triolein and Disease-Models--Animal

Most Staphylococcus aureus strains secrete two lipases SAL1 and SAL2 encoded by gehA and gehB. These two lipases differ with respect to their substrate specificity. Staphylococcus hyicus secretes another lipase, SHL, which is in contrast to S. aureus lipases Ca

Topics: Animals; Bacterial Proteins; Biofilms; Disease Models, Animal; Hemolysis; Host-Pathogen Interactions; Mice; Mutation; Phospholipases; Skin; Staphylococcal Infections; Staphylococcus; Triolein; Virulence

Fat embolism (FE) and the consequent FE syndrome occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FE syndrome is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system plays a significant role in the pathophysiology of FE because drugs interfering with the renin angiotensin system, captopril and losartan reduce the histopathologic pulmonary damage. The purpose of the current study was to determine if inhibition of renin by aliskiren, an FDA-approved drug for treating hypertension, would produce effective protection in the same model.. The FE model used intravenous injection of the neutral fat triolein in unanesthetized rats. Intraperitoneal injections of saline or aliskiren at either 50 or 100 mg/kg were performed 1 hour after FE induction via triolein. Rats were euthanized at 48 hours, and various histologic stains were used to examine the lungs.. (1) Fibrosis: rats treated with triolein showed significant fibrotic changes with increased collagen and myofibroblast activation (p < 0.0001 for both trichrome and α-smooth muscle actin staining). Aliskiren blocked this inflammatory and profibrotic process to a level indistinguishable from the controls (p < 0.0001 for both trichrome and α-smooth muscle actin staining). (2) Fat: rats treated with triolein showed a statistically significant increase in fat (p = 0.0006). Subsequent aliskiren administration at both doses reduced the size, distribution, and amount of fat droplets (low dose, p = 0.0095; high dose, p = 0.0028). (3) Vessel patency: the low dose of aliskiren blocked the reduction of lumen patency observed after triolein administration (p = 0.0058).. Aliskiren protected the lungs of rats from gross and histopathologic FE-induced pulmonary damage at 48 hours. Clinical implications include the use of aliskiren both prophylactically (before certain orthopedic procedures) and therapeutically (after severe trauma) to prevent the consequent severe pulmonary pathologic sequelae.

Topics: Amides; Animals; Disease Models, Animal; Embolism, Fat; Fumarates; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Triolein

Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation of the abdominal aorta and high rupture-related mortality rates. AAA is histologically characterized by oxidative stress, chronic inflammation, and extracellular matrix degradation in the vascular wall. We previously demonstrated that aortic hypoperfusion could cause the vascular inflammation and AAA formation. However, the preventive method for hypoperfusion-induced AAA remains unknown. In this study, we evaluated the effect of fish oil on AAA development using a hypoperfusion-induced AAA animal model. Dilation of the abdominal aorta in the fish oil administration group was smaller than in the control group. Collagen destruction and oxidative stress were suppressed in the fish oil administration group than in the control group. These results suggested that fish oil could prevent the development of AAA induced by hypoperfusion.

Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Collagen; Dietary Supplements; Disease Models, Animal; Endothelium, Vascular; Fish Oils; Male; Oxidative Stress; Perfusion; Proteolysis; Rats; Rats, Sprague-Dawley; Triolein

Cyclosporin A (CsA) is an immunosuppressant commonly used to prevent organ rejection but is associated with hyperlipidemia and an increased risk of cardiovascular disease. Although studies suggest that CsA-induced hyperlipidemia is mediated by inhibition of low-density lipoprotein receptor (LDLr)-mediated lipoprotein clearance, the data supporting this are inconclusive. We therefore sought to investigate the role of the LDLr in CsA-induced hyperlipidemia by using Ldlr-knockout mice (Ldlr(-/-)).. Ldlr(-/-) and wild-type (wt) C57Bl/6 mice were treated with 20 mg/kg per d CsA for 4 weeks. On a chow diet, CsA caused marked dyslipidemia in Ldlr(-/-) but not in wt mice. Hyperlipidemia was characterized by a prominent increase in plasma very low-density lipoprotein and intermediate-density lipoprotein/LDL with unchanged plasma high-density lipoprotein levels, thus mimicking the dyslipidemic profile observed in humans. Analysis of specific lipid species by liquid chromatography-tandem mass spectrometry suggested a predominant effect of CsA on increased very low-density lipoprotein-IDL/LDL lipoprotein number rather than composition. Mechanistic studies indicated that CsA did not alter hepatic lipoprotein production but did inhibit plasma clearance and hepatic uptake of [(14)C]cholesteryl oleate and glycerol tri[(3)H]oleate-double-labeled very low-density lipoprotein-like particles. Further studies showed that CsA inhibited plasma lipoprotein lipase activity and increased levels of apolipoprotein C-III and proprotein convertase subtilisin/kexin type 9.. We demonstrate that CsA does not cause hyperlipidemia via direct effects on the LDLr. Rather, LDLr deficiency plays an important permissive role for CsA-induced hyperlipidemia, which is associated with abnormal lipoprotein clearance, decreased lipoprotein lipase activity, and increased levels of apolipoprotein C-III and proprotein convertase subtilisin/kexin type 9. Enhancing LDLr and lipoprotein lipase activity and decreasing apolipoprotein C-III and proprotein convertase subtilisin/kexin type 9 levels may therefore provide attractive treatment targets for patients with hyperlipidemia receiving CsA.

Topics: Animals; Apolipoprotein C-III; Biomarkers; Cholesterol Esters; Cyclosporine; Disease Models, Animal; Female; Genetic Predisposition to Disease; Hyperlipidemias; Lipid Metabolism; Lipoprotein Lipase; Lipoproteins, HDL; Lipoproteins, IDL; Lipoproteins, VLDL; Liver; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Proprotein Convertase 9; Receptors, LDL; Time Factors; Triolein

Apolipoprotein A-V (apoA-V), a liver-synthesized apolipoprotein discovered in 2001, strongly modulates fasting plasma triglycerides (TG). Little is reported on the effect of apoA-V on postprandial plasma TG, an independent predictor for atherosclerosis. Overexpressing apoA-V in mice suppresses postprandial TG, but mechanisms focus on increased lipolysis or clearance of remnant particles. Unknown is whether apoA-V suppresses the absorption of dietary lipids by the gut. This study examines how apoA-V deficiency affects the steady-state absorption and lymphatic transport of dietary lipids in chow-fed mice. Using apoA-V knockout (KO, n = 8) and wild-type (WT, n = 8) lymph fistula mice, we analyzed the uptake and lymphatic transport of lipids during a continuous infusion of an emulsion containing [(3)H]triolein and [(14)C]cholesterol. ApoA-V KO mice showed a twofold increase in (3)H (P < 0.001) and a threefold increase in (14)C (P < 0.001) transport into the lymph compared with WT. The increased lymphatic transport was accompanied by a twofold reduction (P < 0.05) in mucosal (3)H, suggesting that apoA-V KO mice more rapidly secreted [(3)H]TG out of the mucosa into the lymph. ApoA-V KO mice also produced chylomicrons more rapidly than WT (P < 0.05), as measured by the transit time of [(14)C]oleic acid from the intestinal lumen to lymph. Interestingly, apoA-V KO mice produced a steadily increasing number of chylomicron particles over time, as measured by lymphatic apoB output. The data suggest that apoA-V suppresses the production of chylomicrons, playing a previously unknown role in lipid metabolism that may contribute to the postprandial hypertriglyceridemia associated with apoA-V deficiency.

Topics: Administration, Oral; Animals; Apolipoprotein A-V; Apolipoproteins; Cholesterol; Chylomicrons; Disease Models, Animal; Duodenum; Fistula; Intestinal Absorption; Lymph; Lymphatic Diseases; Lymphatic System; Male; Mice, Inbred C57BL; Mice, Knockout; Postprandial Period; Time Factors; Triolein; Up-Regulation

Pulmonary fat embolism (FE) in patients after major bone fracture and other trauma may lead to acute respiratory distress, but few clinical evidence of lung injury remains, and there is a dearth of histopathologic information after the initial recovery. We recently reported histologic changes in the lungs of a patient who died after cesarian delivery, which were similar to a rat model of FE. In this model, we found that despite an apparent full recovery, modest fibrotic damage persisted up to 6 weeks. We tested whether at that time, an additional insult could exacerbate the effects.. Triolein (0.2 mL intravenously administered) was given to 18 rats and saline to 18 controls. Six weeks later, each group received (intraperitoneal) lipopolysaccharide (LPS, 3 mg/kg; n = 9) or saline (n = 9). At necropsy 48 hours later, lungs and organs were harvested for study. Lung parenchymal, vascular, and bronchial damage was scored by two pathologists and by Image J analysis.. Animals given LPS after triolein showed reduced pulmonary arterial medial diameters compared with those that received LPS alone (p < 0.04). Lung small arterial patency (lumen) was reduced after triolein and even more after combined LPS and triolein (p = 0.018). Triolein increased fibrotic markers (trichrome and smooth muscle actin staining), and this was more severe after LPS. At 6 weeks, fat droplets remained in the lungs, localizing to the subpleural septa. These were smaller and more widespread after LPS.. This report describes an animal model to study exacerbation of lung histopathology induced by FE using a known pulmonary toxicant, LPS (a "second hit"). Vascular and fibrotic lung damage was more severe when LPS was given to rats 6 weeks after triolein compared with LPS alone. FE rendered the lungs extra sensitive to a second hit long after apparent clinical recovery. This experimental model of fat embolism provides useful informations for the treatment of patients suffering for similar conditions.

Topics: Animals; Disease Models, Animal; Embolism, Fat; Lipopolysaccharides; Male; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley; Triolein; Vascular Patency

The multiple prominent hypointense veins on susceptibility-weighted imaging (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. Venous side is the unknown area in the hemodynamics of brain infarction.. To evaluate the venous aspect in acute brain infarction through an animal study.. The acute infarction in cat brains was induced with a bolus infusion of 0.25 mL of triolein through one side of the common carotid artery. The magnetic resonance (MR) images, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were evaluated qualitatively and quantitatively. For qualitative assessment, the signal intensity of the serial MR images was evaluated. The presence or absence and the location with serial changes of infarction were identified on DWI and ADC map images. The presence or absence of prominent hypointense veins and the serial changes of cortical veins were also evaluated on SWI. Quantitative assessment was performed by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit times (MTT) of the lesions with those of the contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF, and MTT ratio were also evaluated.. Acute infarction in the first and second medial gyrus of lesion hemisphere was found by qualitative evaluation of DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The hemorrhage transformation and prominent hypointense veins were seen at 4 days on SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV and rCBF ratios on PWIs in the acute infarction of cat brain.. The prominent hypointense veins on SWI were seen in the half of the acute infarction at 4 days. The prominent hypointense veins on SWI may have good agreement with the increased MTT ratio.

Topics: Acute Disease; Animals; Brain; Brain Infarction; Cats; Contrast Media; Diffusion Magnetic Resonance Imaging; Disease Models, Animal; Echo-Planar Imaging; Gadolinium DTPA; Image Enhancement; Magnetic Resonance Angiography; Triolein

Hemorrhage is a finding of clinical fat embolism syndrome. The purpose of the present study was to evaluate the occurrence of hemorrhage in the cat brain by SW MR imaging after infusion of triolein as a bolus or as an emulsion into the carotid artery.. Twenty-two cats were divided into two groups according to the type of triolein infused: group 1 (n = 11) was infused with a 0.1 ml triolein bolus, group 2 (n = 11) with triolein emulsion containing 0.1 ml triolein in 20 ml saline. SW imaging was performed before and after triolein infusion (at 2 h, 1 and 4 days). After MR imaging on day 4, cats were sacrificed and brains were immediately excised. Hemorrhage was evaluated using H&E staining.. Hemorrhage was observed in eight cats in group 1, in no cats in group 2. Hemorrhage on SW images was found to correspond with light microscopy.. SW images revealed hemorrhage in lesion hemispheres infused with triolein bolus. However, there was no evidence of hemorrhage infused with emulsified triolein. Thus, the occurrence of hemorrhage in cerebral fat embolism may depend on fat status.

Topics: Animals; Cats; Cerebral Hemorrhage; Disease Models, Animal; Embolism, Fat; Fat Emulsions, Intravenous; Intracranial Embolism; Magnetic Resonance Imaging; Triolein

Lipid embolizations from retransfused shed blood during cardiac surgery have been shown to enter the circulation and end up in different organs. The purpose of this investigation was to evaluate differences in the kinetics and deposition between emulsified and non-emulsified lipid emboli in a porcine model.. Twelve animals were anesthetized and put on cardiopulmonary bypass. A shed-blood phantom (6 animals given emulsified and 6 given non-emulsified lipids) was produced from arterial blood, saline, and tritium-labeled triolein. The phantom was infused into the cardiopulmonary bypass circuit. Arterial and venous blood samples were taken at short intervals. Tissue samples were taken post-mortem from examined organs and prepared for scintillation counting. Levels of radioactivity were used to measure lipid emboli content in blood and tissue.. Emulsified lipid emboli generated a 5-fold higher embolic load in the arterial and a 12-fold higher in the venous circulation, compared with non-emulsified lipid emboli. Emulsified lipid micro emboli resulted in a 2-15-fold higher tissue deposition in investigated organs compared with non-emulsified lipid micro emboli.. This study shows that the state of emulsion significantly alter the kinetics and tissue deposition of lipid emboli. Emulsified lipid emboli give higher embolic load in the arterial and venous circulation, and higher tissue deposition versus non-emulsified lipid emboli. In both groups, the embolic load was higher in the arterial circulation than on the venous side.

Topics: Animals; Cardiopulmonary Bypass; Disease Models, Animal; Embolism, Fat; Lipids; Radiopharmaceuticals; Swine; Triolein; Tritium

Topics: Adrenoleukodystrophy; Animals; ATP Binding Cassette Transporter, Subfamily D, Member 1; ATP-Binding Cassette Transporters; Basal Ganglia; Cerebral Ventricles; Child; Delayed Diagnosis; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Disease Models, Animal; Disease Progression; DNA Mutational Analysis; Drug Combinations; Erucic Acids; Humans; Image Enhancement; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Nerve Fibers, Myelinated; Neurologic Examination; Phenotype; Sensitivity and Specificity; Triolein

Fat embolism syndrome is a serious complication observed after trauma, orthopedic surgery, and cardiac surgery. We investigated brain damage in relationship to temporal profiles of water channel aquaporin 4 (AQP4) and astrocyte response to fat embolism in rats.. Triolein (2 microl) was injected into the right internal carotid artery in rats. Neurological outcome (score: range, 0-5 = no deficit-dead), brain water content, histopathology, and immunohistochemistry for AQP4 and glial fibrillary acidic protein (GFAP) were evaluated at 2 h (2 h group, n = 12), 24 h (24 h group, n = 12), and 72 h (72 h group, n = 12) after triolein injection. Saline was injected in the control (C) group (n = 12).. Neurological deficit score (median score of 2) and brain water content (mean value, 86.2%) increased significantly at 2 h with no progressive increase over 72 h. Damaged tissues with shrunken and triangular-shaped neurons with vacuole degeneration in cytoplasm and halo formation were distributed mainly, but not exclusively, to the ipsilateral hemisphere and were associated with increase in infiltration of inflammatory cells during the time course. Increases in immunostaining for AQP4 and GFAP were observed in the peri-affected region but not in the core. Reactive astrocytes with hypertrophy and dendrite elongation were detected at 72 h in the peri-affected region.. The results suggest that brain damage with edema is induced very rapidly after triolein injection in association with increase in AQP4 expression and GFAP in the peri-affected region.

Topics: Animals; Aquaporin 4; Astrocytes; Brain; Disease Models, Animal; Embolism, Fat; Glial Fibrillary Acidic Protein; Male; Random Allocation; Rats; Rats, Wistar; Triolein

Pleurotus eryngii water extract (PEE), which showed the most significant inhibitory activity against pancreatic lipase in vitro among eight edible mushrooms, was investigated to determine the mechanism of its anti-lipase activity in vitro and its hypolipidemic effect in fat-loaded mice. The inhibitory effects of mushroom extracts on pancreatic lipase activity were examined using 4-methylumbelliferyl oleate (4-MUO) or trioleoylglycerol emulsified with lecithin, gum arabic or Triton X-100 as a substrate. For in vivo experiments, blood samples were taken after oral administration of corn oil and [(3)H]trioleoylglycerol with or without PEE to food-deprived mice. PEE inhibited hydrolysis of 4-MUO and trioleoylglycerol emulsified with lecithin or Triton X-100, but not that of trioleoylglycerol emulsified with gum arabic. PEE suppressed the elevations of plasma and chylomicron triacylglycerol levels after oral administration of corn oil, but had no effect on lipoprotein lipase activity. [(3)H]Trioleoylglycerol absorption was also decreased by administration of PEE. The results of in vitro studies suggest that PEE may prevent interactions between lipid emulsions and pancreatic lipase. The hypolipidemic effect of PEE in fat-loaded mice may be due to low absorption of fat caused by the inhibition of pancreatic lipase.

Topics: Animals; Biological Products; Chylomicrons; Corn Oil; Dietary Fats; Disease Models, Animal; Emulsions; Food Deprivation; Hydrolysis; Hymecromone; Hyperlipidemias; Hypolipidemic Agents; Lipase; Lipoprotein Lipase; Male; Mice; Mice, Inbred ICR; Obesity; Phytotherapy; Plant Extracts; Pleurotus; Triglycerides; Triolein

Postprandial hypertriglyceridemia (PHTG) has been shown repeatedly to be associated with metabolic syndrome and atherosclerotic cardiovascular diseases. We have recently reported that ezetimibe inhibits PHTG in patients with type IIb hyperlipidemia. Ezetimibe was also reported to atten-uate PHTG in combination with low-dose statins in patients with obesity or metabolic syndrome. We reported CD36-deficient (CD36KO) mice as a new model for PHTG, in which the synthesis of chylomicron (CM) in the small intestines is enhanced. In the current study, we investigated the effect of ezetimibe on PHTG in this mouse model of metabolic syndrome.. Wild-type (WT) mice fed a western diet, and CD36KO mice fed a normal chow diet, respectively, were treated for 3 weeks with and without ezetimibe, followed by an evaluation of triglyceride (TG) concentrations by enzymatic method and by high performance liquid chromatogra-phy (HPLC) as well as those of and apolipoprotein (Apo) B-48 in plasma and intestinal lymph after oral fat loading with olive oil. Intestinal mucosa was also harvested to evaluate the transcriptional regulation of the genes involved in the intestinal production of ApoB-containing lipoproteins.. Ezetimibe dramatically reduced PHTG in both WT and CD36KO mice. HPLC analysis of plasma showed that the decrease in TG content in CM and CM remnants-sized particles contributed to this suppression, suggesting that CM production in the small intestines might be reduced after ezetimibe treatment. Intestinal lymph was collected after oral fat loading in ezetimibe-treated and non-treated mice. Both TG content and ApoB-48 mass were decreased in ezetimibe-treated mice. The quantitative RT-PCR of intestinal mucosa showed down-regulation of the mRNA expression of FATP4 and ApoB in both groups along with FABP2, DGAT1, DGAT2 and SCD1 in WT mice at postprandial state after ezetimibe treatment.. Ezetimibe alone reduces PHTG by blocking both the absorption of cholesterol and the intracellular trafficking and metabolism of long-chain fatty acids in enterocytes, resulting in the reduction of the formation of ApoB-48 which is necessary for the ApoB48-containing lipoprotein production in the small intestines.

Topics: Animals; Anticholesteremic Agents; Apolipoprotein B-48; Azetidines; Base Sequence; CD36 Antigens; Chylomicrons; Disease Models, Animal; DNA Primers; Ezetimibe; Fatty Acid Transport Proteins; Fatty Acid-Binding Proteins; Hypertriglyceridemia; Intestinal Absorption; Lipoproteins, VLDL; Lymph; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Postprandial Period; RNA, Messenger; Triglycerides; Triolein

Triolein emulsion is under investigation for supplemental use to open the blood-brain barrier during chemotherapy. The effects of triolein emulsion on the blood-retinal barrier (BRB) were investigated.. Fat emboli were induced in 20 cats by injecting triolein emulsion through the carotid artery. At 30 min, 4, 12 and 48 h after embolization, electroretinography (ERG) and fluorescein angiography (FA) were performed. The eyeballs were enucleated for transmission electron-microscopic study.. FA revealed multiple leaking points at 30 min, and prominent diffuse leakage at 4 h when scotopic b-waves showed significant differences between the study and control eyes. Multiple focal disruptions of the blood vessels by fat vacuoles were found with electron microscopic study. ERG improved at 12 and 48 h, and the BRB appeared to be recovered on FA and electron microscopic studies after 48 h.. An experimental embolism with triolein emulsion disrupted the blood retinal barrier. Delayed maximal change was observed, and it could be implicated in the latent interval of clinical fat embolism syndrome.

Topics: Animals; Blood-Retinal Barrier; Capillary Permeability; Cats; Dark Adaptation; Disease Models, Animal; Electron Microscope Tomography; Electroretinography; Embolism, Fat; Emulsions; Eye Diseases; Fluorescein Angiography; Time Factors; Triolein

To study the kinetics of lipid micro-emboli during cardiac surgery.. Eleven pigs were studied. Seven of these were put on extracorporeal circulation. A shed blood phantom consisted of blood, saline and radioactive triolein was added to the circuit. Both venous and arterial blood samples were taken at short intervals. Four animals were used to study renal kinetics without extracorporeal circulation. The same kind of shed blood phantom was infused into the ascending aorta. Samples were taken from the renal artery and vein. All samples were analyzed for radioactivity by scintillation counting.. A median 130-fold increase in radioactivity was seen in the blood and was quickly eliminated. Systemic first-pass wedging was found to be 62%. The first-pass elimination in the kidney was 77%. No radioactivity was found in urine.. This study shows that the turnover of lipid micro-emboli is fast, and that the majority of the emboli are trapped on their first passage through the capillary system. No evidence was found of a renal excretion of these lipid emboli.

Topics: Animals; Aorta; Blood Pressure; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Disease Models, Animal; Embolism, Fat; Kidney; Phantoms, Imaging; Radiopharmaceuticals; Regional Blood Flow; Renal Circulation; Scintillation Counting; Swine; Triolein; Tritium

In experimental studies, embolization of the cerebral hemisphere with triolein emulsion has revealed reversible magnetic resonance imaging (MRI) findings in the subacute stage.. To investigate the changes in the major metabolites, by proton magnetic resonance spectroscopy (MRS), in a cerebral fat embolism induced by a triolein emulsion.. The internal carotid arteries of 19 cats were injected with a triolein emulsion, and multivoxel MRS was performed 30 min, 1 day, and 7 days later. In the control group, six cats were injected with normal saline. The MR spectra were evaluated for N-acetyl aspartate (NAA), creatine (Cr), and choline (Cho), along with the presence of lipid and lactate. Semiquantitative analyses of NAA/Cr, Cho/Cr, NAA/Cho, and lipid/Cr ratios compared the median values of the ipsilateral metabolite ratios with those of the contralateral side and in the control group for each point in time.. The NAA/Cr, Cho/Cr, and NAA/Cho ratios in the ipsilateral cerebral hemisphere of the embolized group after 30 min, 1 day, and 7days were not significantly different from the contralateral hemisphere of the embolized and control groups (P>0.05). The lipid/Cr ratio in the ipsilateral cerebral hemisphere of the embolized group was significantly higher when compared with the control group (P=0.012 at 30 min, P=0.001 on day 1, and P=0.018 on day 7).. Cerebral fat embolism induced by a triolein emulsion resulted in no significant change in the major metabolites of the brain in the acute stage, except for an elevated lipid/Cr ratio, which suggests the absence of any significant hypoxic-ischemic changes in the lesions embolized using a fat emulsion.

Topics: Animals; Aspartic Acid; Brain; Cats; Choline; Contrast Media; Creatine; Disease Models, Animal; Disease Progression; Embolism, Fat; Follow-Up Studies; Gadolinium DTPA; Image Enhancement; Intracranial Embolism; Lactic Acid; Lipid Metabolism; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Sodium Chloride; Triolein

Lipid microemboli found in shed blood during cardiac surgery have been shown to block capillaries of the brain postoperatively. In this study, the distribution of lipid microemboli in different regions of the brain and other organs was examined. A novel porcine model using radioactive lipid particles was used.. Ten animals (2 controls and 8 cases) were anesthetized and put on cardiopulmonary bypass. A shed-blood phantom was produced from arterial blood, saline, and tritium-labeled triolein. The phantom was infused into the cardiopulmonary bypass circuit. Tissue samples were taken postmortem from examined organs and prepared for scintillation counting. Levels of radioactivity were used as a measure of the uptake of lipid microemboli.. High levels of radioactivity were found in kidney and spleen (5 to 10 times higher than in the other organs investigated). In the brain, radioactivity was found in all regions examined. The gray matter of cerebrum showed the highest level of the regions examined.. This study shows that embolization of lipids is not a phenomenon restricted to the brain, but affected all the organs examined. The high levels found in the kidneys, and the relatively high levels in the gray matter of the cerebrum further legitimize the debate on the impact lipid microemboli has on postoperative kidney and cognitive dysfunction.

Topics: Animals; Brain; Cardiopulmonary Bypass; Disease Models, Animal; Embolism, Fat; Kidney; Lipid Metabolism; Spleen; Swine; Tissue Distribution; Triolein; Tritium

The purpose of this study was to evaluate the cerebral hemodynamic change in the hyperacute stage of cerebral fat embolism induced by triolein emulsion, by using MR perfusion imaging in cat brains.. By using the femoral arterial approach, the internal carotid arteries of 14 cats were infused with an emulsion of triolein 0.05 mL. T2-weighted (T2WI), diffusion-weighted (DWI), apparent diffusion coefficient (ADC) map, perfusion-weighted (PWI), and gadolinium-enhanced T1-weighted (Gd-T1WI) images were obtained serially at 30 minutes and 2, 4, and 6 hours after infusion. The MR images were evaluated qualitatively and quantitatively. Qualitative evaluation was performed by assessing the signal intensity of the serial MR images. Quantitative assessment was performed by comparing the signal-intensity ratio (SIR) of the lesions to the contralateral normal side calculated on T2WIs, Gd-T1WIs, DWIs, and ADC maps at each acquisition time and by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (CBF), and mean transit times (MTT) of the lesions to the contralateral normal side calculated on PWI.. In the qualitative evaluation of the MR images, the lesions showed hyperintensity on T2WIs, enhancement on the Gd-T1WIs, and isointensity on DWIs and the ADC maps. In the quantitative studies, SIRs on the Gd-T1WIs, DWIs, and ADC maps peaked at 2 hours after infusion. The SIRs on the T2WIs peaked at 4 hours after infusion and decreased thereafter. On PWIs, the rCBV, rCBF, and MTT of the lesion showed no significant difference from the contralateral normal side (P = .09, .30, and .13, respectively) and showed no significant change of time course (P = .17, .31, and .66, respectively).. The embolized lesions induced by triolein emulsion showed no significant difference in cerebral hemodynamic parameters from those on the contralateral normal side. The result may suggest that consideration of the hemodynamic factor of embolized lesions is not necessary in further studies of the blood-brain barrier with triolein emulsion.

Topics: Acute Disease; Animals; Blood Flow Velocity; Blood Volume; Cats; Cerebral Cortex; Contrast Media; Diffusion Magnetic Resonance Imaging; Disease Models, Animal; Dominance, Cerebral; Embolism, Fat; Fat Emulsions, Intravenous; Hemodynamics; Image Enhancement; Intracranial Embolism; Magnetic Resonance Angiography; Regional Blood Flow; Triolein

Chronic fish oil consumption is associated with reduced postprandial lipaemia, but the mechanism behind this effect is not fully understood. We studied whether lipid absorption might be altered in rats fed fish oil.. Male Wistar rats were fed fish oil enriched chow (n = 6) or control oil enriched chow (n = 6). After 4 weeks, 61 mg 3H-triolein was instilled into duodenal tied-off loops. Intestinal segments were removed after 15, 30, 45, 60 and 90 min. Enterocytes were then isolated by calcium chelation and quantified by DNA determination. Non-absorbed 3H-lipid and 3H-lipid contents of enterocytes were determined by liquid scintillation counting. Two other groups of rats (2 x 6) fed the experimental diets were given an oral fat load and fasting and postprandial blood samples were taken.. The accumulation of 3H-lipids in enterocytes was higher in rats fed fish oil than in controls (area under the 3H-lipid time curve: 1041.3 versus 670.3 nmol oleic acid x min/microg DNA, P < 0.05). Separation of lipids showed that an accumulation of triglycerides and free fatty acids occurred in rats fed fish oil. The amount of non-absorbed 3H-lipid tended to be higher in the fish oil fed rats (P > 0.1). It was confirmed that the fish oil enriched chow caused lower postprandial lipaemia (34% reduction in serum triglyceride concentrations, P < 0.05).. Attenuated postprandial lipaemia following fish oil feeding is explained, at least partly, by a transient lipid accumulation in enterocytes which may result in a delayed triglyceride efflux from the enterocytes into the circulation.

Topics: Animals; Cod Liver Oil; Disease Models, Animal; Enterocytes; Intestinal Absorption; Male; Postprandial Period; Rats; Rats, Wistar; Time Factors; Triglycerides; Triolein; Tritium

Pathophysiologic mechanisms of the fat embolism syndrome are poorly understood. Neutrophils are thought to play a role in the development of many forms of acute lung injury. The objective of this study was to examine the role of intrapulmonary neutrophils in lung injury resulting from fat infusion.. Triolein (0.08 mL/kg) was infused into isolated rabbit lungs perfused with Krebs-Henseleit buffer. Pulmonary arterial pressure was monitored, and pulmonary vascular resistance and microvascular permeability (Kf) were measured at baseline and 60 minutes after triolein infusion.. Triolein produced increases in pulmonary arterial pressure, pulmonary vascular resistance, and Kf. Neutrophil depletion or inhibition of neutrophil elastase prevented the increase in Kf after triolein, and catalase partially blocked this Kf increase.. These results suggest that activated intrapulmonary neutrophils play a major role in developing triolein-induced lung injury, intrapulmonary neutrophils act chiefly via neutrophil elastase release, and reactive oxygen species are involved in the lung injury.

Topics: Animals; Blood Pressure; Capillary Permeability; Disease Models, Animal; Embolism, Fat; Hemodynamics; Lung; Microcirculation; Neutrophils; Peroxidase; Rabbits; Respiratory Distress Syndrome; Triolein; Vascular Resistance

The Drosophila melanogaster recessive mutant bubblegum (bgm) exhibits adult neurodegeneration, with marked dilation of photoreceptor axons. The bubblegum mutant shows elevated levels of very long chain fatty acids (VLCFAs), as seen in the human disease adrenoleukodystrophy (ALD). In ALD, the excess can be lowered by dietary treatment with "Lorenzo's oil," a mixture of unsaturated fatty acids. Feeding the fly mutant one of the components, glyceryl trioleate oil, blocked the accumulation of excess VLCFAs as well as development of the pathology. Mutant flies thus provide a potential model system for studying mechanisms of neurodegenerative disease and screening drugs for treatment.

Topics: Adrenoleukodystrophy; Amino Acid Sequence; Animals; Coenzyme A Ligases; Disease Models, Animal; Drosophila melanogaster; Drosophila Proteins; Drug Combinations; Erucic Acids; Fatty Acids; Female; Genes, Insect; Genes, Recessive; Male; Molecular Sequence Data; Mutation; Nerve Degeneration; Photoreceptor Cells, Invertebrate; Repressor Proteins; Saccharomyces cerevisiae Proteins; Sex Characteristics; Triolein

Topics: Adrenoleukodystrophy; Animals; Blood-Brain Barrier; Coenzyme A Ligases; Disease Models, Animal; Drosophila; Drosophila Proteins; Drug Combinations; Erucic Acids; Fatty Acids; Genes, Insect; Humans; Mutation; Triolein

This study was designed to determine the distribution of fat which reaches the brain by the internal carotid artery, and the consequent alterations in the blood brain barrier, in a rat model of cerebral arterial fat embolism. The distribution of the blood flow in this model was determined by the injection of radiolabelled microspheres. Over 44% were trapped in the brain, 43% in the extracerebral tissues of the head and neck, and 7% in the lungs. Over 30% of radiolabelled triolein was present within the brain 30 min after injection, and 4% still remained after 17 days. Approximately 25% of the triolein which went to the brain moved through the cerebral vessels and left within the first 15 min. The majority of the triolein distributed to the ipsilateral cerebral hemisphere, with significantly less to the contralateral cerebral hemisphere, brain stem and cerebellum. The blood brain barrier opened, as measured by uptake of 99mTc, within the first 15 min and remained open for at least 3 days. A significant percentage of fat reaching the brain persists for days, and causes rapid and long-lasting damage to the blood brain barrier.

Topics: Animals; Blood-Brain Barrier; Carotid Artery, Internal; Disease Models, Animal; Embolism, Fat; Fats; Injections, Intra-Arterial; Intracranial Embolism and Thrombosis; Microspheres; Rats; Rats, Wistar; Tissue Distribution; Triolein

We describe a procedure for monitoring changes in canine prostatic size. Metal beads were sutured to the surface of the prostate and the interbead distances were derived from two X-rays taken at right angles. Prostatic hyperplasia was induced by castration and injection of 5 alpha-androstane-3 alpha, 17 beta-diol and 17 beta-estradiol. Prostatic regression was caused by castration without further treatment. Although growth of the prostate was nonuniform, changes in prostatic volume were shown to be related to the third power of the distance between appropriate beads. This monitoring technique can be repeated every 2nd day if necessary, and thus has an advantage over procedures that require repeated laparotomies. Significant increases in prostatic volume could be detected within 5 days after steroid injection.

Topics: Androstenediol; Animals; Biometry; Disease Models, Animal; Dogs; Drug Administration Schedule; Estradiol; Laparotomy; Male; Organ Size; Prostate; Prostatic Hyperplasia; Triolein

The intravenous injection of triolein in the rabbit, besides general consequences in some viscera (functional ischemic necrosis of the right ventricle, systemic cerebral and kidney embolisms), induces in the lung non specific reactions similar to those observed after other pulmonary agressions. Yet, some peculiarities are observed only in this experimental model: severe and persistent septal oedema due to early endothelial changes; intensive inflammatory response with numerous macrophages. On the other hand, except in zones with epithelio-conjonctive repair process of necrotic foci, the epithelial reaction reduced to a temporary predominance of type 2-pneumonocytes, remains of low intensity.

Topics: Animals; Disease Models, Animal; Edema; Embolism, Fat; Inflammation; Kidney Glomerulus; Lung; Rabbits; Time Factors; Triolein

Topics: Animals; Carbon Radioisotopes; Disease Models, Animal; Embolism, Fat; Glycosaminoglycans; Heparin; Heparitin Sulfate; Injections, Intravenous; Lipase; Lung; Mice; Pulmonary Embolism; Triolein

In considering intravenous injection of lipid as a model of fat embolism, contamination is frequent and purity must be demonstrated. Musculoskeletal trauma causes mild arterial hypoxia whereas intravenous pure triolein 0.1 mg/kg does not. Trauma produced a leukocytosis and elevated sedimentation rate not found in the lipid injected dogs. Evidence for consumptive coagulopathy was found in the trauma group but only a mild thrombocytopenia resulted from intravenous triolein. The traumatized dogs demonstrated an increase in the triglyceride level, an increase in the cholesterol phopholipid ratio and an increase in the cholesterol containing beta and prebeta lipoprotein fractions, all of which could lead to formation of pulmonary fat emboli containing cholesterol.

Topics: Animals; Cholesterol; Consummatory Behavior; Disease Models, Animal; Dogs; Embolism, Fat; Hindlimb; Leukocytosis; Lipid Metabolism; Thrombocytopenia; Triglycerides; Triolein; Wounds and Injuries

Topics: Animals; Centrifugation; Chromatography, Thin Layer; Disease Models, Animal; Dogs; Embolism, Fat; Fatty Acids, Nonesterified; Glycerides; Iodine Radioisotopes; Lung; Male; Perfusion; Phospholipids; Pulmonary Embolism; Sterols; Triglycerides; Triolein

Topics: Animals; Bile Acids and Salts; Blood Proteins; Cholesterol; Diarrhea; Disease Models, Animal; Feces; Female; Ileum; Iodine Radioisotopes; Malabsorption Syndromes; Male; Potassium; Rabbits; Sodium; Triglycerides; Triolein

Male rats were made deficient in essential fatty acids by feeding them a fat-free diet supplemented with 4% tripalmitin for 8-12 wk from the time of weaning. After feeding 0.5 ml of [(14)C]triolein or [(3)H]oleic acid, 72-hr stool recoveries of radioactivity were significantly greater in deficient rats than in chow-fed controls. Essential fatty acid deficiency did not reduce the absorptive capacities for triolein or for a medium-chain fat, trioctanoin, measured after 3 and 2 hr of maximal-rate duodenal infusion. In everted jejunal slices from essential fatty acid-deficient rats, uptake of micellar [(14)C]oleic acid at 0-1 degrees C was similar to that of controls, but the rate of incorporation of fatty acid into triglyceride after rewarming to 37 degrees C was significantly reduced. The specific activities of the microsomal esterifying enzymes, acyl CoA:monoglyceride acyltransferase and fatty acid CoA ligase in jejunal mucosa were 30% lower in essential fatty acid-deficient rats. However, the total microsomal enzyme activity adjusted to constant weight did not differ significantly in deficient rats compared with controls. After intraduodenal perfusion of triolein, accumulation of lipid in the intestinal wall was increased in the deficient rats. Because over 90% of the absorbed mucosal lipid was present as triglyceride, essential fatty acid deficiency appears to affect the synthesis or release of chylomicron lipid from the intestine. Analysis of regions of intestine showed that this delay in transport was most marked in the midportion of the small intestine.

Topics: Acyltransferases; Animals; Biological Transport; Carbon Isotopes; Chromatography, Gas; Chromatography, Thin Layer; Coenzyme A Ligases; Deficiency Diseases; Dietary Fats; Disease Models, Animal; Fatty Acids; Fatty Acids, Essential; Feces; Glycerides; Intestinal Mucosa; Jejunum; Kinetics; Lipids; Malabsorption Syndromes; Male; Oleic Acids; Rats; Time Factors; Triglycerides; Triolein; Tritium

Topics: Animals; Biopsy; Blood Coagulation Tests; Bone and Bones; Collagen; Disease Models, Animal; Disseminated Intravascular Coagulation; Dogs; Embolism, Fat; Exudates and Transudates; Fibrin; Fractures, Bone; Hindlimb; Hypoxia; Leukocytes; Lung; Microscopy; Microscopy, Electron; Muscles; Musculoskeletal System; Pulmonary Edema; Pulmonary Embolism; Triolein

Topics: Animals; Blood Coagulation; Disease Models, Animal; Disseminated Intravascular Coagulation; Embolism, Fat; Female; Male; Pulmonary Embolism; Rabbits; Triolein