acid-induced acute lung injury and this can be explained partly by its failure to reduce the increase of phospholipase A(2) activity and the surfactant degradation in the lung, which might also account for its clinical ineffectiveness against early acute respiratory distress syndrome.