Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to resolve the issue of whether there is a loss of fatty acid binding protein (H-FABP) from heart during ischemia and reperfusion, and to further examine the role of this protein in ischemic-reperfusion injury, the amount of H-FABP of heart was monitored during ischemia and reperfusion. Excellent correlation was obtained between the loss of H-FABP from heart and its appearance in the perfusate buffer when examined by Western blot using the specific antibody to H-FABP. Further quantitation was achieved by densitometric scanning of the Western blot and rocket electrophoresis. Maximum release of H-FABP was observed within 20 min of reperfusion, the total release being 10% of the H-FABP content of the heart. Mepacrine, a membrane stabilizer and a phospholipase inhibitor, reduced the release of H-FABP from the heart and prevented the accumulation of nonesterified fatty acids in the tissue during ischemia and reperfusion. In view of the established role of H-FABP in the preservation of membrane phospholipids by either scavenging free radicals during ischemia and reperfusion or by modulating the enzymes of phospholipid synthesis, it seems likely that the loss of H-FABP may have some contribution towards the ischemic-reperfusion injury.
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PMID:Release of fatty acid-binding protein from ischemic-reperfused rat heart and its prevention by mepacrine. 200 86

In this study, fatty acid binding protein was used to protect an ischemic heart from reperfusion injury. Isolated rat heart was preperfused in the presence of 1.4 microM liposome-bound fatty acid binding protein for 15 minutes, followed by 30 minutes of ischemia and 30 minutes of reperfusion. Our results indicated better preservation of myocardial high-energy phosphate compounds (including ATP and creatine phosphate), reduced creatine kinase and lactate dehydrogenase release from the heart, and improved coronary flow in hearts treated with fatty acid binding protein compared with untreated controls. Fatty acid binding protein enhanced reacylation of arachidonic acid into phospholipids, thereby preserving membrane phospholipids and reducing free fatty acid contents during ischemia and reperfusion. In addition, fatty acid binding protein-bound long-chain free fatty acids and their thioesters as well as carnitine esters were increased in the cytosolic compartment of the heart. These results suggest that fatty acid binding protein may be used as a possible therapeutic agent to improve myocardial function during reperfusion of ischemic heart.
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PMID:Protective role of intracoronary fatty acid binding protein in ischemic and reperfused myocardium. 201 4

Accumulation of free fatty acids and their esters resulting from the degradation of membrane phospholipids is one of the major causes for the myocardial dysfunction during ischemia and reperfusion. In this communication, we have studied the possible physiological role played by fatty acid binding protein (FABP) in stimulating key enzymes involved in phospholipid biosynthesis. Purified rat heart FABP bound a maximum of either 2 mol of [1- 14C]palmitoyl coenzyme A (CoA), oleoyl CoA, or oleic acid per mol of FABP as observed by Scatchard analysis. FABP caused a threefold increase in the incorporation of [1- 14C]palmitoyl CoA into phosphatidic acid as compared to only a 1.5-fold increase by bovine serum albumin (BSA). Myocardial FABP also enhanced acyl CoA monoacylglycerophosphorylcholine acyl transferase minimally at a substrate concentration (greater than 200 microM), the activity of this enzyme was enhanced 4.5- and 2-fold by FABP and BSA, respectively. The maximum stimulation of the enzyme activity took place at the fatty acyl CoA concentration where inhibition of the enzyme activity is usually observed due to the surfactive property of acyl CoAs. These results thus indicate that under abnormal pathophysiological conditions such as ischemia, when acyl CoA concentration increases, FABP may protect acyl CoA monoacylglycerophosphorylcholine acyl transferase as well as stimulate glycerophosphate acyl transferase to limit the loss of membrane phospholipids, suggesting a possible role of FABP in phospholipid biosynthesis.
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PMID:Possible physiological role of myocardial fatty acid binding protein in phospholipid biosynthesis. 251 96

Recent investigations have indicated the presence of a fatty acid binding protein (FABP) in mammalian heart. This protein binds free fatty acids and their esters with high affinity, however, its physiological role remains unknown. Since FABP constitutes a significant amount of cystolic protein, it is likely that it would be a target for free radical attack. To test this hypothesis, FABP was examined for scavenging against free radicals such as the superoxide anion (O2-), hydroxyl radical (OH.) and hypochlorite radical (OCl.) which may be present in an ischemic reperfused heart. Our results suggest that FABP scavenges O2-, OH. and OCl. as indicated by the FABP inhibition of O2- -dependent reduction of cytochrome c, OH.-dependent hydroxybenzoic acid formation and OCl.-mediated chemiluminescence response. FABP was found to be a more potent scavenger of these free radicals compared to bovine serum albumin. Furthermore, FABP was more effective in scavenging OH. than O2-, and inhibited OH. mediated lipid peroxidation process. These results indicate that FABP can scavenge free radicals which may be present in an ischemic/reperfused heart and, thus, may play a significant physiological role in the heart during ischemia and reperfusion.
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PMID:Free radical scavenging by myocardial fatty acid binding protein. 255 51

The present study was performed to monitor the effect of low-flow ischemia and reperfusion on changes in the protein permeability of the cardiomyocyte cell membrane and the endothelial cell layer for two cytoplasmic proteins, i.e., fatty acid binding protein (FABP) and lactate dehydrogenase (LDH), which differ appreciably with respect to physicochemical characteristics. To accomplish this, isolated rat hearts were Langendorff perfused with separate collection of vascular and interstitial effluents. Control hearts were perfused normoxically for 300 min, whereas experimental hearts were subjected to 60 min normoxia (N), 180 min low-flow ischemia (I), and finally 60 min normoxic reperfusion (R). Protein release was measured in 15 min interval fractions. During the first 240 min of perfusion 0.2% of total tissue FABP and 1.1% of total tissue LDH were detected in the effluents in both groups. Moreover, in each case 80% of released FABP and LDH was found in the interstitial effluent. During R, following I in the experimental group, appreciable amounts of both proteins were released (2.2 and 5.1% of total tissue contents for FABP and LDH, respectively). During this period the percentage of protein released in the vascular effluent increased significantly for both proteins. It is concluded that the combination of low-flow ischemia and reperfusion increases the protein permeability of both the cardiomyocyte cell membrane and the endothelial barrier. Since the release patterns of FABP and LDH with respect to time were similar during the entire perfusion protocol, it is tempting to state that protein release from tissue is a nonspecific effect of a noxious intervention.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of fatty acid binding protein and lactate dehydrogenase from isolated rat heart during normoxia, low-flow ischemia, and reperfusion. 818 Aug 91

Necrotizing enterocolitis (NEC) continues to produce significant morbidity and mortality, due in part to the difficulty in detecting its initial manifestations at a stage when compromised intestine may potentially be salvaged. We have previously reported our findings that intestinal fatty acid binding protein (I-FABP) is a sensitive biochemical marker for early intestinal mucosal injury due to mesenteric ischemia. In this study we evaluated the potential of serum I-FABP as a marker for incipient NEC in a nonischemic model of NEC in the rat. Intraluminal instillation of a solution of casein (10 mg/mL) and calcium gluconate (50 mg/mL) in saline acidified to pH 4.0 with propionic acid resulted in a rapid and prolonged increase in serum I-FABP from a baseline of < or = 4.0 ng/mL to 171 +/- 40 ng/mL. Instillation of the same electrolyte solution with either casein or propionic acid alone resulted in a less dramatic elevation of serum I-FABP to 19 +/- 4 ng/mL and 76 +/- 30 ng/mL, respectively. In both cases baseline values of < or = 4.0 ng/mL were reached within 60 minutes. In control animals, which received saline alone, serum I-FABP was undetectable throughout the experiment. Simultaneously, we found that serum hexosaminidase, a putative biochemical marker for intestinal ischemia and NEC, was unchanged in all groups. Light microscopy of the intestinal specimens obtained three hours after instillation of casein and organic acid demonstrated superficial villus necrosis and villus blunting, but no areas of transmural necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevation of circulating intestinal fatty acid binding protein in a luminal contents-initiated model of NEC. 846 48

Serum unbound free fatty acid levels (FFAu) were measured in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) using the fluorescent probe acrylodan intestinal fatty acid binding protein (ADIFAB). These are the first measurements of FFAu, under nonphysiologic conditions. In these studies, FFAu, levels were determined in 22 patients 5 minutes before and 30 minutes after the procedure. Post-PTCA FFAu, levels were higher than pre-PTCA levels in all patients. The average post-PTCA level for all patients was 103 nM, about 14-fold higher than the 7.5 nM value observed in healthy subjects. Although all patients exhibited elevated FFAu levels after PTCA, ischemic ST-segment changes were observed in only 11 of these patients. The average post-PTCA FFAu levels for patients with significant ST-segment changes (123 nM) were significantly higher than those in patients who did not exhibit such changes (47 nM). Average FFAu (22 nM) levels before the procedure were elevated in the patient population relative to healthy subjects and these values correlated positively with post-PTCA levels. These results suggest that increased serum FFAu levels reflect angioplasty-induced ischemia and that FFAu levels may provide a more sensitive measure of ischemia than electrocardiographic measurements. Moreover, because 30% of these patients had post-PTCA FFAu concentrations exceeding those found to alter in vitro cell function, the increased serum FFAu levels that accompany ischemia may be deleterious for myocardial function.
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PMID:Increases in serum unbound free fatty acid levels following coronary angioplasty. 897 Apr 5

In order to obtain baseline information on the secretory function of normal rat bowel for our work on intestinal graft ischemia, we studied several biochemical parameters in rat Thiry-Vella fistulas (TVF). TVFs were created in 200-g male Lewis rats (n = 11) using the 25-cm segment of jejunum normally used as a graft in our intestinal transplant model. The stomas were matured primarily and the animals were allowed to recover. The TVFs were flushed at 0, 6, and 24 h and then daily for up to 21 days with 12 mL normal saline solution. The effluent was collected and analyzed for total protein (TP), secretory phospholipase A2 (sPLA2), intestinal fatty acid binding protein (I-FABP), lactate dehydrogenase (LDH), and N-acetylglucosamine (NAGA). TP content was 0.12 +/- 0.01 mg/mL up to 48 h, then gradually increased and stabilized at 0.39 +/- 0.05 mg/mL at day 21. By sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), one major protein band was identified in the low-molecular-mass range (15 kD), consistent with I-FABP and sPLA2. Secretory PLA2 levels decreased over the first 4 days to a low of 115 +/- 24.8% hydrolysis/min/fraction, then gradually rose to a plateau at approximately 529.76 +/- 88.36% hydrolysis/min/fraction by day 18. I-FABP levels rose rapidly from 0 ng/mL at 2 h to 900 +/- 250.0 ng/mL at 6 h and approximately 3000 +/- 304.9 ng/mL by day 14. LDH levels at 2 h and 48 h did not differ, with 0.03 +/- 0.004 and 0.03 +/- 0.005 optical density units (OD)/min/mL, respectively. NAGA levels were 0.07 +/- 0.05 OD/h/mL at 2 h and rose to 0.14 +/- 0.04 OD/h/mL at 48 h. These data suggest that after an early equilibration period, biochemical secretion into the lumen of normal rat bowel reaches a state of equilibrium, and therefore appears to reflect the baseline biochemical status of the bowel. Some of these levels are not negligible as one would expect in "normal" bowel. This information should prove extremely helpful as a baseline study of abnormal conditions of the intestine, such as ischemia or rejection.
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PMID:Biochemical alterations in rat Thiry-Vella fistulas. 1080 Oct 46

The term intestinal necrosis is nothing but a clinical and pathological concept and always includes intestinal ischemia, whether or not occlusive. In a broad sense, necrotizing enterocolitis involves intestinal ischemia associated to an infectious entity. The precipitating factor for necrosis is very often difficult to identify. Necrotizing enterocolitis occurs in 90% of cases in premature neonates and is less frequent amongst other neonates, being rare in older children and adults. The authors present two clinical cases: one 7 year-old with a history of chronic neutropenia and an eleven-year old with severe cognitive impairment, dysmorphic features and behavioural disturbances. They were both admitted to hospital due to an acute abdominal condition and shock. The necrosis implied the resection of a jejunal segment in one of the cases, and a subtotal colonic resection in the other. Despite the surgery and medical support therapy, they both died due to multiple system organ failure--3 hours and fourteen days after surgery, respectively. In the second case, death occurred subsequent to a second surgery for resection of a segment of necrotic ileum. Necropsy showed an extensive necrosis of the remaining intestine in both cases. These two cases evolved as necrotizing enterocolitis of the child. In one of the cases it was possible to establish the exclusion diagnosis of neutropenic enterocolitis. The etiopathogenic mechanisms are reviewed, including thrombotic, obstructive (both extrinsic and endoluminal), inflammatory, non-occlusive ischemic and infectious. The authors stress the general therapeutic measures, the relevance of early surgical intervention and the use of subsidiary diagnostic/therapeutic technologies, such as serum and urine title of intestinal fatty acid binding protein or selective arteriography.
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PMID:[Intestinal necrosis in children]. 1123 98

Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immunosorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM endotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P < 0.001) and IFABP-t (median 1.14 microg vs. 0.21 microg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median 0.06 microg; P = 0.005) than patients with mild attacks. IFABP correlated positively with the polyethylene glycol 3350 percentage retrieval (r = 0.50; P < 0.001), CRP (r = 0.51; P < 0.001), and inversely with serum IgM EndoCAb levels (r = -0.32; P = 0.02). The results of this study support the hypothesis that splanchnic hypoperfusion contributes to the loss of intestinal mucosal integrity associated with a severe attack of pancreatitis.
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PMID:Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis. 1255 82


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