Oleic Acid Administration Research Articles

Angiotensin-(1–7) Protects From Experimental Acute Lung Injury

Recently, recombinant angiotensin-converting enzyme 2 was shown to protect mice from acute lung injury, an effect attributed to reduced bioavailability of angiotensin II. Since angiotensin-converting enzyme 2 metabolizes angiotensin II to angiotensin-(1-7), we hypothesized that this effect is alternatively mediated by angiotensin-(1-7) and activation of its receptor(s). To test this hypothesis, we investigated the effects of intravenously infused angiotensin-(1-7) in three experimental models of acute lung injury. Animal research laboratory. Male Sprague-Dawley rats, Balb/c mice, and C57Bl6/J mice. Angiotensin-(1-7) was administered with ventilator- or acid aspiration-induced lung injury in mice or 30 minutes after oleic acid infusion in rats. In vitro, the effect of angiotensin-(1-7) on transendothelial electrical resistance of human pulmonary microvascular endothelial cells was analyzed. Infusion of angiotensin-(1-7) starting 30 minutes after oleic acid administration protected rats from acute lung injury as evident by reduced lung edema, myeloperoxidase activity, histological lung injury score, and pulmonary vascular resistance while systemic arterial pressure was stabilized. Such effects were largely reproduced by the nonpeptidic angiotensin-(1-7) analog AVE0991. Infusion of angiotensin-(1-7) was equally protective in murine models of ventilator- or acid aspiration-induced lung injury. In the oleic acid model, the two distinct angiotensin-(1-7) receptor blockers A779 and D-Pro-angiotensin-(1-7) reversed the normalizing effects of angiotensin-(1-7) on systemic and pulmonary hemodynamics, but only D-Pro-angiotensin-(1-7) blocked the protection from lung edema and protein leak, whereas A779 restored the infiltration of neutrophils. Rats were also protected from acute lung injury by the AT1 antagonist irbesartan; however, this effect was again blocked by A779 and D-Pro-angiotensin-(1-7). In vitro, angiotensin-(1-7) protected pulmonary microvascular endothelial cells from thrombin-induced barrier failure, yet D-Pro-angiotensin-(1-7) or NO synthase inhibition blocked this effect. Angiotensin-(1-7) or its analogs attenuate the key features of acute lung injury and may present a promising therapeutic strategy for the treatment of this disease.

Transient Blood Brain Barrier Disruption Induced by Oleic Acid is Mediated by Nitric Oxide

The blood brain barrier (BBB) maintains cerebral microenvironmental homeostasis. Transient disruption of the BBB after brain fat embolism in clinical cases and animal models has been reported but the precise mechanism underlying this occurrence is unclear. In the present study, we investigated BBB alterations in rats treated oleic acid (OA) delivered intra-arterially. Following OA treatment, transient brain edema, extravasation of Evans blue and Fluorescein isothiocyanate (FITC)-labeled dextran, and loss of laminin in the affected brain area were observed. Activation of matrix metalloproteinase (MMP)-2, -3, and -13 was found in the cerebral vessels 2 h after OA administration. Expression of intercellular adhesion molecule (ICAM)-1 in the vessels and neutrophil infiltration into the brain tissue was also observed. Inducible nitric oxide synthase (iNOS) was expressed in the neutrophils and nitrotyrosine was produced mainly in the vessels. Inhibitor of iNOS activity suppressed the loss of laminin, leakage of FITC-labeled dextran and Evans blue, and activation of MMP-2 and -13. Protein level of aquaporin (AQ)-4 was increased after OA administration but was not affected by treatment with iNOS inhibitor. In conclusion, we suggest that nitric oxide (NO) contributes to OA-induced MMP activation, BBB disruption and the development of transient brain edema.

Effect of oleic acid-induced acute lung injury and conventional mechanical ventilation on renal function in piglets.

Animal models that demonstrate changes of renal function in response to acute lung injury (ALI) and mechanical ventilation (MV) are few. The present study was performed to examine the effect of ALI induced by oleic acid (OA) in combination with conventional MV strategy on renal function in piglets. Twelve Chinese mini-piglets were randomly divided into two groups: the OA group (n = 6), animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALI induced by administration of OA, and the control group (n = 6), animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of sterile saline. Six hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen, while no apparent histological abnormalities were observed in the control group. Although we observed an increase in the plasma concentrations of creatinine and urea after ALI, there was no significant difference compared with the control group. Plasma concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C increased (5.6 ± 1.3) and (7.4 ± 1.5) times in the OA group compared to baseline values, and were significantly higher than the values in the control group. OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters, while these parameters remained stable during the experiment in the control group. The plasma expression of TNF-α and IL-6 in the OA group were significantly higher than that in the control group. Compared with high expression in the lung and renal tissue in the OA group, TNF-α and IL-6 were too low to be detected in the lung and renal tissue in the control group. OA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury. The potential mechanisms involved a cytokine response of TNF-α and IL-6 in plasma, lung and renal tissues.

Molecular-biological analysis of acute lung injury (ALI) induced by heat exposure and/or intravenous administration of oleic acid

The aim of this study was to molecular-biologically investigate the interaction between heat exposure and pulmonary fat embolization in regards to the development of acute lung injury (ALI). Ten-week-old Wistar male rats were divided into four groups: (1) oleic acid injected into caudal vein after heat exposure, (2) oleic acid injected without heat exposure, (3) soybean oil injected after heat exposure, and (4) soybean oil injected without heat exposure, and then mRNA expression of eight inflammatory mediators related to ALI/acute respiratory distress syndrome (ARDS) and heat shock protein 70 (Hsp70) in lung was determined 1h after the injection. mRNA expression of interleukin 1 beta (Il1b), tumor necrosis factor alpha (Tnfa), vascular endothelial growth factor A (Vegfa), transforming growth factor beta 1 (Tgfb1) and Hsp70 was significantly increased by heat exposure, while that of Il1b, interleukin 6 (Il6), Tnfa, macrophage inflammatory protein 2 (Mip2) and granulocyte macrophage-colony stimulating factor (Gm-csf) was significantly elevated by the injection of oleic acid. Moreover, the expressions of inflammatory cytokines and chemokines in lung almost paralleled their mRNA expressions. In particular, IL-1β expression was synergistically elevated by heat exposure followed by injection of oleic acid. Additionally, IL-6 expression tended to increase under the same conditions as well. It is likely that heat exposure itself injures lung tissue within a short time, and that more than two conditions which induce ALI/ARDS interact with each other synergistically, exacerbating the development of ALI/ARDS.

Effects of lycopene on the model of oleic acid-induced acute lung injury

This study, we aimed to investigate the protective effect of lycopene in lung injury rat model. Twenty eight Wistar rats were enrolled into the study. Control group (n= 7) were applied PBS + ethanol (9/1). A single dose of 100 mg/kg oleic acid (OA) intravenously was administrated to OA group (n= 7). One mL of corn oil was given daily to corn oil + OA group (n= 7) by gavage for five weeks. Lycopene was given by gavage to lycopene + OA group (n= 7) for five weeks. At the end of the 5th weeks, OA were given. Four hour after OA administration, lung tissue, blood samples were taken. Malondialdehyde, superoxide dismutase, glutathione-peroxidase, catalase levels were determined. Malondialdehyde levels of serum, lung tissues were increased in OA, corn oil + OA groups than control, where as decreased to controls levels in lycopene + OA group (p< 0.05). Superoxide dismutase, glutathione-peroxidase activities of serum, tissue increased moderetaly or they were closed with control values. There was significant increase in lycopene + OA group values. Histopathological examination of control group was normal. OA, cornoil + OA groups had perivascular, alveolar edema, hemorrage, prominent neutrophil infiltration, destruction in alveolar structure. Lycopene + OA group had less neutrophilic infiltration, perivascular, alveolar edema. Lycopene rich diet may have an important role preventing damages in lungs.

Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs) can be toxic to cells. Increased blood concentration of oleic acid (OLA) and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive) were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets.

The impact of sodium aescinate on acute lung injury induced by oleic acid in rats

ABSTRACTAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high rates of morbidity and mortality. Currently, several surfactant or anti-inflammatory drugs are under test as treatments for ALI. Sodium aescinate (SA) has been shown to exert anti-inflammatory and antiedematous effects. In the present work, the authors explored the effects of SA and the possible mechanisms of SA action in rats with ALI induced by oleic acid (OA) administration. Eight groups of rats received infusions of normal saline (NS) or OA. Rats exposed to OA were pretreated with 1 mg/kg of SA, or posttreated with SA at low (1 mg/kg), medium (2 mg/kg), or high (6 mg/kg) dose; a positive-control group received methylprednisolone. The pressure of oxygen in arterial blood (Po2) levels, the pulmonary wet/dry weight (W/D) ratios, and indices of quantitative assessment (IQA) of histological lung injury were obtained 2 or 6 hours after OA injection (0.1 mL/kg, intravenously). The levels of superoxide dismutase (SOD), malondialdehyde (MDA), matrix metalloproteinase gelatinase B (MMP-9), and tissue inhibitor of metalloproteinase (TIMP-1) in both plasma and lung tissue were also determined. Both pre- and posttreatment with SA improved OA-induced pulmonary injury, increased Po2 and SOD values, lowered IQA scores, and decreased the lung W/D ratio and MDA and MMP-9 levels in plasma and lung tissue. SA appeared to abrogate OA-induced ALI by modulating the levels of SOD, MDA, and MMP-9 in plasma and lung tissue.

Effects of mechanical ventilation on cell apoptosis in lung tissue of rat with acute lung injury

Objective To investigate the effects of different tidal volumes and positive end expiratory pressures on cell apoptosis in lung tissue of rats with acute lung injury.Methods Forty healthy male Sprague-Dawley rats were randomly(random number)divided into five groups,namely low tidal volume group(LV,VT 8 mL/kg),high tidal volume group(HV,VT 30 mL/kg),low tidal volume group with PEEP 2cmH2O(LV2P,VT 8 mL/kg,PEEP 2 cmH2O),low tidal volume group and PEEP 5cmH2O (LV5P,VT 8 mL/kg,PEEP 5 cmH2O)and low tidal volume group and PEEP 8 cmH2O(LV8P,VT 8 mL/kg,PEEP 8 cmH2O).After intravenous administration of oleic acid(OA,0.1 mL/kg),the rat model of acute lung injury was made.Mechanical ventilation was employed in rats of the experiment groups.Rats were sacrificed and their whole lungs were taken after mechanical ventilation for 2 hours.The transferase d-UTP end labeling assay(TUNEL)was used to define the extent and distribution of apoptotic cells in bronchus and lung tissues.The level of caspase-3 protein was determined by immunohistochemistry.Results The apoptotic cells on both alveolar septum and bronchial epithelium obviously increased with high level of caaspase-3 protein in HV group.The number of apoptotic cells obviously decreased with decrease in caspase-3 protein after PEEP ventilation.These changes were more significant in LV5P than those in other groups(P ＜ 0.01).Conclusions The mechanical ventilation with low tidal volume and PEEP produces protective effects on lung from injury.The cell apoptosis plays an important role in the course of VILI. Key words: Acute lung injury; Ventilation; Apoptosis; Caspase-3 protein

Essential Role for Protein Kinase Cζ in Oleic Acid-Induced Glucagon-Like Peptide-1 Secretion in Vivo in the Rat

Luminal monounsaturated long-chain fatty acids [e.g. oleic acid (OA)] increase secretion of the incretin, glucagon-like peptide-1 (GLP-1) from the ileocolonic L cell. However, it is not known whether OA ingestion causes a sufficient increase in distal luminal concentrations to directly enhance GLP-1 secretion. Furthermore, we have demonstrated that protein kinase Cζ (PKCζ) is required for OA-induced GLP-1 secretion in vitro; however, the physiological relevance of this finding remains unknown. Therefore, we have determined luminal OA concentrations in OA-fed rats and examined the effects of direct OA stimulation on GLP-1 secretion using a novel model of intestinal-specific PKCζ knockdown. Murine GLUTag L cells express numerous fatty acid transport proteins and take up OA in a saturable manner. Oral administration of OA increased the ileal chyme content of OA by 140-fold over 60-120 min (P < 0.05-0.01), peaking at 105 ± 50 μmol/g. To evaluate the direct effects of OA on GLP-1 secretion, 125 mm OA was rectally infused into the colon and terminal ileum of rats. Plasma bioactive GLP-1 increased from 20 ± 6 to 102 ± 21 pg/ml at 60 min (P < 0.01). However, pretreatment with ileocolonic adenoviral PKCζ small interfering RNA resulted in a 68 ± 8% reduction in the GLP-1 response to rectal OA (P < 0.001). The results of these studies indicate that OA levels in the rat terminal gut after oral ingestion are sufficient to induce GLP-1 secretion and that PKCζ is necessary for the effects of OA on GLP-1 secretion in vivo. PKCζ may therefore serve as a novel therapeutic target to enhance GLP-1 levels in patients with type 2 diabetes.

Differential effects of hypothalamic long-chain fatty acid infusions on suppression of hepatic glucose production

Our objective was to investigate whether the direct bilateral infusion of the monounsaturated fatty acid (MUFA) oleic acid (OA) within the mediobasal hypothalamus (MBH) is sufficient to reproduce the effect of administration of OA (30 nmol) in the third cerebral ventricle, which inhibits glucose production (GP) in rats. We used the pancreatic basal insulin clamp technique (plasma insulin ∼20 mU/ml) in combination with tracer dilution methodology to compare the effect of MBH OA on GP to that of a saturated fatty acid (SFA), palmitic acid (PA), and a polyunsaturated fatty acid (PUFA), linoleic acid (LA). The MBH infusion of 200 but not 40 pmol of OA was sufficient to markedly inhibit GP (by 61% from 12.6 ± 0.6 to 5.1 ± 1.6 mg·kg(-1)·min(-1)) such that exogenous glucose had to be infused at the rate of 6.0 ± 1.2 mg·kg(-1)·min(-1) to prevent hypoglycemia. MBH infusion of PA also caused a significant decrease in GP, but only at a total dose of 4 nmol (GP 5.8 ± 1.6 mg·kg(-1)·min(-1)). Finally, MBH LA at a total dose of 0.2 and 4 nmol failed to modify GP compared with rats receiving MBH vehicle. Increased availability of OA within the MBH is sufficient to markedly inhibit GP. LA does not share the effect of OA, whereas PA can reproduce the potent effect of OA on GP, but only at a higher dose. It remains to be determined whether SFAs need to be converted to MUFAs to exert this effect or whether they activate a separate signaling pathway to inhibit GP.

Effects of the increase in neuronal fatty acids availability on food intake and satiety in mice

Neurons detect free fatty acids (FFAs) availability and use this nutritional status to modulate feeding and control body weight. The work is designed to characterize the impact on feeding behavior of either oleic acid (OA) administration (experiment 1) or the inhibition (experiment 2) of the enzyme carnitine palmitoyltransferase-1 (CPT-1). The structure of feeding behavior and satiation time course were examined through the behavioral satiety sequence (BSS) paradigm. Adult male mice were initially habituated to a palatable diet, then subjected to intracerebroventricular (i.c.v.) infusion of different doses of OA or the CPT-1 inhibitor ST1326. Food intake at different time points, duration, and frequencies of feeding and non-feeding-related behaviors were continuously monitored over 40 min and satiety development profiled according to BSS. Intra-i.c.v. infusion of oleic acid (300 nM) and ST1326 (50 and 75 pM) suppressed food intake. As indicated by the earlier leftward shifting of the normal transition from eating to resting, both strategies similarly accelerated the onset of satiety. The premature onset of satiety resulted in a dose-related fashion with 50 pM of ST1326 producing a marked premature onset than the lower dose. However, at the highest dose injected, the inhibition of CPT-1 disrupted the BSS profile. The increased neuronal availability of FFAs mediates a significant anorectic response which is mirrored by an early occurrence of satiety onset. Besides supporting the role of central nutrient sensing in feeding, the present data demonstrate that the modulation of satiety enhancement can produce appetite suppressant effects within narrow range of neuronal FFAs availability.

Effects of vasoactive cyclooxygenase products on shunt flow and extravascular lung water in acute lung injuries

Using 50 mongrel dogs with alveolar flooding produced by oleic acid administration, the possible roles of vasoactive cyclooxygenase products on intrapulmonary shunt flow (QS/QT) and extravascular lung water (ETVI) in acutely injured lungs were assessed. Suppressing cyclooxygenase activity with indomethacin administration diminished the concentrations of thromboxane (TX) B2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in arterial blood, resulting in a significant reduction in QS/QT. Furthermore, indomethacin completely suppressed the increase in ETVI. Inhibition of TXA2 generation by OKY-046 (thromboxane A2 synthase blocker) diminished the concentration of TXB2 while increasing that of 6-keto-PGF1 alpha in blood. Administration of either OKY-046 or synthetic prostacyclin (PGI2) markedly enhanced QS/QT, in association with an increase in ETVI. In conclusion, the potent vasodilator prostacyclin was considered to enhance shunt flow, leading to the augmentation of edema formation.

High oxygen breathing improves inhomogeneities of ventilation-perfusion distributions in acutely injured lungs

Using twenty-five mongrel dogs either with or without alveolar flooding induced by oleic acid administration, the effects of high oxygen breathing (60% O2) on ventilation--perfusion (VA/Q) distributions in the lungs were systematically investigated. VA/Q distributions were examined by multiple inert gas elimination technique, from which the VA/Q values describing mean positions of perfusion (Q) and ventilation (VA) distributions against the VA/Q axis were calculated (mean Q and mean VA). As the first measure of dispersion for VA/Q distribution, the log standard deviation was estimated (log SD (Q) and logSD (VA)). As the second measure of dispersion, the area under the curve, constructed by plotting inert gas arterial-to-alveolar partial pressure differences as a function of blood-gas partition coefficient, was calculated (aAD area). High oxygen breathing slightly enhanced the dispersion of VA/Q distributions in the normal dogs but decreased that in the dogs injured with oleic acid. Therefore, we concluded that high oxygen breathing worsened the inhomogenieties of VA/Q distributions in normal lungs but did improve those in acutely injured lungs.

Increased isoprostane levels in oleic acid-induced lung injury

The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2α). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

Estabilidade do modelo animal de lesão pulmonar aguda induzida por ácido oleico

To evaluate the stability of hemodynamic, respiratory and gas exchange variables in an animal model of oleic acid-induced acute lung injury. This was an experimental study involving 10 mongrel dogs. The variables were measured at baseline, as well as at 30, 60, 90 and 120 min after the administration of oleic acid. In order to analyze repeated measurements, linear and quadratic effects were tested. Mixed linear models with diversified variance and covariance structures were used, depending on the variable studied. We found that mean arterial blood pressure stabilized at 30 min, as did heart rate, pulmonary arterial pressure and pulmonary capillary pressure at 60 min. Respiratory rate, tidal volume, minute volume and respiratory work stabilized at 30 min. Regarding gas exchange variables, PaO2, PaO2/FiO2 ratio and pulmonary shunt fraction stabilized at 30 min. The remaining variables maintained a continuous rise or fall. This oleic acid-induced acute lung injury model is stable for some of the variables tested, although stabilization occurs at different times. The respiratory and gas exchange variables stabilized at 30 min, whereas the hemodynamic variables stabilized at 60 min.

Identification of intracellular carriers for the endocannabinoid anandamide

The endocannabinoid anandamide (arachidonoyl ethanolamide, AEA) is an uncharged neuromodulatory lipid that, similar to many neurotransmitters, is inactivated through its cellular uptake and subsequent catabolism. AEA is hydrolyzed by fatty acid amide hydrolase (FAAH), an enzyme localized on the endoplasmic reticulum. In contrast to most neuromodulators, the hydrophilic cytosol poses a diffusional barrier for the efficient delivery of AEA to its site of catabolism. Therefore, AEA likely traverses the cytosol with the assistance of an intracellular carrier that increases its solubility and rate of diffusion. To study this process, AEA uptake and hydrolysis were examined in COS-7 cells expressing FAAH restricted to the endoplasmic reticulum, mitochondria, or the Golgi apparatus. AEA hydrolysis was detectable at the earliest measurable time point (3 seconds), suggesting that COS-7 cells, normally devoid of an endocannabinoid system, possess an efficient cytosolic trafficking mechanism for AEA. Three fatty acid binding proteins (FABPs) known to be expressed in brain were examined as possible intracellular AEA carriers. AEA uptake and hydrolysis were significantly potentiated in N18TG2 neuroblastoma cells after overexpression of FABP5 or FABP7, but not FABP3. Similar results were observed in COS-7 cells stably expressing FAAH. Consistent with the roles of FABP as AEA carriers, administration of the competitive FABP ligand oleic acid or the selective non-lipid FABP inhibitor BMS309403 attenuated AEA uptake and hydrolysis by approximately 50% in N18TG2 and COS-7 cells. Taken together, FABPs represent the first proteins known to transport AEA from the plasma membrane to FAAH for inactivation and may therefore be novel pharmacological targets.

A novel and stable "two-hit" acute lung injury model induced by oleic acid in piglets

BackgroundChildren are susceptible to pulmonary injury, and acute lung injury (ALI) often results in a high mortality and financial cost in pediatric patients. Evidence has showed that oleic acid (OA) plays an important role in ALI. Therefore, it has special significance to study ALI in pediatric patients by using OA-induced animal models. Unfortunately, the animal model hs a high mortality due to hemodynamic instability. The aim of this study was to establish a novel hemodynamically stable OA-induced ALI model in piglets with two hits.Methods18 Chinese mini-piglets were randomized into three groups: group C (received saline-ethanol solution), group T (received OA-ethanol solution in routine administration manner) and group H (received OA-ethanol solution in two-hit manner). Hemodynamic and pulmonary function data were measured. Histopathological assessments were performed.ResultsTwo piglets in group T died of radical decline of systemic blood pressure. Group T showed more drastic hemodynamic changes than group H especially during the period of 5 to 30 minutes after OA administration. Both Group T and group H all produced severe lung injury, while group C had no significant pathologic changes. OA-induced hypotension might be caused by pulmonary hypertension rather than comprised left ventricular function.ConclusionOA leads to severe pulmonary hypertension which results in hemodynamic fluctuation in OA-induced ALI model. It is the first report on hemodynamic stable ALI animal model in piglets using two-hit method. The two-hit ALI animal model fulfils the ALI criteria and has the following characteristics: hemodynamic stability, stable damage to gas exchange and comparability with pediatric patients in body weight and corresponding age. The two-hit ALI animal model can be used to study the basic mechanism and the therapeutic strategies for pediatric ALI.

Your brain on fat: dietary-induced obesity impairs central nutrient sensing

the past decade has witnessed a rejuvenated interest in the ability of the central nervous system (CNS) to sense and respond to changes in nutrient availability. This interest has been driven in part by a conceptual framework where the CNS receives signals regarding nutrient availability that are

Comparisons of different mean airway pressure settings during high-frequency oscillation in inflammatory response to oleic acid-induced lung injury in rabbits

The present study was designed to examine effects of different mean airway pressure (MAP) settings during high-frequency oscillation (HFO) on oxygenation and inflammatory responses to acute lung injury (ALI) in rabbits. Anesthetized rabbits were mechanically ventilated with a conventional mechanical ventilation (CMV) mode (tidal volume 6 ml/kg, inspired oxygen fraction [F(Io2)] of 1.0, respiratory rate [RR] of 30/min, positive end-expiratory pressure [PEEP] of 5 cmH(2)O). ALI was induced by intravenous administration of oleic acid (0.08 ml/kg) and the animals were randomly allocated to the following three experimental groups; animals (n = 6) ventilated using the same mode of CMV, or animals ventilated with standard MAP (MAP 10 cmH(2)O, n = 7), and high MAP (15 cmH(2)O, n = 6) settings of HFO (Hz 15). The MAP settings were calculated by the inflation limb of the pressure-volume curve during CMV. HFO with a high MAP setting significantly improved the deteriorated oxygenation during oleic acid-induced ALI and reduced wet/dry ratios, neutrophil counts and interleukin-8 concentration in bronchoalveolar lavage fluid, compared to those parameters in CMV and standard MAP-HFO. These findings suggest that only high MAP setting during HFO could contribute to decreased lung inflammation as well as improved oxygenation during the development of ALI.

Effect of mild hypothermia on blood brain barrier disruption induced by oleic acid in rats

The blood-brain barrier (BBB) is essential for the normal function of the central nervous system. The pathological conditions induced by brain diseases including cerebral ischemia result in the alteration of BBB integrity. This alteration of BBB is relieved by mild hypothermia that has been regarded as an effective therapy for brain injury. Experimental fat embolism by intra-arterial administration of fatty acid induces reversible dysfunction of BBB and is considered as a beneficial method for the research on BBB disruption. However, the implication of hypothermia on the fatty acid-induced BBB disruption is not clear yet. In this study, we aim to investigate the effect of mild hypothermia on BBB disruption by comparing the changes of brain inflammation, free radical production, and matrix metalloproteinases (MMPs) caused by cerebral fatty acid infusion between normothermic (37°C) and hypothermic (33°C) groups. Oleic acid infusion into the carotid artery induced the increase of BBB permeability, which was inhibited by mild hypothermia. Neutrophils were infiltrated and intercellular adhesion molecule-1 (ICAM-1) expression was increased in the vascular structures in the affected brain tissue of normothermic rats at 24 hrs following oleic acid administration. Inducible nitric oxide synthase (iNOS) and nitro-tyrosine immunoreactivities were also observed in the normothermic group. The expression of matrix metalloproteinase (MMP)-2, 3, and 13 were upregulated predominantly in the oleic acid-treated brain of the normothermic rats. In mild hypothermic condition, neutrophil infiltration and ICAM-1 expression were attenuated, whereas the inductions of iNOS, nitrotyrosine and MMPs except MMP3 were not affected. Therefore, we suggest that mild hypothermia contributes to the protective effect on oleic acid-induced BBB damage via reducing neutrophil infiltration and brain inflammation.